Louisiana Society of Health-System Pharmacists 2017 Midyear Meeting
September 30, 2017
Program Book LOUISIANA SOCIETY OF HEALTH-SYSTEM PHARMACISTS BOARD OF DIRECTORS AND COMMITTEE CHAIRS
Joseph Gary LeBlanc Jr.—President Jennifer Smith—Immediate Past President Monica Morgan—President Elect Kisha Gant—Secretary Tommy Mannino—Treasurer Roxie Stewart—Director at Large Scott Dantonio—Director at Large Jason Chou—Director at Large Jessica Brady—Director at Large Liz Lafitte—Director-elect Jill Comeau—Director-elect
Ashley Selby—NLSHP President Savannah Posey—NELSHP President Alexis Horace—SCLSHP President Lori Gordon—SELSHP President Shane Domingue—SWLSHP President Joseph Gary LeBlanc—CLSHP President Jessica Brady-University of Louisiana at Monroe Faculty Liaison Iman Borghol-Xavier University Student Faculty Liaison
Committee Chairs Jamie Terrell—Education & Workforce Development Mike Loftin & Scott Dantonio– Pharmacy Management William Kirchain & Jeff Evans– Public Policy Vacant– Programming & Practitioner Education Dana Jamero– Publications Lisa Ross—Membership & Marketing Tammy Belleau– Pharmacy Practice Cynthia Nguyen & Fancy Manton—Subcommittee on Antimicrobial Stewardship Helen Calmes– Organizational Affairs & Documents Jackie Champagne– Technician Activities Katie Ducote—New Practitioners Committee Elizabeth Lafitte & Katie Astle—Midyear Meeting Coordinators Table of Contents
General Information & Activities……………………………………………………………………..……..1
Midyear Meeting Program………………………………………………………...……………...………..…..3
Sponsors & Exhibitors………………….…………………………………………………………………….…..5
Syllabus (listed chronologically) A Practical Approach to Maintaining USP 797 Standards and Initiating USP 800 Standards………………….………………………………………………………………...…….……..6 Joseph G. LeBlanc, Jr., PharmD, MHA, MBA
Preventing Patient Boomeranging: Transitions of Care………………….……………...... …..22 Kisha Gant, PharmD, BCACP, BCGP, BCPS & Ernest Terry, PharmD, RPh
Antiepileptic Medications: A Review for Pharmacists………………….….…………..…...…..31 Zahra Naini, PharmD
Safe Opioid Prescribing………………….…………………………………………………………..……...…43 Tom Driscoll, PharmD
Review of Current Hyponatremia Management………………….….……………...……..……....52 Andrea Clarke, PharmD
Pharmacy Legislative and Administrative Update………………….….……………....………....61 Jeffery Evans, PharmD
Medical Literature for Practicing Clinicians: Rules and Exceptions…………………..…..67 Bryan Donald, PharmD
Management of the Potentially Deceased Organ Donor: What Pharmacists Need to Know………………….……………………………………………………………………………….….…78 Ethan George, PharmD
Novel Agents Within Pediatric Pain Management………………….….……………...….………..88 Amber Grady, PharmD
Toxidromes & Toxic Homes: A Review of Common Household Poisons………………..100 Haley Smith, PharmD
Advances in Sickle Cell Disease: 20 Years in the Making………………….………...……...... 109 Elizabeth Travers, PharmD
General Information & Activities Registration The Midyear Meeting Registration and Information Desk will be open from 7:00 a.m.-5:00 p.m.
Badges Badges must be worn at all times. Badges are required for admittance to all Midyear Meeting functions. Registrants, staff, guests and speakers have white badges. Exhibitors have blue badges.
Meeting Locations All meeting sessions and exhibits will be held on the 2nd level of the Shreveport Convention Center. Please consult the program-at-a-glance or the schedule in this program book for specific meeting room locations.
Continental Breakfast There will be a continental breakfast from 7:00-7:45 a.m. in the Pre-Function Area on the 2nd floor.
Exhibit Program The exhibit program is located in Ballroom C&D on the 2nd level of the Shreveport Convention Center from 11:00 a.m. to 12:00 p.m. Our exhibitors then join us for lunch at noon. Please take time to visit our exhibitors and express your thanks for their participation. Additionally, please thank your local representative whom you see regularly at your practice site.
Lunch Lunch is provided for all paid registrants and exhibitors. Lunch will be served in the Exhibit Area of Ballroom C&D at 12:00 p.m.; lunch will not be served prior to 12:00. Please remember bring the lunch ticket found in your packet with you; lunch is only served to those with a ticket. Spouses/ guests are invited to attend lunch for $25 per ticket.
Continuing Education Credit The Louisiana Society of Health-System Pharmacists is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education. A total of 11 contact hours (1.10 CEUs) are scheduled for Saturday’s program, of which a maximum of 7 hours (0.7 CEUs) may be earned by an individual participant.
Evaluations Activity evaluations are extremely important in the development of educational needs assessment for future programs. Please take a moment to evaluate each CE activity you attend; we appreciate and value your input. A booklet of evaluations was included in your registration packet. Please personally turn in your evaluation packet at the end of the meeting, or after attending your last CE activity. We must collect this evaluation packet for you to receive CE credit for the activities at this meeting. Also, a separate general meeting evaluation form is in your packet. Please complete it and turn it in at the registration desk.
1 General Information & Activities, continued
Certification of Continuing Education Hours/ How to Receive Credit: To receive credit for continuing education activities at the Midyear Meeting registrants must: 1. Register and pay all applicable fees. 2. Attend the activity. 3. Complete the Continuing Education Credit Report packet that you received at registration. 4. Initial next to each activity that you attend. PARTIAL CREDIT WILL NOT BE GIVEN FOR ANY ACTIVITY. (For example, if you attended only 1 hour of a 2 hour activity, then you will not get any credit for it.) 5. Complete and sign the form and submit to the registration desk at the end of the conference or after attending your last activity. Include on the form your month of birth in “MM” format (for example, January is “01”) and day of birth in “DD” format (for example, the 3rd of the month is “03”). Also include your NABP e-Profile ID.
Due to ACPE credit recordation requirements, LSHP no longer issues statements of credit. Your CE credit will be recorded by the LSHP office electronically via CPE Monitor (see details below) within 60 days after the meeting.
CPE Monitor is a national, collaborative effort by ACPE and the National Association of Boards of Pharmacy (NABP) to provide an electronic system for pharmacists and pharmacy technicians to track their completed continuing pharmacy education (CPE) credits. All pharmacists and pharmacy technicians must obtain their NABP e-Profile ID by going to www.nabp.net. Your NABP e-Profile ID is required to receive credit for the LSHP Midyear Meeting. After the Midyear Meeting, LSHP will send to NABP and ACPE (via the CPE Monitor) the amount of credit you received (using your e-Profile ID) at the Midyear Meeting. Once this information is received by NABP, pharmacists and pharmacy technicians will be able to log in to access information about their completed CPE.
To receive credit, registrants must attend activities designated for their credentials Activities acceptable for pharmacists are indicated by a “P” suffix in the activity number. Programs acceptable for pharmacy technicians are indicated by a “T” suffix in the activity number.
A total of 11 contact hours (1.10 CEUs) are scheduled for Saturday’s program, of which a maximum of 7 hours (0.7 CEUs) may be earned by an individual participant.
2 Program Saturday, September 30, 2017 Registration 7:00 A.M.—5:00 P.M. Continental Breakfast 7:00—7:45 A.M. Pre-function Area - Level 2 Welcome & Announcements 7:45—8:00 A.M. Meeting Rooms 202/203
Joint Session 8:00—9:00 A.M. A Practical Approach to Maintaining USP 797 Standards and Initiating USP 800 Standards Joseph G. LeBlanc, Jr., PharmD, MHA, MBA 0179-0000-17-029-L04-P / 0179-0000-17-029- L04-T Meeting Rooms 202/203
Concurrent Sessions 9:00—10:00 A.M.
Preventing Patient Boomeranging: Antiepileptic Medications: Transitions of Care A Review for Pharmacists Kisha Gant, PharmD, BCACP, BCGP, BCPS & Zahra Naini, PharmD Ernest Terry, PharmD, RPh 0179-0000-17-030-L01-P/ 0179-0000-17-037-L04-P/ 0179-0000-17-030-L01-T 0179-0000-17-037-L04-T Meeting Room 204 Meeting Rooms 202/203
Concurrent Sessions 10:00—11:00 A.M.
Safe Opioid Prescribing Review of Current Tom Driscoll, PharmD Hyponatremia Management 0179-0000-17-038-L01-P/ Andrea Clarke, PharmD 0179-0000-17-038-L01-T 0179-0000-17-031-L01-P/ Meeting Room 202/203 0179-0000-17-031-L01-T Meeting Room 204
Exhibits 11:00 A.M.—12:00 P.M. Ballroom C&D
Lunch 12:00—1:00 P.M. Ballroom C&D Program continued on next page. 3 Program (continued)
Joint Session 1:00—2:00 P.M.
Pharmacy Legislative and Administrative Update Jeffery Evans, PharmD 0179-0000-17-039-L03-P/ 0179-0000-17-039-L03-T Meeting Rooms 202/203
Concurrent Sessions 2:00—3:00 P.M. Medical Literature for Practicing Clinicians: Management of the Potentially Deceased Organ Rules and Exceptions Donor: What Pharmacists Need to Know Bryan Donald, PharmD Ethan George, PharmD 0179-0000-17-033-L01-P 0179-0000-17-032-L01-P/ Meeting Rooms 202/203 0179-0000-17-032-L01-T Meeting Room 204
Concurrent Sessions 3:00—4:00 P.M.
Novel Agents Within Pediatric Toxidromes & Toxic Homes: A Review of Common Pain Management Household Poisons Amber Grady, PharmD Haley Smith, PharmD 0179-0000-17-035-L01-P/ 0179-0000-17-034-L01-P/ 0179-0000-17-035-L01-T 0179-0000-17-034-L01-T Meeting Rooms 202/203 Meeting Room 204
Joint Session 4:00—5:00 P.M. Advances in Sickle Cell Disease: 20 Years in the Making Elizabeth Travers, PharmD 0179-0000-17-036-L01-P / 0179-0000-17-036-L01-T Meeting Rooms 202/203
4
Sponsors The success of LSHP’s Midyear Meeting depends, in large part, on the participation and support of pharmaceutical and related interests. LSHP is very appreciative of the companies listed below that have generously supported the 2017 Midyear Meeting by educational or event sponsorship.
Exhibitors Below are the companies who are exhibiting this year. Please be sure to visit their exhibit table and thank them for supporting LSHP.
Astellas BTG International, Inc CSL Behring IPSEN Pharmaceuticals Morris & Dickson Co., LLC Nephron Pharmaceuticals Omnicell, Inc. PharMEDium Services LLC Piramal Critical Care Teva Oncology VigiLanz
5 Louisiana Society of Health System Pharmacists 2017 Midyear Meeting
8:00—9:00 a.m. A Practical Approach to Maintaining USP 797 Standards and Initiating USP 800 Standards
Joseph G. LeBlanc, Jr., PharmD, MHA, MBA Director of Pharmacy Heart Hospital of Lafayette Lafayette, LA
0179-0000-17-029-L04-P / 0179-0000-17-029-L04-T 1 contact hour (0.1 CEU) Knowledge-based activity
Objectives:
Pharmacist Technician Determine a best practice for cleaning their 1. Discuss the difference between disinfectants compounding area based on environmental and antiseptics and use the products sampling and cleaning product type. appropriately when cleaning the Outline an environmental sampling program compounding area. that follows best practices. 2. Discuss best practices for cleaning and Determine risk categories for compounded disinfecting the clean room environment. sterile products. 3. Recognize personal practices that may allow Discuss current concerns of regulatory contamination into the clean room. agencies dealing with compounded sterile 4. Discuss current concerns of regulatory products. agencies dealing with compounded sterile Discuss a systematic approach towards products. initiating compliance with USP 800 5. Recognize a systematic approach towards Standards. initiating compliance with USP 800 Standards.
Dr. LeBlanc has disclosed that he has no relevant financial relationships.
6 A Practical Approach to Disclosures Maintaining USP 797 I did work as a clean room consultant for independent Standards and Initiating USP pharmacies in Louisiana in 2016. 800 Standards
Joseph G. LeBlanc, Jr., PharmD, MHA, MBA LSHP President Louisiana Society of Health-System Pharmacists Director of Pharmacy Heart Hospital of Lafayette
Acknowledgements Learning Goals for the Pharmacist
Dr. Joann Gibbs, PharmD, BCPS The pharmacist will be able to: Director of Pharmacy at Byrd Regional Hospital 1. Determine a best practice for cleaning their compounding area based on environmental sampling and cleaning product type 2. Implement an environmental sampling program that follows best practices 3. Determine risk categories for compounded sterile products 4. Discuss current concerns of regulatory agencies dealing with compounded sterile products 5. Discuss a systematic approach towards initiating compliance with USP 800 Standards
Learning Goals for the Pharmacy Technician USP <797>
The pharmacy technician will be able to: A standardized methodology used to assist pharmacists in 1. Discuss the difference between disinfectants and antiseptics and use the producing compounded sterile products that are free of products appropriately when cleaning the compounding area deficiency or defect 2. Recognize personal practices that may allow contamination into the clean room Applies to pre-administration manipulations of compounded sterile preparations including compounding, transportation, 3. Recognize personal practices that may allow contamination into the clean room and storage 4. Discuss current concerns of regulatory agencies dealing with Applies to all compounding personnel without distinction to compounded sterile products site or profession- all patients deserve to be protected from 5. Recognize a systematic approach towards initiating compliance with USP errors and contamination 800 Standards
7 USP <797> Quality Monitoring
Notes that direct contact is the principal source of The practices in place to ensure the desired contamination in CSPs outcome and includes: Environmental Controls Applies to CSPs given via application, implantation, Temperature inhalation, injection, insertion, instillation, and irrigation Humidity Provides minimum standard for practice and quality for Cleanliness compounded sterile preparations of drugs and nutrients Airflow based on current scientific information and best sterile Personnel Control compounding practices. Training Technique
ISO Class 5 Sources, Buffer USP (797)—Quality Monitoring Areas, and Ante Areas
Deviations from standard in the items we monitor can result in contamination, loss of potency, or other undesirable outcomes.
Direct Compounding Area Environmental Controls
ISO Class U.S. FS 209E ISO, m3 FS 209E, ft3 3 Class 1 35.2 1 4 Class 10 352 10 5 Class 100 3,520 100 6 Class 1,000 35,200 1,000 7 Class 10,000 352,000 10,000 8 Class 100,000 3,520,000 100,000
ISO Classification of Particulate Mat- ter in Room Air (limits are in particles of 0.5 ìm and larger per cubic meter The DCA is only the portion of the Primary Engineering [current ISO] and cubic feet [former Federal Standard No. Control dedicated to the task of Aseptic manipulation. 209E, FS 209E])*
8 Environmental Controls Environmental Controls
Aimed at creating ISO 5,7, & 8 environments ISO 7 buffer and ISO 8 ante area- are “Secondary engineering controls” ISO 5- LAFW, BSC, CAI, CACI are “Primary Engineering Controls They Utilize HEPA filter air sources
Unidirectional airflow for exposure of critical sites is Must maintain ISO 7 or 8 during dynamic (in use) working required conditions
Must maintain ISO 5 during dynamic (in use) working Minimum of 30 air changes per hours of HEPA filtered air conditions (15 ACPH with recirculating ISO 5 device)
Airflow balance testing required at the installation site
Environmental Controls Environmental Controls
Monitor Frequency ISO 5 Primary engineering control (LAFW, BSC, CAI, Total Particle counts Every 6 months CACI) to be in an ISO 7 environment Pressure differential Every shift or continuously Exception: CAI if its design provides ISO 5 and isolation Temperature and Humidity Continuous from the room during dynamic operating conditions as placed Viable Air Sampling Every 6 months at your site ( including transferring materials in and out) Cleaning ISO class 5 environment At onset of each shift, before batches, when tested by CETA Guidelines after spills or surface contamination, & q 30 min during compounding activities. Only personnel and materials essential for compounding and cleaning are permitted Clean counters, work surfaces, & Floors Daily
Clean walls, ceilings, & storage shelving Monthly
Cleaning
Performing A mechanical process appropriate daily and Uses detergent and water monthly cleaning are Removes dirt, debris, and germs VITAL to risk Prepares the surface for disinfecting reduction.
9 Sanitizing Disinfecting
A Chemical process A Chemical process Decreases the number of microbes Destroys 100% of harmful bacteria, to “safe” levels viruses, and fungi Does not always kill spores
Sporicidal Agents Question for the Audience
Kill microorganisms 70% Isopropyl Alcohol is a sterilant. Kill spores 1. True 2. False
Determine how you are going to Best Practices purchase it?
Determine which germicidal detergent you are going to use. Ready to use Appendix II of USP<797> gives a list of agents No dilution necessary examples: Quaternary ammonium or phenolic Concentrate Requires Dilution Use sterile water for solutions needed to clean inside the Primary Engineering Controls. Can use tap water for diluting solutions for cleaning walls, floors, and other areas.
10 Documentation Cleaning Supplies
MSDS for germicidal detergent and sporicidal agent. Must be dedicated to the area. Store in the area by hanging mop on the wall. Have a measuring devise with clear instructions on how the agent should be measured. The same mop head can be used in the buffer and ante Discourage the practice of estimating measurements area if cleaning takes place in the proper order (cleanest to dirtiest area) Keep a preparation log that includes volume of Ceilings walls floors disposal germicide and type of water to prepare it.
Do I need to rotate cleaning Best Practices agents?
Resistance to disinfect agents does not develop like it Clean the inside of Primary Engineering does to antibiotics because they are more are: controls daily with germicidal detergent, allow Applied in a higher concentration surfaces to dry, the follow with sterile 70% IPA. Have more biocidal activity
Rotation is not required or needed. It is a myth that cleaning with IPA daily is Do use a sporicidal agent at least monthly. enough.
Best Practices Proper Cleaning Technique
Dilute germicidal agents (if dilution required) with STERILE Start in the cleanest area and mop yourself out WATER to clean the inside of the ISO Class 5 space and primary engineering controls. of the room. Clean in the following the primary engineering Tap water has 500 CFU/mL controls in the following order. Defined by US EPA drinking water standards Ceiling back sides IV bar and hooks Purified water has 100 CFU/mL anything in the PEC deck Sterile Water for Injection has <10 CFU/mL Defined by USP NF standards
11 Proper Cleaning Technique Environmental Sampling
Clean using overlapping strokes—pulling one- While the content of Chapter <797> was expanded in the way. Environmental Control section in 2008, the previous Environmental Monitoring section was deleted.
Scrubbing back and forth tends to spread Two subsections form the Environmental Monitoring section contamination. were added to this section. These are: Viable and Nonviable Environmental Sampling Personnel Training and Competency Evaluation of Garbing, Aseptic Work Practices, and Cleaning and Disinfection Procedures
Environmental Sampling Environmental Sampling
Designed to demonstrate that the primary and secondary Count the number of airborne viable microorganisms using engineering controls, disinfecting procedures, abd work volumetric air sampling practices result in a suitable environment for aseptic compounding Evaluation semi-annually with certification of the ISO 5,7, & 8 environments Utilizes several approaches at assess and evaluate Glove fingertip monitoring annually for Low and Medium Electronic Measurement of the total number of airborne Risk and semi-annually for High Risk Level particles
Certification of the ISO 5,7, & 8 environments every 6 months
Staff Controls Staff Controls
Personnel Training & Evaluation Personnel Training & Evaluation Personnel who prepare CSPs shall be trained Adequate training and evaluation must be completed conscientiously and skillfully by expert personnel, multi- BEFORE preparing CSPs media instructional sources, and professional publications Didactic training and pass a written exam in: Observational evaluation of aseptic work practices and Garbing procedures associated media fill Aseptic work practices Observational evaluation of proper hand hygiene, garbing, Achieving and maintaining ISO Class 5 environmental and cleaning and disinfection procedures conditions Cleaning and disinfection procedures
12 Staff Controls Staff Controls
Personnel Training & Evaluation Personnel Training & Evaluation Media-fill testing of aseptic work skills: If facilities cleaning and disinfection is performed by All compounding personnel initially support personnel: Personnel who prepare Low- and Medium-Risk Level CSPs- They must be initially trained in proper hand hygiene, Annually garbing, and cleaning & disinfection procedures Personnell who prepare High-Risk Level CSPs- Semi- Performance evaluation of support personnel shall be annually performed regularly by a qualified expert
Staff Controls Staff Controls
Personnel Training & Evaluation Personnel Training & Evaluation Hand Hygiene and garbing competency evaluation performed Direct contact contamination is the most likely source of initially and: introducing microorganisms Low- and Medium Risk Level- Annually Aseptic work practices observational evaluation using Aseptic High-Risk Level- Semi-Annually Technique Observational Audit Form Use of Hand Hygiene and Garbing Assessment Form Glove finger tip sampling after completion of the media-fill preparation
Staff Controls Microbiological Action Levels
Classifiaction Glove Finger Surface Sample Personnel Training & Evaluation Sample Surface cleaning and disinfection sampling and assessment and employee competency evaluation Agar contact plates or swab collection ISO Class 5 > 3 total > 3 per plate Incubation to determine the amount of growth Low- and Medium Risk Level- Annually ISO Class 7 N/A > 5 per plate High-Risk Level- Semi-Annually
ISO Class 8 N/A > 100 per plate
13 Staff Controls Introduction of Contaminants
Monitor Frequency Environmental factors Didactic Training Prior to working with CSPs, annually 1 hour of CE, and as indicated when Does your staff really follow cleaning procedures? processes or products change. Is your cleaning supplies adequate for the job? Garbing, Hand washing, and gloved Prior to beginning work with CSPs then fingertip sampling. observation and testing annually. Are your quality monitors being check as prescribed? Media Fill Testing Prior to beginning work with CSPs and Are filters being changed according to schedule? annually thereafter. Direct Observation Prior to beginning work with CSPs and annually thereafter. Cleaning and Disinfecting testing Prior to beginning work with CSPs and annually thereafter.
Personnel Cleansing and Dressing Properly Garbing
Remove outer garments and jewelry including piercings above the Head and facial hair covers neck Shoe Covers Recently there have been questions about iPod earbuds and Bluetooth headsets. These are not directly mentioned in the Face masks chapter, but fall under the same category as earrings etc. Sterile gloves Garb order from dirtiest to cleanest Non-shedding gowns Don shoe covers, hair covers, beard covers (any facial hair) and face masks (any order acceptable) No makeup
Perform hand/arm hygiene No externally visible piercings
Don disposable gowns No long fingernails
Staff Errors We are all HUMAN!
Does staff have appropriate attention to detail? Alcohol swabs being used only once. Products wiped with sterile IPA prior to putting inside the Personal practices will Drift over time. compounding chamber? Hand washing complied with? Garbing requirements complied with? Jewelry worn Staff members may pick up bad habits from others. Artificial nails Talking, eating, chewing gum Restocking by bringing cardboard into compounding area, increasing particulates. Pharmacists not gowning prior to going into the compounding area.
14 Questions to Ask To answer these questions you Is your staff doing it? must What are they doing it with? Directly Observe your staff working in the compounding area.
Responsibilities of Compounding Personnel Staff will place a higher Fourteen areas of responsibility are cited importance on what Emphasis on training and education Emphasis on compounding accuracy leadership inspects. Emphasis on avoiding contamination Emphasis on patient safety
Leadership CSP Risk Categories
Educate compounding staff to Immediate Use CSPs Understand Low-Level Low-Risk Level w/12 hour or less Beyond Use Date Believe A subsection of Low-Risk Level
Buy in to the importance of Medium-Risk Level
standards High-Risk Level
15 Determination of Risk Category Determination of Risk Category
Responsibility of the compounding personnel…. Think Exception: When non-sterile raw materials are used in about the risk compounding this will always create a High-Risk Level category No single rule to determination Putting sterile products into a non-sterile container also qualifies as high-risk level. Requires professional judgment
General descriptive statements to aid in compounding personnel
Study criteria for each risk level… no prescriptive way. Example: Reconstitution of sterile powder before injection versus TPN. What is the risk level?
Immediate Use Category Immediate Use Category
Exempt from all requirements in <797> Dose must be labeled if not administered by the preparer
Only simple aseptic measuring and transfer are needed Administration must begin within 1 hour after the start of preparation NMT 3 sterile non-hazardous drugs NMT 2 entries in one container Dose must be discarded if administration has not begun within 1 hour after the start of preparation No delays/interruptions No storing, No recycling No contact contamination of ingredients or critical sites Important: STUDY THE CRITERIA FOR EACH CATEGORY
Low Risk w/12 Hour Beyond Immediate Use Category Use Date
Some Examples: Intended to accommodate facilities/satellite pharmacies compounding only low risk level Compounded Sterile At a patient’s bedside Preparations in environments where the primary engineering In an ambulance controls cannot be located within an ISO Class 7, Clean In an ER Room or buffer area. There are specific conditions that have to be met, which include the following: In a war zone In a code situation “The CSPs must be prepared pursuant to a physician’s order for a specific patient, and administration of the CSP must commence within 12 hours of preparation, or as recommended by the manufacturer, whichever is earlier”
16 Low Risk w/12 Hour Beyond Microbiological Beyond-Use Use Date Dating
The primary engineering control must be in a segregated Risk Room Temp Refrigerator Freezer (-25 compounding area not in a high traffic area. Category C & -10 C)
All personnel cleansing and garbing requirements apply Immediate 1 hour 1 hour N/A Personnel preparing the CSP must follow requirements in the Use Personnel Cleansing and Garbing and Additional Personnel Low 48 Hours 14 days 45 days requirement sections among other sections, listed in the chapter. Low w/12-hr 12 hours or 12 hours or N/A No Hazardous Drugs BUD less less
Administration must begin within 12 hours or as stated in the Medium 30 hours 9 days 45 days package insert, whichever is less High 24 hours 3 days 45 days
Single/Multiple Dose Vials Single/Multiple Dose Vials
Single dose vials Multiple dose vials Opened or punctured in ISO 5 environment may be Contain antimicrobial preservatives used for up to 6 hours. Designed for entry on multiple occasions Opened or punctured in worse than ISO 5 must be Beyond use date- 28 days after initial entry unless used within 1 hour or discarded specified otherwise by the manufacturer Single Dose Ampules Beyond use date of 28 days based on USP <51> Antimicrobial Preservative Testing MUST be discarded and not stored for any time period
Determine the Risk Category Determine the Risk Category
1. Banana Bag (0.9% NS A. Low- Risk 1. Banana Bag (0.9% NS A. Low- Risk 1L, Thiamine 100 mg, 1L, Thiamine 100 mg, Folic Acid 1mg, & MVI B. Medium Risk Folic Acid 1mg, & MVI B. Medium Risk 10 mL) 10 mL) C. High Risk C. High Risk 2. 2 Gram IM Rocephin 2. 2 Gram IM Rocephin Compound (Rocephin 2 Compound (Rocephin 2 Gm, 2.6 mL SWFI, 1 Gm, 2.6 mL SWFI, 1 mL 1% Lidocaine) mL 1% Lidocaine)
3. 5 Grams of Non-Sterile 3. 5 Grams of Non-Sterile Talc in 60 mL SW for Talc in 60 mL SW for irrigation irrigation
17 Can this CSP be Compounded Can this CSP be Compounded in this Environment? in this Environment?
Formula: Clinimix 4.25/5 1000 mL with KPhos 15 mMol/L, No, it cannot be compounded under these conditions NaCl 35 mEq/L, Magnesium Sulfate 5 mEq/L, 10 ml MVI, & This is a medium-risk compound 1 mL Trace Elements to run at 40 cc/hr for 24 hours. More than 3 sterile ingredients and would require more than 2 entries into a single container Environment: Mobile Isolation Chamber (MIC) contributing Though the MIC & Buffer Rooms maintains ISO Class 5 & ISO 10 ACPH the Buffer Room in which it is located. The SEC Class 7 requirements for particle counts they do not for control contributes an additional 5 ACPH into the buffer room minimum ACHP making the MIC ISO 5 environment not through a non-filtered vent. The environmental air sampling contained by an ISO 7 Buffer or Ante Room. taken 60 days prior revealed 3,100 particles/cubic foot inside Assuming that the walls and ceilings are coved an seamless the the MIC and 290,000 particles/cubic foot inside the buffer room highest risk category that could be performed in this environment is that encases the MIC. low-risk compounds with a 12-hour BUD.
USP <800> Hazardous Drugs
USP <800> is: Drugs are classified as hazardous if studies in animals or A Standardized methodology for handling hazardous drugs (HDs) humans indicate that exposures to them have a potential for with the intent of promoting: causing cancer, developmental or reproductive toxicity, or Patient Safety harm to organs Worker Safety Environmental Protection If an API exhibits one or more of the following in humans USP <800> includes: and/or animals it is considered a hazards drug: Receipt, storage, dispensing, administration, & disposal of sterile Carcinogenicity, teratogenicity or other developmental toxicity, and non-sterile products/preparations reproductive toxicity, organ toxicity at low doses, genetoxicity, structure and toxicity profiles of new drugs that mimic existing USP <800 Applies to: drugs determined hazardous by the aforementioned criteria. All healthcare personnel and entities that store, prepare, transport, handle, and administer HDs.
Product Risk Assessment
Any HD API appearing on the NIOSH list must follow USP <800> containment requirements, HOWEVER…… USP <800> Uses and coordinates pharmacy practice into concert with the NIOSH list of Antineoplastic and other A documented risk assessment can be performed and Hazardous drugs in healthcare setting. implemented to exempt drugs on the NIOSH list that are https://www.cdc.gov/niosh/docs/2016-161/pdfs/2016-161.pdf either final dosage forms of compounded HD preparations or conventionally manufactured HD products from USP <800> NIOSH categorizes HDs into 3 groups: containment requirements. Antineoplastic Drugs Non-Antineoplastic Drugs that meet at least one of the If appropriately designed and executed this assessment of aforementioned NIOSH criteria for an HD. risk will allow certain alternative containment strategies and work practices. Drugs that pose a reproductive risk only to men and women who are actively trying to conceive and women who are pregnant or breast feeding.
18 Product Risk Assessment Question for the Audience
An assessment of risk must consider the following Once an assessment of risk has been performed and characteristics: policies/procedures have been developed/implemented for Type of HD (what NIOSH category) alternative work practice and containment for the specified Dosage form HDs how often showed this policy be reviewed and Risk of Exposure documented to remain valid? Packing A. Quarterly Manipulation B. Bi-annually Documentation of what alternative containment strategies C. Annually and/or work practices are being applied to respected HDs to D. On a periodic Basis minimize occupational and environmental exposure is of E. None of the above essence.
Receipt, Storage, Compounding Question for the Audience of HDs
Once an assessment of risk has been performed and A designated area must be dedicated towards: policies/procedures have been developed/implemented for Receipt & Unpacking alternative work practice and containment for the specified Neutral or normal pressure room relative to surrounding HDs how often showed this policy be reviewed and Not to be unpacked in positive pressure or sterile compounding documented to remain valid? areas A. Quarterly Storage of HDs B. Bi-annually Separate from non-HDs in a negative pressure externally ventilated C. Annually room with NLT 12 ACPH (this goes for refrigerated HDs as well)/ D. On a periodic Basis Non-sterile HD compounding (if performed) E. None of the above Sterile HD compounding (if performed) ECs required to prevent product cross-contamination and microbial contamination.
Question for the Audience Question for the Audience
Sterile and Non-Sterile HD compounding may not occur in Sterile and Non-Sterile HD compounding may not occur in the same room under any conditions. the same room under any conditions. True True False False
Sterile and Non-Sterile HD compounding may not occur in the same room if: sterile and non-sterile compounding do not occur simultaneously The PECs are distinguished and separated by NLT 1 meter The PECs are encased by a negative pressure ISO 7 buffer room
19 Stepwise Approach for Cleaning Hazardous Drugs as CSPs Hazardous Drugs
Choosing appropriate Primary Engineering Controls •Renders HD Deactivation inert (Done with bleach)
Decontamination • Removes the HD residue
• Removes organic Cleaning & inorganic material
NIOSH recommends ECs that do not recirculate for use with Disinfection •Destroys hazardous drugs that volatize at room temperature. Consider all microbes repercussions prior to determining the best EC for your application Letter from Ken Mead NIOSH
Surface Wipe Sampling References
Metric for HD Environmental and Quality Monitoring Critical Point. Sterile Compounding Boot Camp. Critical Point, LCC. 2007-2013. Accessed 6/21/2015 http://www.criticalpoint.info/boot- camp/ Evaluates the ability of an entities decontamination methods for removing HD reside from a targeted environment Douglass K, Kastango E. Requirements and Best Practices for Sanitizing Engineering Engineering Controls.Pharmacy Purchasing and Products. September 2013. Accessed Should be performed initially as benchmarked and then 6/21/15http://www.pppmag.com/article/1387/March_2014/Requir every 6 months or as needed verify containment. ements_and_Best_Practices_for_Sanitizing_Engineering_Controls/ Gruson D, Hilbert G, Vargas F, Valentino R, et al. Strategy of Several different methods are documented (6) and the best Antibiotic Rotation: Long-term Effect on Incidence and method of choice should be selected for your facility and Susceptibilities of Gram-negative Bacilli Responsible for Ventilator Associated Pneumonia. Society of Critical CareMedicine and validated. Lippincott Williams. July 2003; 31(7): 1908-1914. Accessed6/20/15 http://journals.lww.com/ccmjournal/Abstract/2003/07000/Strategy_ of_antibiotic_rotation__Long_term_effect.3.aspx
References References
Institute for Safe Medication Practices Medication Safety Alert . NIOSH List of Antineoplastics and Other Hazardous Drugs in Sterile Compounding Tragedy is A Symptom of a Broken System Healthcare Settings 2016. https://www.cdc.gov/niosh/docs/2016- on Many Levels. Institute for Safe Medication Practices. October 161/pdfs/2016-161.pdf
20 References References
Okeke C. USP Chapter<797> Update on Recent Revisions. Yaniv A. Considerations for Environmental and Personnel United States Pharmacopeia. NAPB Annual Meeting 2008. Monitoring. Pharmacy Purchasing and Products. November 2010. Accessed 6/21/15 United States Pharmacopeial Convention. <797 http://www.pppmag.com/article/789/November_2010/Co Pharmaceutical Compounding-Sterile Preparations: Revision nsiderations_for_Environmental_and_Personnel_Monitoring Bulletin. 2008. /?surface%20sampling
United States Pharmacopeial Convention. USP Compounding Compendium. 2015. Accessed 7/1/2015 http://www.usp.org/store/products-services/usp- compounding-compendium
21 Louisiana Society of Health System Pharmacists 2017 Midyear Meeting
9:00—10:00 a.m. Preventing Patient Boomeranging: Transitions of Care
Kisha Gant, PharmD, BCACP, BCGP, BCPS Clinical Coordinator, Pharmacy Slidell Memorial Hospital Slidell, LA
Ernest Terry, PharmD, RPh Transitions of Care Pharmacist Slidell Memorial Hospital Slidell, LA
0179-0000-17-037-L04-P/ 0179-0000-17-037-L04-T 1 contact hour (0.1 CEU) Knowledge-based activity
Objectives:
Pharmacists: Technicians: 1. Define Transitions of Care. 1. Define Transitions of Care. 2. Discuss the implementation of a 2. Outline an interview of a prospective Transitions of Care program, including patient about their home medications to planning, collaboration, and required provide an accurate list for the medication resources. reconciliation process. 3. Outline an interview of a prospective 3. Discuss the follow-up services offered by patient about their home medications to the hospital to patients by members of the provide an accurate list for the medication healthcare team after discharge or other reconciliation process. care transitions. 4. Discuss the handoff communication process involving medication changes made in the inpatient setting to the patient’s medication discharge list. 5. Discuss the follow-up services offered by the hospital to patients by members of the healthcare team after discharge or other care transitions.
Drs. Gant and Terry have disclosed that they have no relevant financial relationships.
22 Pharmacist Objectives At the conclusion of this continuing education activity, the pharmacist should be better able to:
1. Define Transitions of Care. Preventing Patient Boomeranging: 2. Discuss the implementation of a Transitions of Care program, Transitions of Care including planning, collaboration, and required resources. 3. Interview a prospective patient about their home medications to provide an accurate list for the medication reconciliation process. 4. Discuss the handoff communication process involving Kisha O’Neal Gant, PharmD, BCACP, BCPS, BCGP medication changes made in the inpatient setting to the patient’s Clinical Pharmacy Coordinator medication discharge list. 5. Discuss the follow-up services offered by the hospital to patients Ernest Terry, PharmD by members of the healthcare team after discharge or other care Transitions of Care Pharmacist transitions.
Pharmacy Technician Objectives Question 1 What is a Transitions of Care? At the conclusion of this continuing education activity, the pharmacy technician should be better able to: A. The movement of a patient from one hospital room to another during his/her hospital stay. 1. Define Transitions of Care. 2. Interview a prospective patient about their home medications to B. The process of multiple healthcare professionals provide an accurate list for the medication reconciliation process. examining a patient. 3. Discuss the follow-up services offered by the hospital to patients C. The movement of a patient from one healthcare by members of the healthcare team after discharge or other care setting to another. transitions. D. The process of healthcare providers examining multiple patients.
Question 2 Question 3 When implementing a transitions of care When interviewing a patient, one should program, one should consider: consider developing a set of questions A. Meeting with involved parties during the planning for standardization. phase. A. True B. Consider partnering with various departments and outside organizations. B. False C. Developing a documentation tool. D. All of the above.
23 Question 4 Question 5 Based on the SHARE acronym, a reason Which of the following is a follow-up for successful handoff communication service offered to patients by the SMH includes: transitions of care team? A. Having various communication forms to account for A. Home visits by a pharmacist variety in communication style. B. Follow-up phone calls B. Assessing the quality and effectiveness of your C. Behavioral counseling process process every 20 years. D. Personal athletic trainers C. Standardizing critical content. D. Employing a punitive process when handoffs are unsuccessful.
Transitions of Care (TOC) Why TOC ?
• Inadequate TOC leads to more adverse drug events and increased hospital readmissions & cost
• In one study, 80% of serious med errors due to ineffective communication during handoffs
1. J Gen Intern Med, April 2005;20(4):317-23 2. Medicare Payment Advisory Commission, Report to the Congress: Reforming the Delivery System, Washington, D.C.: MedPAC, June 2008 Eligible Professional Meaningful Use Menu Set Measures Measure 7 of 9 Stage 1 (2014 Definition) Last updated: May 2014 3. Acad Med, 2005;80:1094-9
About Slidell Memorial Hospital (SMH) • 229-Bed Acute Care Community Hospital • Clinical Pharmacy Team October 2015 June 2015 Funding & February 2016 – Infectious Diseases Pharmacist Discussion of Position Approval Candidates – Clinical Pharmacist TOC Began Sought Interviewed
August 2015 November 2015 February 2016 Research Position Approved Ernest Terry Hired
24 Planning Planning Transitions of Care Conference Call 1-23-16 Proposed Transitions of Care Pharmacist's (TOCP) Training Schedule • Meetings, meetings, & more meetings
Week 1-2: March 12 – April 1, 2016 – Director of Pharmacy o Train with staff pharmacists
Week 3-4: April 4 – April 15, 2016 o Clinical Training – Xavier University College of Pharmacy . Physicians Webstation . Sentri7 . P & T . Counseling – Case Management Week 5: April 18 – April 22, 2016 o Patient counseling . Kisha will go with pharmacist to assess counseling techniques and intervene if necessary – Senior Management Team Week 6: April 25 – 29, 2016 o Rounding with Case Management for 2-3 days – Documentation Platform [ ]Schedule meeting to assess if any additional training needs exist
– Information Technology Department [ ]Meeting scheduled between Kisha and Michael to determine effectiveness of TOCP's services Possible metrics o Pt satisfaction survey of TOCP's services o Readmission rates o HCAPS Discuss TOCP documentation platform (3M system?) o [ ]Kisha will speak with Gretchen regarding the possible utilization of Sentri7 pending the February 17, 2016 meeting with Martha Cato and Steven Collins from HCS regarding a possible HCS documentation platform
Planning Collaboration
Transitions of Care Pharmacist Daily Schedule • Xavier University College of Pharmacy Time Task
8:00 AM – 9:00 AM Check inbox and run report for high-risk patients who will be discharged • Information Technology Department Review high-risk medication therapy management, discharge, and referral patients
9:00 AM – 12:00 PM Perform discharge medication reconciliations for • Case Management high-risk or referral patients Provide medication specific education Schedule follow-up appointments for medication therapy management if applicable • Documentation Platform Specialists Consult with healthcare providers as needed
12:30 PM – 1:00 PM Lunch • Quality Improvement Department
1:00 PM – 3:00 PM Conduct medication therapy management visits
3:00 PM – 4:30 PM Make follow-up and return phone calls to • Walgreens (located inside SMH) patients and healthcare providers Transmit medication information and recommendations to healthcare providers upon completion of medication therapy management sessions Contact providers for lower cost medication options Review patient referrals
Required Resources • Office Space • Technology (Computers, Telephones, Etc.) • Office Supplies • Documentation Platform TRANSITIONS OF CARE • Workflow IN ACTION – Patient list • Patient Medication Assistance Resources • Durable Medical Equipment
25 Goals of the TOC Program Diagnoses Group Followed
• Acute Myocardial Infarction (AMI) • Reduce 30-day readmission rates • Heart Failure (HF) • Pneumonia • Reduce healthcare spending without reducing health care quality • Chronic Pulmonary Obstructive Disorder (COPD) • Hip Replacement Improve coordination and continuity • • Knee Replacement • Coronary Artery Bypass Graft (CABG) Surgeries – 2017
Failure to Implement an Effective THE FIRST FIVE YEARS OF THE HOSPITAL READMISSION REDUCTION PROGRAM Transitions of Care Program • Hospital Readmissions Reduction Program (HRRP) • Problematic transitions occur from and to virtually every type of health care setting, but especially – Provision in the Affordable Care Act (ACA) – Requires Medicare to reduce payments to hospitals with when patients leave the hospital to receive care in relatively high readmission rates for patients in traditional another setting or at home Medicare. Readmission rates that exceed the national average are penalized • The federal government has taken notice: by a reduction in payments across all of their Medicare Hospitals with unacceptably high readmission admissions—not just those which resulted in readmissions. rates for Medicare & Medicaid patients will face CMS adjusts for certain demographic characteristics of both the patients being readmitted and each hospital’s patient population financial penalties under the Patient Protection (such as age and illness severity) and Affordable Care Act. Posted on CMS website
Root Causes of Ineffective TOC Various Transitions Of Care Programs Models • Care Transitions Intervention • Communication breakdowns • Transitional Care Model Better Outcomes for Older Adults through Safe Patient education breakdowns • • Transitions • Accountability breakdowns • The Bridge Model • Inadequate patient follow-up • Guide Care • Geriatric Resources for Assessment and Care of Elders • Project Red
26 What Our Model Looks Like!
• A combination of all models • Focus on “at risk” patients • Review home medications • Follow up at 7 days • Follow up at 21 days PATIENT INTERVIEW PROCESS • Drug cards, appointments, canes/walkers, etc
Handoff Communication Patient Workup
• The acronym SHARE addresses the specific causes why handoffs are unsuccessful. • SHARE stands for: Standardize critical content Hardwire within your system Allow opportunities to ask questions Reinforce quality & measurement Educate & coach
Assessment (Initial) Interventions Intervention Summary May 2017
OVERALL SUMMARY
Prepared a Drug Card for the Patient 9 Dietary Consult 11 Affordability 7 Medication Underuse/Poor Adherence 1 Treatment Recommendations 19 Gave Patient a Glucometer 4 Inadequate Patient Self Management 2 Patient Requires a Social Worker Consult 7 Access Issue 39 Initial Patient Education 1361 Inadequate Patient Self Management 1 Duplicate Therapy 2
Total Assessments Completed-Successful Phone Follow-up 104 Total Failed Contact Attempts-Unsuccessful Phone Follow-up 143
TOTAL-Assessments+Attempts 247
Total Interventions: 1710
27 .All of the above. a Developing tool. documentation D. C. and with partnering various departments Consider B. parties Meetingwith during the involved planning A. one shouldconsider: program, implementing atransitions When ofcare Medicaton Card outside organizations. outside phase. Intervention Total Interventions: TotalFollow-up Phone Contact Failed Attempts-Unsuccessful Follow-up Phone TotalCompleted-Successful Assessments Total Initial Interventions: Treatment Medication for Indication No Challenges Administration Consult Instruction Respiratory Contraindicated Medications Interaction Drug Polypharmacy Education Patient Initial Issue-Transportation Access Requires Consult a Social Worker Patient Gave aGlucometer Patient Treatment Underuse/Poor Adherence Medication Affordability Consult Diabetic Consult Dietary Patient the for Card aDrug Prepared notOptimal Dosage withSetup Patient aPCP OVERALL SUMMARY TOTAL-Successful+ Unsuccessful P Interventions
Summary Question 2 June 2017 hone Follow-up hone Follow-up Call Attempts 1125 248 165 877 828 83 12 1 1 1 1 4 1 1 5 2 5 1 3 1 7 2 1 D. The process of healthcare providers examining examining providers ofhealthcare process The D. healthcare one from of apatient movement The C. professionals healthcare ofmultiple process The B. room hospital one from of apatient movement The A. What isa Transitions ofCare? .False True B. A. for standardization. developinga setof consider questions interviewing a patient, When one should multiple patients. to setting another. a examining patient. stay. to hospital during his/her another Follow-Up Assessment Question 3 Question 1 28 Question 4 Question 5 Based on the SHARE acronym, a reason Which of the following is a follow-up for successful handoff communication service offered to patients by the SMH includes: transitions of care team? A. Having various communication forms to account for A. Home visits by a pharmacist variety in communication style. B. Follow-up phone calls B. Assessing the quality and effectiveness of your C. Behavioral counseling process every 20 years. D. Personal athletic trainers C. Standardizing critical content. D. Employing a punitive process when handoffs are unsuccessful.
References
• Care Transitions: Best Practices and Evidence-Based Programs. Center for Healthcare Research & Transformation, 15 Jan. 2014. • Clark, Kathy, et al. “Hot Topics in Health Care. Transitions of Care: The Need for a More Effective Approach to Continuing Patient Care , June 2012 • Transitional Care Management Services . Centers for Medicare and Medicaid Services , Department of Health and Human Services . • Transitions of Care Measures . NTOCC Measures Work Group, 2008. • The Joint Commission Center for Transforming Healthcare. Facts Questions? About the Hand-off Communication Project. Accessed August 21, 2017. Available at http://www.centerfortransforminghealthcare.org/assets/4/6/CTH_HOC _Fact_Sheet.pdf
TOC Resources TOC Resources
• Best Practices from the ASHP-APhA Medication Management in • National Transitions of Care Coalition (NTOCC) Care Transitions Initiative – http://www.ntocc.org/Portals/0/PDF/Resources/PolicyPaper.pdf – http://media.pharmacist.com/practice/ASHP_APhA_MedicationManage mentinCareTransitionsBestPracticesReport2_2013.pdf • Center for Medicare & Medicaid Services Readmission and Care Transitions • The Joint Commission Transitions of Care (ToC) Portal – https://partnershipforpatients.cms.gov/p4p_resources/tsp- – https://www.jointcommission.org/toc.aspx preventablereadmissions/toolpreventablereadmissions.html
• Pharmacy Society of Wisconsin Transitions of Care Toolkit – http://www.pswi.org/Resources/PSW-Transitions-of-Care-Toolkit
29 Ernest Terry, PharmD Transitions of Care Pharmacist [email protected]
Kisha O’Neal Gant, PharmD, BCACP, BCPS, BCGP Clinical Pharmacy Coordinator [email protected]
30 Louisiana Society of Health System Pharmacists 2017 Midyear Meeting
9:00—10:00 a.m. Antiepileptic Medications: A Review for Pharmacists
Zahra Naini, Pharm.D. PGY-1 Pharmacy Resident University Health Shreveport Shreveport, LA
0179-0000-17-030-L01-P/ 0179-0000-17-030-L01-T 1 contact hour (0.1 CEU) Knowledge-based activity
Objectives:
Pharmacist Technician 1. Review pathophysiology and 1. Recognize antiepileptic medications (AEDs) classification of seizures. used in treatment of seizures. 2. Outline antiepileptic drugs (AEDs) used 2. Recognize different drug handling in treatment of seizures. techniques in preparing AEDs. 3. Identify appropriate drug monitoring and dosage adjustments required with AEDs
Dr. Naini has disclosed that she has no relevant financial relationships.
31 Disclosure Antiepileptic Medications: A 2 Review for Pharmacists Author of this presentation has nothing to disclose
1 concerning possible financial or personal
ZAHRA NAINI relationships with commercial entities that may have PGY-1 PHARMACY PRACTICE RESIDENT direct or indirect interest in the subject matter of the UNIVERSITY HEALTH SHREVEPORT presentation
Objectives for Pharmacists Objectives for Technicians
3 4
Review pathophysiology and classification of Recognize antiepileptic drugs (AEDs) used in seizures treatment of seizures
Outline antiepileptic drugs (AEDs) used in treatment of seizures Recognize different drug handling techniques in preparing AEDs Identify appropriate drug monitoring and dosage adjustments required with AEDs
History of Seizure History of AEDs
5 6
Babylonians: presence of demons Bromide: 1st AED
400 B.C. Hippocrates: natural disease Phenobarbital: first synthetic agent
1849 Robert Bentely Todd: electrical theory Phenytoin
1873 John Hughlings Jackson
1930 Hans Berger: electroencephalography (EEG)
Yasiry Z, Shorvon S. How phenobarbital revolutionized epilepsy therapy: The story of phenobarbital therapy in epilepsy in the last 100 years http://nawrot.psych.ndsu.nodak.edu/epilepsy/History.htm [Accessed 15 Aug. 2017]. (2012). Epilepsia, 53(Suppl. 8):26–39. c
32 Epidemiology and Pathophysiology of Epileptic Seizures
Hughes JR. Emperor Napoleon Bonaparte: did he have seizures? Psychogenic or epileptic or both? Epilepsy Behav. 2003 Dec;4(6):793-6 7 8
Epidemiology Pathophysiology
9 10
Epilepsy is the second most common neurological Seizure refers to a transient alteration of the disorder after stroke behavior due to the disordered, synchronous, rhythmic firing of population of brain neurons About 1% of adults ages 18 years and older have epilepsy
0.6% of children 17 years and younger have active Epilepsy is the condition of recurrent seizures due to epilepsy abnormal electrical activity of the brain
The total direct and indirect cost of epilepsy in the United States is estimated to be $15.5 million annually
Virtanen AI, Molecular and cellular bases of epileptogenesis in symptomatic epilepsy. Epilepsy & Behavior. 2009; 14. 16-25 Bromfleid, E, Cavazos, J, Sirven, J. An Introduction to Epilepsy, American Epilepsy Society, 2006.
Pathophysiology Cont’d Pathophysiology
11 12
Hyper-excitability can result from: Seizure can arise from an imbalance between
Increased excitatory synaptic neurotransmission excitatory and inhibitory neurotransmitters
Decreased inhibitory neurotransmission Glutamate GABA Alteration in voltage-gated ion channel
Alteration in intra- or extra-cellular ion concentration
Epilepsy
Bromfleid, E, Cavazos, J, Sirven, J. An Introduction to Epilepsy, American Epilepsy Society, 2006. Bromfleid, E, Cavazos, J, Sirven, J. An Introduction to Epilepsy, American Epilepsy Society, 2006.
33 ILAE Seizure Classification 2016
14
Focal Generalized Unknown Onset Motor Motor Motor Tonic Tonic-clonic Tonic-clonic International League Against Epilepsy Atonic Tonic Tonic Myoclonic Atonic Atonic Clonic Myoclonic Epileptic spasm (ILAE) Classification of Seizures Epileptic spasm Myotonic-aclonic Hypermotor Clonic Non-motor Clonic-tonic-clonic Non-motor Epileptic spasm Aware Impaired Unknown Sensory awareness awareness Cognitive Absence Emotional Typical Unclassified Autonomic Atypical Aware Impaired Unknown Myoclonic awareness awareness Eyelid myoclonia
To bilateral tonic-clonic
13 Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH, van Emde Boas W, et al. Revised terminology and concepts for organization of seizures and epilepsies: Report of the ILAE Commission on Classification and Terminology, 2005-2009. Epilepsia 2010;51:676-85.
ILAE Seizure Classification 2017 Risk Factors For Seizures
15 16 Focal Generalized Unknown Onset Head injury or stroke Aware Impaired awareness Motor Motor Tonic-clonic Tonic-clonic Cerebral palsy Motor Onset Clonic Epileptic spasm Automatism Tonic Mental retardation (e.g. down syndrome) Atonic Myoclonic Non-motor Clonic Myoclonic-tonic-clonic Behavior arrest Low birth weight Epileptic spasm Myotonic-aclonic Hyperkinetic Atonic Unclassified Excessive sleep/sleep deprivation Myoclonic Epileptic spasm tonic Emotional stress Non-motor Onset Non-motor Autonomic (absence) Hormonal changes (menses, puberty, pregnancy) Behavior arrest Typical Cognitive Atypical Illicit drug use Emotional Myoclonic Sensory Eyelid myoclonia Alcohol Focal to bilateral tonic-clonic
Sun Y et al. Gestational Age, Birth Weight, Intrauterine Growth and Risk for Epilepsy. American Journal of Epidemiology. 2008 Feb 1; 167(3); 262-270. Scheffer IE, Berkovic S, Capovila G, et al. ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Lott IT, Dierssen M. Cognitive deficits and associated neurological complications in individuals with Down's syndrome. Terminology. Epilepsia 2017. DOI: 10.1111/epi.13709. Lancet Neurol. 2010;9(6):623.
Drugs That Lower Seizure Threshold Antibiotics That Lower Seizure Threshold
17 18
Usage Generic Name Antibiotic Class Medications Respiratory Medications Theophylline Penicillins Ampicillin, amoxicillin Pain Medications Tramadol, meperidine Cephalosporins Cefepime, cephalexin, cefdroxil Antipsychotics Clozapine, quetiapine, olanzapine Carbapenem Imipenem/cilastatin, meropenem, ertapenem, doripenem Antidepressant Bupropion Quinolones Levofloxacin, ciprofloxacin, Anti-parasite Lindane Moxifloxacin Smoking Cessation Aid Varenicline Illicit Drugs Cocaine, amphetamines
Hitchings AW, Drugs that lower the seizure threshold. Adverse Drug Reaction Bulletin 2016; 1151 Hitchings AW, Drugs that lower the seizure threshold. Adverse Drug Reaction Bulletin 2016; 1151. Brothrton TJ, Kelber RL. Seizure-like activity associated with imipenem. Clin Pharmacy 1984;3:536–540 .
34 Diagnosis Diagnosis Cont’d
19 20
Obtain patient’s medical history Electroencephalography (EEG) Description of events Imaging of brain Seizure precipitant or trigger Computed tomography (CT) Prior events Magnetic resonance imaging (MRI) Medications and substances Past medical history Family history
Krumholz A, et al Practice Parameter: Evaluating an apparent unprovoked first seizure in adults (an evidence-based review). American Krumholz A, et al Practice Parameter: Evaluating an apparent unprovoked first seizure in adults (an evidence-based review). American Academy of Academy of Neurology. 2007; 1996- 2007. Neurology. 2007; 1996- 2007. . .
Factors For Choosing AEDs
21
Drug appropriate for seizure type Adverse effects Overview of Antiepileptic Drugs Drug interactions
Comorbidities (Hepatic and renal disease)
Age and gender (e.g. teratogens in childbearing age)
Patient preference
Cost
Glauser T, Ben-Menachem E, Bourgeois B, et al. Updated ILAE evidence review of antiepileptic drug efficacy and effectiveness as initial 22 monotherapy for epileptic seizures and syndromes. Epilepsia. 2013 Mar;54(3):551-63.
Mechanism of Action of AEDs
23
Voltage- Calcium GABA activity Glutamate Multiple Miscellaneous dependent currents receptors mechanism sodium of action channels Adverse Effects of AEDs Carbamazepine Ethosuximide Phenobarbital Perampanel Valproate Gabapentin Oxcarbazepine Tigabine Felbamate Pregabalin Phenytoin Vigabatrin Topiramate Levetiracetam Lamotrigine Benzodiazepines Brivaracetam Zonisamide Ezogabine Lacosamide Rufinamide Eslicarbazepine
24
35 AEDs Warnings
25 All AEDs require MedGuide due to risk of suicidality
All AEDs can increase risk of fractures Drugs that Affect Voltage-dependent Vitamin D Sodium Channels Calcium
The most common side effects are somnolence, fatigue, cognitive impairment, and incoordination
Do not stop abruptly, can increase the risk of seizure
Mula M, Kanner AM, Schmitz B, Schachter S. Antiepileptic drugs and suicidality: an expert consensus statement from the Task Force on Therapeutic Strategies of the ILAE Commission on Neuropsychobiology. Epilepsia 2013; 54:199.. Vestergaard P. Epilepsy, osteoporosis and fracture risk - a meta-analysis. Acta Neurol Scand 2005; 112:277. 26
27 28
Carbamazepine Carbamazepine
29 30
Dosing in renal impairment: avoid use in CrCl< 15 Warnings: Toxic epidermal necrolysis (TEN) and Steven-Johnson ml/min syndrome (SJS); Asian patients should be tested for (HLA)- B*1502 allele Use of extended-release formulation is associated Aplastic anemia with fewer central nervous system adverse effects Agranulocytosis Drug Reaction with Eosinophilia and Systemic Symptoms No adjustments in hepatic impairment (DRESS)
Normal Carbamazepine level: 4-12 mcg/mL
Carbamazepine. [Package Insert].Novartis, NJ. 2014. Carbamazepine. [Package Insert].Novartis, NJ. 2014.
36 Oxcarbazepine Oxcarbazepine
31 32
Initiate at one-half of the usual starting dose when Warnings: CrCl < 30 ml/min Contraindication: hypersensitivity to carbamazepine (25% to 30% cross-sensitivity)
Avoid XR formulations in end-stage renal disease TEN and SJS (ESRD) Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) or hyponatremia No adjustments in hepatic impairment
Oxcarbazepine. [Package Insert].Novartis, NJ. 2014. Oxcarbazepine. [Package Insert].Novartis, NJ. 2014.
Phenytoin Phenytoin
33 34
Boxed warning: IV administration should not exceed Warnings: 50 mg/min in adults and 1-3 mg/kg/min in pediatric TEN and SJS Vesicant patients; if infused faster can cause hypotension and Blood dyscrasias arrhythmia Hepatotoxicity
Loading dose: 20 mg/kg
No renal or hepatic adjustment necessary
Phenytoin. [Package Insert]. Pfizer. 2011. Phenytoin. [Package Insert]. Pfizer. 2011.
Phenytoin IV Administration Phenytoin (PHT) Therapeutic Range
35 36
In-line filter should be used (0.22-0.55 micron) Total PHT level: 10-20 mcg/ml
Do not refrigerate If albumin is low (<3.5 g/dl), the true PHT level will be higher Can be diluted with normal saline only
Phenytoin. [Package Insert]. Pfizer. 2011.
37 PHT Adjustment Lamotrigine
37 38
Adjusted concentration (CrCl>10mL/min) Boxed warning: Serious skin reactions Measured total concentration / [(0.2 x albumin) + 0.1] Use correct starter kit to reduce the risk of rash
Adjusted concentration (CrCl ≤10 mL/min) Starter kit based on concomitant medications Measured total concentration / [(0.1 x albumin) + 0.1]
Lamotrigine. [Package Insert].DSM Pharmaceutical , NC. 2009.
Lamotrigine Titration Schedule Lamotrigine
39 40
Different starter kits depending on concomitant Warnings: medications Aseptic meningitis Orange: not taking interacting medications Blue: valproic acid Blood dyscrasias Green: inducers Remember: Give Izzy Or Nancy Baked Vegetable TEN and SJS
DRESS
Lamotrigine. [Package Insert].DSM Pharmaceutical , NC. 2009. Lamotrigine. [Package Insert].DSM Pharmaceutical , NC. 2009.
Drugs that Affect Calcium Current
41 42
38 Ethosuximide Ethosuximide
43 44
Only used in absence seizure Warnings:
Blood dyscrasias Side effects: abdominal cramps, hiccups, anorexia Effects on liver and kidney
Systemic lupus erythematosus
Ethosuximidel [Package Insert]. Pfizer. 2009. Ethosuximidel [Package Insert]. Pfizer. 2009.
Phenobarbital
46
Controlled substance: C-IV Drugs That Affect GABA Activity Can be used in status epilepticus
No renal or hepatic adjustment necessary
45 Phenobarbital [Package Insert]. West-ward Pharmaceutical Corp. 2011.
Phenobarbital
47
Warnings:
Habit forming Drugs With Multiple Mechanisms of Dermatologic reactions Action Hypotension and respiratory depression with IV administration
Phenobarbital [Package Insert]. West-ward Pharmaceutical Corp. 2011. 48
39 Valproic acid Valproic acid
49 50
Boxed Warnings: Hepatotoxicity (higher risk in Warnings:
mitochondrial disease), teratogenicity, pancreatitis Hyperammonemia and encephalopathy
Concomitant topiramate use
Hypothermia Contraindicated in severe hepatic impairment Concomitant topiramate use
Multi-organ hypersensitivity reactions Normal Valproate level: 50-100 mcg/mL
Valproic acid. [Package Insert]. Banner Pharmacaps .NC 2011. Valproic acid. [Package Insert]. Banner Pharmacaps .NC 2011.
Topiramate Topiramate
51 52
Dosing in renal impairment: use one-half of the Warnings: usual adult dose and titrate slowly Acute myopia and secondary angle closure glaucoma Oligohidrosis and hyperthermia Metabolic acidosis Kidney stones Hypothermia No adjustments in hepatic impairment
Topiramate. [Package Insert]. Janssen Pharm. NJ. 2009. Topiramate. [Package Insert]. Janssen Pharm. NJ. 2009.
Levetiracetam Monitoring Levetiracetam (LEV) Level
53 54 Larger trial No adjustments in hepatic impairment Smaller trial 24 patients 50 patients
Prospective Retrospective Dose adjustment in renal impairment: Focal epilepsy Refractory epilepsy
No correlation between Group CrCl (mL/min) Dosage (mg) Frequency Only considered peak blood level LEV serum level and Normal >80 500-1500 Every 12 hours clinical efficacy, The LEV blood level was Mild 50-80 500-1000 Every 12 hours tolerability or Moderate 30-50 250-750 Every 12 hours higher (20-30 mcg/mL) in administered dosage was Severe <30 250-500 Every 12 hours effective cases ESRD (hemodialysis) ------500-1000 Every 24 hours found
Sheinberg et al. Correlation Between Efficacy of Levetiracetam and Serum Lvels Among Children With Refractory Epilepsy. Pediatr Neurol 2015; 52: 624- Levetiracetam. [Package Insert]. Mylan. IL. 2011. 628 Iwasaki et al. The efficacy of levetiracetam for focal seizures and its blood levels in children. Brain & Development 37 (2015) 773–779
40 Therapeutic Drug Monitoring (TDM) Summary
55 56
AEDs Level TDM Required? Focal Generalized Monotherapy Adjunctive therapy Carbemazepine 4-12 mcg/mL Yes Carbamazepine X X X X Oxcarbazepine 3-35 mcg/mL Maybe Oxcarbazepine X X X X Phenytoin 10-20 mcg/mL Yes Lamotrigine 2.5-15 mcg/mL Maybe Phenytoin X X X X Ethosuximide 40-100 mcg/mL Maybe Lamotrigine X X X X Phenobarbital 10-40 mcg/mL Maybe Ethosuximide Absence Only X X Topiramate 5-20 mcg/mL Maybe Phenobarbital X X X X Valproic acid 50-100 mcg/mL Yes Valproate X X X X Levetiracetam 12-46 mcg/mL Maybe Topiramate X X X X
Levetiracetam X X X
Patsalos P, Berry D, Bourgeois B, et al. Antiepileptic drugs—best practice guidelines fortherapeutic drug monitoring: A position paper by thesubcommission on therapeutic drug monitoring, ILAECommission on Therapeutic Strategies. Epilepsia, 49(7):1239–1276, 2008.
Which of the following adverse effects is associated with all AEDs?
A. Hepatotoxicity Assessment Questions B. Increased risk of bone fractures
C. Metabolic effects
D. Alopecia
57 58
Which of the following adverse effects is associated Which of the following AEDs require an in-line filter? with all AEDs? A. Levetiracetam A. Hepatotoxicity B. Phenobarbital B. Increased risk of bone fractures C. Phenytoin C. Metabolic effects D. Carbamazepine D. Alopecia
59 60
41 Which of the following AEDs require an in-line filter? AR is an 18 year old with a history of generalized tonic- clonic seizures presents to the pharmacy to pick up his Lamotrigine Starter kit . He is currently taking valproic A. Levetiracetam acid. Which of the following is the appropriate starter kit for AR? B. Phenobarbital A. Blue
C. Phenytoin B. Green
D. Carbamazepine C. Orange
D. Pink
61 62
AR is an 18 year old with a history of generalized tonic- Any Questions?
clonic seizures presents to the pharmacy to pick up his 64 Lamotrigine Starter kit . He is currently taking valproic acid. Which of the following is the appropriate starter kit for AR? A. Blue
B. Green
C. Orange
D. Pink
63
42 Louisiana Society of Health System Pharmacists 2017 Midyear Meeting
10:00—11:00 a.m. Safe Opioid Prescribing
Tom Driscoll, PharmD Clinical Pharmacist Christus Schumpert Health Shreveport-Bossier Shreveport, LA
0179-0000-17-038-L01-P/ 0179-0000-17-038-L01-T 1 contact hour (0.1 CEU) Knowledge-based activity
Objectives:
Pharmacists: Technicians: 1. Describe the extent and demographics of 1. Describe the extent and demographics of the opioid epidemic. the opioid epidemic. 2. Integrate best practices for safe opioid 2. Review pharmacy’s role in safe opioid prescribing into patient care. prescribing. 3. Identify and refer patients with potential 3. Identify and refer patients with potential opioid abuse or misuse to appropriate care. opioid abuse or misuse to appropriate care. 4. Review the role of polymodal pain 4. Review the importance of polymodal pain management for chronic pain patients. management for chronic pain patients.
Dr. Driscoll has disclosed that he has no relevant financial relationships.
43 Learning Objectives: Pharmacists An Approach to Safe Describe the extent and demographics of the opioid epidemic Opioid Prescribing Integrate best practices for safe opioid prescribing into patient care Identify and refer patients with potential opioid abuse and misuse to appropriate care BY Understand the role of multimodal pain DR. TOM DRISCOLL management for chronic pain patients
Learning Objectives: Pharmacy Scope of the Opioid Epidemic: Technicians United States
Describe the extent and demographics of the opioid epidemic Understand pharmacy’s role in safe opioid prescribing Identify and refer patients with potential opioid abuse and misuse to appropriate care Understand the importance of multimodal pain management for chronic pain patients
Scope of the Opioid Epidemic: Scope of the Opioid Epidemic: United States Louisiana Opioid abuse has become an Among the states with the highest epidemic – 12.5 million misuse rate of opioid deaths – top 40%1 prescription opioids1 118 prescriptions for every 100 About 100 overdose deaths/day 2 from opioids1 residents – top 26% 1 MMWR 2016; 65(50-51);1445-1452 Rx opioids twice as high as heroin2 2 MMWR 2014; 63(26);563-568 1 MMWR, 2016; 65(50-51);1445-1452 2 www.asa.org/docs/default-source/.../opioid-addiction-facts-figures.pdf
44 Scope of the Opioid Epidemic: Scope of the Opioid Epidemic: Inpatients Inpatients Overused on inpatient too!1 Half are discharged with an 1 1. 50% of non-surgical patients opioid prescription. are given opioids (33 – 64%) 4% of patients discharged on an 2. They are also used at relatively opioid continued to take them for 2 high doses. greater > 90 days. 1 J Hosp Med. 2014;9(2):73-81 1 J Hosp Med. 2014; 9(2):73-81 2 JIGM. 2016;31(5):478-485
Step One: Creating a Team Step Two: Creating a Plan
1,2 Support from administration 1. Evidence-based guidelines Create a multidisciplinary team – 2. Pain management plan RN’s and RPh’s, case managers, 3. Education: pain assessment, social workers, lab, infomaticists1 treatment, patient education, patient referrals Broad representation of MD’s 1 JAMA. 2016: 315(15);1624-1645 2 1 Use of Opioids for the Treatment of Chronic Pain - A Statement from http://www.aaem.org/publications/news-release/model- the American Academy of Pain Medicine 2013 emergency-department-pain-treatment-guidelines
Step Two: Creating a Plan Step Two: Creating a Plan
4. Monitor success of program 8. Mechanism for referrals to rehab1 5. Track and trend data or pain management specialists 6. Provide feedback to staff 9. Access LAPMP for pharmacists 7. Re-enforce and re-educate staff and physicians – includes data as needed based on monitoring for TX, AR, MS, and 13 other states data 1 https://findtreatment.samhsa.gov
45 Implement the Plan: H&P Implement the Plan: H&P
A. Thorough H&P on admission1 3. Pain characteristics – dull, 1. Personal/family history of sharp, throbbing, shooting, alcohol and drug abuse burning, aching 2. Psychiatric history 4. Type of pain – visceral, 1 Pain Physician. 2017;20(2S): S3-S92 somatic, neuropathic, central
Implement the Plan: H&P Implement the Plan: Multimodal Pain Management
5. Pain medication – current and Pain may have one or more past history of opioids, adjuvant mechanisms1 analgesics, dosage, pain relief, Select pain management aggravating/mitigating factors 6. Drug screen – Hx of chronic appropriate for the mechanism(s) pain, overdose, abuse, misuse, of pain illicit drug use 1 J Clin Invest. 2010;120:3742-3744
Implement the Plan: Implement the Plan Multimodal Pain Management A. Opioids1 A. Opioids 1. Short acting opioids for acute 3. Avoid Demerol if possible pain – avoid methadone 4. Avoid “non-use's” – headaches, 2. Restrict long acting opioids to uncomplicated musculoskeletal hospice, oncology and pain pain, fibromyalgia, and vague management specialists1 unsubstantiated pain – other 1 Pain Physician. 2017;20(2S):3S-S92 drugs better w/o risk of addiction
46 Implement the Plan: Multimodal Implement the Plan: Polymodal Pain Management Pain Management B. Adjuvant Analgesics B. Adjuvant Analgesics 1. Indications other than pain, 3. TCA’s, SNRI’s, NSAID’s, muscle but have analgesic properties relaxers, anticonvulsants for certain indications 4. Limit use of opioids for NCCP: 2. Agents of choice for many maximize or change adjuvant Non-Cancer Chronic Pain analgesic first before a trial of (NCCP) syndromes1 opioids due to limited efficacy vs. 1 J Anaesthiol Clin Pharmacol. 2013 Jan-Mar; 29(1):6-12 risk of addiction and ADR’s
Implement the Plan Implement the Plan
C. Select Route of Administration D. Use pain score to initiate therapy: 1. Reserve IVP for NPO patients or 1-3: Motrin 600 mg PO q6h PRN those requiring rapid or 4-6: Norco 5/325 PO q6h PRN additional pain relief 7-10: Norco 10/325 PO q6h PRN 2. Transition to PO therapy ASAP Avoid a pain scale of 4-10 – too broad and ambiguous
Implement the Plan Implement the Plan
E. Avoid Overdose and Abuse E. Avoid Overdose and Abuse 1. Avoid benzodiazepines, Soma 4. Limit use of opioids on discharge 2. Limit the use of opioids for 5. Drug screen for suspected NCCP abuse, noncompliance, misuse, 3. Refer patients to drug illicit drug use or overdose hx treatment or pain specialist as indicated 6. Use LAPMP to verify compliance or abuse
47 Implement the Plan Discharge Management
E. Avoid Overdose and Abuse 1. Review goals, risks and benefits 7. Send personal opioids home with patient/family 8. Pain assessment made before and after each dose of opioids 2. Review patient’s role for safe 9. Provide feedback on response to opioid use with patient/family therapy, side effects, LAPMP 3. Provide discharge medication results to attending physician education
Discharge Management Discharge Management
4. Counsel patients at high risk of 5. Offer drug abuse counseling for overdose: morphine equivalent patients abusing or misusing dose (MED) > 90, history of opioids overdose, opioid abuse or 6. Discharge prescriptions limited misuse, illicit drug use, and to 4 doses/day tapering dose patients taking CNS depressants downward over 3 – 5 days
Discharge Management Turning Theory Into Practice
7. Forward concerns of abuse or misuse to patient’s PCP 8. For patients with a MED > 90, refer to a pain care specialist, create a patient opioid treatment plan, and notify PCP of overdose risk
48 Real Life Application Real Life Application Goal #1: Reduce opioid Opioids prescribed by the hospitalists consumption by 20% were retrieved from Meditech Goal #2: Maintain pain satisfaction scores Narcan use data was retrieved from Pyxis Secondary Goal: Reduce Narcan use Press-Ganey pain management Initiate safe opioid prescribing plan satisfaction scores were obtained from the patient advocate
Hydromorphone Injectable Results Morphine Injectable Results
For the five months following initiation of safe opioid IV morphine prescribing, IV Dilaudid ® consumption consumption declined 45% declined 20%
The most significant decrease in opioid consumption came from a 45% decline in IV Dilaudid ® use which continued to decline throughout the study period.
33 © Copyright 2017, Cardinal Health. All rights reserved. CARDINAL HEALTH, the Cardinal Health LOGO and ESSENTIAL TO CARE are trademarks or registered trademarks of Cardinal Health. © Copyright 2017, Cardinal Health. All rights reserved. CARDINAL HEALTH, the Cardinal Health LOGO and ESSENTIAL TO CARE are trademarks or registered trademarks of Cardinal Health.
Hydromorphone/Acetaminophen 7.5/325 results Real Life Application
Norco ® consumption declined 11%
The prescribing of Norco® demonstrated the greatest variability during the study period
35 © Copyright 2017, Cardinal Health. All rights reserved. CARDINAL HEALTH, the Cardinal Health LOGO and ESSENTIAL TO CARE are trademarks or registered trademarks of Cardinal Health.
49 Real Life Application Lessons Learned
Good pain management can be accomplished with less opioid medication than commonly used. Safe opioid prescribing requires a multidisciplinary approach. Pharmacists play an integral role in safe opioid prescribing.
Epic Epidemics Mirror, Mirror on the Wall Who has the Best Practice of Them All?
This epidemic kills at least These are elements of this best practice. 100 people per day 1. Avoiding opioid “non-use” indications 2. Take a multimodal approach to pain nationwide and has put 3. Maximizing use of adjuvant analgesics Louisiana in the top 40% of 4. Using short acting opioids and limit overdose deaths. the use of long acting opioids
Do That Voodoo That You Do Whoops I Did it Again So Well The next treatment for this 72 These patients are at risk of this ADE. YOM s/p radical neck 1. Patients taking > 90 mg MEDD dissection treated without 2. Patients with a history of overdose relief for severe burning pain 3. Patients taking benzodiazepines shooting down his neck while 4. Patients with a history of opioid on a morphine infusion. abuse
50 Yes, you have a question?
51 Louisiana Society of Health System Pharmacists 2017 Midyear Meeting
10:00—11:00 a.m. Review of Current Hyponatremia Management
Andrea Clarke, PharmD PGY1 Pharmacy Resident University Health Shreveport Shreveport, LA
0179-0000-17-031-L01-P/ 0179-0000-17-031-L01-T 1 contact hour (0.1 CEU) Knowledge-based activity
Objectives:
Pharmacists: Technicians: 1. Discuss the pathophysiology and 1. Describe the presentation of hyponatremia. differentiate between the types of 2. Identify drugs commonly used for the hyponatremia. treatment of hyponatremia. 2. Outline a treatment plan to correct 3. Recognize that hypertonic 3% saline is a hyponatremia. high-risk medication. 3. Arrange a treatment plan appropriately based on the progression of serum sodium values and patient’s signs & symptoms.
Dr. Clarke has disclosed that she has no relevant financial relationships. 52 Disclosure
I have no relevant conflicts of interest or financial disclosures in relation to this continuing education presentation REVIEW OF CURRENT HYPONATREMIA MANAGEMENT
Andrea Clarke, Pharm.D. University Health Shreveport
Objectives Objectives
At the end of this lecture, the pharmacist shall be able At the end of this lecture, the pharmacy technician to... shall be able to...
Discuss the pathophysiology and differentiate Describe the presentation of hyponatremia
between the types of hyponatremia Identify drugs commonly used for the treatment of Outline a treatment plan to correct hyponatremia hyponatremia
Arrange a treatment plan appropriately based on Recognize that hypertonic 3% saline is a high-risk the progression of serum sodium values and medication patient’s signs & symptoms
What is hyponatremia? Pathophysiology
Most common electrolyte abnormality Classification by serum osmolality Associated with significant morbidity, mortality, and Isotonic hyponatremia (~280 mOsm/L) costs Pseudohyponatremia
Serum Na < 135 mEq/L Hypertonic hyponatremia (>280 mOsm/L) Hyperglycemia Mild Moderate Severe Hypotonic hyponatremia (<280 mOsm/L) 130-135 mEq/L 120-129 mEq/L <120 mEq/L Many potential causes Subdivided by volume status
Deitelzweig et al. Hosp Prac. 2011. Adrogue HJ, et al. J Am Soc Nephrol. 2012. Adrogue HJ, et al. J Am Soc Nephrol. 2012. Hoorn EJ & R Zietse. J Am Soc Nephrol. 2017. Hoorn EJ & R Zietse. J Am Soc Nephrol. 2017.
53 Pathophysiology Pathophysiology
Antidiuretic hormone Aldosterone AKA arginine vasopressin, ADH, Acts on the renal epithelial cells in the distal tubules to AVP increase sodium and water reabsorption and increase Acts on V2 receptors in the potassium excretion collecting tubules to increase aquaporins at the membrane, which allow for increased water reabsorption into systemic circulation
Rosner MH. Kidney Int. 2012. Dineen et al. Clinical Medicine. 2017. Chessman KH & J Haney. Pharmacotherapy: A Pathophysiological Approach, 10e. 2017.
Pathophysiology Pathophysiology
Dineen et al. Clinical Medicine. 2017. Dineen et al. Clinical Medicine. 2017. Chessman KH & J Haney. Pharmacotherapy: A Pathophysiological Approach, 10e. 2017. Chessman KH & J Haney. Pharmacotherapy: A Pathophysiological Approach, 10e. 2017.
Pathophysiology Pathophysiology
Dineen et al. Clinical Medicine. 2017. Dineen et al. Clinical Medicine. 2017. Chessman KH & J Haney. Pharmacotherapy: A Pathophysiological Approach, 10e. 2017. Chessman KH & J Haney. Pharmacotherapy: A Pathophysiological Approach, 10e. 2017.
54 SIADH Causes of SIADH
Induced pituitary release of antidiuretic hormone (ADH) Drugs Diseases Other Hypo-osmolality fails to suppress General anesthesia Cancers Genetic disorders ADH secretion SSRIs Pneumonia Nausea Excessive ADH Phenothiazines Hemorrhage Pain Carbamazepine Stroke Stress Impaired renal water excretion; Increased total body water Amiodarone HIV
Euvolemic hyponatremia
Verbalis et al. Am J Med. 2013. Pillai et al. Indian J Endocrinol Metab. 2011. Spasovski et al. Eur J Endochrinol. 2014. Verbalis et al. Am J Med. 2013. Spasovski et al. Eur J Endochrinol. 2014.
Effect of Hyponatremia on Outcomes Guidelines
Table 1. Zieschang et al. 2016 Variable Hyponatremic (n = 141) Normonatremic (n = 141) P value Unites States - 2013 European - 2014 Delirium 22.7% 8.5% 0.002 In-hospital mortality 10.6% 2.1% 0.005 Diagnosis, evaluation, and Hyponatraemia Guideline 6-mo later mortality 31.9% 22.7% 0.080 treatment of Development Group: hyponatremia: Expert Clinical practice guideline Table 2. Zilberberg et al. 2008 Variable Hyponatremic Normonatremic P value panel recommendations. on diagnosis and treatment (n = 10,899) (n = 187,400) of hyponatraemia. ICU required 17.3% 10.9% <0.001 MV required by 48h 5% 2.8% <0.001 In-hospital mortality 5.9% 3% <0.001 Costs $16502 $13558 <0.001 Zieschang et al. Dtsch Arztebl Int. 2016. Verbalis et al. Am J Med. 2013. Zilberberg et al. Curr Med Res Opin. 2008. Spasovski et al. Eur J Endochrinol. 2014.
General Approach to Treatment Cerebral Demyelination
Timeline of hyponatremia AKA Osmotic Demyelination Syndrome Acute Chronic Symptoms ≤ 48 hours > 48 hours Risk factors Correction >25 mEq/L in first 48 hours Presence of neurologic symptoms Correction past 140 mEq/L Correction rates Hypokalemia Monitoring of levels Alcoholism Malnutrition Volume status Advanced liver disease Treatment choice Verbalis et al. Am J Med. 2013. Image retrieved from http://hkuelcn.med.hku.hk/osmotic-demyelination-syndrome/ Spasovski et al. Eur J Endochrinol. 2014. Achinger SG & JC Ayus. Crit Care Med. 2017.
55 Symptomatic Hyponatremia Hyponatremic Encephalopathy
Symptoms Early – nausea, vomiting, headache Hypertonic saline Late – seizures, respiratory failure (3% sodium chloride) Hypertonic 3% saline 100 mL bolus over 10 minutes immediately Repeat as symptoms persist Check serum Na every 1-2 hours until stable – no more than 5 mEq/L in first 1-2 hours
Image retrieved from https://dailymed.nlm.nih.gov/ Achinger SG & JC Ayus. Crit Care Med. 2017. Hoorn EJ & R Zietse. J Am Soc Nephrol. 2017.
Calculation Calculation example
80 kg male with serum Na of 112 mEq/L IV Na concentrations 3% NaCl = 512 mEq/L 0.9% NaCl = 154 mEq/L = 8 mEq increase in serum Na with 1L Total body water (TBW) of hypertonic saline Females = 50% of body weight Males = 60% of body weight
Verbalis et al. Am J Med. 2013. Verbalis et al. Am J Med. 2013. Spasovski et al. Eur J Endochrinol. 2014. Spasovski et al. Eur J Endochrinol. 2014.
Overcorrection Desmopressin
Mechanism of Action US Guidelines 2013 European Guidelines 2014 Synthetic analogue of ADH; Starting Na > 120 mEq/L Initiate once Na correction increases water permeability Intervention likely unnecessary rate limit is exceeded Starting Na < 120 mEq/L, in renal tubular cells, resulting Consult an expert to discuss Administer desmopressin 2-4 in decreased urine volume and infusion containing electrolyte- mcg every 8 hours IV increased urine osmolality Replace water orally or as free water with or without 5% dextrose in water desmopressin 2 mcg IV Fixes overcorrection of Na by intravenously: 3 mL/kg/h Recheck Na hourly and decreasing urinary water loss continue therapy infusion until Na is reduced to goal which would result in increased serum Na
Verbalis et al. Am J Med. 2013. Rafat et al. Clin J Am Soc Nephrol. 2014. Spasovski et al. Eur J Endochrinol. 2014. DDAVP injection (desmopressin acetate) [prescribing information]. 2007. Rosner MH. Kidney Int. 2012.
56 Assessment Question #1 Assessment Question #1
Patient BC was started on hydrochlorothiazide Patient BC was started on hydrochlorothiazide approximately 2 weeks ago and during her follow-up is approximately 2 weeks ago and during her follow-up is noted to be confused, lethargic, and weak. Her serum noted to be confused, lethargic, and weak. Her serum sodium is found to be 118 mEq/L. Which one of the sodium is found to be 118 mEq/L. Which one of the following is the most appropriate initial therapy to following is the most appropriate initial therapy to administer to this patient? administer to this patient? A. Tolvaptan 15 mg daily A. Tolvaptan 15 mg daily B. Urea 30 g daily B. Urea 30 g daily C. Sodium chloride 3% bolus C. Sodium chloride 3% bolus D. Normal saline continuous infusion D. Normal saline continuous infusion
Chronic Hyponatremia Pathophysiology
Often fluid restriction
Common drug therapy Loop diuretics Urea Vasopressin receptor antagonists (vaptans)
Hoorn EJ & R Zietse. J Am Soc Nephrol. 2017. Dineen et al. Clinical Medicine. 2017. Chessman KH & J Haney. Pharmacotherapy: A Pathophysiological Approach, 10e. 2017.
Hypovolemic Pathophysiology
Treat with hypertonic saline if symptomatic
If asymptomatic and mild-moderate hyponatremia, replete with isotonic saline or balanced crystalloid solutions
Identify and treat underlying cause Adrenal insufficiency – hydrocortisone Discontinue diuretics
Verbalis et al. Am J Med. 2013. Dineen et al. Clinical Medicine. 2017. Spasovski et al. Eur J Endochrinol. 2014. Chessman KH & J Haney. Pharmacotherapy: A Pathophysiological Approach, 10e. 2017.
57 Hypervolemia Vasopressin Receptor Antagonists
Fluid restriction Mechanism of action US guidelines recommend restrict to 500 mL less than 24- Block vasopressin type 2 hour urine volume receptors in collecting duct Awareness of volume of IV medications principal cells and thereby Salt restriction induce excretion of water Diuretics without substantially Loop diuretics affecting electrolyte Loop/spironolactone for cirrhosis excretion ACEI or ARB Vaptans
Verbalis et al. Am J Med. 2013. VAPRISOL® (conivaptan hydrochloride) Injection [prescribing information]. 2012. Spasovski et al. Eur J Endochrinol. 2014. Rosner MH. Kidney Int. 2012.
Conivaptan Tolvaptan
IV through large veins - rotate infusion site (infusion Oral tablets site reactions common) Dosing Must be initiated and re-initiated in hospital setting Dosing Initial: 15 mg daily; can increase up to 60 mg daily max if LD: 20 mg IV over 30 min, then needed at intervals ≥ 24 hours CI: 20 mg over 24 hours x2-4 days (max duration) Limit to 30 days due to liver injury Hepatic adjustment Contraindications Contraindications Hypovolemic hyponatremia Strong CYP 3A4 inhibitors Hypovolemic hyponatremia Anuria Strong CYP 3A4 inhibitors Need to raise serum sodium acutely Anuria
VAPRISOL® (conivaptan hydrochloride) Injection [prescribing information]. 2012. SAMSCA® (tolvaptan) tablets [prescribing information]. 2013.
Pathophysiology Euvolemic
Fluid restriction US guidelines recommend restrict to 500 mL less than 24-hour urine volume Awareness of volume of IV medications
Treatment of underlying cause Increased intake of salt Thyroid hormone replacement for hypothyroidism Glucocorticoid replacement for hypocortisolism SIADH treatment of cause
Dineen et al. Clinical Medicine. 2017. Verbalis et al. Am J Med. 2013. Chessman KH & J Haney. Pharmacotherapy: A Pathophysiological Approach, 10e. 2017. Spasovski et al. Eur J Endochrinol. 2014.
58 Euvolemic Urea
SIADH Mechanism of Action Fluid restriction Induces osmotic diuresis, increasing renal Increased intake of osmotic solutes free water excretion Oral urea Dosing – 15-60 g by mouth daily Oral salt tablets Availability Loop diuretics Difficult to obtain in the US Controversial Currently available as a medical food as Demeclocycline 15 g of flavored powder Vaptans
Verbalis et al. Am J Med. 2013. Ure-NA® (urea) powder. www.ure-na.com. 2017. Spasovski et al. Eur J Endochrinol. 2014. Decaux et al. Critical Care. 2010.
Urea Urea vs. Vaptans Long-Term for SIADH
Retrospective study/Case series looking at ICU patients N = 13 Group 1 – Mild hyponatremia (n=50) Received vaptans x 1year, holiday, then urea x 1 year Treated with urea Average serum sodium was Na = 135 mEq/L on both 128 135 mEq/L over 2 days using 0.5-1 g/kg/day the vaptans and the urea despite large fluid intake Adverse effects 6 patients developed hypernatremia One patient withdrew while being treated with tolvaptan due to excessive thirst Group 2 – Severe hyponatremia (n=35) One patient receiving urea developed hypernatremia Treated with isotonic saline and urea without complications 111 122 in one day Similar efficacy between vaptans and urea for chronic No side effects SIADH
Ure-NA® (urea) powder. www.ure-na.com. 2017. Ure-NA® (urea) powder. www.ure-na.com. 2017. Decaux et al. Critical Care. 2010. Soupart et al. Clin J Am Soc Nephrol. 2012.
Assessment Question #2 Assessment Question #2
Which of the following is not used to raise serum Which of the following is not used to raise serum sodium levels? sodium levels?
A. Desmopressin A. Desmopressin
B. Conivaptan B. Conivaptan
C. Tolvaptan C. Tolvaptan
D. Hypertonic saline D. Hypertonic saline
59 Key Points & Summary Key Points & Summary
Timeline of hyponatremia Symptomatic hyponatremia
Contribution of home medications Prompt treatment
Presence of neurologic symptoms 3% sodium chloride Correction rates Careful monitoring of serum levels Maintenance of safe rates of correction Monitoring of levels Max 8 mEq/L increase daily for chronic hyponatremia Treatment choice Max 6 mEq/L if risk factors for ODS Prevention of demyelination
Key Points & Summary Assessment Question #3
Chronic hyponatremia Patient BC was started on a hypertonic saline bolus. As she was still showing signs of confusion, another bolus was Hypovolemic administered. Upon examination, her confusion now appears Fluid repletion to have resolved. When her 2 hour labs return, her serum Hypervolemic Na has increased from 118 mEq/L to 128 mEq/L. Which of Fluid/Salt restriction the following treatments would be most appropriate at this Diuretics point? Vaptans Euvolemic A. Initiate 2 mcg desmopressin and D5W infusion Fluid restriction B. Initiate 3% saline continuous infusion until Na normalizes Underlying cause C. Initiate urea oral regimen Vaptans D. Initiate demeclocycline oral regimen Oral osmolar supplementation
Assessment Question #3
Patient BC was started on a hypertonic saline bolus. As she was still showing signs of confusion, another bolus was administered. Upon examination, her confusion now appears Questions? to have resolved. When her 2 hour labs return, her serum Na has increased from 118 mEq/L to 128 mEq/L. Which of the following treatments would be most appropriate at this point?
A. Initiate 2 mcg desmopressin and initiate D5W infusion B. Initiate 3% saline continuous infusion until Na normalizes C. Initiate urea oral regimen D. Initiate demeclocycline oral regimen
60 Louisiana Society of Health System Pharmacists 2017 Midyear Meeting
1:00—2:00 pm Pharmacy Legislative and Administrative Update
Jeffery D. Evans, Pharm.D. Associate Professor of Pharmacy Practice College of Pharmacy, University of Louisiana at Monroe Clinical Assistant Professor of Family Medicine and Comprehensive Care College of Medicine, Louisiana State University Health Science Center - Shreveport
0179-0000-17-039-L03-P/ 0179-0000-17-039-L03-T 1 contact hour (0.1 CEU) Knowledge-based activity
Objectives:
Pharmacists: Technicians: 1. Outline potential applications of Board rule 1. Outline potential applications of Board rule changes to current pharmacy practice. changes to current pharmacy practice. 2. Identify areas of positive change in 2. Identify areas of positive change in upcoming rule and law changes. upcoming rule and law changes. 3. Recognize implications of recent opioid 3. Recognize implications of recent opioid abuse/misuse actions on pharmacy abuse/misuse actions on pharmacy practice and patient care. practice and patient care.
Dr. Evans has disclosed that he has no relevant financial relationships.
61 Final
Objectives
• At the end of this presentation the 2017 Louisiana Pharmacy Law pharmacist/technician will be able to: – Outline potential application of Board rule Update changes to current pharmacy practice – Identify areas of positive change in upcoming rule A brief one, that is and law changes – Recognize implications of recent opioid abuse/misuse actions on pharmacy practice and patient care
HB – 250 Needle exchange
• Representive Pylant – Allows for the creation of needle exchange programs – Must be created/approved by the local authorities • City • Parish LOUISIANA LAW CHANGES – Passed and signed into law
HB – 488 Pharmacy Practice HB 314 –LSU Hospital Patients alterations • Requires that any public –private partnership • A bill created that changes wording of the PPA hospital take ANY patient from another but does nothing really. Example: hospital that is either indigent or on Medicaid
• Sent to Health Committee on 04/10 • Never made it out of committee • Never made it out of committee
62 Final
HB 436 /SB 59 – Requires manufacturers to disclose drug costs when advertising HB – 428 HCPs and drug prices • Bill requires two things • Bill prohibits and makes it a crime for any – Creation of a committee to evaluate drug costs medication benefit company to prohibit an and which drugs are essential to LA families HCP from several things – Requires drug reps to provide cost information to – Discussing cheaper alternatives with patients prescribers when detailing
– Passed • 04/10 sent to insurance committee to die • Amended to provide info the BOP instead of provider • Never made it out of committee
SB ‐55 Senator Mills SB96 –PMP expansion by Sen Johns
• Several changes • Allows for – Medical examiners – 3 hours of CDS CE every three years – Coroners – CDS license=PMP registration – Licensed substance abuse addiction counselors – Check PMP for all new opioid prescribing – Probation and parole officers • Except for cancer, hospice… – ‘Criminal’ courts – • And at least once per 90days if opioids are continued Parents and legal guardians – Executors of a will or court appointed representitive – Passed Senate 4/24 • Creates a definition of audit trail • House 06/12 • Passed
SB 216 –Physician Assistant SB ‐133 Preschool Vaccines emergency certificates • Requires that parents be notified if less than • Adds Physician Assistants to the list of providers 100% of children are vaccinated able to detain people for – Psych issues – Harmful drug abuse
• In committee, not on agenda • Adds language for Nurse Practitioners – Resurrected as SB 255 – But only requires notification of policies, not if students are vaccinated • Passed
63 Final
Board Actions
• 2017 –2 Equilivant Drug Product Interchange
• 2017 –1 Internship Requirements
• 2016 –6 Marijuana Pharmacy FEDERAL BILLS
HR 592/S109 –Pharmacy and Medically Underserved Areas Enhancement Act Overdose Stats 2013 • AS of 04/27/17 • Of the 22767 rx related deaths – House 163 cosponsors (Rep Lee and Richmond) – 16235 (71.3%) were opioid related – Senate 35 cosponsors ( ) – 6973 (30.6%) were BZD related – Many were both • ~1 million ER visits – 501,207 ED visits for opioids – 420,040 ED visits for BZDs
Copyright Jeffery Evans, Pharm.D. 16
RX related deaths Opioid and BZD related deaths
• All rx medication related deaths – Note overdose only
Copyright Jeffery Evans, Pharm.D. 17 Copyright Jeffery Evans, Pharm.D. 18
64 Final
Illegal drug deaths So what are we doing about this
• 2007 –Prescription Monitoring Program rolls out – 2011 Expansion to include a limited number of states. – 2015 Expanded to most states
Copyright Jeffery Evans, Pharm.D. 19 Copyright Jeffery Evans, Pharm.D. 20
What impact has this had? Narcan
• Who knows? • In 2013 – The purpose is to ‘Monitor’ prescription use – Approved for to be dispensed by pharmacies – Relies on Pharmacist and Physicians to check • In 2015 – Approved for pharmacies to dispense to first • In 2014 allowed delegation of access to others responders by rx, • In 2015 requires physicians to check for CIIs prior to – Denied family members the same ability first prescription • In 2016 – Approved ability to buy it per standing orders • Pharmacy • Other location
Copyright Jeffery Evans, Pharm.D. 21 Copyright Jeffery Evans, Pharm.D. 22
Pharmacist must provide education Finally, prescribing changes
• Pharmacist must show patient • 2014 – Techniques to recognize overdose – Limit Out of state CII (opioid) prescribing to – How to store and administer the product • A 10 day fill every 60 days – Emergency follow‐up • 2015 – Added if you can check their PMP you are ok • 2016 – Added if the words for ‘cancer pain’ or terminally ill
Copyright Jeffery Evans, Pharm.D. 23 Copyright Jeffery Evans, Pharm.D. 24
65 Final
Questions
• Thank you!
66 Louisiana Society of Health System Pharmacists 2017 Midyear Meeting
2:00—3:00 p.m. Medical Literature for Practicing Clinicians: Rules and Exceptions
Bryan Donald, PharmD Clinical Assistant Professor University of Louisiana at Monroe Monroe, LA
0179-0000-17-033-L01-P 1 contact hour (0.1 CEU) Knowledge-based activity
Objectives:
Pharmacists: 1. Describe the place of medical literature in the context of pharmacy practice. 2. Identify resources for finding and retrieving journal articles. 3. Discuss basic medical literature evaluation. 4. Recognize statistics in a practical setting. 5. Indicate common mistakes in evaluating medical literature.
Dr. Donald has disclosed that he has no relevant financial relationships.
67 Objectives Medical Literature for Practicing • Describe the place of medical literature in the context of pharmacy Clinicians: practice Rules and Exceptions • Identify resources for finding and retrieving journal articles • Discuss basic medical literature evaluation Bryan J. Donald, PharmD • Understand statistics in a practical setting • Avoid common mistakes in evaluating medical literature
Get to know the room Why?
• Practice Setting: • Why do we read medical literature? • Community • Hospital • Centralized, Decentralized, Clinical • Ambulatory • Preceptors • Students
Why evaluate medical literature?
• Stay current on advances in the field • Understand consequences of medical decisions • Therapy • Assessment/Diagnostics Using literature to make or • Improve patient outcomes • Save costs support clinical decisions • Evidence‐Based Medicine
68 ACLS
In the ED during a cardiac arrest, the lead physician orders an amiodarone bolus to be followed by a drip. The pharmacist prepares the bolus dose and calls the pharmacy for a drip.
One of the nurses in the room complains loudly that, “lidocaine and ventricular arrhythmias go hand‐in‐hand,” andt tha “doctors ignore experience and just use books to treat patients.”
Link MS, Berkow LC, Kudenchuk PJ, et al. Part 7: adult advanced cardiovascular life support: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency cardiovascular Care. Circulation. 2015;132(suppl 2):S444‐S464.
Amiodarone as compared with lidocaine for Consult Window shock‐resistant ventricular fibrillation A 65‐year‐old hispanic patient with heart failure and diabetes chooses not to pick up his lisinopril with his other maintenance medications. At the consult window, he tells the pharmacist that his physician gave him samples for “the new heart failure medication.”
He wonders if it is really better than his old medication, and admits to the pharmacist that his doctor didn’t really tell him anything about the new medication.
Dorian P, Cass D, Schwartz, B, et al. Amiodarone as compared with lidocaine for shock‐ resistant ventricular fibrillation. N Engl J Med. 2002;346(12):884‐890.
PARADIGM‐HF PARADIGM‐HF Angiotensin‐neprilysin inhibition versus enalapril in heart failure Angiotensin‐neprilysin inhibition versus enalapril in heart failure
Primary end point is a composite of death from cardiovascular causes or first hospitalization for heart failure.
McMurray JJV, Packer M, Desai AS, et al. Angiotensin‐ neprilysin inhibition versus enalapril in heart failure. N Engl J McMurray JJV, Packer M, Desai AS, et al. Angiotensin‐ Med. 2014;371:993‐1004. neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371:993‐1004.
69 PARADIGM‐HF Medical Literature: Who is the audience? Angiotensin‐neprilysin inhibition versus enalapril in heart failure
McMurray JJV, Packer M, Desai AS, et al. Angiotensin‐ neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371:993‐1004.
Medical Literature: Who is the audience?
• Clinicians • Administrators • Researchers Clinicians’ Perspective What are practicing pharmacists looking for?
What? Three Critical Questions:
• What are we looking for when we evaluate medical literature? • Is it a True finding? • Can I apply the finding to My Patients? • Will the finding change My Practice?
70 Is it a true finding? ACC/AHA Clasification Scheme
• Reproducible • Study design • What is the ideal study design?
Halperin JL, Levine GN, Al‐Khatib SM, et al. Further evolution of the ACC/AHA clinical practice guideline recommendation classification system: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice guidelines. J Am Coll Cardiol. 2016;67:1572‐1574.
Centre for Evidence‐Based Medicine What is the ideal study design? Level Type of evidence Level 1 Systematic review of randomized trials • How do we establish truth in clinical practice? or n‐of‐1 trials Level 2 Randomized trial or observational study with dramatic effect Level 3Non‐randomized controlled cohort/follow‐up study Level 4Case‐series, case‐control studies, or historically controlled studies Level 5 Mechanism‐based reasoning
OCEBM Levels of Evidence Working Group. The Oxford Levels of Evidence 2. Oxford Centre for Evidence‐Based Medicine. http://www.cebm.net/index.aspx?o=5653
What is the ideal study design? Study Introduction
A good physiological experiment, like a good physical one, requires that • Authors’ affiliations it should be present anywhere, at any time, under identical conditions, • Support the same certain and unequivocal phenomena that can always be confirmed. • Objectives ‐Johannes Peter Muller • Rationale
71 Study Methods ‐ Design Study Methods –Patients
• Controlled, case‐control, cohort • How enrolled? • Cross‐over, parallel, sequential • Inclusion/Exclusion criteria • Type of assignment used (randomized, protocol) • Number enrolled per groop • Blinding Bleeds into second critical question: my patients
Study Methods – Treatment Regimens Study Methods –Outcome Measures
• Treatments used • Primary measures • Dosages/administration • Secondary measures • Therapy duration • Therapeutic goals and targets
Study Methods –Data Handling Study methods ‐ Statistics
• Intention to treat, per protocol • Tests used • Number lost to follow‐up • Power of Study • Reasons for dropouts • Probability of Type I error • RESULTS: • Baseline characteristics
72 Can I apply the finding to my patients? Will this change my practice?
• RESULTS: • RESULTS: • Baseline characteristics • Statistical significance • Clinical significance • Efficacy • Safety
Statistical Tests Used
• Central Tendency • Mean –normal • Median – outliers • Sample Size Basic Statistics • Type of data
Type I and Type II error: DIG Power and p‐values The effect of digoxin on mortality and morbidity in patients with heart failure. • α – Probability of committing Type I error • p‐value: (< α) probability that the findings are due to chance • ß – Probability of committing Type II error • Power: (1 ‐ ß) • Number of patients required to detect a difference between groups
The Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med. 197;336:525‐533.
73 ARISTOTLE Apixaban versus warfarin in patients with atrial fibrillation Confidence intervals
• Cross line of unity
Granger CB, Alexander JH, McMurray JJV, et Granger CB, Alexander JH, McMurray JJV, et al. Apixaban versus warfarin in patients al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. with atrial fibrillation. N Engl J Med. 2011;365;981‐992. 2011;365;981‐992.
What contributes to clinical significance? What contributes to clinical significance?
• Outcome • Number needed to treat (1 / absolute risk reduction) • Number needed to harm • Intervention or therapy • Must conform to results reported: • Number of patients to treat • Outcome to prevent (or cause) • Time/duration • Patient characteristics
Additional factors about therapy
• Complexity of regimen • Duration • Cost • Adverse events Common Mistakes Pitfalls in evaluating medical literature
74 Secondary Outcomes ILLUMINATE Effects of torcetrapib in patients at high risk for coronary events
• How many is too many? Atorvastatin Only Torcetrapib plus P atorvastatin • When is statistically significant no longer statistically significant? Absolute Change (mg/dL) at 12 months HDL +0.5 (6.8) +34.2 (17.0) <0.001 LDL +0.9 (17.1) ‐21.5 (22.7) <0.001 %Change HDL +1.8 (14.0) +72.1 (34.7) <0.001 LDL +3.0 (23.7) ‐24.9 (28.5) <0.001
Barter PJ, Caulfield M, Eriksson M, et al. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med. 2007;357:2109‐2122.
ILLUMINATE Clinical vs Surrogate Outcomes torcetrapib Atorvastatin only Torcetrapib plus HR (95% CI) P • Clinical Outcomes: (n=7534) atorvastatin (n=7533) • Desired (or disliked) for their own sake Primary composite 373 (5.0) 464 (6.2) 1.25 (1.09‐1.44) 0.001 • The “so what” of medical interventions outcome • Examples: • Surrogate Outcomes: Primary composite outcome: time to first occurrence of major • Substitutes for clinical outcomes cardiovascular event: death from coronary heart disease, • Closely correlate with clinical outcomes nonfatal myocardial infarction, stroke, hospitalization for unstable angina • Management of medical interventions –don’t wait on clinical outcome • Examples: • Surrogate outcomes are not bad outcomes Barter PJ, Caulfield M, Eriksson M, et al. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med. 2007;357:2109‐2122. Cohn JN. Introduction to surrogate markers. Circulation. 2004;109:IV‐20‐IV‐21.
Where to find resources
• Guidelines: • Guidelines.gov • Organization websites: AHA, ADA • Journal Articles • Pubmed Extra Help • Drug Information Resources Resources for finding articles or that big bag of weird. • Students
75 Navigating Journals Leading a Journal Club Discussion
• ICMJE Guidelines • Use a structured rubric • Varied for type of article • Local College or School of Pharmacy • Controlled trial: CONSORT • Blommel & Abate (West Virginia University) • Pharmacoeconomic: CHEERS • Focus an analysis and interpretation • EQUATOR Network
International Committee of Medical Journal Editors. Recommendations for the conduct, reporting, editing and publication of scholarly work in medical journals [accessed 31 August 2017]. Available from: http://www.icmje.org. Blommel ML, Abate MA. A rubric to assess critical literature evaluation skills. Am J Pharm Ed. 2007;71(4):Article 63.
Which of the following has the highest level of evidence when developing local guidelines for using anti‐arrhythmic agents in ACLS?
• Systematic review of randomized trials describing anti‐arrhythmic agents in cardiac arrest • Randomized controlled trial comparing amiodarone to lidocaine Assessment Questions • Observations from experienced Code Blue team members
Which of the following is important to consider The NICE‐SUGAR trial showed a 2.6% absolute risk when educating a patient switching from an ACE‐ increase (OR 1.14; 95% CI 1.02‐1.28) in 90‐day inhibitor to sacubitril/valsartan? mortality with intensive versus conventional glycemic control. • Efficacy: prevention of cardiac‐related death and hospitalization • Safety: symptomatic hypotension Is this result statistically significant? • Safety: angioedema • All are important • Unable to tell: no p‐value given • Yes: the confidence interval does not include 1 • No: the number needed to treat is 1/0.026 ≃ 40
Finfer S, Chittock DR, Su SY, et al. Intensive versus conventional glucose control in critically ill patients. N Engl J Med. 2009;360(13):1283‐1297.
76 In the previous question, 90‐day mortality is The Parachute Problem what type of outcome? • Clinical outcome I will not intentionally put myself in a position where I must jump out of • Surrogate outcome a perfectly fine aircraft until parachutes are investigated in a randomized, controlled trial. ‐Me
77 Louisiana Society of Health System Pharmacists 2017 Midyear Meeting
2:00—3:00 p.m. Management of the Potentially Deceased Organ Donor: What Pharmacists Need to Know
Ethan George, PharmD PGY1 Pharmacy Resident University Health Shreveport Shreveport, LA
0179-0000-17-032-L01-P/ 0179-0000-17-032-L01-T 1 contact hour (0.1 CEU) Knowledge-based activity
Objectives:
Pharmacists: Technicians: 1. Recognize the criteria for a potential organ 1. Recognize medications commonly used in donor. organ procurement. 2. Review the pathophysiologic responses that 2. Discuss the storage and handling of occur after brain death. medications used in organ procurement. 3. Discuss medications commonly used in organ procurement.
Dr. George has disclosed that he has no relevant financial relationships.
78 Disclosure
● No relevant disclosures
The Management of the Potential Organ Donor: What Pharmacists Need to Know
Ethan George, Pharm.D. PGY1 Pharmacy Resident University Health Shreveport
2
Objectives Background
● After this presentation, the pharmacist should be able to: ● At the end of 2015 ○ Recognize the criteria to qualify as a potential organ donor ○ 122,071 people on waiting list ○ Review the pathophysiologic responses that occur after brain death ○ 30,975 transplants performed ○ Discuss medications commonly used in organ procurement ○ 15,068 donors ● After this presentation, the pharmacy technician should be able to: ● Brain death causes a number of pathophysiologic changes ○ Recognize medications commonly used in organ procurement ● Recovery is dependent upon appropriate medical management ○ Discuss the storage and handling of medications used in organ procurement
Health Resources and Services Administration. U.S. Department of Health and Human Services. Organ Procurement and Transplantation Network website. 3 https://optn.transplant.hrsa.gov/ Accessed August 18, 2017. 4
What is the Louisiana Organ Procurement Agency? LOPA: General Workflow
● LOPA is the organ procurement organization for Louisiana Determination of brain death by primary team ● Two main functions Contact LOPA for donation opportunities ○ Maintain the Louisiana Donor Registry ○ Recover organs and tissue for transplant LOPA representative discusses process with the next of kin
LOPA assumes care of the patient
Organs are match and recovered
About LOPA. Louisiana Organ Procurement Agency website. https://www.lopa.org/about. Accessed August 18, 2017. 5 Organ Donation. Louisiana Organ Procurement Agency website. https://www.lopa.org/organ-donation/. Accessed August 18, 2017. 6
79 Pathways to Become an Organ Donor Donation after Brain Death (DBD)
1. Donation after brain death (DBD) ● Irreversible cessation of all functions of the entire brain, including the brainstem 2. Donation after cardiac death (DCD) ● Four steps to determine brain death (per American Academy of Neurology) 3. Live donor 1. The clinical evaluation (prerequisites) 2. The clinical evaluation (neurologic assessment) 3. Ancillary tests 4. Documentation
Wijdicks EF, Varelas PN, Gronseth GS, Greer DM. American Academy of Neurology. Evidence-based guideline update: Determining brain death in adults: Understanding brain death. Finger Lakes Donor Recovery Network website. http://www.donorrecovery.org/learn/understanding-brain-death/. Accessed Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2010;74:1911–1918. August 17, 2017. 7 National Conference of Commissioners on Uniform State Laws. 1981. The Uniform Determination of Death Act 1981. 8 Kootstra G, Kievit J, Nederstigt A. Organ donors: heartbeating and non-heartbeating. World J Surg. 2002 Feb;26(2):181-4. http://www.uniformlaws.org/shared/docs/determination %20of%20death/udda80.pdf. Accessed August 10, 2017.
DBD: The Clinical Evaluation (Prerequisites) DBD: The Clinical Evaluation (Neurologic Assessment)
● Establish cause of coma/brain death ● Coma - must lack all evidence of responsiveness ○ Exclude other possible causes ● Complete absence of brainstem reflexes ● Achieve near-normal core temperature (>36℃/97℉) ● Apnea
● Achieve normal systolic blood pressure (≥100 mmHg) ○ Test with a CO2 challenge
Wijdicks EF, Varelas PN, Gronseth GS, Greer DM. American Academy of Neurology. Evidence-based guideline update: Determining brain death in adults: 9 Wijdicks EF, Varelas PN, Gronseth GS, Greer DM. American Academy of Neurology. Evidence-based guideline update: Determining brain death in adults: 10 Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2010;74:1911–1918. Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2010;74:1911–1918.
DBD: Ancillary Tests and Documentation Donation after Cardiac Death (DCD)
● Ancillary tests ● Irreversible cessation of circulatory and respiratory function ○ Commonly used: EEG, cerebral angiography, nuclear scan ● Controlled - planned withdrawal of ventilatory and/or organ perfusion ● Documentation support ○ Document time of brain death in medical record ● Uncontrolled - unexpected cardiopulmonary arrest and/or unsuccessful resuscitation ○ Contact organ procurement agency (LOPA) ● Outcomes are similar to those for organs transplanted after brain death
Wijdicks EF, Varelas PN, Gronseth GS, Greer DM. American Academy of Neurology. Evidence-based guideline update: Determining brain death in adults: 11 Reich DJ, Mulligan DC, Abt PL, Pruett TL, Abecassis MM, D'Alessandro A, et al. ASTS recommended practice guidelines for controlled donation after cardiac 12 Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2010;74:1911–1918. death organ procurement and transplantation. Am J Transplant. 2009; 9: 2004–2011.
80 Quiz Time! Quiz Time!
Q. You have a patient who comes into the ER after experiencing a hemorrhagic Q. You have a patient who comes into the ER after experiencing a hemorrhagic stroke. The patient is found to have a pulse, but lacks all signs of responsiveness, stroke. The patient is found to have a pulse, but lacks all signs of responsiveness, have no reflexes, and no respiratory drive. Would they most likely be considered have no reflexes, and no respiratory drive. Would they most likely be considered for donation after brain death or donation after cardiac death? for donation after brain death or donation after cardiac death?
A. Donation after brain death
13 14
Medical Management Overview “Increased Transplanted Organs from the Use of a Standardized Donor Management Protocol”
● Aggressive donor management ● 10 US OPOs with 88 critical care units ● Minimize time between brain death and procurement ● Managed according to The Critical Pathway for the Organ Donor ○ Complications increase progressively with time ● Four-month period prior to and after standardized pathway ● Goals are to achieve hemodynamic stability and optimal function of all ● Results: organs ○ 140 donors before, and 130 donors after implementation ● Treatments: hormone resuscitation, cardiovascular support, respiratory ○ There was a 10.3% increase in organs recovered support, infection prophylaxis, anticoagulation, and maintenance of ○ There was a 11.3% increase in organs transplanted normothermia ○ There was no difference in 1-year graft survival ○ There was no significant difference in donor management time
Smith M. Physiologic changes during brain stem death--lessons for management of the organ donor. J Heart Lung Transplant. 2004;23(9) Suppl:S217–S222. Wood KE, Becker BN, McCartney JG, et al. Care of the potential organ donor. N Engl J Med. 2004;351:2730–2739. 15 Rosendale JD, Chabalewski FL, McBride MA, Garrity ER, Rosengard BR, Delmonico FL, et al. Increased transplanted organs from the use of a standardized 16 donor management protocol. Am J Transplant. 2002;2:761–8.
Physiologic Changes: Overview Medical Management
● Brain death occurs due to a rise in intracranial pressure until intracranial ● Hormonal System circulation ceases ● Cardiovascular System ● Systemic changes occur as ischemia progresses ● Pulmonary System ○ Pons - Cushing’s response ● Other Changes ○ Medulla - unopposed sympathetic stimulation ○ Spinal sympathetic pathways - total sympathetic denervation ○ Pituitary and hypothalamic ischemia
Smith M. Physiologic changes during brain stem death--lessons for management of the organ donor. J Heart Lung Transplant. 2004;23(9) Suppl:S217–S222. 17 18
81 Hormonal System: Changes “Aggressive Pharmacologic Donor Management Results in More Transplanted Organs”
● Result from pituitary and hypothalamic ischemia ● Retrospective study of 10,292 donors who either did or did not receive hormone resuscitation (HR) ● Depletion of antidiuretic hormone (ADH) ○ Diabetes insipidus ● Mean number of organs from donors who received HR was 22.5% greater than that from non-HR donors (3.8 vs 3.1) (P <0.001) ● Impaired thyroid stimulating hormone (TSH) secretion ● HR was associated with the following increased probabilities of an organ ○ Depletion of free triiodothyronine (T3) being transplanted from a donor ● Impaired insulin secretion Kidney Heart Liver Lung Pancreas ○ Decreased intracellular glucose, and hyperglycemia 7.3% 4.7% 4.9% 2.8% 6% ● Decreased release of adrenocorticotropic hormone (ACTH) ○ Decreased cortisol levels
Shah VR. Aggressive management of multiorgan donor. Transplant Proc. 2008;40:1087–90. 19 Rosendale JD, Kauffman HM, McBride MA, et al: Aggressive pharmacologic donor management results in more transplanted organs. Transplantation 75:482, 20 2003
Hormonal System: Treatment Hormonal System: Treatment
● Methylprednisolone 15 mg/kg IV bolus ● Vasopressin 1 unit bolus, continuous infusion at 0.5 to 4 unit/hr ○ LOPA recommends following with 500 mg IV Q4-8H ○ LOPA recommends starting dose of 0.1 unit/hr ● Liothyronine (T3) 4 mcg bolus, continuous infusion of 3 mcg/hr ○ Desmopressin is an alternative (0.5–2.0 mg/hr every 2-3 hours) ○ Must be refrigerated ○ Both must be refrigerated ○ Levothyroxine (T4) is an alternative ● Insulin drip started at 1unit/hr titrated for blood sugar 120-180 mg/dL ■ 20 mcg bolus, continuous infusion of 10 mcg/hr ■ LOPA recommends 200 mcg bolus ■ Stable for 4 hours after reconstitution
Rosengard BR, Feng S, Alfrey EJ, et al. Report of the Crystal City Meeting to Maximize the Use of Organs Recovered from the Cadaver Donor. Am J 21 Rosengard BR, Feng S, Alfrey EJ, et al. Report of the Crystal City Meeting to Maximize the Use of Organs Recovered from the Cadaver Donor. Am J 22 Transplant 2002; 2: 701–711. Transplant 2002; 2: 701–711.
Quiz Time! Quiz Time!
True/false: Brain death is proposed to cause a surge in free triiodothyronine True/false: Brain death is proposed to cause a surge in free triiodothyronine (T3). (T3).
False
23 24
82 Medical Management Cardiovascular System: Changes
● Hormonal System ● Brief surge of catecholamines ● Cardiovascular System ○ Vasoconstriction ● Pulmonary System ○ Can lead to myocardial injury ● Other Changes ● Followed by deactivation of the SNS and loss of sympathetic tone ○ Massive reduction in systemic vascular resistance ● Hypotension ○ Can lead to cardiac arrest and loss of transplantable organs ○ The cause of is often multifactorial
Smith M. Physiologic changes during brain stem death--lessons for management of the organ donor. J Heart Lung Transplant. 2004;23(9) Suppl:S217–S222. 25 Wood KE, Becker BN, McCartney JG, et al. Care of the potential organ donor. N Engl J Med. 2004;351:2730–2739. 26
Cardiovascular System: Causes of Hypotension Cardiovascular System: Goals
● To protect the heart from damage and to maintain adequate perfusion to Hypovolemia Cardiac Dysfunction Vasodilation (Volume) (Pump) (Resistance) organs ● Maintain normovolemia, adequate blood pressure, and cardiac output with Absolute hypovolemia ○ Preexisting disease ○ Catecholamine depletion the least amount of vasoactive-drug support ○ Inadequate ○ Metabolic depression ○ Adrenal insufficiency resuscitation ○ Volume overload with ○ Endocrinopathy Volume Pump Resistance ○ Fluid/blood loss resultant CHF ○ Sepsis ○ Pulmonary capillary ○ Cardiac index ≥2.4 ○ Mean arterial pressure ○ Hyperglycemia- ○ Arrhythmias wedge pressure 8-12 L/min/m2 ≥60 mmHg induced diuresis mmHg ○ Left ventricular ejection ○ Systemic vascular ○ Diabetes insipidus ○ Central venous fraction ≥45% resistance (SVR) of 800- Effective hypovolemia pressure 6-10 mmHg ○ Urinary output ≥1 1,200 dynes/sec-cm ○ Pooling of blood in mL/kg/hr venous system ➢ Fluids or diuretics ➢ Inotropes ➢ Vasopressors
Wood KE, Becker BN, McCartney JG, et al. Care of the potential organ donor. N Engl J Med. 2004;351:2730–2739. 27 Rosengard BR, Feng S, Alfrey EJ, et al. Report of the Crystal City meeting to maximize the use of organs recovered from the cadaver donor. Am J Transplant 28 Wood KE, Becker BN, McCartney JG, et al. Care of the potential organ donor. N Engl J Med. 2004;351:2730–2739. 2002; 2: 701–711.
“Impact of Restrictive Fluid Balance Focused to Increase Lung Cardiovascular System: Treatment (Fluids) Procurement on Renal Function After Kidney Transplantation”
● Evaluated the effect of restrictive fluid balance (CVP <6) in brain-dead ● Maintain a neutral/minimally positive fluid balance donors and it’s impact in 242 kidney recipients ● Packed red blood cells - used for excessive blood loss ● CVP <6 affected neither graft survival (P = 0.983) nor the development of ○ Goal hematocrit of >30% delayed graft function (P = 0.573) ● Fluid replacement: NS, ½ NS, ¼ NS, or D5W
○ Can add electrolytes (Na, K, Mg, PO4) ○ Can add sodium bicarbonate (50 mmol/L)
Miñambres E, Rodrigo E, Ballesteros MA, et al. Impact of restrictive fluid balance focused to increase lung procurement on renal function after kidney 29 Wood KE, Becker BN, McCartney JG, et al. Care of the potential organ donor. N Engl J Med. 2004;351:2730–2739. 30 transplantation, Nephrology Dialysis Transplantation, Volume 25, Issue 7, 1 July 2010, Pages 2352–2356.
83 Cardiovascular System: Treatment (Fluids) Cardiovascular System: Treatment (Vasoactive Meds)
● D5W also used for deficits of free water seen with diabetes insipidus ● Necessary when further hemodynamic support is needed despite adequate ○ Must monitor for hyperglycemia fluid resuscitation ● Colloid solutions (i.e. albumin) can be used to avoid fluid overload and ● Use the lowest dose possible for the shortest duration of time pulmonary edema ○ When administered at high doses, decrease chance of organ utilization ● Fluids can be warmed to 37°C (98.6°F) to reduce the risk of hypothermia
Wood KE, Becker BN, McCartney JG, et al. Care of the potential organ donor. N Engl J Med. 2004;351:2730–2739. Westphal GA, Filho MC, Fiorelli A, et al. Guidelines for Maintenance of Adult Patients With Brain Death and Potential for Multiple Organ Donations: The Task Force of the Brazilian Association of Intensive Medicine the Brazilian Association of Organs Transplantation, and the Transplantation Center of Santa Wood KE, Becker BN, McCartney JG, et al. Care of the potential organ donor. N Engl J Med. 2004;351:2730–2739. 31 32 Catarina, Transplantation Proceedings, Volume 44, Issue 8, 2012, Pages 2260-2267,
“Arginine Vasopressin Significantly Increases the Rate of Successful Cardiovascular System: Treatment (Vasoactive Meds) Organ Procurement in Potential Donors”
● Retrospective study looking at 10,431 donors who received HR and ● Vasopressin commonly first-line vasopressors ○ “Catecholamine-sparing” ● Compared those that did and did not receive vasopressin (AVP) ○ 1 unit bolus, continuous infusion at 0.5 to 4 unit/hr ● Associated with an increased rate of high-yield procurement (51% vs 36%, P ■ LOPA recommends starting dose of 0.1 unit/hr <.001) and less graft refusal (39% vs 46%, P <.001) ● Mechanism of action: ○ Produces vasoconstriction ○ Enhances fluid resorption ○ Stimulates ACTH release ● Also used to treat diabetes insipidus
Pennefather SH, Bullock RE, Mantle D, et al. Use of low dose arginine vasopressin to support brain-dead organ donors. Transplantation 1995; 59: 58–62. 33 Wood KE, Becker BN, McCartney JG, et al. Care of the potential organ donor. N Engl J Med. 2004;351:2730–2739. 34 Lexicomp Online® , Lexi-Drugs® , Hudson, Ohio: Lexi-Comp, Inc.; Accessed August 17, 2017.
Cardiovascular System: Treatment (Vasoactive Meds) Cardiovascular System: Treatment (Vasoactive Meds)
● Dopamine (3-10 mcg/kg/min) - commonly first-line ● Norepinephrine and epinephrine as add-ons ○ Lower doses - cardiac stimulation and renal vasodilation ○ Produce increased contractility and heart rate and vasoconstriction ○ Higher doses - produce vasoconstriction ○ Norepinephrine (0.1–2 mcg/kg/min), Epinephrine (0.05–0.5 mcg/kg/min) ○ Must protect from light ○ Must protect from light ● Dobutamine (5–10 mcg/kg/min) ● Phenylephrine may also be used (0.1–1 mcg/kg/min) ○ Produces increased contractility and heart rate ○ Produces potent systemic arterial vasoconstriction ● Goal: <10 mcg/kg/min dopamine or dobutamine
Wood KE, Becker BN, McCartney JG, et al. Care of the potential organ donor. N Engl J Med. 2004;351:2730–2739. 35 Wood KE, Becker BN, McCartney JG, et al. Care of the potential organ donor. N Engl J Med. 2004;351:2730–2739. 36 Lexicomp Online® , Lexi-Drugs® , Hudson, Ohio: Lexi-Comp, Inc.; Accessed August 17, 2017. Lexicomp Online® , Lexi-Drugs® , Hudson, Ohio: Lexi-Comp, Inc.; Accessed August 17, 2017.
84 Quiz Time! Quiz Time!
Which of the following medications is used for the treatment of diabetes Which of the following medications is used for the treatment of diabetes insipidus, as well as for hemodynamic support due to it’s “catecholamine- insipidus, as well as for hemodynamic support due to it’s “catecholamine- sparing” effect? sparing” effect? a. Insulin a. Insulin b. Vasopressin b. Vasopressin c. Levothyroxine c. Levothyroxine d. Dopamine d. Dopamine
37 38
Medical Management Pulmonary System: Changes
● Hormonal System ● Complete absence of respiratory drive ● Cardiovascular System ● Problems include pulmonary edema, pneumonia, trauma, and intense inflammatory response ● Pulmonary System ● ● Other Changes Increase in pulmonary capillary permeability due to inflammatory responses
39 Wood KE, Becker BN, McCartney JG, et al. Care of the potential organ donor. N Engl J Med. 2004;351:2730–2739. 40 Shah VR. Aggressive management of multiorgan donor. Transplant Proc. 2008;40:1087–90.
Pulmonary System: Goals “A Randomized Trial of the Effects of Nebulized Albuterol on Pulmonary Edema in Brain Dead Organ Donors”
● Provide adequate oxygenation and to preserve lung function ● Prospective, randomized trial comparing albuterol (5 mg q4h) and saline nebulization in 506 organ donors ● Goals of mechanical ventilation include: ● No difference in change in oxygenation, donor lung utilization, or transplant ○ Maintain adequate oxygenation (SaO2 >90%) recipient survival ○ Minimize fraction of inspired oxygen (FiO2 <40%) ● Donors in albuterol group more likely to have the study drug reduced (13% ○ Maintain acid-base status (PaCO 35-40 mmHg, pH 7.35-7.45) 2 vs. 1%) or stopped (8% vs. 0%) due to tachycardia ● Maintain adequate pulmonary hygiene ● Maintain adequate fluid balance
Ware LB, Landeck M, Koyama T, et al. A randomized trial of the effects of nebulized albuterol on pulmonary edema in brain dead organ donors. American Wood KE, Becker BN, McCartney JG, et al. Care of the potential organ donor. N Engl J Med. 2004;351:2730–2739. 41 journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2014;14(3):621- 42 628.
85 “Improved Oxygenation and Increased Lung Donor Recovery with Pulmonary System: Treatment High-Dose Steroid Administration After Brain Death”
● Retrospective analysis of 118 donors comparing the use of high-dose ● Albuterol and/or ipratropium nebulizations for bronchospasms steroids (methylprednisolone 14.5+/-0.06 mg/kg) to no steroids ● Methylprednisolone 15 mg/kg bolus ● Steroid-receiving donors had a significant and progressive increase in ○ LOPA also recommends 500 mg Q4-8H oxygenation; non-steroid donors showed an overall decrease in oxygenation ● The number of procured lungs was greater in steroid-receiving donors (31.25% vs 7.89%)
Follette DM, Rudich SM, Babcock WD. Improved oxygenation and increased lung donor recovery with high-dose steroid administration after brain death. J 43 44 Heart Lung Transplant 1998;17:423-9.
Medical Management Other Changes
● Hormonal System ● Brain ischemia results in the release of tissue thromboplastin ● Cardiovascular System ● Infection ● Pulmonary System ● Hypothermia ● Other Changes ○ Results from loss of hypothalamic control
45 Smith M. Physiologic changes during brain stem death--lessons for management of the organ donor. J Heart Lung Transplant. 2004;23(9) Suppl:S217–S222. 46
Other Medications Conclusion
● Heparin before aortic cross-clamping to avoid thrombotic complications ● The care given to one organ donor can greatly affect several transplant (30,000–40,000 units IV) recipients ● Empiric broad-spectrum antibiotics ● Aggressive donor management ensures that the largest number of organs ○ LOPA recommends ampicillin-sulbactam (1.5 g Q6H) can be successfully procured and improves the organs’ overall quality ● LOPA recommends nystatin (4,000,000 units PO Q4H) for pancreas donors ● Common medications: hormone resuscitation, cardiovascular support, respiratory support, infection prophylaxis, anticoagulation, and ● Neuromuscular blockers to manage movements due to spinal reflexes maintenance of normothermia ● Eye drops/ointments (ex: natural tears Q4H)
Wood KE, Becker BN, McCartney JG, et al. Care of the potential organ donor. N Engl J Med. 2004;351:2730–2739. Freeman RB, Giatras I, Falagas ME, et al. Outcome of transplantation of organs procured from bacteremic donors. Transplantation 1999;68:1107-11. 47 48
86 Become a Donor
● Currently 116,740 people that need a lifesaving organ transplant ● Every 10 minutes someone is added to the waiting list ● One organ donor can save up to The Management of the Potential Organ 8 lives ● Register to Donor: What Pharmacists Need to Know be a donor or edit Ethan George, Pharm.D. your registration at PGY1 Pharmacy Resident registerme.org University Health Shreveport
Health Resources and Services Administration. U.S. Department of Health and Human Services. Organ Procurement and Transplantation Network website. 49 https://optn.transplant.hrsa.gov/ Accessed August 20, 2017.
87 Louisiana Society of Health System Pharmacists 2017 Midyear Meeting
3:00 p.m.—4:00 p.m. Novel Agents Within Pediatric Pain Management
Amber Grady, PharmD PGY1 Pharmacy Resident University Health Shreveport Shreveport, LA
0179-0000-17-035-L01-P/ 0179-0000-17-035-L01-T 1 contact hour (0.1 CEU) Knowledge-based activity
Objectives:
Pharmacists: 1. Identify novel agents for pain management in pediatric patients. 1. Describe the current standards of care for 2. Distinguish the difference in oral, topical, pain management in pediatric patients, and intra-nasal formulations of novel while identifying major limitations agents utilized in the pediatric pain associated with these therapies. management. 2. Discuss novel treatment options and potential limitations for their utilization in pediatric pain management. 3. Define the appropriateness of utilizing novel agents for pain management in pediatric patients.
Technicians:
Dr. Grady has disclosed that she has no relevant financial relationships.
88 Disclosures Novel Agents in Pediatric • I have no relevant conflicts of interest or financial Pain Management disclosures in relation to this continuing education presentation Amber Grady, PharmD
Objectives Objectives
By the end of this presentation pharmacist are expected to be By the end of this presentation pharmacy technicians are able to… expected to be able to…
• Describe the current standards of care for pain management • Identify novel agents for pain management in pediatric in pediatric patients, while identifying major limitations patients associated with these therapies • Distinguish the difference in oral, topical, and intra‐nasal • Discuss novel treatment options and potential limitations for formulations of novel agents utilized in the pediatric pain their utilization in pediatric pain management management
• Define the appropriateness of utilizing novel agents for pain management in pediatric patients
Background What is Pain?
• Pain • Chronic pain among children is wide spread but • “usually localized physical suffering associated with bodily frequently under‐recognized disorder” • According to the American Pain Society pain is the • Acute Pain “result of a dynamic integration of biological • Pain that is directly related to soft tissue damage processes, psychological factors, and sociocultural context considered within a developmental trajectory” • Chronic Pain • Chronic pain in children can have a profound impact • Pain which lasts beyond the ordinary duration of time that on life an insult or injury to the body needs to heal
Gregoire M, Drugs for chronic pain in children commentary on clinical practice and the absence of evidence Rosenquist E. Definition and pathogenesis of chronic pain [Internet]. Waltham (MA): UpToDate.
89 How is Pain Classified? Pediatric Chronic Pain
• There are two types of pain • Children can be affected by chronic • Nociceptive diseases just as adults • Pain caused by stimulation of intact • Additionally neurological impairment nociceptors as a result of tissue injury and inflammation can lead to chronic pain in pediatric • Neuropathic patients • Pain caused by stimulation or abnormal • These patients are often excluded from functioning of damaged sensory nerves clinical trials, due to inability to communicate
Hauer J, Jones B. Evaluation and management of pain in children [Internet]. Waltham (MA): UpToDate. Breau LM, et al. The incidence of pain in children with severe cognitive impairments. Arch Pediatr Adolesc Med
How is Pain Managed WHO Two‐Step Strategy
• The main goals of pediatric pain • The World Health Organization (WHO) management are to reduce, control, and suggests a two‐step approach to pain prevent pain management • Mild Pain • Management will vary depending on type, • APAP source, severity, and duration of pain • NSAIDS • All of these things should be taken into consideration when selecting analgesic agents Moderate to Severe Pain Opioids
Hauer J, Jones B. Evaluation and management of pain in children [Internet]. Waltham (MA): UpToDate. WHO guidelines on the pharmacological treatment of persisting pain in children with medical illnesses.
Assessing Pain Oucher Scale
• Pain must be assessed in order to correctly • A poster developed to help children treat the patient communicate how much pain they feel • Assessing pain in children can be • There are two versions of this scale particularly difficult • Picture • There are several measures that have been • Number designed to assess pediatric pain
"How To Use The Oucher." Oucher.org. N.p., 2003. Web Cohen, L. L. et al. Evidence‐Based Assessment Of Pediatric Pain. Journal of Pediatric Psychology
90 Numeric Scale
"How To Use The Oucher." Oucher.org. N.p., 2003. Web "How To Use The Oucher." Oucher.org. N.p., 2003. Web
Visual Analog Scale (VAS)
• A continuous scale comprised of a horizontal or vertical line, anchored by 2 verbal descriptors • The patient is asked to place a perpendicular line to the VAS line at the point that represents their pain intensity • A ruler is used to measure the distance between “no pain” and the patient’s mark • No pain (0‐4 mm) • Mild pain (5‐44 mm) • Moderate pain (45‐75 mm) • Severe pain (75‐100 mm)
Hawker, Gillian A. et al. Measures Of Adult Pain: Visual Analog Scale For Pain (VAS Pain), Numeric Rating Scale For Pain (NRS Pain), Mcgill Pain Questionnaire (MPQ), Short‐Form Mcgill Pain Questionnaire (SF‐MPQ), Chronic Hawker, Gillian A. et al. Measures Of Adult Pain: Visual Analog Scale For Pain (VAS Pain), Numeric Rating Scale For Pain (NRS Pain), Mcgill Pain Questionnaire (MPQ), Short‐Form Mcgill Pain Questionnaire (SF‐MPQ), Chronic Pain Grade Scale (CPGS), Short Form‐36 Bodily Pain Scale (SF. Arthritis Care & Research Pain Grade Scale (CPGS), Short Form‐36 Bodily Pain Scale (SF. Arthritis Care & Research
Mild to Moderate Pain Severe Pain
• Acetaminophen is the most widely used analgesic • Mainstay for the treatment of severe pain in because it has minimal side effects at therapeutic pediatric patients is opioids doses • There are a variety of opioids • Ibuprofen is the preferred NSAID in children due to its fewer side effects. • Choice of opioid are generally dependent on • Aspirin use has declined in pediatric patients due to intensity and duration of pain, mode of Reye’s syndrome administration, adverse effects, and prior experience
Hauer J, Jones B. Evaluation and management of pain in children [Internet]. Waltham (MA): UpToDate. Hauer J, Jones B. Evaluation and management of pain in children [Internet]. Waltham (MA): UpToDate.
91 Adverse Effects of Opioids Opioid Induced Constipation
• Nausea • Opioid‐induced constipation is the most • Vomiting common adverse effect
• Constipation • Opioids mediate their gastrointestinal and analgesic effects through the same • Sedation subclasses of receptors • Respiratory Depression • Unlike the analgesic effects, opioid tolerance • Pruritus does not extend to gastrointestinal motility and transit
Hauer J, Jones B. Evaluation and management of pain in children [Internet]. Waltham (MA): UpToDate. Wang, Chong‐Zhi, and Chun‐Su Yuan. "Pharmacologic Treatment Of Opioid‐Induced Constipation." Expert Opinion on Investigational Drugs
Barriers to Opioid Use Novel Agents
• Drug Abuse • Alpha Agonists • Addiction • Gabepentinoids • Local Anesthetics • Diversion • Adverse Events
Portenoy R, Mehta Z, Ahmed E. Cancer pain management: general principles and risk management for patients receiving opioids. [Internet]. Waltham (MA): UpToDate.
Alpha‐Agonists Mechanism of Action
• A family of G‐protein‐coupled receptors with 3 pharmacological subtypes, 2A, 2B, and 2C • These subtypes can be found in different places in the body with 2A and 2C being found primarily in the central nervous system and 2B being found on vascular smooth muscle • Subtypes 2A and 2C subtypes are associated with sedation, analgesia, and sympatholytic effects
Kaur M, Singh P M. Current role of dexmedetomidine in clinical anesthesia and intensive care. Anesth Essays Res Giovannitti, et al. "Alpha‐2 Adrenergic Receptor Agonists: A Review Of Current Clinical Applications." Anesthesia Progress
92 Mechanism of Analgesia Clonidine vs Dexmedetomidine
Clonidine Dexmedetomidine
• Prototypical agent • Agent created for increased selectivity • ‐2: ‐1 affinity 220:1 • 8‐10 times more • Partial agonist at the selective for ‐2 ‐2 adrenergic receptors receptor • Full agonist at the ‐2 adrenergic receptor
Kaur M, Singh P M. Current role of dexmedetomidine in clinical anesthesia and intensive care. Anesth Essays Res Kaur M, Singh P M. Current role of dexmedetomidine in clinical anesthesia and intensive care. Anesth Essays Res
Dexmedetomidine
Dexmedetomidine • Selective alpha 2 adrenergic agonist • Commonly utilized for its sedative properties • Adverse Events • Hypertension, xerostomia, hypotension, hypoxia • Storage • Unopened bottles and vials can be stored at room temperature • Diluted solutions can be stored at room temperature for 4 hours
Dexmedetomidine. Micromedex [Internet]. Greenwood Village: Truhaven Health Analytics
Dexmedetomidine vs Fentanyl in Children Dexmedetomidine Pharmacokinetics Undergoing Tonsillectomy and Adenoidectomy
• Pharmacokinetics of dexmedetomidine varies amongst different age groups • A prospective, randomized study of 122 patients with obstructive sleep apnea undergoing • Variability is most substantial when it applies to adenotonsillectomy (T&A) distribution • Preterm neonates (28 to <36 weeks): 2.7 L/kg • Randomized to dexmedetomidine 2 mcg/kg IV over 10 minutes then 0.7 mcg/kg/hour vs fentanyl 1 • Term neonates: 3.9 L/kg mcg/kg IV bolus • Infants and Children < 2 years: 3.8 L/kg (0.1 to 10.9 L/kg) • Children 2 to 11 years: 2.2 L/kg (1.3 to 2.8 L/kg) • Rescue morphine was required by 16.3% in the dexmedetomidine group vs. 47.5% in the fentanyl group (P‐value=0.002)
Chrysostomou C, et al. A phase II/III, multicenter, safety, efficacy, and pharmacokinetic study of dexmedetomidine in preterm and term neonates Vilo S,, et al. Pharmacokinetics of intravenous dexmedetomidine in children under 11 yr of age. Br J Anaesth. Patel, Anuradha et al. "Dexmedetomidine Infusion For Analgesia And Prevention Of Emergence Agitation In Children With Obstructive Sleep Apnea Syndrome Undergoing Tonsillectomy And Adenoidectomy." Anesthesia & Analgesia
93 Long‐Term Dexmedetomidine in Gabapentinoids Children and Neonates
• A retrospective, observational study to • Despite being structural analogs of ‐ evaluate the safety and efficacy of long‐term aminobutyric acid, they have no activity at dexmedetomidine these receptors • Comfort scores were significantly lower at 2 • They bind to the presynaptic voltage‐gated and 72 hours of dexmedetomidine infusion calcium channels and modulate their traffic and function • Withdrawal symptoms were seen in 30% of the patients who were taken of • Thus modulating the release of excitatory dexmedetomidine neurotransmitters
Whalen D. et al. Long‐Term Dexmedetomidine Use And Safety Profile Among Critically Ill Children And Neonates. Pediatric Critical Care Medicine Schmidt, Peter C. et al. "Perioperative Gabapentinoids." Anesthesiology.
Mechanism of Action Pharmacokinetics
• Both of the gabapentinoids are metabolized by the liver • They are also renally excreted • There is some variation in absorption • Gabapentin’s absorption is facilitated by saturable transporters
Schmidt, Peter C. et al. "Perioperative Gabapentinoids." Anesthesiology
Gabapentin
Gabapentin • An anticonvulsant that is structurally related to GABA, but does not influence synthesis or uptake of GABA
• FDA approved for post‐herpatic neuralgia and adjunct partial seizure treatment
• Adverse Effects • Peripheral edema, ataxia, somnolence, disorder of thought
Gabapentin. Micromedex [Internet]. Greenwood Village: Truhaven Health Analytics
94 Gabapentin, Bupivacaine and Intravenous Gabapentin and Hyperalgesia Pethidine on Tonsillectomy Pain
• A randomized double‐blind study comparing gabapentin, • A case series of neurologically impaired infants bupivacaine, and meperidine for analgesia in children treated with gabapentin for visceral hyperalgesia undergoing tonsillectomy saw decreased irritability • A total of 105 patients were randomized to receive oral • The case series included 11 infants both term and gabapentin, bupivacaine, or meperidine preterm • Pain was assessed using the Oucher scale at 3, 6, and 12 • Adverse effects were seen in 5 of the 11 patients, 3 hours of which were related to the abrupt discontinuation of gabapentin • Mean pain score was lowest in the gabapentin group
Edwards, Laura et al. "Gabapentin Use In The Neonatal Intensive Care Unit." The Journal of Pediatrics Amani S, Abedinzadeh MR. Effects of oral gabapentin, local bupivacaine and intravenous pethidine on post tonsillectomy pain. Iran J Otorhinolaryngol
Pregabalin (Lyrica®)
Pregabalin • Anticonvulsant that is structurally related to GABA
• Commonly utilized for both its anticonvulsant and analgesic effects
• Adverse Effects • Peripheral edema, drowsiness, weight gain, abnormality in thinking, insomnia, intoxicate feeling
McKeage K, Keam SJ. Pregabalin: in the treatment of postherpetic neuralgia. Drugs Aging.
Pregabalin in Neuropathic Pain Abuse Potential of Oncological Patients
• An open‐label study evaluating the efficacy of • Effective as of July 2005 pregabalin and all of its salt pregabalin in children who developed a painful forms were classified as a Scheduled V substance neuropathy after treatment for solid tumor or per the DEA leukemia • Clinical trials suggest that the positive psychic • Relatively small population effects are limited
• A significant and long‐lasting pain relief was noted • Pregabalin does not substitute for benzodiazepines in 86% of these patients. Median VAS score in benzodiazepine‐dependent animals decreased by 59% at the 8th week from baseline.
Vondracek, Petr et al. Efficacy Of Pregabalin In Neuropathic Pain In Paediatric Oncological Patients. European Journal of Paediatric Neurology "Rules ‐ 2005 ‐ Schedules Of Controlled Substances: Placement Of Pregabalin Into Schedule V." Deadiversion.usdoj.gov. N.p., 2005
95 Food & Drug Administration Local Anesthetics (FDA) Warnings
• Starting in 2008 the Food & Drug Administration • Commonly utilized as topical (FDA) began issuing safety alerts concerning antiepileptic drugs (AEDS) formulations
• A pooled analysis of 11 AEDS was performed • Often preferred for procedural pain
• Based on this information the FDA has required that especially in very young children and manufacturers update product labeling to include a neonates warning to patients. • Data is limited and inconclusive
"Suicidal Behavior And Ideation And Antiepileptic Drugs." Fda.gov. N.p., 2009.. Anand K, Prevention and treatment of neonatal pain. [Internet]. Waltham (MA): UpToDate.
Local Anesthetic Formulations
• There are several formulations of topical Lidocaine anesthetics that can be utilized • Examples of local anesthetics include: • Lidocaine • Tetracaine • Bupivacaine • Many of the products utilized are combination products including lidocaine
Hsu D, Topical anesthetics in children. [Internet]. Waltham (MA): UpToDate.
Lidocaine Lidocaine Preparations
• Blocks the generation and conduction of nerve • Available as topical creams, ophthalmic, and impulses by increasing the threshold for electrical topical patch formulations excitation and reducing the rate of rise of action potential • Utilized topically in younger children and • Utilized for local or regional anesthesia in surgical neonates procedures • Systemic lidocaine use can lead to cardiac • Adverse Effects arrhythmias, but topical formulations have • Hypotension, cardiac dysrhythmia minimal side effects
Lidocaine. Micromedex [Internet]. Greenwood Village: Truhaven Health Analytics Lidocaine. Micromedex [Internet]. Greenwood Village: Truhaven Health Analytics
96 Eutectic Mixture of Local Tolerability of Topical Lidocaine Anesthetics
• A prospective, nonrandomized, open‐label trial • Eutectic mixture of local anesthetics (EMLA) is evaluated the pharmacokinetics of lidocaine 5% generally utilized to treat pain associated with patches on healthy volunteers procedures
• Assessments included: • A double‐blind, placebo‐controlled trial examined • skin evaluations, monitoring of clinical adverse events the difference in pain scores between EMLA and and vital signs, 12‐lead electrocardiograms, and placebo in intravenous catheter insertion laboratory testing • This study found that patients in the EMLA group • No clinically significant changes were observed in had lower pain scores than those in the placebo vital signs, 12‐lead ECGs, or laboratory tests. group
Gammaitoni A, et al. Pharmacokinetics And Tolerability Of Lidocaine Patch 5% With Extended Dosing. The Annals of Pharmacotherapy Cordoni A et al. Eutectic Mixture Of Local Anesthetics Reduces Pain During Intravenous Catheter Insertion In The Pediatric Patient. The Clinical Journal of Pain
Conclusions Questions
• Pain management in pediatric patients continues to be an issue that needs further research
• While there have been some advances in pediatric pain management, there is still much research that is left to be done
• These agents that are now being utilized for this indication are providing opportunities to better care for this patient population
Objectives Assessment #1
By the end of this presentation pharmacist are expected to be able to… • Describe the current standards of care for pain management in pediatric All of the following are barriers to current standards of patients, while identifying major limitations associated with these therapies pediatric pain management except: • Discuss novel treatment options and potential limitations for their utilization in pediatric pain management a) Addiction • Define the appropriateness of utilizing novel agents for pain management in pediatric patients b) Diversion By the end of this presentation pharmacy technicians are expected to be able c) Lack of pain relief to… • Identify novel agents for pain management in pediatric patients d) Adverse effects
• Distinguish the difference in oral, topical, and intra‐nasal formulations of novel agents utilized in the pediatric pain management
97 Assessment #1 Assessment #2
All of the following are barriers to current standards of True/False: In 2008 the FDA issued a statement pediatric pain management except: mandating that the gabapentinoids labeling include warnings of increased suicidal ideation a) Addiction b) Diversion c) Lack of pain relief d) Adverse effects
Assessment #2 Assessment #3
True/False: In 2008 the FDA issued a statement Lidocaine is NOT available as which of the following mandating that the gabapentinoids labeling include preparations warnings of increased suicidal ideation a) Intravenous True b) Oral
c) Ophthalmic
d) Topical
Assessment #3 Assessment #4
Lidocaine is NOT available as which of the following A 12 year old boy with history of acute lymphoblastic preparations leukemia (ALL) presents with complaints of tingling pain that has been present for the past 5 months. a) Intravenous Which of class of agents discussed in this presentation b) Oral would be most appropriate to treat his pain? c) Ophthalmic a) Alpha Agonists d) Topical b) Gabapentinoids c) Local Anasthetics
98 Assessment #4
A 12 year old boy with history of acute lymphoblastic leukemia (ALL) presents with complaints of tingling pain that has been present for the past 5 months. Which of class of agents discussed in this presentation would be most appropriate to treat his pain? a) Alpha Agonists b) Gabapentinoids c) Local Anesthetics
99 Louisiana Society of Health System Pharmacists 2017 Midyear Meeting
3:00—4:00 p.m. Toxidromes & Toxic Homes: A Review of Common Household Poisons
Haley Smith, PharmD PGY1 Pharmacy Resident University Health Shreveport Shreveport, LA
0179-0000-17-034-L01-P/ 0179-0000-17-034-L01-T 1 contact hour (0.1 CEU) Knowledge-based activity
Objectives:
Pharmacists: Technicians: 1. Describe the structure of the Poison Control 1. Identify commonly ingested agents. Center and statistics related to ingestions. 2. Recognize commonly used antidotes/ 2. Identify commonly ingested agents and the treatments for ingested agents. toxidromes associated with them. 3. Recommend drug therapy/antidotes for ingested agents.
Dr. Smith has disclosed that she has no relevant financial relationships.
100 Disclosure
• I have no relevant conflicts of interest or financial disclosure in relation to this continuing education presentation
Toxidromes and Toxic Homes
Objectives: National Poison Data System • By the end of this presentation, Pharmacists should be able to: • 55 poison centers in the United States 1. Describe the structure of the Poison Control Center and • 1 in Louisiana statistics related to ingestions • American Association of Poison Control Centers (AAPCC) 2. Identify commonly ingested agents and the toxidromes uploads data to the National Poison Data System every 8 associated with them minutes 3. Recommend drug therapy/antidotes for ingested agents • Real‐time snapshots nationwide • Technicians should be able to: • Used to answer questions about use/exposure of 1. Identify commonly ingested agents potentially toxic substances 2. Recognize commonly used antidotes • Number is 1‐800‐222‐1222
Mowry et al. Clinical Toxicology 54.10 (2016): 924‐1109.
Poison Exposures Nationwide Routes of Exposure •2.8 million cases were reported in 2015, of those 2.2 million were considered exposures
• Children/teens under 19 = 66% of exposures • 24.6% of childhood exposures involved cosmetics/personal care or cleaning agents
• Adults = 34% of all exposures • 57% of adult exposures involved medications or pharmaceuticals
Mowry et al. Clinical Toxicology 54.10 (2016): 924‐1109 Mowry et al. Clinical Toxicology 54.10 (2016): 924‐1109
101 Exposures Q1. Where did the majority of human poison exposures take place in 2015 • 93% of human exposures reported occurred at a place of residence A. Workplace • 67% of human exposures were treated onsite B. School C. Outdoors • 29.3% of cases were treated in a health‐care facility D. Home • 78% of exposures were unintentional
Mowry et al. Clinical Toxicology 54.10 (2016): 924‐1109
Top 10 Exposure Substances By Age Category Mowry et al. Clinical Toxicology 54.10 (2016): 924‐1109 Q2. What is the most common exposure All Human Exposures Pediatric Exposures (≤ 6 years) Adult Exposures ( ≥ 20 years) substance reported in 2015? Analgesics 11.1% Cosmetics/ Personal Care 13.6% Analgesics 11.6%
Household Cleaning Household Cleaning Sedative/Hypnotics/ A. Household cleaning products 7.6% 11.2% 10.3% Products Products Antipsychotics B. Pesticides Cosmetics/Personal Care 7.4% Analgesics 9.1% Antidepressants 6.9%
Sedative/Hypnotics/ Foreign C. Sedatives 5.8% 6.5% Cardiovascular Drugs 6.1% Antipsychotics Bodies/Toys/Misc. Household Cleaning Antidepressants 4.6% Topical Medications 5.3% 5.4% D. Analgesics Products Antihistamines 4.1% Vitamins 4.6% Alcohols 4.7%
Cardiovascular Drugs 4% Antihistamines 4.4% Anticonvulsants 3.9%
Foreign Bodies/Toys/Misc. 3.7% Pesticides 3.3% Pesticides 3.6%
Dietary Bites and Pesticides 3.3% 3% 3.4% Supplements/Herbals Envenomations
Topical Medications 2.9% Plants 2.7% Antihistamines 3.1%
Toxidromes Toxidrome Signs and Examples Symptoms Anticholinergic Urinary retention, tachycardia, Antihistamines, carbamazepine, delirium, coma, seizures, dilated pupils, cyclobenzaprine, atropine, clozapine, dry and hot skin (decreased sweating) quetiapine, amitriptyline, doxepin
Serotonin Syndrome Hyperthermia, tachycardia, Dextromethorphan hypertension/hypotension, agitation, confusion, diaphoretic, neuromuscular hyper‐excitability, clonus, confusion, dilated pupils Cholinergic SLUDGE: Salivation, Lacrimation, Insecticides (organophosphates) Urination, Defecation, GI cramping, Emesis MTWTF: Muscle cramps, tachycardia, weakness, twitching, fasciculations
Acetaminophen (APAP) Nausea, vomiting, malaise, right upper Acetaminophen quadrant abdominal pain, jaundice, confusion, and coma may develop later Images available from: lifeinthefastlane.com Holstege et al. Crit Care Clin. 28.4 (2012): 479‐498.
102 Top 10 Exposure Substances By Age Category Q3. What are the common symptoms Mowry et al. Clinical Toxicology 54.10 (2016): 924‐1109 for the cholinergic toxidrome? All Human Exposures Pediatric Exposures (≤ 6 years) Adult Exposures ( ≥ 20 years) Cosmetics/ Personal Analgesics 11.1% 13.6% Analgesics 11.6% A. Mad as a Hatter, Blind as a Bat, Dry as a Bone, Red as Care Household Cleaning Household Cleaning Sedative/Hypnotics/Anti 7.6% 11.2% 10.3% a Beet, Hot as a Pistol Products Products psychotics B. Salivation, Lacrimation, Urination, Defecation, GI Cosmetics/Personal Care 7.4% Analgesics 9.1% Antidepressants 6.9% Sedative/Hypnotics/Antips Foreign 5.8% 6.5% Cardiovascular Drugs 6.1% cramping, Emesis ychotics Bodies/Toys/Misc. Household Cleaning Antidepressants 4.6% Topical Medications 5.3% 5.4% C. Mydriasis, Tachycardia, Hyperthermia, Seizures Products D. Miosis, Hypoventilation, Coma, Bradycardia, Antihistamines 4.1% Vitamins 4.6% Alcohols 4.7% Cardiovascular Drugs 4% Antihistamines 4.4% Anticonvulsants 3.9% Hypotension Foreign Bodies/Toys/Misc. 3.7% Pesticides 3.3% Pesticides 3.6%
Dietary Pesticides 3.3% 3% Bites and Envenomations 3.4% Supplements/Herbals
Topical Medications 2.9% Plants 2.7% Antihistamines 3.1%
Acetaminophen Toxicity Pathway
Toxicity occurs when nontoxic •One of the top drugs associated with overdose pathways are overwhelmed deaths • Used in > 100 OTC and many Rx products • Glutathione stores are depleted • Delayed toxicity with high doses of acetaminophen • Easy to obtain
• Once glutathione is depleted, NAPQI accumulates leading to hepatotoxicity
O’Malley et al. Merck Manual. Internet. 2015 O’Malley et al. Merck Manual. Internet. 2015
Stages of APAP Toxicity Toxic Doses of APAP Dose (g) Dose (mg/kg) Clinical Effects >15 >215 50% hepatotoxicity 10-15 140-215 Possible hepatotoxic Initial stage: 0‐24 Middle Stage: 24‐ Hepatic stage: 3‐ Recovery stage: 5 4-10 60-140 Not generally toxic hours 48 hours 4 days days‐ 3 months <4 <60 Therapeutic •Symptoms •Increase in • Fulminant •Chronic liver absent aminotransfer hepatic necrosis, dysfunction encephalopathy ‐ases rare except in •GI irritation – •Hepato‐renal Rumack – Matthew N/V syndrome, alcoholics coagulopathy nomogram • Hemorrhagic pancreatitis
Brooks et al. CHEST Journal. 2011 Volume 140 Issue 4 Pages 1072‐ O’Malley et al. Merck Manual. Internet. 2015 1085
103 Study 1: The Toxicology Investigator Network Authorship Group. A Multi‐center Comparison of the Safety of Oral versus Treatment Intravenous Acetylcysteine for Treatment of Acetaminophen Overdose. Clinical toxicology (Philadelphia, PA). • Activated charcoal –within the first hour 2010;48(5):424‐430. doi:10.3109/15563650.2010.486381. Nausea Vomiting Pruritus Flushing Tachycardia • N‐Acetylcysteine IV N‐acetylcysteine 28 (7.2%) 23 (6.4%) 10 (2.8%) 7 (2%) 10 (2%) • Free radical scavenger and cysteine donor to facilitate glutathione regeneration (N=358) • Should be started within 8 hours of overdose, but patients presenting as late as 24 hours Oral N‐ 40 (20.3%) 29 (14.7%) 1 (0.5%) 0 (0%) 3 (1.5%) after ingestion can still benefit acetylcysteine • AE: anaphylactoid reaction,N‐ Acetylcysteinehyponatremia, and hypervolemia Dosing (N=197) Study 2: Prescott, L. F., et al. "Intravenous N‐acetylcysteine: the treatment of choice for paracetamol poisoning." Br Med Route Dose J 2.6198 (1979): 1097‐1100. Oral Loading dose: 140 mg/kg IV Acetylcysteine IV Acetylcysteine IV acetylcysteine IV acetylcysteine Maintenance dose: 70 mg/kg q4h x 12 doses given w/in 10 hrs given w/in 10‐24 given to high risk given to high risk Intravenous Loading dose: 150 mg/kg (max 15 g) over 60 min (dose was hrs (N=38) patients w/in 10 pts w/in 8 hours Maintenance dose: 50 mg/kg (max 5 g) over 4 hours appropriate) hrs (levels >300 (N=19) Then 100 mg/kg (max 10 g) over 16 hrs (N=62) mg/L at 4 hours, 45 mg/L at 15 hrs Effervescent Tablets Loading dose: 140 mg/kg (N=33) Maintenance dose: 70mg/kg repeated every 4 hours for a Liver damage 1 (1.6%) 20 (53%) 1 (3%) ALT’s remained total of 17 doses normal in 17 Comes in 500 mg and 2.5 gram tablets (89%) Smilkstein et al. New England Journal of Medicine 319.24 (1988): 1557‐1562.\2.
Signs/Symptoms Dextromethorphan • CNS effects are the most prevalent • Sedation, dysphoria, nystagmus • Found in many cough and cold preparations • Combination products can lead to other health complications and • Opium alkaloid derivative different clinical presentations • Binds to opioid receptors at high doses causing • Increased blood pressure with pseudoephedrine miosis, respiratory depression, and CNS depression • Liver damage with acetaminophen • Common drug of abuse in teens due to its • With more severe toxicity, psychosis, delirium, seizures, and coma can be hallucinatory and dissociative effects seen • Common street names: DXM, Dex, Orange Crush Dose‐Dependent Plateaus 100 – 200 mg: Mild Stimulation 200 – 400 mg: Euphoria and hallucinations 300 – 600 mg: Distorted visual 500 – 1500 mg: Dissociative sedation perceptions and loss of motor Image available from coordination delsym.com Rumack et al. POISINDEX® 2017. CCIS Volume 172 Rumack et al. POISINDEX® 2017. CCIS Volume 172
Range of Toxicity Normal Dosing Toxic Dosing Treatment Adults and children >12yo: 10 mL (60 See plateaus on previous slide mg) Q12H (MAX 120mg/day or 20 • Supportive and Symptomatic treatment mL/day) • Benzodiazepines for agitation and seizures Children >6yo – Mild toxicity was seen • Seizures have been seen within 30 minutes of ingestion with acute ingestion of 2.2 mg/kg to 7.7 • Nitroprusside, labetalol, and nitroglycerin for severe Children (6-12yo) – 5 mL (30 mg) Q12H mg/kg hypertension (MAX 60mg/day) More severe toxicity was seen with • Naloxone has been successful, but not consistently ingestions of > 7.8 mg/kg • Decontamination with Activated Charcoal • Not usually indicated outside of hospital due to CNS depression, Child (2-6yo) – 2.5 mL (15 mg) Q12H Children < 6yo – 5-38 mg/kg (MAX 30mg/day) but sometimes given by EMS on certain occasions • Can be given at the hospital
Rumack et al. POISINDEX® 2017. CCIS Volume 172 Rumack et al. POISINDEX® 2017. CCIS Volume 172
104 Top 10 Exposure Substances By Age Category Mowry et al. Clinical Toxicology 54.10 (2016): 924‐1109 Organophosphates All Human Exposures Pediatric Exposures (≤ 6 years) Adult Exposures ( ≥ 20 years)
Cosmetics/ Personal Analgesics 11.1% 13.6% Analgesics 11.6% Care • AKA pesticides • Common Organophosphates Household Cleaning Household Cleaning Sedative/Hypnotics/ 7.6% 11.2% 10.3% • Acephate Products Products Antipsychotics • Make up 70% of the pesticides • Diazinon Cosmetics/Personal used in the US 7.4% Analgesics 9.1% Antidepressants 6.9% Care • Malathion • Inhibit acetylcholinesterase Sedative/Hypnotics/An Foreign 5.8% 6.5% Cardiovascular Drugs 6.1% tipsychotics Bodies/Toys/Misc. preventing hydrolysis of Household Cleaning • Account for 200,000 deaths each Antidepressants 4.6% Topical Medications 5.3% 5.4% acetylcholine Products year Antihistamines 4.1% Vitamins 4.6% Alcohols 4.7% • Accumulation at the nerve Cardiovascular Drugs 4% Antihistamines 4.4% Anticonvulsants 3.9% endings causes the sympathetic,
Foreign 3.7% Pesticides 3.3% Pesticides 3.6% parasympathetic and peripheral Bodies/Toys/Misc. nervous system to go haywire Dietary Bites and Pesticides 3.3% 3% 3.4% Supplements/Herbals Envenomations
Topical Medications 2.9% Plants 2.7% Antihistamines 3.1% Rumack et al. POISINDEX® 2017. CCIS Volume 172
Signs/Symptoms Treatment Muscarinic Nicotinic CNS effects effects Effects • Ensure clear airway Mild - Moderate Bradycardia, Tachycardia, salivation, hypertension, diaphoresis, muscle cramps, • Administer atropine or glycopyrrolate vomiting/diarrhea hyperglycemia, acidemia Moderate - Severe Bronchospasm Respiratory failure, CNS depression, weakness, confusion, delirium, • Administer pralidoxime if indicated fasciculations seizures, coma Children Excessive salivation Flaccid muscle Seizures, lethargy, • weakness coma Decontaminate concurrently
Rumack et al. POISINDEX® 2017. CCIS Volume 172 Rumack et al. POISINDEX® 2017. CCIS Volume 172
Antidotes DuoDote Dosing Mild Symptoms Severe Symptoms •DuoDote Blurred vision, increased Confusion, severe difficulty salivation, chest tightness, breathing, muscular twitching, • Atropine 2.1 mg and pralidoxime 600 mg Nausea/vomiting, wheezing, involuntary urination, stomach cramps, tachycardia convulsions, unconsciousness • Auto‐injector for use by EMS who recognize insecticide toxicity First Dose If two or more: give 1 dose in mid‐ • IM injection lateral thigh • Currently no pediatric dosing Wait 10‐15 minutes to take effect Additional Doses If at any time after first dose these occur, give two doses in rapid succession
DuoDote Package Insert. Meridian Medical Technologies. Pfizer
105 Atropine • Competitively antagonizes the effects of acetylcholine at the muscarinic receptors –does NOT reactivate the cholinesterase enzyme Glycopyrrolate • Test Dosage: • Adults: 1 mg • Anticholinergic agent that inhibits acetylcholine on smooth muscles • Children < 12 yo: 0.01 mg/kg • Helps to diminish excessive pharyngeal, tracheal, and bronchial Treatment Dosing of Atropine secretions Children < 12 yo • Recent studies recommend starting • In some ICU settings children are at 0.02 mg/kg and doubling the given 0.05 mg/kg every 15 minutes dose every 5 minutes Dosing Adults and children >12 yo • Initial dose 1‐3 mg IV • Dose may be doubled with each • Repeat in 3‐5 minutes if no change administration until pulmonary Ampules of 7.5 mg should Titrate to desired effects 0.2 mg IM stat can be used in symptoms secretions have ceased be added to 200 mL of saline (dry mucus membranes, and may be repeated every • Once achieved, an atropine heart rate > 60 beats/min) 6 hours if needed continuous infusion at around 10‐ 20% of the loading dose and titrated to effect Atropine Package Insert. Hospira.1960 Glycopyrrolate Package Insert. Baxter Healthcare Corporation Rumack et al. POISINDEX® 2017. CCIS Volume 172
Pawar et al. Control: Bolus dose 1 g over 1 hour Q4H for 48 Primary outcome: Percentage of Number of days on the vent: Median of 10 days vs 5 days hours (N=100) vs Study: Constant infusion of 1 patients needing intubation: (p<0.0001) g over an hour every hour for 48 hours 88% vs 64% RR= 0.72, p=0.0001 Pralidoxime (N=100) • Reactivates acetylcholinesterase inactivated by phosphorylation Johnson et al. • Either single bolus 1 g dose followed by placebo infusion over the nest 4 days or single placebo bolus followed by pralidoxime 12 g as continuous infusion over 4 days
• Most effective within 48 hours • Ventilatory requirement was greater in those receiving the high dose (p= 0.09) • Significant reduction in intermediate syndrome (p=0.05) was seen in patients receiving the 1 gram dose within 12 hours of ingestion Treatment Dosing of Pralidoxime • Concluded that high dose should not be used
Chugh et al. Atropine alone vs • Pralidoxime neither decreased the amount of atropine needed, days on the vent, days Children Loading Dose: 20‐40 mg/kg Repeat initial bolus in 1 hour An infusion of 10‐20 Atropine + pralidoxime in the ICU (MAX 2 g/dose) infused over and then every 3‐8 hours if mg/kg/hr up to 500 mg/hr • Mortality was negligible in either group 30‐60 min in 0.9% sodium muscle weakness persists should be considered in Syed et al. Pralidoxime + atropine vs atropine alone • Fatality was slightly higher in the atropine group (28%) vs those in the pralidoxime + chloride patients with serious signs of Assessed for mortality, need for intubation, atropine (26%) group, ANOVA showed no statistical difference toxicity duration of ventilation, duration of ICU stay • Vent support was required in 62% in the pralidoxime + atropine group vs 58% in the atropine alone group Adults Loading Dose: 30 mg/kg (MAX Can also start continuous IM Dosing: • Duration of ventilation and ICU stay was comparable 2g) over 30 minutes followed infusion of 8‐10 mg/kg/hr. Mild: 600 mg (2 mL) up to 3 by additional 1000‐2000 mg An infusion of 500‐1000 doses every 15 minutes Eddleston et al. Double‐blind randomised control trial Mortality was non‐significantly higher in pralidoxime group, 24.8% died compared to pralidoxime vs saline 15.8% receiving saline doses after 1 hour if symptoms mg/hr can be started in Severe: three 600 mg doses Primary outcome was mortality, secondary Need for intubation was similarh in bot groups persist patients with severe in rapid succession outcome was need for intubation Despite reactivation, no evidence that pralidoxime improves survival or reduces need for cholinergic toxicity intubation
Johnson et al. The Journal of the Association of Physicians of India 1996 Syed, et al. Saudi Journal of Anaesthesia. 9.1 (2015): 49. Pralidoxime chloride Package Insert. Baxter Healthcare Corporation Eddleston et al. PLoS medicine 6.6 2009 Pawar et al. The Lancet 2006
Q4. A patient presents with seizure, altered senses, and respiratory distress after self‐injected methyl parathion. What treatment would you give? Would you be more likely to call A. N‐acetylcysteine poison control if your child drank a B. Fluids cup of bleach or ate a tablespoon of C. Atropine + pralidoxime D. Narcan salt?
106 Top 10 Exposure Substances By Age Category Mowry et al. Clinical Toxicology 54.10 (2016): 924‐1109 Sodium Hypochlorite All Human Exposures Pediatric Exposures (≤ 6 years) Adult Exposures ( ≥ 20 years)
Cosmetics/ Personal Analgesics 11.1% 13.6% Analgesics 11.6% Care • Found in bleach Household Cleaning Household Cleaning Sedative/Hypnotics/ 7.6% 11.2% 10.3% Products Products Antipsychotics • Aqueous solution produced via reaction of chlorine Cosmetics/Personal 7.4% Analgesics 9.1% Antidepressants 6.9% Care gas with water Sedative/Hypnotics/An Foreign 5.8% 6.5% Cardiovascular Drugs 6.1% tipsychotics Bodies/Toys/Misc. • How much does my bleach contain? Household Cleaning Antidepressants 4.6% Topical Medications 5.3% 5.4% Products • Household bleach contains 3%‐5% Antihistamines 4.1% Vitamins 4.6% Alcohols 4.7% • Cardiovascular Drugs 4% Antihistamines 4.4% Anticonvulsants 3.9% Industrial and swimming pool cleaners contains up to
Foreign 20% 3.7% Pesticides 3.3% Pesticides 3.6% Bodies/Toys/Misc. Dietary Bites and Pesticides 3.3% 3% 3.4% Supplements/Herbals Envenomations
Topical Medications 2.9% Plants 2.7% Antihistamines 3.1% Rumack et al. POISINDEX® 2017. CCIS Volume 172
Signs/Symptoms Treatment
• Dilute solutions may cause moderate irritation • Most important is SUPPORTIVE CARE • Rarely causes serious adverse effects • Activated charcoal should not be used • May see burning in the throat or mouth • Rinse the mouth out • More concentrated solutions (20%) can lead to more serious corrosive injuries • In patients with more severe ingestions (>10% or with • Significant esophageal and gastric burns symptoms) • Dysphagia • Endoscopy could help evaluate esophageal or gastric injury • Severe throat pain • Gastric aspiration could be helpful • Parenteral hydration • Chest and abdominal pain • H ‐receptor antagonists or proton pump inhibitors • GI perforations can occur 2
Rumack et al. POISINDEX® 2017. CCIS Volume 172 Rumack et al. POISINDEX® 2017. CCIS Volume 172
Range of Toxicity Table Salt
• Pretty rare • Sodium Chloride • Ingestions < 150 mL of household bleaches usually do not • Intentional salt poisoning has been reported cause significant corrosive injury Mild‐Moderate Labs Severe Symptoms • 90 yo woman presented to the ER with dyspnea and facial Symptoms swelling, and vomiting Hypernatremia Nausea Seizures • CT showed esophageal rupture due to ingestion of 250 mL of commercial bleach Hyperchloremia Vomiting Altered Mental Status • Pt received care in ICU for 2 months and was discharged in stable condition Diarrhea Coma Abdominal pain/discomfort Respiratory arrest
Yong, et al. J Emerg Crit Care Med. Vol 17.4 (2006): 161‐168. Rumack et al. POISINDEX® 2017. CCIS Volume 172 Rumack et al. POISINDEX® 2017. CCIS Volume 172
107 Treatment Range of Toxicity
• Usually supportive care • Ingestions of 0.5‐1 g/kg (8.6‐17.2 mEq/kg) is toxic in majority of patients • CNS signs and symptoms are common with concentrations of 150‐160 • Mild‐Moderate toxicity mEq/L • Dilute with milk or water • 10% chance of seizures • Death is frequent with concentrations > 185 mEq/L • ONE TABLESPOON is approx. 305 mEq of sodium • Severe toxicity • This would raise a child’s sodium level by 30.3 mEq/L • Decontamination: Immediately dilute with 4‐8 ounces of water (120 • Fatal case of 55 yo woman suffering from depression, drank a large mLs for kids) quantity of soy sauce • IV fluids with 30‐50 mEq/L of sodium such as ¼ Normal Saline • Serum sodium level of 187 mmol/L • Acute, severe hypernatremia, rapid correction with IV D5W or other • Caused massive pulmonary edema hypotonic solutions, free water or hemodialysis is needed • Child died after drinking a glass of salt water (8 teaspoons of salt)
Furukawa S et al; J Forensic Leg Med 18.2: 91‐2. 2011 Dart, R.C. . Medical Toxicology. 3rd Edition.2004., p. 1057 Rumack et al. POISINDEX® 2017. CCIS Volume 172 Rumack et al. POISINDEX® 2017. CCIS Volume 172
Conclusions
• Poison Control Number is 1‐800‐222‐1222 • 93% of human exposures reported occurred at a place of residence • Toxidromes can help healthcare professionals start empirical therapy Questions? Commonly Ingested Antidote/Treatment Commonly Ingested Antidote/Treatment Agents Agents Acetaminophen Activated charcoal Sodium Hypochlorite Supportive therapy N‐Acetylcysteine (Bleach) Rinse out mouth Dextromethorphan Supportive therapy Sodium Chloride Dilution with (Table Salt) milk/water D5W or ¼NaCl Organophosphates Atropine Pralidoxime Glycopyrrolate
108 Louisiana Society of Health System Pharmacists 2017 Midyear Meeting
4:00—5:00 p.m. Advances in Sickle Cell Disease: 20 Years in the Making
Elizabeth Travers, PharmD PGY1 Pharmacy Resident University Health Shreveport Shreveport, LA
0179-0000-17-036-L01-P / 0179-0000-17-036-L01-T 1 contact hour (0.1 CEU) Knowledge-based activity
Objectives:
Pharmacists: Technicians: 1. Describe sickle cell disease 1. Identify agents used for SCD. pathophysiology and current treatment 2. Describe proper storage and administration (hydroxyurea). of Endari. 2. Identify novel pathways being explored for SCD. 3. Recommend proper use of Endari (L- glutamine oral powder).
Dr. Travers has disclosed that she has no relevant financial relationships.
109 Disclosures Advances In Sickle Cell Disease: • I have no relevant financial disclosures • This presentation will be discussing off‐label uses for FDA 20 Years In The Making approved medications
Elizabeth A. Travers, PharmD PGY1 Pharmacy Practice Resident University Health Shreveport 2
Pharmacist Objectives Pharmacy Technician Objectives
1. Describe sickle cell disease (SCD) pathophysiology and 1. Identify agents used for SCD current treatments (hydroxyurea)
2. Describe proper storage and administration of Endari (L‐ 2. Identify novel pathways being explored for SCD glutamine oral powder)
3. Recommend proper use of Endari (L‐glutamine oral powder)
3 4
Background
• Sickle Cell Disease (SCD) is an inherited blood disorder that causes abnormal hemoglobin formation • SCD affects approximately 100,000 Americans Pathophysiology • The life expectancy of a person with SCD is about 40–60 years
What is sickle cell disease?, National Heart, Lung and Blood Institute 5
110 Types of Sickle Cell Disease Pathophysiology
• HbSS • HbS beta thalassemia • Sickle cell disease is caused by mutations in the β‐globin gene Two sickle cell genes (HgS) One sickle cell gene and one Sickle cell anemia gene for beta thalassemia Most severe form of the disease There are two types of beta • These mutations cause the sixth amino acid to be changed thalassemia: “0” and “+” from glutamic acid to valine
• HbSC • HbSD, HbSE, and HbSO One sickle cell gene and one • The resulting hemoglobin (HbS) has abnormal physicochemical abnormal gene (HgC) Inherit one sickle cell gene and one gene from an abnormal properties a milder form of SCD. type of hemoglobin (“D”, “E”, Form stiff rods within the red cell, changing it into a sickle shape. or “O”) Sickle‐shaped cells are inflexible and stick to vessel walls
What is sickle cell disease?, National Heart, Lung and Blood Institute 7 Herman M, Chaudhry S. Sickle Cell Disease. McMaster Pathophysiology Review. 8
Vaso‐Occlusive Crisis (VOC)
• Sickled red cells can obstruct and reduce blood flow to vital organs Ischemia Necrosis Pain
• Repeated episodes can lead to bone infarction and necrosis Long bones are affected most commonly But can affect any bone marrow‐containing structure
HTN
9 Herman M, Chaudhry S. Sickle Cell Disease. McMaster Pathophysiology Review. 10 Herman M, Chaudhry S. Sickle Cell Disease. McMaster Pathophysiology Review.
Hemolysis Endothelial Dysfunction
• Intravascular hemolysis • Hypercoagulopathy Sickled red blood cells are mechanically weak and prone to hemolysis Platelets are chronically activated Chronic thrombin generation, elevated d‐dimers, thrombin‐ antithrombin (TAT) complexes • Extravascular hemolysis Sickle cells become trapped in the spleen Cells are then cleared by the reticuloendothelial system • Inflammation Splenic sequestration Multiple inflammatory markers are known to be elevated in SCD TNFα, C‐reactive protein, interleukins‐1 and ‐8
• A normal RBC survives for an average of 90‐120 days, a sickle cell • Markers of endothelial activation are also elevated survives 10‐20 days Vascular cell adhesion molecule‐1 (VCAM‐1), endothelin‐1, and sCD40 ligand
Herman M, Chaudhry S. Sickle Cell Disease. McMaster Pathophysiology Review. 11 Telen MJ. Role of adhesion molecules and vascular endothelium in 12 the pathogenesis of sickle cell disease. Hematology. 2007;:84‐90.
111 Pulmonary/Cardiovascular Complications Asplenia
• Stroke and myocardial infarction • Sickle cells accumulate in the spleen, leading to splenic congestion, splenomegaly, and reduced immune function Eventually leads to infarction and loss of splenic function • Acute chest syndrome The appearance of new infiltrate with pulmonary symptoms • Patients with SCD are prone to bacteremia with encapsulated Presence of fever bacterial pathogens Hypoxia and chest pain Streptococcus pneumoniae Causes include include infection, infarction and/or pulmonary fat Haemophilus Influenzae embolism Neisseria meningitidis
Herman M, Chaudhry S. Sickle Cell Disease. McMaster Pathophysiology Review. 13 Herman M, Chaudhry S. Sickle Cell Disease. McMaster Pathophysiology Review. 14
https://www.cdc.gov/vaccines 15 https://www.cdc.gov/vaccines 16
Hydroxyurea
• A myelosuppressive agent that raises fetal hemoglobin (HbF)
• Until recently, it was the only effective drug proven to reduce the frequency of painful episodes
Approved Treatments • Decreases the rate of painful episodes, ACS episodes and blood transfusions by approximately 50 % in adults
• Can be used in children ≥ 6 months
Agrawal RK. Hydroxyurea in Sickle Cell Disease: Drug Review. Indian Journal of Hematology. 2014 18
112 Mechanisms of Action Dosing
• The mechanism of HbF induction is not completely understood • Initial: 15 mg/kg/day as a single dose Increase by 5 mg/kg/day every 12 weeks until maximum tolerated dose Max: 35 mg/kg/day • HbS is prone to polymerization Forming sickle cell shape • Dose adjustments needed if: Neutrophils ≤ 2,500/mm3 Platelets ≤ 95,000/mm3 • Hydroxyurea increases HbF Hemoglobin < 5.3 g/dL Reticulocytes ≤ 95,000/mm3 (if Hgb < 9 g/dL)
• • Mean corpuscular volume will be increased, despite reduced HgF is resistant to polymerization reticulocytes
Agrawal RK. Hydroxyurea in Sickle Cell Disease: Drug Agrawal RK. Hydroxyurea in Sickle Cell Disease: Drug Review. Indian Journal of Hematology. 2014 19 Review. Indian Journal of Hematology. 2014 20
Adverse Effects
• Headache • Hematologic Toxicities Transient and reversible myelosuppression • Mild gastrointestinal symptoms Primarily neutropenia Abdominal discomfort Severe cytopenias are rare Nausea • No known teratogenic effects Endari • Dermatologic changes L‐glutamine oral powder Skin hyperpigmentation Darkening of the nails • Does not appear to increase risk of malignancy
Agrawal RK. Hydroxyurea in Sickle Cell Disease: Drug Review. Indian Journal of Hematology. 2014 21
Endari Mechanism of Action
• L‐glutamine oral powder • The mechanism of action is not fully understood
• An amino acid indicated to reduce the acute complications of • HgS containing RBC are more susceptible to oxidative damage sickle cell disease Associated with their sickle cell shape
• Approved in adults and pediatric patients 5 years of age and • Endari increases amount of free glutamine older Used by RBC as an antioxidant to prevent sickling Approved July 2017 Expected to be available by the end of 2017
ENDARI (L‐glutamine oral powder ) Package Insert 23 ENDARI (L‐glutamine oral powder ) Package Insert 24
113 Dosing Administration
• Endari is given orally, twice per day • Mix each dose in 8 oz. of cold or room temperature beverage or 4 to 6 oz. of food
• Dose is based on actual body weight • Complete dissolution is not required prior to administration
• Supplied in 5 gram oral powder • Advise patients to take a missed dose as soon as they remember Patients should not double the next dose if missed
ENDARI (L‐glutamine oral powder ) Package Insert 25 ENDARI (L‐glutamine oral powder ) Package Insert 26
Storage Side Effects
• Supplied in paper‐foil‐plastic laminate packets Containing 5 grams of L‐glutamine white crystalline powder
• Store at 20‐25oC away from direct sunlight 68‐77oF
• Avoid wet or humid environments
ENDARI (L‐glutamine oral powder ) Package Insert 27 ENDARI (L‐glutamine oral powder ) Package Insert 28
Miscellaneous Clinical Trials‐ Safety
• The package insert has no information regarding: • Endari was studied in 2 placebo‐controlled clinical trials with a Monitoring total of 187 patients Contraindications Renal or hepatic dosing • Patients received Endari or placebo orally twice daily for 48 Drug interactions weeks followed by 3 weeks of tapering Data on pregnancy and lactation • Both studies included pediatric and adult patients (5‐58) • Use caution and appropriate clinical judgement 54% were female Majority of patients were African American (97.3%) Over half were receiving hydroxyurea at baseline (63.4%)
ENDARI (L‐glutamine oral powder ) Package Insert 29 ENDARI (L‐glutamine oral powder ) Package Insert 30
114 Clinical Trials‐ Safety Clinical Trials‐ Efficacy
• Treatment discontinuation due to adverse reactions was • 230 patients were evaluated in a randomized, double‐blind, reported in 2.7% (n=5) of patients receiving Endari placebo‐ controlled, multi‐center clinical trial Hypersplenism, abdominal pain, dyspepsia, burning sensation, hot flash • Inclusion Criteria: Sickle cell anemia or sickle β0‐thalassemia • Serious adverse reactions were reported more frequently 2 or more painful crises within 12 months prior to enrollment in the placebo group (78.15% vs. 87.18%) Stabilized on hydroxyurea for at least 3 months
• Exclusion Criteria: • Three deaths (1.6%) occurred in the Endari treatment group Received blood products within 3 weeks compared to zero in the placebo group Renal insufficiency None of the deaths were considered to be related to treatment Uncontrolled liver disease Pregnant or lactating
ENDARI (L‐glutamine oral powder ) Package Insert 31 ENDARI (L‐glutamine oral powder ) Package Insert 32
Clinical Trials‐ Efficacy Clinical Trials‐ Efficacy
• Efficacy was demonstrated by a reduction in the number of sickle cell crises
• A sickle cell crisis was defined as: A visit to an emergency room/medical facility for sickle cell disease‐related pain Acute chest syndrome Priapism Splenic sequestration
• Treatment with Endari also resulted in fewer hospitalizations due to sickle cell pain, fewer cumulative days in hospital and a lower incidence of acute chest syndrome
ENDARI (L‐glutamine oral powder ) Package Insert 33 ENDARI (L‐glutamine oral powder ) Package Insert 34
Important Considerations
• All of this data comes from the package insert and Clinicaltrials.gov
• Until these trials are published we cannot evaluate the data ourselves No statistics or methods to analyze
• All the patients in the efficacy trials were stabilized on hydroxyurea
35 36 ENDARI (L‐glutamine oral powder ) Package Insert
115 Novel Therapies
• Anti‐sickling agents
• Drugs targeting cell adhesion Novel Therapies • Drugs targeting inflammation
• Drugs targeting coagulation
Telen, Marilyn J.. "Beyond hydroxyurea: new and old drugs in the pipeline for sickle cell disease." Blood 127.7 (2016): 810‐819. 38
Anti‐Sickling Agents Sanguinate
• Sickling slows passage of cells through capillaries and leads to • Bovine pegylated Hgb product hemolysis
• Reduces sickling by delivering CO to sickled Hgb and then carrying O 1. Sanguinate 2
• Only anti‐sickling biologic currently in development for SCD 2. GBT440
• Orphan drug status
Telen, Marilyn J.. "Beyond hydroxyurea: new and old drugs in the Abuchowski A. PEGylated Bovine Carboxyhemoglobin (SANGUINATE™): Results of Clinical pipeline for sickle cell disease." Blood 127.7 (2016): 810‐819. 39 40 Safety Testing and Use in Patients. Adv Exp Med Biol. 2016
Sanguinate Trials GBT440
• Phase 1 (n=24) • Anovel small molecule hemoglobin modifier which increases Safe and well tolerated with no serious adverse effects hemoglobin’s oxygen affinity
• Oxygenated HbS does not polymerize • Phase 2 trials for VOC treatment is currently ongoing GBT440 blocks polymerization and the resultant sickling of red Interim results demonstrated that 10 patients showed a reduced blood cells number of abnormally shaped red blood cells within few hours after treatment This effect was sustained for at least 72 hours • Fast Track and orphan drug status Placebo‐treated patients did not show any alteration in the number of abnormal blood cells. • Currently being studied in patients 12 and older in a phase III trial Abuchowski A. PEGylated Bovine Carboxyhemoglobin (SANGUINATE™): Results of Clinical 41 Lehrer‐Graiwer J. GBT440, a Potent Anti‐Sickling 42 Safety Testing and Use in Patients. Adv Exp Med Biol. 2016 Hemoglobin Modifier. Blood. 2015
116 GBT440 Phase I/II Drugs Targeting Cell Adhesion
• GBT440 was generally well‐tolerated (n=46) • Adhesive interactions contribute to vaso‐occlusive crisis Most adverse events were mild There were no deaths 1. Selectin inhibitors Rivipansel • GBT440‐treated patients showed increased hemoglobin, Crizanlizumab hematocrit and erythrocyte counts Sevuparin Along with corresponding decreases in LDH, unconjugated bilirubin, reticulocytes and erythropoietin levels 2. Propranolol • Analysis of peripheral blood smears revealed a marked reduction in sickle cells with GBT440 treatment 3. Poloxamer 188 Telen, Marilyn J.. "Beyond hydroxyurea: new and old drugs in the Lehrer‐Graiwer J. GBT440, a Potent Anti‐Sickling 43 pipeline for sickle cell disease." Blood 127.7 (2016): 810‐819. 44 Hemoglobin Modifier. Blood. 2015
Selectin Inhibitors‐ Rivipansel Selectin Inhibitors‐ Rivipansel
• Treats VOC by reducing the cell adhesion, activation and • Phase 1 studies (n=15) inflammation that are believed to contribute to reducing blood Well tolerated Biomarkers of endothelial activation, leukocyte activation, and activation flow through the microvasculature of coagulation were reduced
• Fast Track and orphan drug status • Phase 2 study during VOC (n=76) Showed a marked reduction in opioid requirements Trends toward shorter duration of VOC and shorter length of hospital stays • Currently in a phase 3 study for acute vaso‐occlusive episodes
• Phase 3 study during VOC is expected to be completed in July 2018 Telen, Marilyn J.. "Beyond hydroxyurea: new and old drugs in the Wun T. Phase 1 study of the E‐selectin inhibitor GMI 1070 in pipeline for sickle cell disease." Blood 127.7 (2016): 810‐819. 45 46 patients with sickle cell anemia. PLoS ONE. 2014.
Selectin Inhibitors‐ Crizanlizumab Selectin Inhibitors‐ Sevuparin
• Humanized monoclonal antibody against P‐selectin • Sevuparin is being developed as a P‐selectin blocker A derivative of low‐molecular‐weight heparin (LMWH) Retains the P‐selectin–binding properties of heparin but lacks • Phase 1 dose‐finding study (n=27) anticoagulant activity Well‐tolerated Effective in blocking P‐selectin function for approximately one • month at well‐tolerated dose levels Laboratory studies show inhibited sickled red blood cell adhesion to endothelial cells and reduced tumor necrosis factor induced vaso‐occlusion • Phase 2 study is a prophylactic study to evaluate efficacy in preventing VOC • Now in an international phase 2 trial for the management of acute VOC Mandarino, D. Study Of Intravenous‐Administered SelG1 For 47 Batchvarova, M. Sevuparin Reduces Adhesion Of Both Sickle 48 Sickle Cell Disease. Blood, 122(21), 970. Red Cells and Leukocytes. Blood, 122(21), 182.
117 Propranolol Poloxamer 188
• Beta‐blockers may reduce RBC adhesion by blocking • Intravenous surfactant that acts: epinephrine’s effect on cell adhesion By inhibiting cell adhesion By lowering blood viscosity • Phase 1 studies (n=20) By decreasing friction along the vessel wall Associated with a reduction in the ability of epinephrine to stimulate sickled red blood cell adhesion • Tested for efficacy during acute VOC in a phase 3 trial (n=255) Showed a modest reduction in duration of painful episodes • Phase 2 double‐blind crossover study (n=25) Associated with decreased levels of all measured biomarkers These differences were not statistically significant • It is now being studied in a second phase 3 trial for its ability to reduce the time to resolution of VOC
De castro LM. Effect of propranolol as antiadhesive therapy 49 Orringer EP. Purified poloxamer 188 for treatment of acute 50 in sickle cell disease. Clin Transl Sci. 2012;5(6):437‐44. vaso‐occlusive crisis of sickle cell disease. JAMA. 2001
Drugs Targeting Inflammation Regadenoson
• Inflammation contributes to the pathophysiology of SCD • Currently FDA‐approved as a pharmacologic stress agent for myocardial perfusion imaging 1. Regadenoson
• Regadenoson is a partially selective adenosine A2A receptor 2. Montelukast agonist Invariant natural killer T (iNKT) cells play a role in ischemia and inflammation response 3. IVIG iNKT cell activation can be downregulated by activation of the adenosine A2A receptor 4. Simvastatin
Telen, Marilyn J.. "Beyond hydroxyurea: new and old drugs in the Field, J. J. Sickle cell vaso‐occlusion causes activation of iNKT pipeline for sickle cell disease." Blood 127.7 (2016): 810‐819. 51 cells that is decreased by regadenoson. Blood. 52
Regadenoson Montelukast
• Cysteinyl leukotriene is elevated in steady‐state SCD, and its level is • Phase 1 human study (n=27) correlated with pain Can be safely administered to both children and adults
• Montelukast is a leukotriene inhibitor • Phase 2 study Already FDA‐approved for treatment of asthma Currently underway to determine whether regadenoson infusion reduces iNKT cell activation • Phase 2 study is being conducted in patients on stable doses of Designed to look at length of hospital stay to determine whether hydroxyurea regadenoson improves respiratory symptoms and reduces opioid Comparing effects of montelukast plus hydroxyurea vs. hydroxyurea use Measuring markers of tissue injury, lung function, and forearm microvascular blood flow
Field, J. J. Sickle cell vaso‐occlusion causes activation of iNKT Telen, Marilyn J.. "Beyond hydroxyurea: new and old drugs in the cells that is decreased by regadenoson. Blood. 53 pipeline for sickle cell disease." Blood 127.7 (2016): 810‐819. 54
118 IVIG Simvastatin
• Intravenous immunoglobulin (IVIG) reduces inflammation via inhibition of neutrophil adhesion • A pilot study of 21 days of simvastatin in children (n=26) Resulted in dose‐dependent increases in NO levels, decreased C‐ reactive protein and decreased IL‐6 levels • IVIG infusion: No effect on vascular endothelial growth factor, sVCAM‐1, or tissue Reduces adherent leukocytes and leukocyte‐erythrocyte interactions factor expression Increases microcirculatory blood flow
• Phase I/II study for vaso‐occlusion confirmed that IVIG decreased • A phase 2 study of simvastatin's ability to reduce the frequency human neutrophil function (n=15) of acute pain episodes is currently ongoing Was not associated with reduced duration of pain crisis, total opioid use, or time to hospital discharge
Manwani D. Single‐dose intravenous gammaglobulin in Hoppe C. A pilot study of the short‐term use of simvastatin in sickle cell sickle cell pain crisis. American journal of hematology. 2015. 55 disease: effects on markers of vascular dysfunction. Br J Haematol. 2011. 56
Drugs Targeting Coagulation Anticoagulants
• Coagulation is chronically activated in SCD • Warfarin (n=12) A small study reported a slight decrease in VOC rate But a significant number of bleeding episodes 1. Anticoagulants Warfarin Dalteparin Apixaban • Dalteparin (n=34) Did not significantly affect markers of activation of coagulation Although pain scores at days 1 and 3 decreased more markedly in patients 2. Antiplatlets Eptifibatide Prasugrel • Apixaban Ticagrelor Currently studying the impact on daily pain scores
Telen, Marilyn J.. "Beyond hydroxyurea: new and old drugs in the Telen, Marilyn J.. "Beyond hydroxyurea: new and old drugs in the pipeline for sickle cell disease." Blood 127.7 (2016): 810‐819. 57 pipeline for sickle cell disease." Blood 127.7 (2016): 810‐819. 58
Antiplatelets
• Eptifibatide Failed to reduce time to VOC resolution in a small study (n=13)
• Prasugrel Biomarkers of in vivo platelet activation were significantly reduced Non‐significant decreases in pain during phase 2 study Phase 3 study to determine effect on number of VOC events per year is ongoing Summary • Ticagrelor Phase 2 study is currently ongoing Determine impact on number of days of pain, pain intensity, and analgesic use
Telen, Marilyn J.. "Beyond hydroxyurea: new and old drugs in the pipeline for sickle cell disease." Blood 127.7 (2016): 810‐819. 59
119 Summary
• Sickle cell disease can be a debilitating chronic condition
• Currently there are 2 therapies approved to reduced complications of sickle cell disease Hydroxyurea Endari Assessment Questions
• There are a variety of novel mechanisms being explored for SCD that will hopefully yield more therapy alternatives 61
What is the appropriate daily dose of At what temperature should Endari be Endari for a 52 kg female? stored? a) 5 grams a) 15oC to 25oC b) 10 grams b) 20oC to 25oC c) 15 grams c) 25oC to 30oC d) 20 grams d) 0oC to 15oC e) 30 grams e) 30oC to 35oC
63 64
What is the mechanism of action of Based on patients studied in clinical trials, Poloxamer 188? who is an appropriate Endari Candidate? a) Anti‐sickling agent a) A 12 year old girl on stable hydroxyurea therapy b) Leukotriene inhibitor b) A pregnant female c) A2A receptor agonist c) A 4 year old boy d) P‐selectin blocker d) A lactating female e) Surfactant e) A 33 year old male with liver disease 65 66
120 Citations
• What Is Sickle Cell Disease? https://www.nhlbi.nih.gov/health/health‐topics/topics/sca
• Herman M, Chaudhry S. Sickle Cell Disease. McMaster Pathophysiology Review. http://www.pathophys.org/scd/
• Telen MJ. Role of adhesion molecules and vascular endothelium in the pathogenesis of sickle cell disease. Hematology Am Soc Hematol Educ Program. 2007;:84‐90.
• Agrawal RK, Patel RK, shah V, Nainiwal L, Trivedi B. Hydroxyurea in Sickle Cell Disease: Drug Review. Indian Journal of Hematology & Blood Transfusion. 2014;30(2):91‐96. doi:10.1007/s12288‐013‐0261‐4.
• ENDARI (L‐glutamine oral powder ) Package Insert
• Abuchowski A. PEGylated Bovine Carboxyhemoglobin (SANGUINATE™): Results of Clinical Safety Testing Questions? and Use in Patients. Adv Exp Med Biol. 2016;876:461‐7. • Lehrer‐Graiwer, Josh et al "GBT440, a Potent Anti‐Sickling Hemoglobin Modifier Reduces Hemolysis, Improves Anemia and Nearly Eliminates Sickle Cells in Peripheral Blood of Patients with Sickle Cell Disease." Blood 126.23(2015): 542.
• Telen, Marilyn J.. "Beyond hydroxyurea: new and old drugs in the pipeline for sickle cell disease." Blood 127.7 (2016): 810‐819.
68
Citations
• Wun T, Styles L, Decastro L, et al. Phase 1 study of the E‐selectin inhibitor GMI 1070 in patients with sickle cell anemia. PLoS ONE. 2014;9(7):e101301.
• Mandarino, D., Kawar, Z., Alvarez, R., et al. Placebo‐Controlled, Double‐Blind, First‐In‐Human, Ascending Single Dose and Multiple Dose, Healthy Subject Study Of Intravenous‐Administered SelG1, a Humanized Anti‐ P‐Selectin Antibody In Development For Sickle Cell Disease.Blood, 122(21), 970.
• Batchvarova, M., Shan, S., Zennadi, R., et al. Sevuparin Reduces Adhesion Of Both Sickle Red Cells and Leukocytes To Endothelial Cells In Vitro and Inhibits Vaso‐Occlusion In Vivo.Blood, 122(21), 182.
• De castro LM, Zennadi R, Jonassaint JC, Batchvarova M, Telen MJ. Effect of propranolol as antiadhesive therapy in sickle cell disease. Clin Transl Sci. 2012;5(6):437‐44.
• Orringer EP, Casella JF, Ataga KI, et al. Purified poloxamer 188 for treatment of acute vaso‐occlusive crisis of sickle cell disease: A randomized controlled trial. JAMA. 2001;286(17):2099‐106.
• Field, J. J., Lin, G., Okam, M. M., et al. Sickle cell vaso‐occlusion causes activation of iNKT cells that is decreased by the adenosine A2A receptor agonist regadenoson. Blood, 121(17), 3329‐3334.
• Manwani D, Chen G, Carullo V, et al. Single‐dose intravenous gammaglobulin can stabilize neutrophil Mac‐1 activation in sickle cell pain crisis. American journal of hematology. 2015;90(5):381‐385.
• Hoppe C, Kuypers F, Larkin S, Hagar W, Vichinsky E, Styles L. A pilot study of the short‐term use of simvastatin in sickle cell disease: effects on markers of vascular dysfunction. Br J Haematol. 2011;153(5):655‐ 63. 69
121 Louisiana Society of Health System Pharmacists 2017 Midyear Meeting NOTES
122 Louisiana Society of Health System Pharmacists 2017 Midyear Meeting NOTES
Thanks for attending the 2017 LSHP Midyear Meeting.
We hope to see you next year!
123