Shuffle Off to Buffalo PSSNY Tammie Lee Demler, BS., Pharm.D, MBA., BCGP

Shuffle off to Buffalo PSSNY Tammie Lee Demler, BS., Pharm.D, MBA., BCGP,. BCPP Director of Pharmacy Services and Pharmacy Residency Training New York State Office of Mental Health at the Buffalo Psychiatric Center Adjunct Associate Professor Pharmacy Practice University of Buffalo School of Pharmacy and Pharmaceutical Sciences DISCLOSURE

I have nothing to disclose Objectives

• Identify treatment options for neuropsychiatric disorders commonly seen in older adults (depression & dementia) • Describe the role and use of medications as treatment options • Discuss current guidelines and controversies in the medical and neuropsychiatric management of older adults • Develop and recommend optimal medication management interventions to ensure safe and effective drug therapy in aging adults Pre-test Question #1

Which pharmacokinetic aspect accurately describes the changes to an otherwise health aging adult:

1. Increased liver size; decreased CYP P450 activity 2. Decreased creatinine; increased creatinine clearance 3. Increased body fat; decreased lean muscle mass 4. Increased plasma proteins; increased free active drug concentrations Pre-test Question #2

Which of the following treatment interventions would be most appropriate as 1st line for an aging adult with depression with anxiety?

1. TCA (amitriptyline) 2. SSRI (sertraline) 3. Benzodiazepine (lorazepam) 4. No medication is safe for older adult depression Pre-test Question #3

Which of the following is considered the therapeutic focus of Alzheimer's Disease currently?

1. Avoidance of environmental toxins such as aluminum 2. Order an Ancestry DNA to determine individualized, predisposed ethnic risk 3. Early diagnosis and drug intervention will stop the progression of AD 4. Lifestyle modifications that decrease ASCVD risks & promote heart health Pre-test Question #4

Which of the following is considered a “high intensity” statin appropriate for the treatment of a candidate who needs this specific therapy:

1. Atorvastatin 20mg 2. Rosuvastatin 20mg 3. Pravastatin 20mg 4. Lovastatin 20mg What is an “older adult”

Older than 65

• By 2030, projected 1 of every 4 people • Currently 13% of the population • consume 34% of prescriptions • 28% of hospitalizations for seniors attributed to adverse drug effects

Drug Therapy Considerations in Older Adults (CA-BOP) and Commission for Certification in Geriatric Pharmacy (CCGP) 8 Care requires increased attention

Being older than 65…

• Physiologic and pathological changes • Decreased ability of body to maintain homeostasis (stable biologic processes) • May impact pharmacokinetic and dynamic parameters • Can lead to drug toxicity or unexpected pharmacologic responses • May affect adherence to medications

Drug Therapy Considerations in Older Adults (CA-BOP) and Commission for Certification in Geriatric Pharmacy (CCGP) 9 Body composition and PK impacts

Being older than 65… Decreased total body water Increased volume of distribution for lipid soluble medications (benzodiazepines) Decreased lean body mass Decreased volume of distribution for water soluble medications (digoxin) Increased body fat Increased free drug concentrations of highly protein bound acidic medications (warfarin, phenytoin) Increased alpha-1-acid Decreased free drug concentration of highly protein bound glycoprotein (binds basic drugs alkaline meds (imipramine, propranolol) and hormones) Altered number and/or affinity of some receptor sites

Drug Therapy Considerations in Older Adults (CA-BOP) and Commission for Certification in Geriatric Pharmacy (CCGP) 10 Age related changes and impact on medication management Being older than 65… Decreased myocardial sensitivity Altered (decreased) drug effects

Decreased cardiac output Decreased response to beta blockers and increased response to warfarin, narcotic analgesics, benzodiazepines, and anticholinergic agents

Increased peripheral vascular Increased risk of toxicity due to decreased metabolism and resistance excretion of medications due to decreased blood flow to liver and kidneys

Drug Therapy Considerations in Older Adults (CA-BOP) and Commission for Certification in Geriatric Pharmacy (CCGP) 11 Age related changes and impact on medication management Being older than 65… • Decreased weight and volume of the brain • Alteration in cognition • Increased sensitivity to adverse effects of centrally active medications • Catabolism exceeds anabolism • Robust versus frail older adult • Robust> 5 years+ • Frail < 5 years(< 3 albumen)

Drug Therapy Considerations in Older Adults (CA-BOP) and Commission for Certification in Geriatric Pharmacy (CCGP) 12 Age related changes and impact on medication management Being older than 65…

• Don’t assume that the bioavailability of all drugs will be decreased… • Peak serum concentration may be lower and delayed • Exception: drugs with extensive 1st pass effect • Bioavailability may increase and serum concentration may be higher because less drug is extracted by the liver (age related decreased size and blood flow)

Drug Therapy Considerations in Older Adults (CA-BOP) and Commission for Certification in Geriatric Pharmacy (CCGP) 13 System Condition Outcome Endocrine system • Thyroid gland atrophies • Increases incidence of diabetes and thyroid disease Gastrointestinal • Increased gastric PH (less acidic) • Delayed drug absorption • Decreased gastric emptying and • Altered bioavailability of blood flow drugs (increased alkaline, • Decreased motility decreased acidic) Oral changes • Altered dentition • Decreased ability to swallow decreased taste solids • Decreased tolerance to certain dosage forms

Drug Therapy Considerations in Older Adults (CA-BOP) and Commission for Certification in Geriatric Pharmacy (CCGP) 14 Pharmacodynamics Nova Southeastern School of Pharmacy http://pharmacy.nova.edu/Pharmacodynamics/Modules/AcidsSaltsBases/Main_P5.html 15 System Condition Outcome Genitourinary • Prostate hypertrophy • Incontinence • Decreased estrogen • Vaginal atrophy • Erectile dysfunction Immune system • Decreased efficiency of cell • Increased risk of infection mediated immunity Pulmonary • Decreased muscle strength • Decreased ability to decreased alveolar surface effectively use MDI

Liver • Decreased size • Decreased metabolism and • Decreased blood flow hepatic clearance • Decreased enzyme activity

16 Liver

• Decreased size • Decreased blood flow • Decreased enzyme activity • Decreased metabolism and hepatic clearance • Phase I hydroxylation: Converts drugs to metabolites with less, equal or more effects than parent compound via oxidation, dealkylation and reduction • Phase II: converts drugs to inactive metabolites that do not accumulate • (preferred for older adults)

17 other System Condition Outcome Skeletal system • Loss of bone mass • Osteoporosis bone breakage Skin system • Drying, thinning, wrinkling, pigment • Increased sensitivity to changes, decreased dermal thickness topical agents, injections, etc. Renal • Decreased GFR • Decreased renal elimination decreased blood flow parent and metabolites decreased function (morphine-3- glucoronide/M3G)

18 Drug Therapy Considerations in Older Adults (CA-BOP) and Commission for Certification in Geriatric Pharmacy (CCGP) Renal

• Decreased GFR • decreased blood flow • decreased function • Decreased renal elimination parent and metabolites (morphine-3- glucoronide/M3G) • Most drugs exit body via kidney • Age related decreased elimination=increased drug accumulation and toxicity

19 Drug Therapy Considerations in Older Adults (CA-BOP) and Commission for Certification in Geriatric Pharmacy (CCGP) Renal Serum creatinine does not reflect creatinine clearance for older adults • Decreased lean body mass=lower creatinine production • Older adult serum creatinine appears normal, and masks changes in CrCl • Obesity

2 ways to determine/measure • 24 hour urine collection • Estimation based on equation

20 Drug Therapy Considerations in Older Adults (CA-BOP) and Commission for Certification in Geriatric Pharmacy (CCGP) Renal Equations: • Cockcroft-Gault IBW (Kg) x (140-age) x 0.85 (for females) 72 x Serum Creatinine • Limitations to these equations • Underestimation of CrCl for those without significant age-related decline • Overestimation of Cr Cl for those with muscle mass reduced beyond expected for age (use “1” to manage the difference) • Most studies use CG, however insufficient representation of the “older adult” in these studies • Other equations not validated in older adults • MDRD (modification of diet in renal disease) for GFR estimates

21 Drug Therapy Considerations in Older Adults (CA-BOP) and Commission for Certification in Geriatric Pharmacy (CCGP) Medications require renal dose adjustments

22 Medication related problems in geriatric patients

Factors increasing risk for ADRs Adverse drug reactions Inappropriate drug selection (BEERS list) Drug interactions Medication omission Therapeutic duplication Greater number of medications (9 or more) Treatment failure/subtherapeutic Multiple chronic disease states and drug dosing (ie antidepressants) therapy for concurrent conditions (6 or more) Overdose/supratherapeutic CrCl <50 ml/min dosing/toxicity (ie digoxin) Drug use without indication Age over 85

23 Factors increasing the potential for ADRS in older adults • Inactive ingredients (ethanol, sucrose, sorbitol) may have greater impact • Selective non-adherence (cost, ADRs)… • In 2008, over 17 million Americans over the age of 45 smoked, (22% all of adult smokers) • 9% of Americans over 65 years of age currently smoke • Drug interactions more likely due to increased exposure • To cations (Ca, Mg, Fe) and bind to other drugs (fluoroquinolones) • To drugs that change the gastric pH • To drugs that change GI motility • To enteral nutrition that can bind/block absorption (phenytoin)

http://www.lung.org/stop-smoking/about-smoking/facts-figures/smoking-and-older- 24 adults.html accessed 1/24/15 Medication ADR and changes associated with aging

• Constipation More severe, more common • Dehydration-decreased sensory perception “High Alert” categories seen with intensified risk • Urinary incontinence • Insulin/diabetic agents • Cognitive decline, depression, • Anticoagulants/anti-platelet agents dementia • Cardiovascular • Postural hypotension-falls risk • NSAIDS/pain • Osteoporosis • Psychotropic agents • Impaired glucose tolerance • Parkinsonism • Diminished acuity of senses (vision, hearing..)

25 Considerations in medication management of older adults

Recommend and advise more strategic prescribing: • Limit drug initiation to 1 drug at a time • Avoid unproven (off-label) drug uses • Avoid use of new drugs “guilty until proven innocent” • Defer or delay non urgent treatment • Avoid treating side effects of first drug with a second drug • Avoid dose adjustments (ie: increase) until adherence can be verified • When starting a new drug ask: • Is it necessary? • What are the goals and endpoints? • Can I use one drug to treat more than one chronic condition? • Do the benefits outweigh the risks? 26 Factors that contribute to non-adherence • Unpleasant side effects • Uncertainty about medication’s purpose effect and expected outcomes • Delays in ordering and/or picking up medication refills • Transportation limitations (pick up refills) • Confusing directions or changes in directions (“hold” coumadin) • Taking several medications (pill burden) and complicated schedules • Some meds are dangerous if stopped and restarted at same dose (ie rivastigmine, lamotrigine) • Dividing dose forms that should not be altered: overdose • Progressive loss of memory/dementia and decreased vision/hearing (misinterpretation) • Use of multiple prescribers, providers and pharmacies

27 Considerations in medication management of older adults

Staying current with new drugs available • Especially those that target issues in older populations Maintaining clinical knowledge and accessing updated information to improve safe medication use Always consider “perfect drug” attributes • Little if any drug interactions • Fewest doses/less complicated regimens Watch for drugs that are used sub-optimally • Conditions that need treatment should be treated adequately • Prescribers may “fear” using adequate doses

28 Mental health considerations for older adults

Depression • Underdiagnosed • Not adequately treated • Symptoms unique to older adults • SSRI are 1st line • Changes to some SSRI dosing • Celexa (maybe not?) • Others used (mirtazapine) • To avoid: TCAs, MAOs

29 Mental health considerations for older adults

Insomnia • Age related decreased efficiency (decreased TST, increased sleep latency) • Advanced sleep phase • Decreased deeper phases of sleep • Chronic illness, physical disability, psychiatric comorbidity (depression) • Dementia, institutionalization worsen condition • Use of sedatives can fracture sleep even more • RLS

30 Mental health considerations for older adults Insomnia • Non-pharmacologic interventions first • Sleep hygeine, structured activity, AM exposure to bright light • Don’t start a sleep medication before ruling out all other causes • Base medication intervention on type of sleep issue • Sleep latency: short acting (Lunesta (eszopiclone), Sonata (zaleplon), Ambien (zolpidem and all forms…) Be mindful of changes in starting doses of Z-hypnotics • Sleep continuity: temazepam • Other novel agents? • Newer agents are coming with same “complex behaviors” • Orexin antagonists (Suvorexant) • Older agents with new name (but same baggage-ie doxepin)

31 Mental health considerations for older adults

Dementia • 5.3 million Americans with Alzheimer’s disease with estimated 15 million in 2060 • 47 million have preclinical AD with 75 expected by 2060 • 22 million have amyloidosis, 8 million have neurodegeneration and the remaining 16+ have both • Researchers reference cholesterol and CV disease as biomarkers predicting preclinical AD • Alzheimer’s disease and other dementias cost the nation $226 billion in direct costs • 6th leading cause of death in the United States • 1 in 3 seniors dies with Alzheimer’s or another dementia

Alzheimer’s Association® 2016 ALZ.org Cognitive Decline Risk Factors

Dementia Major/Mild Neurocognitive Disorder • Remove stigma associated with “dementia” • Memory is no longer the first domain needed to be affected • “Decline” rather than “deficit” • Promote early detection and early treatment of cognitive decline

American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA: American Psychiatric Publishing. Siberski J. Dementia and DSM-5: Changes, Cost, and Confusion. Aging Well. 2012; 5(6):12. Mental health considerations for older adults Neurocognitive Disorders and Disease • Alzheimer’s Disease • Vascular Neurocognitive Disorder • Previously Vascular Dementia • Fronto-temporal Neurocognitive Disorder • Previously Fronto-temporal Lobar Degeneration • Lewy Body Dementia • Other • Alcohol related/Substance-induced neurocognitive disorder • HIV associated • Parkinson’s disease • Neurocognitive disorder due to Huntington’s disease • Prion disease American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA: American Psychiatric Publishing. • Neurocognitive disorder NOS Siberski J. Dementia and DSM-5: Changes, Cost, and Confusion. Aging Well. 2012; 5(6):12. Behavioral Symptoms

Activity Mood Disturbances Thought Disturbances Disturbances Agitation Anxiety Delusions Apathy Dysphoria Hallucinations Appetite/eating Euphoria Paranoia Sleep-wake cycle Irritability Impulsiveness Mood lability/fluctuations Purposeless hyperactivity Repetitive behavior Resistiveness with care Socially inappropriateness Verbal/Physical aggression Wandering

Finney G, Minagar A, Heilman K. Assessment of Mental Status. Neurol Clin. 2016; 34:1-16 Scale/Test Areas Evaluated Score Results Strengths/Weaknesses Episodic memory 25-30: Normal 10-15 minutes to complete Working memory 21-24: Mild Mini-Mental Speech/language 10-20: Does not test executive Status Exam Agraphia, alexia, apraxia Moderate functions (MMSE) <10: Severe

Copyrighted material Spatial attention 27-30: Normal Examines more cognitive Viso-constructive 18-26: Mild domains Montreal Language function 10-17: Does not test naming deficits Cognitive Verbal episodic memory Moderate Assessment Working memory <10: Severe (MoCA) Auditory attention Vigilance Attention Max. 144 points 30 minutes to complete/10 Initiation/Perseveration Scaled to age min to score Construction group Can differentiate AD from Mattis Dementia Conceptualization Parkinsonian syndromes Rating Scale Memory Given in Identifies vascular dementia Visuospatial function percentile

Finney G, Minagar A, Heilman K. Assessment of Mental Status. Neurol Clin. 2016; 34:1-16 Common Causes of dementia Mental health considerations for older adults Common Causes Alzheimer’s Disease • Accumulation of abnormal amyloid protein plaques and neurofibrillary tangles • Some thought that this is a form of diabetes Vascular Dementia • Large or small vessel strokes • Injuries accumulate over time in the brain leading to gradual cognitive decline Lewy Body Disorder • Lewy Bodies (-Synuclein protein) in cortical areas • May also have -Amyloid plaques present Fronto-temporal Neurocognitive Disorder • Accumulation of Tau proteins with brain shrinkage in affected areas

Baumgart M, Snyder H, Carrillo M, et al. Summary of the evidence on modifiable risk factors for cognitive decline and dementia: A population-based perspective. Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association. June 2015; 11(6):718-726 Mental health considerations for older adults Prevention Review and treat, if appropriate, vascular and other modifiable risk factors, such as: • Smoking • Excessive alcohol consumption • Obesity • Diabetes • Hypertension • Dyslipidemia • Sedentary lifestyle • Medications approved for dementia/neurocognitive impairment are NOT effective at treating memory impairment, preventing dementia, or delaying the onset of dementia

• Prevent the breakdown of acetylcholine • Neurotransmitter important for learning/memory • Increased synaptic acetylcholine supports continued communication between neurons • Donepezil • Approved for all stages of AD • Galantamine • Approved for mild to moderate AD • Rivastigmine • Approved for mild to moderate AD • Available in transdermal patch

Qaseem A, et al. Current Pharmacologic Treatment of Dementia: A Clinical Practice Guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med. 2008; 148:370-378 NMDA Receptor Antagonist

• Regulates the activity of glutamate • Can be used alone or in combination with cholinesterase inhibitors • Memantine: • Moderate to severe AD • Significantly more GI disturbances/side effects compared to cholinesterase inhibitors

• Memantine HCl extended release and donepezil HCl (Namzaric®) • Fixed dose combination • 28 mg / 10 mg • 14 mg / 10 mg (renal impairment)

• FDA Approved December 2014

Greig SL. Memantine ER/Donepezil: A Review in Alzheimer’s Disease. CNS Drugs. 2015; 29(11):963-970. Disappointing news for 2018… January 2018 intepirdine • Announced three months after Axovant said it would stop testing intepirdine on patients suffering from Alzheimer’s after a late-stage trial failed. • “Based on the totality of intepirdine data to date, there is no evidence to support its further development,” Chief Executive David Hung said in a statement January 2018 Pfizer • Announced its plans for abandoning research to find new drugs aimed at treating Alzheimer’s and Parkinson’s disease, the U.S. pharmaceutical company announced on Saturday. • The company said it expects to eliminate 300 positions from the neuroscience discovery and early development programs in Andover and Cambridge, Massachusetts, and Groton, Connecticut, as it redistributes the money spent on research, according to the emailed statement. • "As a result of a recent comprehensive review, we have made the decision to end our neuroscience discovery and early development efforts and re-allocate [spending] to those areas where we have strong scientific leadership and that will allow us to provide the greatest impact for patients," Pfizer said in a statement emailed to NPR.

https://www.reuters.com/article/us-axovant-sciences-study/axovant-shares-plunge-after-key-drug-program-scrapped-idUSKBN1EX14X https://www.npr.org/sections/thetwo-way/2018/01/08/576443442/pfizer-halts-research-efforts-into-alzheimers-and-parkinsons-treatments Eligible Population Line Medication Dosing Maximum dose Early cognitive Medications are not recommended impairment 5 mg QDay x 4 weeks; increase to 1st Donepezil 10 mg / day 10 mg daily Galantamine 4 mg BID x 4 weeks, then 8 mg BID immediate x4 weeks; then 12 mg BID if 12 mg BID release tolerated 2nd Galantamine 8 mg QDay x 4 weeks, 16 mg QDay Early to midstage extended x 4 weeks, then 24 mg QDay if 24 mg / day dementia release tolerated Rivastigmine 1.5 mg BID x 2 weeks, 3 mg BID x 2 immediate weeks, 4.5 mg BID x 2 weeks, then 6 mg BID release 6 mg BID if tolerated 2nd Rivastigmine 4.6 mg QDay x 4 weeks, increase to transdermal 9.5 mg / day 9.5 mg QDay if tolerated patch Mental health considerations for older adults Medication management

Maximum Eligible Population Line Medication Dosing dose 5 mg QDay x 1 week, then 5 mg BID x 1 week, then 5 mg QAM Memantine 10 mg BID Midstage dementia, and 10 mg QHS x 1 week, then 10 or no longer Add mg BID responding to above Memantine 7 mg QDay x1 week, then 14 mg extended QDay x1 week, then 21 mg QDay 28 mg/day release x1 week, then 28 mg QDay Late stage Medications may pose more harm then benefit. Mental health considerations for older adults Prevention DO YOU REMEMBER THIS SLIDE? Review and treat, if appropriate, vascular and other modifiable risk factors, such as: • Smoking • Excessive alcohol consumption • Obesity • Diabetes • Hypertension • Dyslipidemia • Sedentary lifestyle • Medications approved for dementia/neurocognitive impairment are NOT effective at treating memory impairment, preventing dementia, or delaying the onset of dementia

Definition of metabolic syndrome (3 or more criteria) Central or abdominal Men - 40 inches or above obesity Women - 35 inches or above Abnormal lipid Panel: Greater than or equal to 150 milligrams Triglycerides: per deciliter of blood (mg/dL)

HDL Cholesterol: Men - Less than 40 mg/dL Women - Less than 50 mg/dL Blood pressure Greater than or equal to 130/85 millimeters of mercury (mmHg) Fasting glucose Greater than or equal to 100 mg/dL

International Diabetes Federation. The IDF consensus worldwide definition of the metabolic syndrome. International Diabetes Federation (IDF), 2006. https://www.idf.org/our-activities/advocacy-awareness/resources-and-tools/60:idfconsensus- worldwide-definitionof-the-metabolic-syndrome.html Testing, monitoring and treatment plans

Abnormal lipid panel Goals: Prevent primary & secondary ASCVD events • Lipids include cholesterol, triglycerides, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) • Hyperlipidemia: new goals based on risk groups, statin “intensity” with % reduction (not LDL goal values) • Obesity, uncontrolled diabetes, hypothyroidism, kidney disease, excessive alcohol consumption and certain medications (Steroids, beta blockers, diuretics, estrogen, OC)

New York State Prescriber Education http://nypep.nysdoh.suny.edu/

Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults.Circulation. 2014;129(25 Suppl 2):S1-45. d Abnormal lipid panel

• Key Message : The goal of lipid-lowering therapy (LLT) is to reduce the risk of atherosclerotic cardiovascular disease(ASCVD) and in patients with ASCVD to prevent future cardiovascular events. • Key Message : Statins are first-line agents for the primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD). Statin intensity and treatment goals should be determined based on presence of ASCVD or ASCVD risk factors. • Key message : Non-statin agents should be used as second-line for the treatment of hypercholesterolemia.

New York State Prescriber Education http://nypep.nysdoh.suny.edu/

53 Screening of Lipoprotein Levels the debate continues Screen of Lipoprotein Levels U.S. Preventive Services Task Recommendations: Force (USPSTF) • High-risk patients: ≥20 years • Males without elevated risk: ≥35 years • Females without elevated risk: ≥45 years

American College of Recommendations: Cardiology / American Heart • Do not treat to a target LDL-C level

Association (ACC/AHA)

New York State Prescriber Education http://nypep.nysdoh.suny.edu/ 54 Screening of Lipoprotein Levels the debate continues

Screen of Lipoprotein Levels National Lipid Recommandations: Association • At least every 5 years in all patients ≥20 years (NLA) • Lipoprotein profile: total-C and HDL-C • Targets of therapy: non-HDL-C and LDL-C • Optional, secondary target: Apolipoprotein B • Calculate non-HDL-C3-7 (non-HDL-C = TC – HDL-C) • Calculate LDL-C8-10 (Friedewald equation: [LDL] = [TC] – [HDL] – [TG/5]) Limitations of the HDL and LDL equations: TG <400 mg/dL2; fasting state; overestimation of LDL-C in sera with low TG and high TC, type 3 hyperlipidemia, dysbetalipoproteinemia; T2DM, nephrotic syndrome, alcoholism

55 New York State Prescriber Education http://nypep.nysdoh.suny.edu/ Lipid Panel References TOTAL CHOLESTEROL Borderline high: High: > or =240 mg/dL Desirable: <200 mg/dL 200-239 mg/dL TRIGLYCERIDES Borderline high: High: 200-499 mg/dL Normal: <150 mg/dL 150-199 mg/dL Very high: > or =500 mg/dL HDL CHOLESTEROL Males > or =40 mg/dL Females > or =50 mg/dL LDL CHOLESTEROL Above Desirable: Borderline high: 130-159 mg/dL Desirable: <100 mg/dL 100-129 mg/dL High: 160-189 mg/dL Very high: > or =190 mg/dL NON HDL CHOLESTEROL Above Desirable: Borderline High: 160-189 mg/dL Desirable: <130 mg/dL 130-159 mg/dL High: 190-219 Very high: > or =220 mg/dL

http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/8053 Testing, monitoring and treatment plans

Goals: Prevent primary & secondary ASCVD events

New York State Prescriber Education http://nypep.nysdoh.suny.edu/

New York State Prescriber Education http://nypep.nysdoh.suny.edu/ 58 ASCVD Risk Calculator

59 http://tools.acc.org/ASCVD-Risk-Estimator Who benefits from statin therapy?

Statin Benefit Group Additional Factors Intensity Type Clinical ASCVD* < 75 years old High-Intensity > 75 years old Moderate-intensity LDL > 190 mg/dL High-Intensity Age 40 – 75 ASCVD > 7.5% High-Intensity WITH DM ASCVD < 7.5% Moderate-intensity & LDL 70 – 189 mg/dL

Age 40 – 75 ASCVD > 7.5% Moderate to high W/O DM ASCVD < 7.5% Weigh risk/benefit LDL 70 – 189 mg/dL

Abnormal lipid panel Goals: Prevent primary & secondary ASCVD events Preferred pharmacologic therapy: • Statins (high intensity for specific “risk groups”: atorvastatin 40 or 80mg & rosuvastatin 20 or 40mg); moderate or low for other risk groups; limited use of non-statins • Non-statin fibrates and/or niacin no longer combined with statins Non-pharmacologic activities: • Diet, exercise, weight loss • Review medications for potential contribution

New York State Prescriber Education http://nypep.nysdoh.suny.edu/

High Intensity Moderate Intensity Low Intensity >50% 30-49% <30% Atorvastatin 40-80mg Atorvastatin 10-20mg Simvastatin 10mg Rosuvastatin 20-40mg Rosuvastatin 5-10mg Pravastatin 10-20mg Simvastatin 20-40mg Lovastatin 20mg Pravastatin 40-80mg Fluvastatin 20-40mg Lovastatin 40mg Pitavastatin 1mg Fluvastatin 80mg Pitavastatin 2-4mg

New York State Prescriber Education http://nypep.nysdoh.suny.edu/

Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce 63 Atherosclerotic Cardiovascular Risk in Adults.Circulation. 2014;129(25 Suppl 2):S1-45. Testing, monitoring and treatment plans

Health outcomes & potential impact of managing co-occurring medical & behavioral health Hyperlipidemia: • Patients may experience myalgia & not desire rechallenge (consider use of less lipophilic agents pravastatin & rosuvastatin) • Hypothesized risk of low cholesterol contributing to possible aggression (previously “linked” to statins)? • Increase risk of diabetes (NNT vs NNH different in psych?) • Memory impairment associated with statins? • Diminished influenza immunization response?

Leppien E, Mulcahy KB, Demler TL, et al. Effects of statins and cholesterol on patient aggression: Is there a connection? Innov Clin Neurosci. 2017;14(11–12): Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults.Circulation. 2014;129(25 Suppl 2):S1-45. d NLA provisional statin “intolerance” definition

New York State Prescriber Education http://nypep.nysdoh.suny.edu/

Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce 65 Atherosclerotic Cardiovascular Risk in Adults.Circulation. 2014;129(25 Suppl 2):S1-45. Testing, monitoring and treatment plans

Hypertension Previous goals: BP < 140/90 for most patients now <130/80 however (geriatric still less strict) What about the newest recommendations from ACC/AHA? Preferred pharmacologic therapy: • Thiazides, ACE/ARB, CCB Non-pharmacologic activities: • Smoking cessation (impact of CYP1A2 and chronic NRT) • Weight loss • Dietary (DASH) interventions • Exercise Hypertension Staging Criteria

JNC 8 (2014) ACC/AHA (2017) • Normal: SBP<120 and DBP<80 • • “Prehypertension”: SBP=120-139 and Normal: SBP<120 and DBP<80 DBP=80-89 • “Elevated”: SBP=120-129 and DBP<80 • Stage 1 Hypertension: SBP=140-159 and/or • Stage 1 Hypertension: SBP=130-139 and/or DBP=90-99 DBP=80-89 • Stage 2 Hypertension: SBP>160 and/or • Stage 2 Hypertension: SBP>140 and/or DBP>100 DBP>90 • NOTE: JNC 8 (2014) did not make any changes to hypertension staging criteria ***In both guidelines if SBP and DBP fall into and carried over staging criteria set by JNC different categories stage the patient into the 7 (2003) more severe category When should pharmacologic treatment be initiated? JNC 8 (2014)

• Patients who fall into the Stage 1 and Stage 2 Hypertension categories should receive pharmacologic treatment • Patients aged 60 and over without CKD and diabetes should be treated to a SBP goal of less than 150 and a DBP goal of less than 90 • NOTE: this SBP goal technically classifies as Stage 1 hypertension according to the guidelines • Authors of JNC 8 (2014) felt that based on the evidence reviewed treating below a SBP of 150 is not necessary in the 60 years old and up without CKD and diabetes subgroup • All other patients including patients aged 60 and over with CKD and/or diabetes should be treated to a SBP goal of less than 140 and DBP goal less that 90

James PA, Oparil S, Carter BL et al. 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8). JAMA, Published online December 18, 2013. Pages: E1-E14. Whelton PK et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults. Published 2017. Pages: 1-481 When should pharmacologic treatment be initiated? ACC/AHA (2017)

• Patients who fall into the “elevated BP” category should receive nonpharmacological therapy and be reassessed in 3 to 6 months – Class I • Patients in the Stage 1 hypertension category with an ASCVD Risk Score of greater than or equal to 10% should receive nonpharmacologic therapy and a blood pressure lowering medication and be reassessed in 1 month – Class I • Patients in the Stage 1 hypertension category with an ASCVD Risk of less than 10% should receive nonpharmacologic therapy and be reassessed in 3 to 6 months – Class I • Patients in the Stage 2 hypertension category should receive nonpharmacologic therapy and a blood pressure lowering medication and be reassessed in 3 to 6 months regardless of ASCVD Risk Score – Class I • Initial therapy involving 2 different antihypertensive medications should be considered in patients with Stage 2 hypertension – Class I Testing monitoring and treatment plans

Hyperglycemia Goals: HbA1C goals should be individualized for each patient with type 2 diabetes: less than 7% for most patients and less than 8% for specific high‐risk subgroups (i.e. older adults) Preferred pharmacologic therapy: • Metformin as 1st line for most patients with NIDDM • If after 3 months of maximized metformin patient has not achieved A1C goals; consider adding 2nd agent based on patient specific factors to achieve goal Non-pharmacologic activities: diet, exercise, weight loss, consider: • APS induced increases in appetite • Risk and extent of weight gain are higher in younger first-episode psychosis patients with no previous APS exposure compared with patients in long-term treatment

Álvarez-Jiménez, M., González-Blanch, C., Crespo-Facorro, B., Hetrick, S., Rodríguez-Sánchez, J. M., Pérez-Iglesias, R., & Vázquez-Barquero, J. L. (2008). Antipsychotic-induced weight gain in chronic and first-episodepsychotic disorders: A systematic critical reappraisal.CNS Drugs, 22, 547-562. New York State Prescriber Education http://nypep.nysdoh.suny.edu/ Outcomes of intensive vs. standard blood glucose lowering: no significant benefit in CV outcomes when an intensive A1C goal is targeted but did have ADR

New York State Prescriber Education http://nypep.nysdoh.suny.edu/ Testing monitoring and treatment plans in the older adult Here caveats to consider when selecting and using different types of diabetic agents • Insulin: Injection, high risk/high alert errors associated; consider cognitive ability, motor skills and visual acuity • Glucagon like peptide receptor agonists (GLP-1 RA): injection: consider cognitive ability, motor skills, visual acuity and cost/coverage limitations pancreatitis, thyroid cancer (“tide” drugs exenatide, liraglutide, etc) • SGLT2: increased risk of UTI UTI, yeast infections, hyperkalemia, renal dosing (“flozin” drugs canagliflozin, empagliflozin, etc) • Dipeptidyl peptidase 4 inhibitors (DPP-4): increased risk of pancreatitis, renal adjustments often needed as well as cost/coverage limitations (increased risk of pancreatitis, renal adjustments often needed as well as cost/coverage limitations: heart failure, joint pain/arthralgia, renal dosing (“Liptin” “PP” drugs alogliptin, saxagliptin) • Sulfonylureas: Beers list, increased risk of hypoglycemia, weight gain (glipizide, glyburide) • Thiazolidinediones (TZDs): Beers list, use cautiously (hypoglycemia), weight gain, bladder cancer, increased risk of fracture, hepatic dosing (“glitazone” drugs ie pioglitazone)

Post-test Question #1

Which pharmacokinetic aspect accurately describes the changes to an otherwise health aging adult:

Which of the following treatment interventions would be most appropriate as 1st line for an aging adult with depression with anxiety?

1. TCA (amitriptyline) 2. SSRI (sertraline) 3. Benzodiazepine (lorazepam) 4. No medication is safe for older adult depression Post-test Question #3

Which of the following is considered the therapeutic focus of Alzheimer's Disease currently?

Which of the following is considered a “high intensity” statin appropriate for the treatment of a candidate who needs this specific therapy:

1. Atorvastatin 20mg 2. Rosuvastatin 20mg 3. Pravastatin 20mg 4. Lovastatin 20mg

THANK YOU! Questions?