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Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

TOXICOLOGY PEARLS

Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN Toxicology Nurse Practitioner

1 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

DISCLOSURES

Nancy Denke, DNP, FNP-BC, ACNP-BC, FAEN, CEN, CCRN has no financial relationships with commercial interests to disclose

Any unlabeled/unapproved uses of or products referenced will be disclosed

2 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

OBJECTIVES

• Describe tools/pearls that can be used to identify commonly seen toxicological conditions

• Assimilate toxicological facts into a framework of knowledge

• Describe the of common exposures

3 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

DRUG INDUCED QTC PROLONGATION

• • • • • Senna

4 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

A NEW CUP OF

5 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

CASE

• 56 y.o. male asked to consult for evaluation and treatment transaminitis • Notes that while in Hawaii (arrived 2/20/21) he noted abdominal pain, , clay-colored stools, dark , decreased appetite and a • Prior to this trip he had been sick with a respiratory problem and was on a regimen of steroids () and . • In December he stopped taking his BP meds and began taking an herbal mushroom powder that his son recommended along with numerous other herbal supplements (listed below). • Comes to ED on 2/28/21 with weakness and abdominal pain- along with "yellowing of his eyes". • Current symptoms include: down trending of transaminitis, slight decreased appetite

6 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

OTHER INFORMATION

• Supplements • Mushroom powder (Mudwater) • Green Vibrance • Puerh with B pollen (with AZ Rango honey) • Ginseng • Ginseng with royal jelly • Wheat germ • Wheat grass • Thyme extract- a tincture • Fish oil • Gingko

7 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

REISHI MUSHROOM (GANODERMA LUCIDUM)

OTHER EFFECTS

8 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

SHROOMS MAGIC MUSHROOMS

• Magic mushrooms cause physical and psychological effects • Street name for mushrooms containing • Famous for causing • Causes a wide range of effects because it’s chemically similar to serotonin • Long-term side effects include flashbacks and memory problems

9 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

CAN MAGIC MUSHROOMS MEASURE UP TO SSRIS FOR TREATMENT?

10 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

11 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

WHAT 3 SPICES ARE COMMONLY ABUSED

12 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

I WILL HUFF AND I WILL PUFF

13 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

SOME STATISTICS

• Over 2.6 million children, aged 12 to 17 uses an , each year to get high • 1 in 4 students in America has intentionally abused the common household product, Air Duster, to get high by the time they reach 8th grade • 59% children are aware of friends huffing at age 12 • are 4th most-abused substance after , and marijuana

14 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

https://www.drugabuse.gov/drug-topics/inhalants/inhalants-trends-statistics

15 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

AIR DUSTERS • Inhalants everyday household products • Who does it? • Usually, pre-teens and teenagers • Nearly one in five 8th graders has tried • When? • Before school. During school. After school. Nights. Weekends. • Why? • In the words of one teen, "Because they can. Because they're bored! Because they're upset." In short, for any reason or no reason!

High is euphoric but short term!

16 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

CASE STUDY

• 20 yo male brought to the ED by PD for erratic driving • Altered mental status & ingestion of & oxy PMH- untreated HTN • 3 cans of Dust-Off (only 1 empty) In ED • High flow oxygen, ABG • ECG • Check Mg and lytes

17 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

18 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

• •Lightheadedness •Nausea •Headache SHORT TERM •Confusion/Hallucinations EFFECTS •Slurred speech •Loss of motor control and coordination •Seizures

19 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

• Weight loss • Depression/Mood changes LONG • Muscle spasms TERM • Arrhythmias EFFECTS • Damage to lungs and kidneys

20 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

RECOGNIZING ABUSE OF CANNED AIR

• Empty cans of canned air in trashcans or in one’s room or car • Presence of Dust-Off in easy-to-reach locations (e.g., bedside table, handbag, etc.) • Hoarseness and complaints of numb tongue or throat • Bloodshot eyes • Out-of-character behaviors and an overall change in social circle

21 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

QUESTION

22 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

WHAT WAS THE KEY INGREDIENT IN MRS. WINSLOW’S SOOTHING SYRUP

• sulfate 65 mg/oz & alcohol

• Used for babies who were crying, teething, or had dysentery

• Sold more than 1.5 million bottles of the remedy annually & sold until the 1930s

23 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

BUT IT’S ONLY TYLENOL

24 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

CASE

• A 73yo M presents with confusion and weakness • Appears jaundiced and unable to provide history • Hx previous admissions for alcohol use • CBC, electrolytes, creatinine, , coagulation studies, and EtOH level • Severe elevations in AST, ALT, ALP and bilirubin • EtOH level is 70mg/dL • What additional bloodwork in this patient could reveal a treatable cause of acute ?

25 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

Acetaminophen (APAP) most widely used OTC pain reliever & antipyretic worldwide

Peak serum transaminase usually occur 48-96h after acute ingestion

Acute OD, most adults must ingest ≈ >12 g APAP before risk of serious hepatotoxicity is of concern OVERVIEW Nomogram of serum APAP vs hours post-ingestion

Patients can present in liver failure days after ingestion with undetectable serum APAP levels and renal failure NAC's main action is to maintain intracellular glutathione stores so to detoxify APAP , NAPQI

26 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

Rumack-Matthew Nomogram

https://en.wikipedia.org/wiki/File:Rumack _Matthew_nomogram_with_treatment_ (study)_line.pdf

27 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

STAGES OF ACETAMINOPHEN TOXICITY

Stead, T. S., Jeong, J. Y., Ganti, L., & Rubero, J. (2020). Massive Acetaminophen Overdose. Cureus, 12(7), e9262. https://doi.org/10.7759/cureus.9262

28 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

APAP TREATMENT

• If time or amount of ingestion is unknown or if ingestion spans more than 24 hours: • Screen with labs (APAP level, hepatic and renal function, coagulation) • Assess patient risk factors • Clinical assessment • If ASTs are elevated - NAC 2 bag • If APAP is detectable - Treat with 2 bag NAC • If APAP not detectable and ASTs are normal - No NAC indicated • If lab testing shows progressive hepatic failure - Repeat infusion of Bag # 2 (16- hour bag)

29 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

WHAT STREET DRUG CAN CAUSE THIS

COCAINE

Bhagavathula A. et.al. (2020). -induced vasculitis. The American Journal of Gastroenterology, 115, S 1609-1610

30 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

PHENIBUT AN EMERGING “”

31 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

CASE

• 30 y.o. male consult for evaluation and treatment ingestion • He admits to using phenibut sometime yesterday and became very anxious and altered as the evening progressed this worsened until his friend became so concerned that he brought him to the ED to be seen • Patient notes that he has abused "the stuff" previously and then began taking it again • Had from using & this is why he stopped. Upset because "I screwed up and lost the best job I ever had as a coach" • Unable to tell me how much he uses on a daily basis • Current symptoms include: alert, confused, but redirectable • Circumstances behind ingestion include: to help with • BP 137/91, Pulse 79 Temp 98 °F (36.7 °C) (Oral) , Resp 18

32 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

WHAT IS PHENIBUT?

• Supplement started in in the 1960s, prescribed as an anti- anxiety med to treat depression, , PTSD, and

• Potent psychoactive substance with GABAB properties • Can be purchased easily online & marketed as a nutritional supplement but in practice used for psychotropic effects with potential for abuse • Known as a mood enhancer, aid, exercise recovery booster, and even a “smart drug” currently sold as a

Jouney E.A. (2019). Phenibut (β-Phenyl-γ-Aminobutyric Acid): An easily obtainable "Dietary Supplement" with propensities for and . Current Psychiatry Reports. 21(4),23 doi:10.1007/s11920-019-1009-0. PMID: 30852710.

33 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

INTERNET INFLUENCE IN OPENING ACCESS TO A WIDE RANGE OF RECREATIONAL AGENTS OF ABUSE

• Exposure calls to a Minnesota poison center from January 2000 through December 2018 regarding Phenibut • Saw an increase over 5year period (2014-2019) • CNS depression and respiratory failure requiring intubation

34 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

Hardman M.I., Sprung J. & Weingarten T.N. (2019).

35 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

TREATMENT PLAN

• Phenibut is an analog of the GABA and is a GABA- B agonist, can causing variable clinical toxicity, ranging from coma/ to agitation and seizures • Patient presenting with psychosis and confusion, which can be consistent • Recommend symptomatic management • In severe withdrawal, such as with seizures, then can consider GABA-A such as , , or GABA-B agonists such as .

36 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

SIDE EFFECTS

• Phenibut withdrawal may mimic withdrawal with symptoms including anxiety, insomnia, and tension

• Baclofen use for phenibut withdrawal given its similar molecular structure and

Hardman M.I., Sprung J. & Weingarten T.N. (2019).

37 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

WHIPPETS “NO LAUGHING MATTER”

38 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

HOW THEY ARE USED

• Empty balloons and balloons smelling of strange chemicals are signs of inhalant abuse • Increasing at festivals with the gas filled balloons

39 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

CASE STUDY

40 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

30 Y.O MALE

• Bilateral weakness to lower (bilateral) extremities for 1 week • Was using 50-100 whippets/day at least 4x/week for 1 year until 3/20 • Went to detox and was discharged on 3/25. He notes that about 1 week ago he began to have some difficulties lifting his feet (worse on than R). He also noted some pain to that area. • Placed on a rivaroxaban 20 mg starter pack and ran out about 4 days ago and just got his Rx refilled today. He was started on this due to bilateral DVT of lower extremities which he notes is related to a genetic condition. • Current symptoms include: alert, cooperative. Able to ambulate with some balance issues with weakness noted to RLE.

41 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

EXAM

• Reflex Scores: • Tricep reflexes are 0 on the right side and 0 on the left side. • Bicep reflexes are 0 on the right side and 0 on the left side. • Patellar reflexes are 0 on the right side and 0 on the left side. • Achilles reflexes are 0 on the right side and 0 on the left side • Strength 5/5 except as below • Right anterior tibial: 0/5 • Left anterior tibial: 0/5 • Right peroneal: 0/5 • Left peroneal: 0/5

42 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

Savag & Ma, 2014

43 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

EXAM

• Sensory Exam • Right leg pinprick: decreased from ankle • Left leg pinprick: decreased from ankle

• Gait, Coordination, and Reflexes Reflexes Right biceps: 0 Left biceps: 0 Right triceps: 0 Left triceps: 0 Right patellar: 0 Left patellar: 0 Right achilles: 0 Left achilles: 0

44 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

Homocysteine elevated well before B12 deficiency detected

Megaloblastic Macrocytic Anemia EFFECTS OF NITROUS Other Signs and Symptoms

• Paralysis of lower body • Paresthesia & spasm extremities • Incontinence • Weak immune system

45 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

MYELOPATHY OR SUBACUTE DEGENERATION OF THE SPINAL CORD

• NO oxidizes B12, which is important for DNA synthesis and maintenance of the myelin sheath around nerve cells • MRI • Abuse of nitrites can result in dorsal and lateral spinal column disorders due to effects on B12

46 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

MRI

• MRI Cervical • Straightening and slight reversal of cervical lordosis. 2. Mild cervical spondylosis, primarily at C5-6 and C6-C7. No evidence for significant spinal canal or neural foraminal stenosis. 3. No evidence for cord pathology. No abnormal cord enhancement. Specifically, no evidence for demyelinating disease • MRI Thoracic spine • Unremarkable MRI of the thoracic spine. No evidence for cord abnormality. Specifically, no evidence for demyelinating disease • MRI Lumbar • No evidence for conus pathology. No abnormal enhancement of the conus or nerve roots of the cauda equina. 2. Spondylitic changes, primarily at L4-5 and L5-S1 with left foraminal annular fissure and disc protrusion at L4-5. There is resultant narrowing of the left L4 neural foramen and minimal abutment of exiting left L4 nerve root

47 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

HOW TO TREAT

• Personality changes subtle • IM B12 injection • Rehab- cognitive therapy

48 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

QUESTION BREAK

What common condition can this bug threat?

Warts and Molluscum Contagiosum

49 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

MEDICINAL CLEANSING RITUAL

A patient presents with her Shaman with nausea, , flushing and altered mental status after participating in a cleanse earlier that day You note this on her ankle

What is the exposure?

50 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

KAMBO • It is a deep cleansing treatment from the Amazon that is as old as legend • It is becoming more and more popular with the rest of the world these days due to its powerful effects. • Treatment entails creating small burns in the skin and the application of a small mound of reconstituted venom (gel) from an Amazonian giant tree frog called Phyllomedusa Bicolor • Kambo is absorbed through the lymphatic system

Li K et al. Prolonged toxicity from Kambo cleansing ritual. Clin Tox 2018; 56(11): 1165

51 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

ADVERSE EFFECTS • Symptoms attributed to the pharmacological activity of Kambo peptides • Effects on smooth muscles and vessels • Symptoms include BP, flushing, palpitation, n/v, bile secretion and angioedema • Symptom-complex NOT anaphylactic in nature, but directly related to Kambo pharmacological effects

52 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

A TALE OF INTRACTABLE VOMITING

• 43 yo male who works as a greenskeeper • Friend gave him a “cookie” that he began to eat at about 0600 and finished right before his 0800 meeting • Began vomiting and brought to ED at 1100 with intractable • VS. HR. 124 BP 110/68 • Vomited several times in the ED

53 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

CANNABINOID HYPEREMESIS SYNDROME • With legalization of the presentation to ED’s for cyclic vomiting has nearly doubled • Pathophysiology of CHS is largely unknown

Criteria for this syndrome • Cyclic nausea and vomiting • Resolution with marijuana cessation • Hot showers/baths relieve symptoms • Abdominal pain • At least weekly use of marijuana (often daily)

Stinnett V.L. and. Kuhlmann K.L. (2018). hyperemesis syndrome: An update for primary care providers. The Journal for Nurse Practitioners, 14(6),450-455

54 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

• Antiemetics • Ondansetron (Zofran®) • Prochlorperazine (Compazine) • (Phenergan) • Haldol TREATMENT • Hot shower • Capsaicin cream 0.075% applied to the abdomen • Proton pump inhibitors

55 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

MIXING THC/CBD WITH SOME COMMON

• Warfarin –THC/CBD increases INR • Ketaconazole – can double the effects of THC/CBD, enhance effects • Rifampin- may decrease the effects of THC/CBD • Sulfamethoxazole- may increase level of THC, but no effect on CBD • - may decrease levels of THC, no effects on CBD • - no reaction with THC, but may have reaction with CBD • - with CBD can cause increased liver enzymes • Alcohol- increases THC levels

Because of all new laws and less restriction- always be aware of interaction with your patient’s medications https://www.drugs.com/drug-interactions/cannabis.html

56 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

HYDROGEN PEROXIDE

57 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

THIS “NATURAL CURE” CAN BE DEADLY

BROWN BOTTLE A SMALL AMOUNT OF A SIP ISN'T A GOOD OF 3 % DILUTED CONCENTRATED PEROXIDE IDEA, IT PROBABLY (35%) ON CONTACT WITH PEROXIDE WOULDN'T MAKE YOU TISSUE RELEASES 100 ML OF SEVERELY ILL O2

58 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

SIDE EFFECTS

• In the 10-year retrospective study, 41 of 294 (13.9%) symptomatic peroxide ingestion cases demonstrated evidence of a possible embolic event • Time to onset of a possible embolic event varied greatly immediate-25 hours) • Ingestion of small amounts (mouthful or 2), of concentrated hydrogen peroxide led to critical illness caused by suspected embolism in 13.9% & severe long-term outcomes (death or continued disability) in 6.8% cases • Focal neurologic deficits suggestive of CVA, tachycardia, & suspected arterial embolic effects • Local injury to the gut vascular wall (extraluminal air)

59 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

TREATMENT

• Symptomatic care • Chest CT • Early hyperbaric oxygen therapy for gas embolism • Esophagogastroduodenoscopy (EGD) for caustic effects • Deep ulcerations, necrosis, GI bleed or pneumomediastinum found

60 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

WHAT WERE THE MOST COMMON FINDINGS IDENTIFIED IN CHILDREN EXPOSED TO ?

61 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

• Retrospective review done by Malashock HR, et al. (2021) of patients presenting to a pediatric tertiary care center HYPERTENSION identified 79 patients with AND suspected methamphetamine TACHYCARDIA toxicity • In addition to typical sympathomimetic findings, common symptoms identified in this population included abnormal motor activity and GI symptoms

62 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

ANTIDOTE CHALLENGE

Oleander leaves

Digoxin specific immune Fab fragments

63 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

OLEANDER INGESTION CASE

• 19 month old female who was with her mother at 1645 the child picked up a small pod from an oleander plant • The bottom part of the pod and possibly some of the seeds were a missing. It is unclear if the patient swallowed any of the pod or seeds. • The patient was admitted to the hospital for continued observation • Has been asymptomatic with normal vital signs and laboratory studies • 127/74 , Pulse 123, Temp 98.6 °F (37 °C) (Temporal). Resp 30 • 0.2

64 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

CALCIUM

65 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

CALCIUM CHANNEL BLOCKER

• Severe toxicity is highly lethal, as a result of cardiovascular collapse • Good outcomes can be achieved with aggressive treatment • and most lethal calcium-channel blockers OD • Cardiac toxicity results from: • excessive negative inotropy: myocardial depression • negative chronotropy: sinus bradycardia • negative dromotropy: AV node blockade • Effects on vascular smooth muscle tone result in: • decreased afterload • systemic hypotension • coronary vasodilation

66 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

CALCIUM CHANNEL BLOCKER

67 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

Hyperglycemia

Hypoinsulinemia METABOLIC EFFECTS Calcium channel blocker-induced insulin resistance Calcium channel blockers also impair the cardiac myocyte adaptive

response due to: • Uptake of glucose & free fatty acids by cardiac myocytes • Inhibition of Ca-dependent mitochondrial activity required for glucose catabolism

68 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

CLINICAL FEATURES

• Onset of symptoms typically within 1-2 hours of ingestion • Slow release preps onset delayed 12-16 hrs with peak effects after 24 hours • Early signs bradycardia, 1st degree block and hypotension • May progress to refractory shock and death • Complications may include MI, stroke and non-occlusive mesenteric ischemia • Hyperglycaemia • Seizures and coma are rare

69 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

LAB TEST THAT CAN BE PROGNOSTIC OF MORTALITY IN CALCIUM CHANNEL BLOCKER POISONING

• Serum lactate • In a recent retrospective review of 177 patients, initial blood lactate concentration accurately predicted CCB-poisoning related mortality • In this study, initial blood glucose was an early predictor for severity but not mortality

Chen C , Voicu S , Diallo A , et al. (2020). The severity and mortality prediction of calcium-channel blocker poisoning in the intensive care unit. Clinical Toxicology, 58(6):508

70 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

TREATMENT • Calcium can be a useful to increase HR and BP • 10% calcium gluconate 60mL IV (0.6-1.0 mL/kg in children) • 10% calcium chloride 20mL IV (0.2 mL/kg in children) • Glucagon 1-5 mg IV • : 0.6mg every 2 min up to 1.8 mg (often ineffective) • High dose insulin – euglycaemic therapy • 1 u/kg bolus then 0.5 u/kg/hr • Vasopressors & intotropic • Norepi or Epi • Intralipids • ECMO

71 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

Beta Blockers

ANTIDOTE CHALLENGE Glucagon, calcium gluconate or chloride, high-dose insulin euglycemic therapy, lipid emulsion

72 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

• A docuseries on Vice TV • The show follows a guy named Hamilton as he explores the history, chemistry, & social impact of psychoactive substances HAMILTON’S • It chronicles his travels PHARMACOPEIA and first-hand experiences, as well as interviews with scientists, shamans and culture figures • https://www.youtube.com/ watch?v=C3Yd7M3JNlw

73 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

74 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

REFERENCES

• Downs, J. W., Cumpston, K. L., Kershner, E. K., Troendle, M. M., Rose, S. R., & Wills, B. K. (2021). Clinical outcome of massive acetaminophen overdose treated with standard-dose N-acetylcysteine. Clinical Toxicology , 1–8. Advance online publication. https://doi.org/10.1080/15563650.2021.1887493 • Fisher, E. S., & Curry, S. C. (2019). Evaluation and treatment of acetaminophen toxicity. Advances in , 85, 263–272. https://doi.org/10.1016/bs.apha.2018.12.004 • Fratt K (2018). Everything you need to know about Reishi mushrooms. Retrieved from https://www.plantsnap.com/wp-content/uploads/2018/11/ganoderma-lucidum-bonsai-2641558_1920.jpg • Panchal AR, Bartos JA, Cabañas JG, et al; Adult Basic and Advanced Life Support Writing Group. Part 3: Adult Basic and Advanced Life Support: 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2020 Oct 20;142(16_suppl_2):S366-S468. doi: 10.1161/CIR.0000000000000916. Epub 2020 Oct 21. PMID: 33081529. • Stead, T. S., Jeong, J. Y., Ganti, L., & Rubero, J. (2020). Massive acetaminophen overdose. Cureus, 12(7), e9262. https://doi.org/10.7759/cureus.9262 • Wanmuang, H., Leopairut, J., Kositchaiwat, C., Wananukul, W., & Bunyaratvej, S. (2007). Fatal fulminant hepatitis associated with Ganoderma lucidum (Lingzhi) mushroom powder. Journal of the Medical Association of Thailand = Chotmaihet thangphaet, 90(1), 179–181.

75 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

REFERENCES

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76 Toxicology Pearls Nancy Denke ACNP-BC, FNP-BC, CEN, CCRN, FAEN B3

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