Spring Meeting February 9, 2019

Transcription

1 Spring Meeting February 9,

2 Small Doses with Deadly Consequences Amberly R. Johnson, PharmD, DABAT Specialist in Poison Information Supervisor Utah Poison Control Center 2

3 Disclosure I have no conflicts of interest to disclose I will be discussing off-label uses of drugs 3

4 Learning Objectives At the conclusion of this activity, pharmacists should be able to successfully: 1. List medications associated with morbidity and mortality in small doses 2. Predict serious clinical effects related to ingestion of benzonatate, buprenorphine, calcium channel blockers, colchicine, hydroxychloroquine, and sulfonylureas 3. Examine patient and medication factors that increase the risk of toxicity from benzonatate, buprenorphine, calcium channel blockers, colchicine, hydroxychloroquine, and sulfonylureas 4. Develop counseling points that address toxicity of discussed medications 4

5 Learning Objectives At the conclusion of this activity, pharmacy technicians should be able to successfully: 1. Identify medication classes associated with morbidity and mortality in small doses 2. Describe patient and medication factors that increase risk of toxicity from benzonatate, buprenorphine, calcium channel blockers, colchicine, hydroxychloroquine, and sulfonylureas 3. Propose prevention strategies to decrease morbidity and mortality in relation to discussed medications 5

6 Outline National Poison Data System Deadly in a Dose Specific medications benzonatate, buprenorphine, calcium channel blockers, colchicine, hydroxychloroquine, and sulfonylureas Prevention strategies 6

7 National Poison Data System (NPDS) 2% 1% 1% 19% Unintentional Intentional Adverse reactions Unknown Other 77% Reference: 1 7

8 Most Common Exposures 2017 Analgesics Cleaning substances (household) Cosmetic/personal care products Sedative/hypnotics/antipsychotics Antidepressants Antihistamines Cardiovascular drugs Foreign bodies/toys/miscellaneous Pesticides Alcohols Stimulants and Street drugs Topical Preparations Anticonvulsants Vitamins Reference: 1 8

9 Most Common in Fatalities 2017 Miscellaneous sedative/hypnotic/antipsychotics Opioids Miscellaneous Stimulants/Street Drugs Miscellaneous alcohols Calcium channel blockers Acetaminophen combinations Acetaminophen alone Beta blockers Miscellaneous antidepressants Miscellaneous unknown drug Selective serotonin reuptake inhibitors (SSRI) Miscellaneous antihistamines Hypoglycemic, single agent Tricyclic antidepressants (TCA) Reference: 1 9

10 Deadly in a Dose (Bar-Oz et al.) Medications that could harm a 10kg toddler with 1-2 doses Anti-arrhythmics Antimalarials Antipsychotics (typical) Calcium channel blockers Camphor Methyl salicylate Narcotics Oral hypoglycemics Podophyllin Theophylline Tricyclic antidepressants Can also be dangerous in adults Reference: 2 10

11 Benzonatate FDA approved indication Cough Mechanism of action/toxicity Acts on mucosal stretch receptors (central and peripheral) Local anesthetic properties sodium channel blockade Reference: 3,4 11

12 Benzonatate Toxic Effects Seizures Ventricular dysrhythmias Cardiac arrest Reference: 3,4 12

13 Risk Factors for Toxicity MEDICATION FACTORS Size Formulation Reference: 3,4 13

14 NPDS Fatalities Benzonatate related, n = 19 Single substance, n = 3 Multi-substance, n = 16 Patient ages 6-12 years, n = years, n = 4 > 20 years, n = 11 Toxic dose not well defined Reference: 1,4-8 14

15 Benzonatate Counseling Points Do not break, chew, crush, or dissolve Do not take more than is directed Keep out of reach of children Contact the Utah Poison Control Center (UPCC) if more is taken than prescribed or taken by the wrong patient Reference: 3,4 15

16 Buprenorphine Single ingredient or combined with naloxone FDA approved indications Opioid dependence Chronic pain (only certain formulations) Mechanism of action/toxicity Opioid mu receptor partial agonist, opioid kappa receptor antagonist Reference: 3 16

17 Buprenorphine Toxic Effects CNS depression Coma Respiratory depression Respiratory arrest What about buprenorphine s ceiling effect? Reference: 3,9 17

18 Risk Factors for Toxicity PATIENT FACTORS Opioid naïve MEDICATION FACTORS Formulation Duration of action Reference: 3,9 18

19 NPDS Fatalities Buprenorphine related, n = 49 Single substance, n = 8 Multi-substance, n = 41 Patient ages < 5 years, n = years, n = 2 > 20 years, n = 43 Taste/lick can produce toxicity in a child Reference: 1,5-9 19

20 Buprenorphine Counseling Points Taste amounts can be life-threatening in children Keep out of reach of children Do not take more than is directed Contact the UPCC if more is taken than prescribed or taken by the wrong patient Reference: 3,9 20

21 Calcium Channel Blockers (CCBs) Amlodipine, diltiazem, nifedipine, verapamil Also in combination with diuretics, angiotensin converting enzyme inhibitors (ACE-I), angiotensin II receptor blockers (ARB) FDA approved indications Hypertension, stable/variant angina Atrial arrhythmia (non-dihydropyridine only) Mechanism of action/toxicity L-type calcium channel antagonists in cardiac muscle and vascular smooth muscle Reference: 3,10,11 21

22 CCB Toxic Effects Hypotension Bradycardia Hyperglycemia Cardiovascular collapse Reference: 3,10,11 22

23 Risk Factors For Toxicity PATIENT FACTORS Past medical history MEDICATION FACTORS Dosing frequency Formulation Reference: 3,10,11 23

24 NPDS Fatalities CCB related, n = 698 Single substance, n = 137 Multi-substance, n = 561 Patient ages < 5 years, n = years, n = years, n = 8 > 20 years, n = 687 Reference: 1,5-8 24

25 CCB Counseling Points Do not take more than is directed Keep out of reach of children Contact the UPCC if more is taken than prescribed or taken by the wrong patient Reference: 3,10,11 25

26 Colchicine Alone or in combination with probenecid FDA approved indication Gout, Familial Mediterranean Fever (FMF) Mechanism of action/toxicity Microtubule toxin Reference: 3,12 Image: 26

27 Colchicine Toxic Effects Phase 1 (0-24 hours) Gastrointestinal toxicity Phase 2 (1-7 days) Multi-organ dysfunction, metabolic derangements, myelosuppression Death from fatal dysrhythmias, cardiovascular collapse, coagulopathies, infection Phase 3 (>7 days post ingestion) Recovery phase Reference: 3,12 27

28 Risk Factors for Toxicity PATIENT FACTORS Impaired renal function MEDICATION FACTORS Dosing frequency Reference: 3,12 28

29 NPDS Fatalities Colchicine related, n = 25 Single substance, n = 18 Multi-substance, n = 7 Patient ages years, n = 1 > 20 years, n = 24 Toxic dose not well defined Reference: 1,5-8 29

30 Colchicine Counseling Points Do not exceed 1.8 mg for a gout flare Do not take more than is directed Keep out of reach of children Contact the UPCC if more is taken than prescribed or taken by the wrong patient Reference: 3,12 30

31 Hydroxychloroquine FDA approved indications Rheumatoid arthritis, malaria, lupus erythematosus Mechanism of action/toxicity Interferes with synthesis of DNA and RNA Sodium and potassium channel blockade in overdose Reference: 3,11,13 31

32 Hydroxychloroquine Toxic Effects CNS depression Hypokalemia Seizures Ventricular dysrhythmias Cardiac arrest Reference: 3,11,13 32

33 Risk Factors for Toxicity PATIENT FACTORS Medication storage Reference: 3,11,13 33

34 NPDS Fatalities Hydroxychloroquine related, n = 10 Single substance, n = 1 Multi-substance, n = 9 Patient ages years, n = 2 > 20 years, n = 8 Reference: 1,5-8 34

35 Hydroxychloroquine Counseling Points Keep out of reach of children Do not take more than is directed Contact the UPCC if more is taken than prescribed or taken by the wrong patient Reference: 3,11,13 35

36 Sulfonylureas Glipizide, glyburide, glimepiride Alone or in combination with metformin, thiazolidinediones FDA approved indication Type 2 Diabetes Mechanism of action/toxicity Stimulate endogenous insulin secretion from the pancreas Reference: 3,14,15 36

37 Sulfonylurea Toxic Effects Hypoglycemia Reference: 14,15 37

38 Risk Factors for Toxicity PATIENT FACTORS Age Functioning pancreas Treatment naïve MEDICATION FACTORS Peak effect Duration of action Reference: 14,15 38

39 NPDS Fatalities Sulfonylurea related, n = 44 Single substance, n = 8 Multi-substance, n = 36 Patient ages > 20 years, n = 44 Reference: 1,5-8 39

40 Sulfonylurea Counseling Points Keep out of reach of children Do not take more than is directed Contact the UPCC if more is taken than prescribed or taken by the wrong patient Reference: 14,15 40

41 Prevention Strategies Put it up, lock it up Keep medications out of the reach of children Store medications in original containers Use safety devices Close the lid tightly after using a medicine Never leave open medications unattended Child resistant DOES NOT mean child proof Reference: 16 41

42 Prevention Strategies Medication administration Follow dosing instructions carefully Unclear instructions? Contact prescribing doctor Be aware of multiple ingredients Never call medicine candy Don t take medicine when children are watching Don t take medications in the dark Reference: 16 42

43 Question 1 Pharmacists/Technicians Divide the room into thirds (see below): In groups of 2-3, discuss medications and medication classes associated with morbidity and mortality in small doses Left side room Middle room Right side Benzonatate Hydroxychloroquine Buprenorphine CCBs Sulfonylureas Colchicine 43

44 Questions 2 Technicians Match the medication to its risk factors for toxicity (select all that apply): 1. Benzonatate 2. Buprenorphine 3. CCB 4. Colchicine 5. Hydroxyzine 6. Sulfonylurea A. Dosing frequency B. Duration of action C. Formulation D. Medication naïve E. Medication storage 44

45 Questions 3 Pharmacists Match the mechanism of action to its medication and toxic effects 1. Partial mu opioid agonism 2. Sodium channel blockade 3. L-type calcium channel antagonism 4. Stimulate endogenous insulin release A. CCB hypotension and bradycardia B. Sulfonylurea hypoglycemia C. Benzonatate ventricular dysrhythmias D. Buprenorphine respiratory depression 45

46 Questions 4 Technicians Choose prevention strategies that may decrease morbidity and mortality of medications discussed today (select all that apply): A. Keep medications out of the reach of children B. Don t take medicine when children are watching C. Use child resistant containers or other safety devices D. Don t take medications in the dark 46

47 Questions 5 Pharmacists Counsel your neighbor on the potential toxic effects of benzonatate, buprenorphine, calcium channel blockers, colchicine, hydroxyzine, and sulfonylureas 47

48 Questions 48

49 References 1. Gummin DD, Mowry JB, Spyker DA et al Annual Report of the American Association of Poison Control Centers National Poison Data System (NPDS): 35 th Annual Report. Clin Toxicol (Phila). 2018: Epub online. 2. Bar-Oz B, Levichek Z, Koren G. Medications that can be fatal for a toddler with one tablet or teaspoonful. Pediatr Drugs. 2004; 6(2): Micromedex (electronic version). IBM Watson Health, Greenwood Village, Colorado, USA. Available at: cited: January 3, Winter ML, Spiller HA, Griffith JR. Benzonatate ingestion reported to the National Poison Data System (NPDS). J Med Toxicol. 2010; 6(4): Mowry JB, Spyker DA, Cantilena LR Jr, et al Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 31st Annual Report. Clin Toxicol (Phila). 2014; 52(10): Mowry JB, Spyker DA, Brooks DE, et al Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 32nd Annual Report. Clin Toxicol (Phila). 2015; 53(10): Mowry JB, Spyker DA, Brooks DE, et al Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 33rd Annual Report. Clin Toxicol (Phila). 2016; 54(10): Gummin DD, Mowry JB, Spyker DA, et al Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 34th Annual Report. Clin Toxicol (Phila). 2017; 55(10): Geib AJ, Babu K, Ewald MB et al. Adverse effects in children after unintentional buprenorphine exposure. Pediatrics. 2006; 118(4): Jang DH, DeRoos F. Calcium Channel Blockers. In: Hoffman RS, Howland M, Lewin NA, Nelson LS, Goldfrank LR. eds. Goldfrank's Toxicologic Emergencies, 10e New York, NY: McGraw-Hill; Accessed January 03, Specific Poisons and Drugs: Diagnosis and Treatment. In: Olson KR, Anderson IB, Benowitz NL, Blanc PD, Clark RF, Kearney TE, Kim-Katz SY, Wu AB. eds. Poisoning & Drug Overdose, 7e New York, NY: McGraw-Hill;. Accessed January 03, Schier JG. Colchicine, Podophyllin, and the Vinca Alkaloids. In: Hoffman RS, Howland M, Lewin NA, Nelson LS, Goldfrank LR. eds. Goldfrank's Toxicologic Emergencies, 10e New York, NY: McGraw-Hill; Accessed January 03, Barry J. Antimalarials. In: Hoffman RS, Howland M, Lewin NA, Nelson LS, Goldfrank LR. eds. Goldfrank's Toxicologic Emergencies, 10e New York, NY: McGraw-Hill; Accessed January 03, Bosse GM. Antidiabetics and Hypoglycemics. In: Hoffman RS, Howland M, Lewin NA, Nelson LS, Goldfrank LR. eds. Goldfrank's Toxicologic Emergencies, 10e New York, NY: McGraw-Hill; Accessed January 03, Rowden, A. K., & Fasano, C. J. Emergency management of oral hypoglycemic drug toxicity. Emergency medicine clinics of North America. 2007; 25(2), Lesson Plans for Educators. Utah Poison Control Center. Accessed January 2,