Dent4060 2024 Adverse Drug Reactions & Alternative Medicines PDF

Dent4060 (2024) – Adverse drugs reactions and alternative medicines Dr David Fu BDSc, DClinDent(SND) Acknowledgements to Prof Laurence J Walsh Dr Claudia Lopez-Silva Learning Objectives Definition of adverse drugs reactions Recording medications Common side effects of drugs Anti-thrombotic...

Dent4060 (2024) – Adverse drugs reactions and alternative medicines Dr David Fu BDSc, DClinDent(SND) Acknowledgements to Prof Laurence J Walsh Dr Claudia Lopez-Silva Learning Objectives Definition of adverse drugs reactions Recording medications Common side effects of drugs Anti-thrombotic agents Understanding lifestyle/alternative/complementary medications Understanding ADR versus Allergies and recording ADR and Alternative Medicine | 2021 2  Definition Adverse drug reaction (ADR) – “a response to a drug that is noxious and unintended and occurs at doses normally used in [hu]man[s] for the prophylaxis, diagnosis or therapy of disease, or for modification of physiological function” (WHO 1972) Issues with documenting ADR include: How minor/severe ‘noxious’ response should be reported? Whether drug received had contaminants (especially for herbal medications) or inactive excipients Errors as a source of ADR Page 3 ADR and Alternative Medicine | 2021 CRICOS code 00025B Medication history For details of medicines, check the Australian Medicines Handbook www.amh.net.au as the FIRST source (ideally not MIMS), then if needed use the Australian Drug Information (Aus DI) site. Forms of medicines Tablets and pills Lotions, creams, gels, suppositories Injections, implants, drugs delivered in bolus doses Sprays, inhalers/puffers, patches, chewing gums, douches, pastilles, eyedrops, other drops Dietary supplements, herb preparations 4 ADR and Alternative Medicine | 2021  Page 5 ADR and Alternative Medicine | 2021 Prescription drugs Drugs you are now using ALSO: Drugs you have recently stopped taking Collate GP lists; Use Pharmacy Medicare service MEDS CHECK For generic medicines Type 1: Clone (same MFR, identical to name brand) Type 2: Shared recipe (different MFR, similar ingredients, so similar but not identical) Type 3: Me too (different MFR, same active, but different fillers, coatings etc – alters bioavailability) ADR and Alternative Medicine | 2021 6  ADRs - Australia 27% of deaths recorded in Australia had ADRs as implicating factor in 1997-1998 (Runciman et al.) Major cause of morbidity and mortality worldwide – 100k deaths per year in USA attributed to ADRs Miller et al. 2006 noted 10.4% of patients reporting ADR over 6-month period in 2003-2004 20-30% of all admissions for patients over age of 65 are estimated to be medication- related 1. Runciman, W. B., Roughead, E. E., Semple, S. J., & Adams, R. J. (2003). Adverse drug events and medication errors in Australia. International Journal for Quality in Health Care, 15(suppl_1), i49-i59. 2. Miller, G. C., Britt, H. C., & Valenti, L. (2006). Adverse drug events in general practice patients in Australia. Medical Journal of Australia, 184(7), 321-324. 3. Roughead, L., Semple, S., & Rosenfeld, E. (2013). Literature review: medication safety in Australia. Sydney: Australian Commission on Safety and Quality in Health Care. Page 7 ADR and Alternative Medicine | 2021 CRICOS code 00025B  More drugs – more ADRs Page 8 ADR and Alternative Medicine | 2021 CRICOS code 00025B  Page 9 ADR and Alternative Medicine | 2021  Page 10 ADR and Alternative Medicine | 2021 Medications with hyposalivatory effects Anti-hypertensives Narcotic analgesics Anti-spasmodics Anti-convulsants Systemic bronchodilators Anti-emetics Anti-nauseants Skeletal muscle relaxants Anti-Parkinsonian agents Cardiac anti-arrhythmics Anti-psychotics Anxiolytics Anti-depressants (TCA) Expectorants Diuretics Decongestants Monoamine oxidase inhibitors Tranquillisers Anti-pruritics Sedatives Anti-histamines Anti-neoplastic agents. ADR and Alternative Medicine | 2021 11 ADR and Alternative Medicine | 2021 12 ADR and Alternative Medicine | 2021 13 ADR and Alternative Medicine | 2021 14 ADR and Alternative Medicine | 2021 15  Anti-Coagulant Versus Anti-Platelet Medication Anti-platelet medication inhibit platelet aggregation (clumping together) through various methods Anti-coagulant medication affect coagulation factors to impede thrombosis/coagulation cascade after the initial platelet aggregation Gurbel, P. A., & Tantry, U. S. (2014). Antiplatelet and anticoagulant agents in heart failure: current status and future perspectives. JACC: Heart Failure, 2(1), 1-14. Page ADR and Alternative Medicine | 2021 16 Common anti-coagulant pharmacokinetics Warfarin Dabigatran Rivaroxaban Apixaban Heparin Coumadin/ Trade name Praxada Xarelto Eliquis Heparin sodium Marevan Direct Vit K Direct Factor Xa Direct Factor Indirect Factor Class thrombin antagonists inhibitor Xa inhibitor IIa/Xa inhibitor inhibitor Route Oral Oral Oral Oral Subcut/IV Frequency Daily Twice daily Once Daily Twice Daily Once/Twice T Max 4 hours 2 hours 2.5-4 hours 1-3 hours Minutes 5-9 hours (healthy) Half Life 20-60 hours 12-1 7 hours 8-15 hours 1hr 11-13 hours (elderly) Metabolism and Almost entirely Renal: 80% Renal: 35% Renal: 27% Hepatic, reticulo- Elimination hepatic Hepatic: 20% Hepatic: 65% Hepatic: 73% endothelial system Andexanet alpha, Andexanet Protamine Reversal Vitamin K Idarucizumab (complete) aripazine alpha, aripazine Page 17 ADR and Alternative Medicine | 2021 Acknowledgements to Dr. Linda Gu CRICOS code 00025B  Warfarin Most widely used anticoagulant in the world WARF (Wisconsin Alumni Research Foundation) –arin Synthesised in 1948 Used a rodenticide in the USA in 1952 Human use 1954 Vitamin K Antagonist – Affects Factor II, VII, IX and X Page 18 ADR and Alternative Medicine | 2021 Other Traditional Anti-Coagulants ADR and Alternative Medicine | 2021 19 NOAC (or DOAC) Therapy AKA Non-Vitamin K antagonist Oral Anti-Coagulant Therapy AKA Novel Oral Anti-Coagulant Therapy AKA Direct Oral Anti-Coagulant Selective in Coagulation Factor Inhibition (Eg. Dabigatran inhibits Factor IIa/Thrombin) Higher compliance and lower side effect profile (?) No blood test needed/possible Page 20 ADR and Alternative Medicine | 2021 Novel oral anticoagulants (NOACs) NOACs inhibit clot formation and unlike warfarin are not Vitamin K antagonists. Have a short half life. As good or possibly better than the coumarins with less serious side effects, but much more expensive and not readily monitored. Inhibitors of factor IIa (dabigatran) Reversal agent is Idarucizumab Inhibitors of factor Xa (rivaroxaban, apixaban and edoxaban) No antidote for the factor Xa inhibitors, so difficult to stop their effects in the body in cases of emergency (accidents, urgent surgery). Page ADR and Alternative Medicine | 2021 21  Anti-platelets Pharmacokinetics Summary Aspirin Dipyridamole Clopidogrel (2nd Prasugrel (3rd Ticagrelor generation generation thienopyridine) thienopyridine) Route Oral Oral Oral Oral Oral T max 30-40mins 75mins 2 hours 30mins 1.5hrs Binding Irreversible Reversible Irreversible Irreversible Reversible Duration of action 7-10days 24hours 7-10days 7-10days 3-5days Half life 15-20mins (active 8-15hrs 7-9 hrs (15% active 7 hrs (85% active 7-9hrs (active metabolites) metabolites) metabolites) metabolites) Metabolism Hepatic, some role Hepatic Hepatic, requires Hepatic, requires Hepatic for cytochrome cytochrome P450 cytochrome P450 P450 Acknowledgements to Dr. Linda Gu Page 22 ADR and Alternative Medicine | 2021 CRICOS code 00025B  Page 23 ADR and Alternative Medicine | 2021 CRICOS code 00025B  Anti-platelet drugs: Clopidogrel (Plavix) Acts by inhibiting the ADP receptor on platelet cell membranes, so it prevents activation of platelets and eventual cross-linking by the protein fibrin. Used, along with acetylsalicylic acid (aspirin), for the prevention of thrombosis after placement of a coronary stent Used as an alternative antiplatelet drug for people intolerant to aspirin Activated in the liver by cytochrome P450 enzymes Low potential to interact with other pharmaceutical drugs but main risk is with the proton pump inhibitors omeprazole or esomeprazole Page 24 ADR and Alternative Medicine | 2021 CRICOS code 00025B  NOAC dosing: Why bother changing it? Modifications to use/dosage of NOACs prior to dental treatments are based on the balance of likely effects of each option of each procedure, and also the individual’s bleeding risks and renal functionality. With low bleeding risk of dental procedures, the NOAC medicine is still taken by patient as per normal, so as to avoid increase in the risk of thromboembolic event. For dental procedures with a higher risk of bleeding complications, the patient may be asked to miss or delay a dose of their NOAC before such procedures so as to minimize the effect on thromboembolic risk. Study in Westmead Sydney Hospital concludes no major events of bleeding when anti-thrombotic agents were not cased for 107 patients. Brennan, Y., Gu, Y., Schifter, M., Crowther, H., Favaloro, E. J., & Curnow, J. (2020). Dental extractions on direct oral anticoagulants vs. warfarin: The DENTST study. Research and Practice in Thrombosis and Haemostasis, 4(2), 278-284. Page 25 ADR and Alternative Medicine | 2021 CRICOS code 00025B Bleeding Risk and Dental Procedures Page 26 ADR and Alternative Medicine | 2021 CRICOS code 00025B  Page 27 ADR and Alternative Medicine | 2021 CRICOS code 00025B Bleeding Control: Thermal effects accelerate coagulation! !???? Page 28 ADR and Alternative Medicine | 2021 CRICOS code 00025B  “Lifestyle medication” Caffeine Alcohol Viagra, etc Recreational drugs (cannabis, cocaine, methamphetamines, hallicinogens, heroin, etc) Vitamins Mineral supplements “Alternative health” products Herbal products e.g. St John’s wort Fish oil supplements etc Page 29 ADR and Alternative Medicine | 2021 CRICOS code 00025B  Reasons Alternate/Complementary Medication Are Taken Well-being Increased immune system Prevention of hypertension Prevention of heart disease Symptomatic relief/prevention of joint pain Etc. ADR and Alternative Medicine | 2021 30  Page 31 ADR and Alternative Medicine | 2021 Foods/supplements with blood thinning effects Licorice Nattokinase Lumbrokinase Niacin Beer Onion Celery Papaya Cranberries Pomegranate Fish oil Red clover Garlic Soybean Ginger St. John’s Wort Ginkgo Tumeric Ginseng Wheatgrass Green tea Willow bark Horse chestnut Danshen Feverfew Page 32 ADR and Alternative Medicine | 2021 Foods and supplements that encourage clotting Avocado Co-enzyme Q10 Dark leafy greens such as spinach Grapefruit Page 33 ADR and Alternative Medicine | 2021  Documentation – Dental point of view 1. Offending medication 2. Timing of onset 3. Reaction description and severity (especially if hospitalisation occurred) 4. Original indications 5. Cofactors – e.g. other medications involved, fever? Page 34 ADR and Alternative Medicine | 2021  Separate Adverse Drug Reaction to Allergy ADR and Alternative Medicine | 2021 35 Susceptibility/Risk Factors Aronson, J. K., & Ferner, R. E. (2003). Joining the DoTS: new approach to classifying adverse drug reactions. Bmj, 327(7425), 1222-1225. Page 36 ADR and Alternative Medicine | 2021  Edwards, I. R., & Aronson, J. K. (2000). Adverse drug reactions: definitions, diagnosis, and management. The lancet, 356(9237), 1255-1259. Page 37 ADR and Alternative Medicine | 2021 Hypersensitivites Riedl, M. A., & Casillas, A. M. (2003). Adverse drug reactions: types and treatment options. American family physician, 68(9), 1781-1790. Page 38 ADR and Alternative Medicine | 2021 When patients indicate drug allergies Record what they say, but remember Penicillin allergy – only 10% are actually true, and may decrease over time. Reaction does not involve beta lactam ring; early reports of cross reactions were due to contamination of cephalosporins with penicillin Cephalosporins have a 0.1-2.0% cross reaction probability if the patient is allergic to penicillin SULFA = sulphonamide historical antibiotics from 1950s - like the sulphamethoxazole component of Bactrim – the reaction us to the acrylamine group Sulphite = antioxidant used to preserve adrenaline vasoconstrictor. No link between a sulphite allergy and a SULFA allergy. ADR and Alternative Medicine | 2021 39 Case Scenario: Drug Brand Name Dosage Indication Gabapentin Neurontin 900mg TID Neuropathic Pain Patient who is female and aged 35-40 years old Esomeprazole Nexium 40mg BD Gastric Reflux Registered nurse until 2011 Hydroxychloroquine Plaquenil 200mg BD Lupus, rheumatoid arthritis? Heavy smoking for 25+ years Topiramate Topamax 75mg Nocte Anti-convulsant/Epilepsy Medical history includes Ehler-Danlos Syndrome, Crohn’s Duloxetine Cymbalta 125mg Nocte Neuropathic Pain disease, scleroderma, Sjogren’s syndrome, trigeminal Pregabalin Lyrica 125mg Morn Neuropathic Pain/Anti-anxiety neuralgia, systemic lupus erythematous, osteogenesis Estrogen/Progestogen Femme tab + Contraceptive Implant left imperfecta, HIV, IBS, Rheumatoid arthritis arm Methotrexate Methoblast 25mg Rheumatoid Arthritis in Weekly Folic Acid 5mg To reduce side effects of Methotrexate Lignocaine 40 ml IV 3-6 Trigeminal Neuralgia monthly Tramadol Ultram Daily PRN Tapentadol Palexia 200mg BD PRN Something seems wrong? ADR and Alternative Medicine | 2021 40 Allergies?? Peanuts Latex Green Ants Bees Wasps Vibramycin Chlorhexidine Doxycycline Erythromycin NSAIDs ADR and Alternative Medicine | 2021 41  Allergies and Adverse Reactions 42 Allergies Adverse Reactions Latex (Rash, swelling of throat) Doxycycline (Vomit) Type A Immune-mediated Erythromycin (Vomit) Type A Chlorhexidine (Rash) Immune- NSAIDs (Thrombocytopenia) Type A mediated Peanut/Nuts - Anaphylaxis Vibramycin (Rash) - Immune- mediated Green Ant? Bees? Wasps? ADR and Alternative Medicine | 2021  Conclusion Common side effect of medication: Hyposalivation Important to consider alternative/complementary medication during risk assessment for bleeding and ADRs. Documentation is important, especially for patients who advise they have “multiple allergies” Differentiate between ADRs and hypersensitivity as the management differs Page 43 ADR and Alternative Medicine | 2021  Thank you for listening [email protected] CRICOS code 00025B Page 44 ADR and Alternative Medicine | 2021