Tương tác thuốc

TƯƠNG TÁC THUỐC (DRUG INTERACTIONS) PGS.TS Nguyễn Thị Thu Hương INTRODUCTION Where Outcome Drug Incompatibility Tương kỵ thuốc Outside the body Visible Increase/Decrease therapeutic effect Route Only injection, esp IV administration Drug Interaction Tương tác thuốc Inside the body Invisible -Increase/Decrease therapeutic effect -Increase drug toxicity All INTRODUCTION Polypharmacy Wrong choice of drug ↓ Hepatic & Renal function Wrong dosage Serious unwanted effects Reduction in the therapeutic effects Wrong route of administration BACKGROUND BACKGROUND Perticides stimulate GI enzymes → increase cortisol metabolism DrugDisease Interaction DrugEnvironmental Interaction Paracetamol-liver cirrhosis Sulfonamide-nephritis Drug-Alcohol Interaction AlcoholCNS depressants Smoking increases diazepam metabolism DrugSmoking Interaction BACKGROUND Polypharmacy Specific populations/ Illness - Elderly, female Obese/malnourished Transplant recipients Hepatic Diseases Renal dysfunction HIV infection, Diabetes Long hospital stay Drug Interaction Narrow Therapeutic Index Drugs Multiple Prescribers/ Pharmacies Insulin, cyclosporine, digoxin, warfarin, lithium, antidepressants BACKGROUND Percentage of reports with potential drug-drug interactions (DDIs) in relation to the number of drugs Lara Magro et al., Front Pharmacol 2020; 11: 622862 BACKGROUND Major Moderate Minor Little effect Deteriotion of patients status High clinical significant Life threatening Avoid combination BACKGROUND LARS BJERRUM -European Journal of General Practice 2008; 14: 23-29 BACKGROUND LARS BJERRUM -European Journal of General Practice 2008; 14: 23-29 10 GRAPEFRUIT JUICE Grapefruit juice and naringin inhibit the uptake transporter OATP1A2 Co-administration of grapefruit juice and fexofenadine resulted in an AUC0–8 h that had dropped by 52% compared to fexofenadine co-administered with water Drinking grapefruit juice (GFJ) 2 h before taking fexofenadine reduced the average AUC by 38% and drinking grapefruit juice 4 h in advance had no effect on drug absorption (Bailey et al., 1998; Glaeser et al., 2007) 53 GRAPEFRUIT JUICE Calcium Channel Blockers and Statins + Grapefruit Felodipine undergoes high presystemic (first-pass) CYP3A4-mediated metabolism in the gut and liver resulting in a low bioavailability (15%) An amount of 250 mL of grapefruit juice increases the AUC and Cmax to 267% and 345%, respectively → orthostatic hypotension K.S Lown et al., J Clin Invest., 99 (1997), pp 2545-2553 54 VITAMIN K-RICH FOODS Diminish warfarin’s effectiveness 55 VITAMIN K-RICH FOODS Increase risk of bleeding or clot formation 56 HIGH FAT DIETS Antiretroviral protease inhibitors has been shown to be associated with alterations in plasma lipids (i.e prompt and sustained increases in total cholesterol, low-density lipoprotein cholesterol, and triglycerides) and insulin levels → dyslipidemia High fat meals can increase drug absorption by improving solubility of some antiretroviral protease inhibitors (e.g., saquinavir, atazanavir) 57 TYRAMIN-RICH FOODS 58 TYRAMIN-RICH FOODS Isoniazid and MAO inhibitors inhibit the breakdown of endogenous and dietary amines; a tyramine-rich diet can potentiate a hypertensive crisis 59 ALCOHOL DRINKING  Cytochrome P450 2E1 (CYP2E1), the key enzyme of the microsomal pathway of ethanol oxidation, is inducible by chronic ethanol consumption and its activity is increased by three to five fold in liver from alcoholics subjects  Alcohol is also known to strongly inhibit CYP2C9 60 ALCOHOL DRINKING Enzyme inhibited Acute amount of alcohol (large amount over a short period of time) Enzyme induced Enzyme inhibited 61 FOOD - DRUG INTERACTION Acetaminophen Diazepam (BZDs) SSRIs Alcohol beverages Metronidazole Insulin, Oral Diabetic Drugs 62 ALCOHOL DRINKING 63 ALCOHOL DRINKING Disulfiram, dùng để điều trị chứng nghiện rượu, hoạt động cách ức chế acetaldehyde dehydrogenase, làm tăng nồng độ acetaldehyde thể lên gấp đến 10 lần → hạ huyết áp, đánh trống ngực, buồn nơn, khó chịu, gây cảm giác sợ rượu (hội chứng cai nghiện) 64 ALCOHOL DRINKING Drug Interactions With Alcohol (cited in Drug.com/Drug Interactions Checker) • • • • • • • • • • High blood pressure medication Antipsychotics, Sleeping pills (sedatives and hypnotics) Antidepressants, Anxiety Medications Pain medications (analgesics) Skeletal muscle relaxants Diabetes medicine Cholesterol medications, Blood Thinners Antibiotic Medications Birth Control Medications Caffeine, Energy Drinks 65 TEA DRINKING Dessi P Zaharieva and Michael C Riddell, Applied Physiology Nutrition and Metabolism 38(8):813-22, 2013 66 CAFFEINE DRINKING 67