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Drug Drug Interactions_27-01-2024_Dr. Jeenal Mistry.pdf
- 1. DRUG DRUG INTERACTIONS Dr. Jeenal Mistry Senior resident, Dept. of Pharmacology, GMERS Medical College, Navsari. Date: 27th January 2024
- 2. OUTLINES Definitions 01 Epidemiology & Risk factors 02 Classifications 03 Types 04 Outcome 05 Clinical Applications 06 Drug & Herb 07 NDD 08 2
- 3. Drug interaction can be defined as the modifications of the effect of one drug by the prior or concomitant administration of another drug / food/ exogenous substance. 3
- 4. ▪ About 7% of hospitalizations are due to drug interactions. ▪ As the number of medications a patient takes increases, the potential for drug interactions increases. ▪ It causes increased duration of stay, cost and mortality. Epidemiology of Drug Interactions 4
- 5. ▪ Poly pharmacy Eg. Chronic disease ▪ Complex Pharmacokinetic of drug Eg. Enzyme inducer or inhibitor ▪ Low therapeutic index Eg. Lithium ▪ Diseases Eg. CCF, Renal Or Liver disease ▪ Elderly patient : Beers Criteria Risk factors for drug interaction 5
- 6. Drug interaction can be classified by following ways- ▪ Nature of drug interaction ▪ Depending on the interacting substance ▪ Outcome of drug interaction Classification of Drug Interaction 6
- 7. Pharmaceutical interaction Minor Pharmacokinetic (PK) interaction Major Pharmacodynamic (PD) interaction Major Types of drug interaction based on nature of interaction 7
- 8. ▪ Drug – Drug Interaction ▪ Drug – Food Interaction ▪ Drug – Chemical Interaction ▪ Drug – Laboratory Interaction ▪ Drug-Disease Interaction Types of drug interaction based on interacting substance 8
- 9. Harmful Decreased therapeutic effect Increased toxic effect Beneficial Increased therapeutic effect Decreased toxic effect Types of drug interaction based on outcome 9
- 10. Also called as incompatibility. It is a physicochemical interaction that occurs when drugs are mixed in i.v. Infusions causing precipitation or inactivation of active principles. Pharmaceutical Interaction Diazepam + Infusion fluids ====➔ Precipitation Phenytoin + Infusion fluids ====➔ Precipitation Heparin + Hydrocortisone ====➔ Inactivation of heparin Kanamycin + Hydrocortisone ====➔ Inactivation of kanamycin Carbenicillin + Gentamicin ====➔ Inactivation of Gentamicin 10
- 11. Pharmacokinetic Interaction These interactions are those in which ADME properties of the object drug is altered by the precipitant and hence such interactions are also called as ADME interactions The resultant effect is altered plasma concentration of the object drug. Absorption Interaction 01 03 Metabolism Interaction 04 Excretion Interaction 02 Distribution Interaction 11
- 12. Pharmacokinetic Absorption Interaction 01 Altered pH 05 Altered GIT motility 03 Formation of drug chelates or complexes 06 Malabsorption syndrome 02 Altered bacterial flora 04 Drug induced mucosal damage (1) Altered GIT absorption 12
- 13. A) Altered pH The non-ionized form of a drug is more lipid soluble and more readily absorbed from GIT than the ionized form. Eg Antacids Decrease efficacy of PPI Eg H2 antagonists ↑pH Therefore, these drugs must be separated by at least 2h. ↑pH 13
- 14. B) Altered intestinal bacterial flora Eg: In patients receiving digoxin ↓ 40% or more of the administered dose is metabolized by the intestinal flora ↓ Antibiotics kill a large number of the normal flora of the intestine ↓ Increase digoxin conc. and increase its toxicity 14
- 15. C) Complexation or chelation ✓Tetracycline interacts with iron preparations ✓Sucralfate interferes with bioavailability of phenytoin ✓Cholestyramine binds with warfarin decreased absorption ✓ Antacid (aluminum or magnesium) hydroxide Decrease absorption of ciprofloxacin by 85% due to chelation 15
- 16. D) Drug-induced mucosal damage Antineoplastic agents e.g., Cyclophosphamide Vincristine Procarbazine Inhibit absorption of several drugs eg., digoxin 16
- 17. E) Altered motility ➢Narcotics, atropine, antacids ↓ motility ➢Domperidone, metoclopramide, cisapride, ↑motility Erythromycin ➢Methadone with didanosine → ↓GI motility→↑disintegration→↓bioavailability ➢Metoclopramide and digoxin 17
- 18. 2) Plasma protein binding Acidic drug BasicDrug Albumin ᾳ1 Acid Glycoprotein Competitive protein binding by another drug Increase concentration of free drug more drug response 18 Phenytoin (90%), Tolbutamide (96%), and warfarin (99%) is highly bound to plasma protein→ Drugs that displace these agents are: Aspirin, Sulfonamides, Phenylbutazone
- 19. 3) drug transporters Transporters play key role in Drug Absorption and Excretion Most important drug transporters P-glycoproteins (PgP) Interaction usually result in Inhibit function of transporters Inhibit drug excretion Ultimately drug concentration increases in body 19
- 20. 4) Altered metabolism Liver → Major site of drug metabolism Other organs → WBC, skin, lung and GIT. Altered phase I metabolism CYP450 induction CYP450 inhibition Altered phase II metabolism ➢ Induction of phase II enzyme UDP-glucuronyl transferases (UGTs) ➢ Inhibition of phase II enzyme Competitive use of conjugate molecules 20
- 21. Renal excretion A. Alkaline urine: Na HCO3 urine pH, renal excretion of (weak acid) salicylates & NSAIDs Acetazolamide, excrete bicarbonate, urine pH, quinidine (weak base) excretion & its toxicity B. Acidic urine: Salicylates urine pH, methotraxate (weak acid) excretion & its toxicity 21
- 22. Renal excretion (Cont.) c. Competition for active secretion: a. Weak acids Probenecid methotraxate excretion, its toxicity Probenecid penicillin secretion, its duration of action b. Weak bases Cimetidine excretion of procainamide, its toxicity d. Excretion related to electrolyte balance: Low Na+ intake causes lithium retention & toxicity Diuretics (thiazides), excrete more Na+, retain lithium, its toxicity 22
- 23. Pharmacodynamic Interaction Are those in which the activity of the object drug at its site of action is altered by the precipitant. Such interactions may be direct or indirect. These are of two types: 1.Direct pharmacodynamic interactions 2.Indirect pharmacodynamic interaction 23
- 24. Direct Pharmacodynamic Interaction In which drugs having similar or opposing pharmacological effects are used concurrently The three consequences of direct interactions are: 1. Antagonism 2. Addition or summation 3. Synergism or potentiation 24
- 25. Indirect Pharmacodynamic Interaction In which both the object and the precipitant drugs have unrelated effects but the latter in some way alerts the effects of the former. Example: salicylates decrease the ability of the platelets to aggregate thus impairing the Homeostasis if warfarin induced bleeding occurs 25
- 26. Food drug interaction ❑Pharmaceutical Phase Drug Dissolution and Disintegration Eg. High levels of Ascorbic acid (vitamin C) ie ↓ pH ↓ ↓ Efficacy of saquinavir Foods that raise gastric pH ↓ Prevent dissolution of isoniazid ↓ ↓ Efficacy 26
- 27. Grapefruit juice and Drug Interactions •Calcium channel blockers •Amlodipine •Fenoldopam •Nifedipine •Nimodipine 27
- 28. Other Clinically Significant Herb- Drug Interactions Object Drug Interacting Drug Outcome Anticonvulsants Wormwood seizure threshold Anticonvulsants Gingko biloba seizure threshold Digoxin Hawthorne digoxin activity Saquinavir Garlic saquinavir levels Warfarin Feverfew risk of bleeding Warfarin Garlic risk of bleeding Warfarin Ginger risk of bleeding Warfarin Ginkgo risk of bleeding Warfarin Ginseng anticoagulant . 28
- 29. Drug-Disease Interactions Drug Disease ○ Anticholinergics BPH, constipation, dementia ○ Antiarrhythmics (Type 1A) CHF (systolic dysfunction) ○ CCB 1st generation CHF (systolic dysfunction) ○ Amphetamines HTN, insomnia ○ Benzodiazepines COPD, Dementia ○ Beta-blockers COPD, DM ○ Digoxin Heart block ○ Tricyclic antidepressants Arrhythmias, BPH, constipation dementia, falls, heart block postural hypotension ○ Metoclopramide Parkinson’s disease ○ Nitrofurantoin Chronic renal failure ○ Non-aspirin NSAIDs CRF, CHF, HTN ○ Opioid analgesics BPH, constipation, dementia 29
- 30. 30
- 31. Drug Laboratory Interaction A. Nalidixic acid, salicylate and vitamin C → provide a false positive test of urine sugar with benedict’s solution B. Oestrogens exhibit false positive rise in the values of serum thyroxine (as they cause hyperproteinaemia) 31
- 32. 1. National Prescribing Service, 2009. 2. Bailey, David G.; Dresser, George; Arnold, J. Malcolm O. (2012) 3. Emergency Hospitalizations for Adverse Drug Events in Older Americans" Daniel S. Budnitz, M.D., M.P.H., Maribeth C. Lovegrove, M.P.H., Nadine Shehab, Pharm.D., M.P.H., and Chesley L. Richards, M.D., M.P.H. N Engl J Med 2011;365:2002-12. Copyright © 2011 Massachusetts Medical Society. 4. Hilary Hamilton, MB, MRCPI; Paul Gallagher, PhD, MRCPI; Cristin Ryan, PhD, MPSI; Stephen Byrne, PhD, MPSI; Denis O’Mahony, MD, FRCPI. Potentially Inappropriate Medications Defined by STOPP Criteria and the Risk of Adverse Drug Events in Older Hospitalized Patients. Arch Intern Med. 2011;171(11):1013-1019. References 32
- 33. Free Online Drug Interaction Checking https://www.drugs.com/drug_interactions.php (Drugs.com) http://reference.medscape.com/drug-interactionchecker (Medscape) http://www.webmd.com/interaction-checker/ (Web MD) http://ukhealthcare.uky.edu/Library/DrugReference/Druginteractionchecke r/ (UK Healthcare Drug Interaction Checker) http://desktopindia.com/Drug-inter.aspx (Doctor's Desktop: Medical Practice Software - Indian) Alternative resources 33
- 34. Thank You ☺