Drug interactions

Drug interactions

1. DRUG INTERACTIONS DR. UMA TEKUR Drug Interactions 1 DR SAHIL KUMAR DRUG INTERACTIONS

2. OUTLINE Definition Outcomes of Drug Interactions Factors Contributing to Drug Interactions Drugs Commonly involved in Interactions Types of Drug Interactions Mechanisms of Drug Interactions Pharmaceutical Interactions Pharmacokinetic Interactions (A/D/M/E interactions) Pharmacodynamic interactions Drug-Food Interactions Drug-Disease Interactions Role of Pharmacist Newer Approaches to check interactions Drug Interactions 2

3. DEFINITION Drug Interactions 3 Drug Interaction is defined as the pharmacological activity of one drug being altered by the concomitant use of another drug or by the presence of some other substance . DEFINITION

4. OUTCOMES OF DRUG INTERACTIONS Beneficial well-recognized interactions; do not pose any undue risk to the patient . Eg Amoxicillin-Clavulanic Acid Eg Sulfadoxine-Pyrimethamine Drug Interactions 4 Harmful Unintended antagonism & loss of therapeutic effect. Toxicity

5. Factors contributing to drug interactions Multiple diseases or predisposing illnesses. Multiple drug therapy. Multiple prescribers. Poor patient compliance to instructions. Advancing age of patient. Drug related factors. Drug Interactions 5

6. Drugs Commonly Involved in Interactions Drugs with narrow safety margin : aminoglycosides, digoxin, lithium. Drugs affecting closely regulated body functions : antihypertensives , antidiabetics, anticoagulants. Highly plasma protein bound drugs : NSAIDs , oral anticoagulants, sulfonylureas. Drugs metabolized by saturation kinetics : phenytoin , theophylline. Drug Interactions 6

7. TYPES OF DRUG INTERACTIONS Drug-Drug Interaction Drug-Food Interaction Drug-Disease Interaction Drug Interactions 7

8. Mechanisms of Drug Interactions Three mechanisms by which an interaction can occur are: Pharmaceutical Interaction Pharmacokinetic Interaction Pharmacodynamic interaction Drug Interactions 8

9. Pharmaceutical Interaction Certain drugs react with each other and get inactivated if their solutions are mixed before administration . In practice, these in vitro interactions occur when injectable drugs are mixed in the same syringe or infusion bottle . Diazepam + Infusion fluid----------- Precipitation Phenytoin + Infusion fluid-----------Precipitation Heparin + Hydrocortisone-------------Inactivation of heparin Kanamycin + Hydrocortisone-----------Inactivation of kanamycin Carbenicillin + Gentamicin-----------Inactivation of Gentamicin Drug Interactions 9

10. Pharmacokinetic Interaction I nvolve the effect of a drug on another from the point of view that includes absorption, distribution, metabolism and excretion . I) ABSORPTION INTERACTIONS Drug Interactions 10

11. A) Altered pH : Non-ionized form more lipid soluble and more readily absorbed from GIT than ionized form. Eg 1, Antacids   Eg 2, H2 antagonists ↓pH Therefore , these drugs must be separated by at least 2h in the time of administration of both . Drug Interactions 11 Decrease the tablet dissolution of Ketoconazole (acidic)

12. B ) Complexation or chelation Eg 1 , Tetracycline interacts with iron preparations or Milk (Ca 2+ ) Unabsorbable complex Eg 2, Antacids ( aluminum or magnesium hydroxide) Decrease absorption of Tetracycline by 85% due to chelation. Drug Interactions 12

13. C) Drug-induced mucosal damage. D ) Altered motility Metoclopramide ( anti-emetic) Increased toxicity of cyclosporine Drug Interactions 13 Antineoplastic agents  e.g., cyclophosphamide vincristine procarbazine Inhibit absorption of several drugs eg., digoxin ↑ absorption of cyclosporine due to ↑ of stomach emptying time

14. E) Altered intestinal bacterial flora In 10% of patients receiving digoxin …..40% or more of administered dose metabolized by intestinal flora Drug Interactions 14 Broad Spectrum Antibiotics kill a large number of the normal flora of intestine ↑ digoxin conc. and ↑ its toxicity

15. Drug Interactions 15 DISTRIBUTION INTERACTIONS Distribution pattern of object drug is altered. Major mechanism for distribution interaction is alteration in protein drug binding. DISPLACED DRUG DISPLACER EFFECT

16. METABOLISM INTERACTIONS Enzyme induction: A drug may induce the enzyme that is responsible for the metabolism of another drug or even itself Eg: Rifampicin - ↓ Plasma conc. of OCPs – Contraceptive Failure. Enzyme inhibition: Decrease in rate of metabolism of a drug by another. This will lead to increased conc. of target drug, leading to its increased toxicity. Eg: Erythromycin - ↑ Plasma conc. of Terfenadine – Cardiotoxicity (QT). Drug Interactions 16

17. EXCRETION INTERACTIONS Drug Interactions 17 Changes in active tubular secretion: Changes in Renal Blood Flow:

18. Pharmacodynamic Interaction Modification of the action of one drug at the target site by another drug, independent of a change in its concentration. May result in synergism/additive effects/antagonism. SYNERGISM : When the therapeutic or toxic effects of two drugs are greater than the sum of effects of individual drugs. Eg : Combination of sulfamethoxazole and trimethoprim is used as antimicrobial agent. Drug Interactions 18

19. ADDITIVE EFFECT : Net effect of two drugs used together is equal to the sum of the individual drug effects. Eg: Combination of thiazide diuretic and beta adrenergic blocking drug is used for the treatment of hypertension. ANTAGONISM : The effects of one drug can be reduced or abolished by the presence of another drug. Eg: Blockade of antiparkinsonian action of levodopa by neuroleptics and metoclopramide having anti-dopaminergic action. Drug Interactions 19

20. Drug Food Interactions Drug Interactions 20 GARLIC when combined with diabetes medication could cause dangerous decrease in blood sugar level. Some garlic sensitive individuals may experience heart burn and flatulence. Garlic also has anti-clotting properties (interaction with anticoagulants). ORANGE JUICE must not be consumed with antacids containing aluminum. The juice increases the absorption of aluminum and leads to severe constipation.

21. MILK contains elements like Mg and Ca which chelate antibiotics like tetracycline and hence decrease its absorption and effect . GRAPEFRUIT JUICE inhibits CYP3A4; increasing levels of antidepressants (sertraline), benzodiazepines, verapamil. VITAMIN K rich foods reduce the effectiveness of anticoagulants (such as warfarin), increasing the risk of clotting . Fiber in OATMEAL and other cereals, when consumed in large amounts, can interfere with the absorption of digoxin. Drug Interactions 21

22. ALCOHOLIC BEVERAGES tend to increase the depressive effect of medications such as benzodiazepines, antihistamines, antidepressants, antipsychotics, muscle relaxants and narcotics . Disulfiram like reaction with metronidazole . Increase metabolism of warfarin and phenytoin . SMOKING increases activity of drug metabolizing enzymes in the liver. Diazepam, Theophylline, Olanzapine are metabolized rapidly and their effect is decreased. Drug Interactions 22

23. Drug Disease Interaction Drug – Condition interaction occurs when a drug worsens or exacerbates an existing medical condition. Nasal decongestants + Hypertension… ↑ Blood Pressure NSAIDs + Asthmatic Patients … Airway obstruction Nicotine + Hypertension … ↑ Heart Rate Metformin + Heart failure … ↑ Lactate level Drug Interactions 23

24. Role of Pharmacist Be vigilant in monitoring for potential drug interactions. Advising patients regarding proper use. Educate the patient on foods and beverages to avoid when taking certain medications. Advising patients in disease conditions. Keep up-to-date on potential drug-drug and drug-food interactions of medications to counsel the patients . (ASHP Guidelines American Society of Health-System Pharmacists) Drug Interactions 24

25. Newer Approaches to check interactions Free Online Drug Interaction Checking Software : 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/Druginteractionchecker/ (UK Healthcare Drug Interaction Checker) http :// desktopindia.com/Drug-inter.aspx ( Doc tor’s Desktop: Medical Practice Software - Indian) Drug Interactions 25

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28. Android App – “MICROMEDEX Drug Interactions” Drug Interactions 28

29. THANK YOU Drug Interactions 29