Drug interactions
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This document defines drug interactions and outlines their outcomes, contributing factors, commonly involved drugs, types, mechanisms, and approaches to checking for interactions. It discusses how drug interactions can be beneficial or harmful and result from multiple drug therapy, diseases, prescribers, or noncompliance. The main types are drug-drug, drug-food, and drug-disease interactions, which can occur via pharmaceutical, pharmacokinetic, or pharmacodynamic mechanisms. Factors like absorption, distribution, metabolism, and excretion can be affected. The role of pharmacists in monitoring interactions and educating patients is also covered, as are newer online and mobile tools for checking drug interactions.
Drug interactions
- 1. 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 GentamicinDrug Interactions 9
- 10. Pharmacokinetic Interaction • Involve 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 Altered bacterial flora Altered pH Altered GIT motility Drug induced mucosal damage Formation of drug chelates or complexes
- 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 (Ca2+ ) 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/Druginteractionchecke r/ (UK Healthcare Drug Interaction Checker) • http://desktopindia.com/Drug-inter.aspx (Doctor’s Desktop: Medical Practice Software - Indian) Drug Interactions 25
- 28. • Android App – “MICROMEDEX Drug Interactions” Drug Interactions 28
- 29. THANK YOU Drug Interactions 29