DRUG INTERACTIONS-BPHARM SYLLABUS PHARMACOLOGY

This presentation covers the type and factors affecting drug interactions including pharmacokinetic and pharmacodynamic drug interactions.

1. DRUG INTERACTIONS Ms. FATHIMATH RAIHANA ASSISTANT PROFESSOR P A COLLEGE OF PHARMACY

2. Drug interaction is the alteration of the pharmacological effect of the drug by drug, food, drink , disease or any chemical.

3. DRUG DRUG + Increase action Decrease action Adverse reaction

4. Drug interactions may occur : In VITRO : In the syringe before administration . Mixing of drugs – physical or chemical interactions. Eg : Penicillin and gentamicin should never be mixed in the same syringe. In VIVO : In the body after administration. It include pharmacokinetic and pharmacodynamics interaction.

5. Drug interaction is classified based upon : Mechanism C ause

6. i . Pharmacokinetic interaction : These occur when one drug alters the absorption, distribution, metabolism or excretion of drugs. 1. Absorption : Binding : Tetracyclines chelate iron and antacids – reduce absorption. ii. Altering gastric pH : Antacids with iron and anticoagulants. Antacids raise gastric pH and interfere with absorption of drugs like iron and anticoagulants. iii. Altering gastric motility : Atropine and morphine – slow gastric emptying and hence delay absorption. I. Based on mechanism of interaction :

7. 2. Distribution : Plasma protein binding can cause displacement interactions because of the competition between two drugs having affinity towards same binding site. Competition for plasma protein – displacement reactions. Eg : Warfarin displaced by phenyl butazone . 3. Metabolism : microsomal enzyme induction and inhibition Hepatic results in drug interactions. Eg : Phenytoin , rifampicin – enzyme inducers Chloramphenicol, cimetidine – enzyme inhibitors

8. ii. Pharmacodynamic interaction : This interaction is due to the action of drugs on receptors or physiological system. They may lead to Additive Synergistic Antagonistic effects.

9. iii. Pharmaceutical interaction : It occurs when two or more drugs physically or chemically interact outside the body, usually before administration, leading to incompatibility or inactivation . This type of interaction typically happens when drugs are mixed: in the same IV solution in syringes during compounding or preparation It occurs before the drug enters the body. Eg : Penicillin + Gentamicin should not be mixed together Penicillin inactivates gentamicin → loss of therapeutic effect of gentamicin

10. II. By cause : Drug-drug interaction Drug-food interaction Drug-disease interaction Drug-laboratory interaction

11. i . Drug-drug interaction : It is the phenomenon where the effect of drug is altered by the presence of another drug when they are administered simultaneously. This may enhance, reduce or lead to unexpected effects. Eg : Warfarin + Aspirin → Increased risk of bleeding

12. ii. Drug – food interaction : It occurs when the food or drink affects the pharmacological effect of a drug leading to reduced effectiveness or increased side effects. Eg : Grapefruit juice + Atorvastatin → Increases statin levels → Risk of muscle toxicity

13. iii. Drug – disease interaction : It occurs when a drug worsens an already existing medical condition or when a disease alters the pharmacological effect of a drug. Eg : NSAIDs + Peptic ulcer disease → May worsen gastric irritation or cause bleeding Beta-blockers (e.g., propranolol) + Asthma → May worsen bronchoconstriction and trigger asthma attacks

14. iv. Drug-laboratory interaction : It occurs when a drug interferes with the accuracy or interpretation of laboratory test results, leading to false-positive or false-negative findings . Eg : Vitamin C (ascorbic acid) + Glucose urine test High doses of vitamin C can interfere with urine dipstick test, masking the presence of glucose in diabetic patients.

15. Factors affecting drug interaction : Multiple drug therapy : Mutiple prescribers Multiple diseases Poor patient compliance Advancing age of patient Drug related factors

16. 1. Multiple Drug Therapy : When a patient is prescribed several drugs (polypharmacy), the risk of drug-drug interactions, side effects, and medication errors increases. Eg : A diabetic patient taking insulin, metformin, antihypertensives , and statins may experience hypoglycemia or kidney issues due to combined effects .

17. 2. Multiple Prescribers : When multiple doctors prescribe medications without knowledge of the patient’s current drug list, it may lead to duplicate therapy, interactions, or conflicting medications . Eg : A cardiologist and a general physician may both prescribe NSAIDs or anti-hypertensives , leading to overdose or interaction.

18. 3. Multiple Diseases : Comorbidities ( e.g : diabetes + hypertension + kidney disease) require complex medication regimens, increasing the chance of complications or contraindications . Eg : NSAIDs + hypertensive patient + chronic kidney disease can worsen kidney function.

19. 4. Poor Patient Compliance: When patients forget, skip, or misuse their medications, it can lead to treatment failure or rebound symptoms, sometimes causing hospitalization . Eg : A patient not regularly taking antiepileptic drugs may have breakthrough seizures.

20. 5. Age of Patient: Elderly patients often have reduced kidney and liver function, which affects drug metabolism and excretion, making them more sensitive to drugs and side effects. Eg : Older adults are more prone to falling due to sedative effects of benzodiazepines.

21. 6. Drug-Related Factors : Some drugs have narrow therapeutic windows, require monitoring, or have complex dosing. Eg : Drugs like warfarin (requires INR monitoring) or digoxin (narrow safety range) need precise dosing and monitoring to avoid toxicity.