Drug_Interactions [Autosaved].pptx pharmacology

Drug_Interactions [Autosaved].pptx pharmacology

1. Drug Interactions Mr Collins lagat

2. Drug – Drug interaction It is the modification of the effect of one drug (the object drug) By The prior or concomitant administration of another drug (precipitant drug).

3. Outcomes of drug interactions Desired (Beneficial Effects) Undesired (Harmful Effects)

4. Risk Factors High Risk Patients: Elderly, young Very sick Multiple diseases Multiple drug therapy Renal, liver impairment

5. Risk Factors High Risk Drugs Narrow therapeutic index - digoxin , warfarin Enzyme inhibitors or inducers

6. Site of Interaction Outside the body. Inside the body.

7. Outside the body Incompatibilities: reaction of IV drugs resulting in solutions after mixing that are no longer safe. alter stability or structure leading to: Loss of drug activity. Formation of precipitates. Development of toxic product.

8. Penicillin and aminoglycoside : formation of inactive complex. Protamine zinc insulin + soluble insulin: reduced efficacy of soluble insulin. Calcium + ceftriaxone : precipitates in the lung and kidneys .

9. Inside the body Pharmacokinetics drug interactions Pharmacodynamics drug interactions

10. Pharmacokinetic Drug Interactions Involve the effect of a drug on another from the point of view that includes: Absorption. Distribution. Metabolism. Excretion.

11. Interaction at Site of Absorption Formation of drug chelates or complexes. Altered gut flora Altered GIT motility. Altered pH. Drug induced mucosal damage. Malabsorption caused by other drugs.

12. Formation of Drug Chelates or Complexes Ca 2+ , Fe 2+ , antacids (Al/ Mg hydroxide) + tetracycline = insoluble complex Levothyroxine , digoxin , warfarin + Cholestyramine = decrease absorption.

13. Altered Gut Flora Antibiotics kill a large number of the normal flora of the intestine. Increase digoxin concentration and toxicity (40% of the dose is metabolised by intestinal flora).

14. Altered Gut Motility Slowing of gastric emptying by anticholinergics and opiate analgesics. Delayed absorption of acetaminophen when combined with an anticholinergic .

15. Altered pH The non-ionized form of a drug is more lipid soluble and more readily absorbed from GIT than the ionized form. H 2 blockers, antacids + ketoconazole = d ecreased gastric acid, dissolution of ketoconazole is decreased, resulting in reduced absorption

16. Drug induced Mucosal Damage Colchicine (causes local mucosal damage) can decrease absorption of poorly absorbed drugs ( phenytoin ).

17. Malabsorption by other drugs. Orlistat inhibits pancreatic lipases (preventing hydrolysis of ingested fat) leading to malabsorption of fat soluble vitamins (A, D, E, K).

18. Effect of Drug Distribution Displacement from plasma protein binding: depends on the affinity of the drug to plasma protein. most likely bound drugs displace other drugs (increased free drug). sodium valproate displaces phenytoin from its binding site on plasma albumin.

19. Effect of Drug Distributiom Displacement from tissue binding: Quinidine displaces digoxin from its tissue binding site increasing concentration of free digoxin .

20. Effect on Drug Metabolism Enzyme induction : A drug may induce the enzyme that is responsible for the metabolism of another drug or even itself. Carbamazepine increases its own metabolism. Phenytoin increases metabolism of oral contraceptives leading to reduced levels and failed contraception.

21. Important enzyme inducers : Carbamazepine . Phenytoin . Phenobarbital. Rifampicin .

22. Enzyme Inhibition Decrease of the rate of metabolism of a drug by another one. Increase of the concentration of the target drug and its toxicity. C imetidine reduces the clearance of theophylline causing an increase of its adverse effects.

23. Quinolones inhibit oxidative metabolism of theophylline . Inducer ( carbamazepine ) + Inhibitor ( verapamil ) = Effect of the Inhibitor will predominant.

24. Important enzyme Inhibitors: Cimetidine . Erythromycin. Quinolones . Sodium valproate .

25. Alterations in Renal Clearance Increase in renal blood flow. Inhibition of active tubular secretion. Alterations in tubular reabsorption .

26. Increase in Renal Blood Flow Hydralazine increases the renal clearance of digoxin .

27. Active Tubular Secretion Occurs in the proximal tubules. A drug combines to the transport protein that is responsible for active transport of another drug. This will reduce drug excretion, increasing its concentration. Probenecid decreases tubular secretion of penicillin.

28. Passive Tubular Reabsorption Acidification of urine: increases reabsorption and decreases excretion of weak acids decreases reabsorption of weak bases. Alkalinization of urine has the opposite effect.

29. Passive Tubular Reabsorption These principles are used in cases of overdose Sodium bicarbonate decrease reabsorption of and increase excretion of salicylates (weak acid).

30. Pharmacodynamic Interaction Are related to the pharmacological activity of the interacting drugs. Both drugs act on the target site of clinical action.

31. Results of Pharmacodynamic Interactions Synergism: Occurs when the effects of 2 drugs increase the action of another drugs Summation(Additive): 1 + 1 = 2 β- adrenoceptor blocker + thiazide = additive anti hypertension effect Potentiation : 1 + 1 = >2 Trimethoprim + sulfamethaxazole

32. Results of Pharmacodynamic Interactions Antagonism: Action of one drug opposes the action of another. 1 + 1 = 0 Histamine and Adrenaline on bronchi (physiological antagonism). Flumazenil and diazepam compete reversibly for the same drug receptor(competitive antagonism)

33. Action on Body Systems NSAIDs lead to loss of antihypertensive efficacy of α - adrenoceptor blocker By inhibiting production of vasodilator prostaglandins leading to sodium retention at the kidney level.

34. Onset May be seconds to weeks. Enzyme induction requires weeks due to protein synthesis. Enzyme inhibition occurs rapidly.