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Drug interaction final edition -- animated
- 1. Drug Interactions By: Ahmed Omar
- 2. Review Definitions. Types. Mechanisms. High risk patients. How to handle an interaction?! Resources.
- 3. Definition An interaction is said to occur when the effects of one drug are changed by the presence of other drug, herb, food, drink. An interaction occurs when pharmacokinetics or pharmacodynamics of drug are changed.
- 4. Types Drug - drug interactions. Herbal - drug interactions. Food - drug interactions. Drink - drug interactions. Pharmacogenetic interactions.
- 5. Mechanisms Pharmacokinetics : Absorption interactions Distribution interactions Metabolism interactions Excretion interactions Pharmacodynamics : Synergistic interactions Antagonistic interactions
- 6. Absorption interactions Two important items we should consider: ( rate of absorption and absorbed amount ) - Rate of adsorption is not clinically important in multiple doses e.g. anticoagulants. - But in single doses we should reach therapeutic level rapidly e.g. hypnotics and analgesics.
- 7. Absorption interactions Mechanisms : Altered PH. Altered bacterial flora. Formation of insoluble complexes. Altered GIT motility.
- 8. 1- altered PH Some drugs are absorbed from stomach (acidic media), so when this media become neutral or alkaline, this will affect the absorption of drug. Ex : - antacid and ciprofloxacin
- 9. 2- Altered bacterial flora Bacterial flora has a marked role in metabolization of some drugs. Long term antibiotics may kill normal flora and affect drug absorption. Ex : erythromycin and digoxin
- 10. 3-Formation of insoluble complexes Ex : Tetracycline and quinolones with divalent and trivalent e.g. Ca , Al …etc
- 11. 4- Altered GIT motility Some drugs increase peristalsis and decrease time of absorption and absorbed amount. Ex : Prokinetic
- 13. Distribution interactions There is an important factor : Vd Protein binding interactions : - unbound molecules remain free and pharmacological active. - bound molecules are pharmacological inactive. Some drugs may compete others for binding to protein depending on affinity and concentration.
- 14. Distribution interactions cont. Only drugs with low Vd will be affected. Ex : Warfarin (99% bound) and Phenytoin (90% bound)
- 15. Metabolism (biotransformation) Most drugs are chemically altered within Liver to less toxic and less lipid- soluble metabolites. Hepatic metabolism has two pathways : ◦ Phase 1 (modification) ◦ Phase 11 (conjugation)
- 16. Pathways of drug metabolism CYP450
- 17. Metabolism cont. CYP450 most important isoenzymes responsible for liver metabolism. ◦ CYP 3A4 ◦ CYP 2D6 ◦ CYP 2C8
- 18. Metabolism cont. Types of drug metabolism interaction : ◦ Enzyme induction ◦ Enzyme inhibition
- 19. Enzyme Induction St john's wort increase metabolism of ciclosporin by inducing CYP 3A4.
- 20. Rifampicin increase metabolism of Ciclosporin by inducing CYP 3A4
- 21. Enzyme Induction Notes: ◦ Onset of enzyme induction is slow (days – 2weeks). ◦ Also slow to solve. ◦ We can overcome this problem by increase the dose
- 22. Enzyme Inhibition Most common than enzyme induction. This interaction decrease drug metabolism and so increase its concentration in serum. It takes 2-3 days EX : Ritonavir inhibit metabolism of sildenafil by inhibiting CYP 3A4
- 24. Notes : ◦ If serum levels within therapeutic ranges so it is not clinically important. ◦ Some drugs can be metabolized by more than one of CYP450 isoenzymes, so the reaction may be not clinically important.
- 25. Excretion Most drug are excreted in Urine or Bile. Some drugs are reabsorbed from renal tubules or enterohepatic recirculation. Some drugs are excreted in acidic urine, so changing urine PH will affect there serum level. These interaction is rare.
- 26. Excretion Mechanisms : ◦ Altered urine PH ◦ Change in active tubular secretion. Some drugs may compete for excretion. E.g. probenecid and penicillin. ◦ Enterohepatic recirculation. E.g. penicillins and oral contraceptives.
- 28. Pharmacodynamics interactions they occur when the effects of a drug are changed due to presence of another drug at its site of action either directly (on the same receptor) or indirectly (on different receptor). Two types : ◦ Synergistic interactions. ◦ Antagonist interactions.
- 29. Synergistic interactions When two drugs have the same effect are given together, so the total effect will increase. It may be desired : ◦ e.g. sulfonamides and trimethoprim. May be not desired : ◦ e.g. K-sparing drugs (ACEIs , K-sparing diuretics) and K-supplement >> cause hyperkalemia.
- 30. Antagonistic Interactions When the effects of two drugs are opposite. EX : Warfarin and vitamin K
- 31. Herbal - drug interactions
- 32. St john’s wort and Ciclosporin Explained
- 33. Food - drug interactions
- 34. Liquorice Liquorice contain glycyrrhizin (glycyrrhizinic or glycyrrhizic acid) Glycyrrhizinic acid is hydrolyzed in the intestine to pharmacologically active compound glycyrrhetic acid which inhibit 11 betahydroxysteroid dehydrogenase. This increase cortisol in kidney and act as aldosterone (fluid retention, hypokalemia, hypertension) Ex: ◦ Liqourice and antihypertensive
- 35. Patients in high risk of drug interactions Polypharmacy people (elder) Hepatic disorders Renal disorders Genetic factors
- 36. How to handle an interaction?! If the previous solutions don’t work ?!!! Adjust drug dosage with monitoring of drug level and physiological functions Is the the interaction clinically important?! No Yes Using the dose space will solve the interaction?! Yes No Using alternative will solve the interaction?! Yes No
- 37. Resources
- 39. Tables of Drugs
- 42. References Stockley’s Drug Interactions 9th E Book. Color Atlas of Pharmacology 3rd E book. Material of Dr. Mohamed Emam. Notebook of drug interaction of pharmacology department-Benisuef pharmacy faculty.