5 Pharmacogenetic interactions Pathways of drug metabolism CYP

5. Pharmacogenetic interactions.

Pathways of drug metabolism CYP 450

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.

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.

Antagonistic Interactions • When the effects of two drugs are opposite. • EX : Warfarin and vitamin K

Herbal - drug interactions St john’s wort and Ciclosporin

Food - drug interactions • 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

Drug-Food interactions • • Grapefruit juice and Terfenadine Grapefruit juice and cyclosporin Grapefruit juice and felodipine Grapefruit contains : furanocoumarin compounds that can selectively inhibit CYP 3 A 4

Patients in high risk of drug interactions • • Polypharmacy people (elder) Hepatic disorders Renal disorders Genetic factors

Pharmacogenetics Pharmacogenomics Pharmacology + Genetics/Genomics • The study of how individual’s genetic inheritance affects the body’s response to drugs (efficacy & toxicity( • The use of genetic content of humans for drug discovery

Variations in drug response and drug toxicity may result from Variation in drug metabolizing enzymes • Cytochromes P 450 • Thiopurine S-methyltransferase Variation in drug targets • Beta 2 -adrenergic receptor • ACE • Dopamine receptor Variation in drug transporters • P-glycoprotien Variation in disease modifying genes • Apolipoprotein (APOE(

Thiopurine Smethyltransferase Caucasians & Asians 0. 3% Azathioprine 6 -Mercaptopurine 6 -Thioguanine

References • Stockley’s Drug Interactions 9 th E Book. • Color Atlas of Pharmacology 3 rd E book.

THANKS TO ALL