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What drugs undergo enterohepatal circulation What drugs undergo enterohepatal circulation? a/ tetracycline atibiotics b/ morphine

What can you expect, if your patient is a heavy smoker of tobacco What can you expect, if your patient is a heavy smoker of tobacco? Please, choose, only one correct answer. 1/ induction of biotransformation of some drugs 2/ decrease of drug metabolism 3/ it does not matter, nothing will happen

What can you expect after drinking grep juice with statins? a/ decrease of drug concentration b/ increase of statine concetration c/ nothing will happen

Majority of drugs that undergo biotransformation in liver by system cytochrome P450 enzymes are metabolized by? a/ 3A4 b/ 2D6 c/ 2E1 d/ 2C19 e/ 1A2

Practice general pharmacology III.yr.: med. students Pharmacokinetic interactions at the level of biotransformation and elimination of drugs Key words: Elimination of drugs Biotransformation System of cytochrome P450 Pharmacokinetic drug interactions

Elimination of drugs = metabolism + elimination Metabolism of drugs (biotransformation) increase of solubility in water and subsequently renal excretion in liver by microsomal enzymes oxidases – cytochrom P450: a/ induction of enzymes by St. Worth (tutsan,rose of sharon) rifampicin, carbamazepine or b/ inhibition of enzymes during application of antimycotic drugs like ketokonazol, fluconazol, itraconazol or macrolide ATB, or HIV protease inhibitors Excretion renal GIT a/ mucosa b/ gall – enterohepatal circulation 3. pulmonary: inhalatory anesthetics

Where to find info about drug interactions? Several possibilities I. SPC or PIL 1/ SPC – point 4.5, in section 4 clinical data II. Drug database 1/ AISLP a/ comercially available CD with programme b/ www.aislp.cz 2/ Micromedex: http://pez.cuni.cz, micromedex, 3.LF

Where to find info about drug interactions? III. Internet: 1/ www.uptodate.com 2/ pubmed.com 3/ www.drugs.com IV. Books 1/ PDR: physician desk reference 2/ Martindale : the complete drug reference

Pharmacokinet. interactions : other quiz questions or case study A/ simvastatin or lovastatin + Klacid SR (clarithromycin) = ? Demonstration: 1/ http://pez.cuni.cz, 2/ micromedex, 3/ 3.LF, micromedex, 4/ drug interactions B/ simvastatin or klaritromycin +grep juice? C/ sildenafil (Viagra) + grapefruit juice? D/ will it be OK to prescribe fluvastatin? E/ OK to prescribe another antibiotic instead of clarithromycin? Will you ask about smoking?

Quiz about other combinations levonoregestrel (Postinor) ? + other medicin. products? Tablets with extract of St. worth (Jarsin) + cyklosporin? Clarithromycine + solifenacine = ? grep +sildenafil nebo vardenafil antihistamine rupatadine, or loratadine/desloratadine with grapefruit juice? (contrariwise some other antihistamine drugs, like cetirizine, bilastine do not undergo biotransformation in liver) “toxicologic“ example: paracetamol + alcohol = ? Omeprazol+diazepam = Omeprazol+citalopram = ? NSAIDs +lithium = ? Fluvoxamine+ enoxacine =?

Genetic variability of PK 1/ azatioprin undergoes biotransform. by enzyme thiopurinmetyltransferase, if deficiency of this enzyme is present then it can be necessary to reduce dosis by 90% (the case of complete defic. of enzyme) 2/ genetic deficiency of CYP 2D6 leads in approximately 8% europeans to decrease of metabolizm of metoprolol, venlafaxine etc.

Interactions at the level of cyp P450 3A4 inhibition of CYP 3A4 1/ macrolide antibiotics claritromycin, erytromycin 2/ antimycotic ketokonazol, itrakonazol 3/ antivirotics inhibitors of HIV protease ritonavir/lopinavir induction CYP 3A4 1/ st. Worth extract (hypericum perforatum): CAVE can be present about 3 weeks after end of therapy a/ teas, food suppl. b/ medicinal product named Jarsin 2/ rifampicin 3/ carbamazepine (antiepileptic)

Intoxication by codeine (morphine) 62 yrs old patient used codein 25 mg 3 times daily, treatment with clarithromycine and voriconazole was started, leading to development of coma, respiratory depression, renal failure showed: Ultrarapid Metabolizer CYP2D6 with increased ability of codeine biotransformation to morphine