1. English version

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

3. 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

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

5. 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

6. 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

7. 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

8. 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/
2/ Micromedex:
micromedex, 3.LF

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

10. Pharmacokinet. interactions : other quiz questions or case study
A/ simvastatin or lovastatin + Klacid SR (clarithromycin) = ?
Demonstration: 1/
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?

11. 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 =?

12. 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.

13. 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)

14. 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