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Glyceryl Trinitrate - page 5
Keywords: GTN, Glyceryl trinitrate, Nutrition and Energy
By Einstein10 on 30/12/2009
Level: Foundation Degree
Page Number: 5 of 6 pages: 1 2 3 4 5 6CYP1A2 catalyses the 3-demethylation of 1, 3-dimethylxanthine, which produces 1-methylxanthine. The 1-methylxanthine is not directly excreted into the urine. Instead it is catalysed by xanthine oxidase and undergoes rapid 8-oxidation to form 1-methyluric acid.
Secondly, as well as CYP1A2 catalysing the 3-demethylation of 1,3-dimethylxanthine to produce 1-methylxanthine, the Cytochrome P450 enzyme also catalyses the 1-demethylation, of 1,3-dimethylxanthine which forms 3-methylxanthine. This metabolite is excreted in the urine, unchanged. The CYP2E1 also catalyses 8-hydroxylation reaction. CYP1A1 is also an important enzyme. CYP2D6 only shows a minor role.
7. Why is the half-life of theophylline longer in premature infants and neonates than normal adults (5 marks) ?
8. Why is the half-life of theophylline shorter in young children than adults? What are the consequences for drug administration (5 marks) ?
9. Explain why clearance of theophylline is increased in smokers (6 marks).
10.
10. Smoking is also the major cause of lung cancer. Show how metabolism is involved in the production of carcinogenic products from polycyclic hydrocarbons in tobacco smoke. (5 marks)
11. What would the effect of taking rifampicin, an antibiotic, with the contraceptive pill? Explain your answer (6 Marks).
CYP 3A4 is the major form of Cytochrome P450 in the liver. It is also present in the small intestine and
is responsible for the metabolism of a wide range of drugs and steroid hormones. Interactions between
drugs metabolised by CP3A4 can lead to serious side effects and fatalities.
12. Which are the main inhibitors of CYP3A4 (8 marks) ?
Hyperforin (constituent of St Johns Wort)
Protease inhibitors- ritonavir,indinavir and nelfinavir
Nefazodone- (5-HT2A receptor antagonist)
Macrolide antibiotics- erythromycin,telithromycin and clarithromycin
Grapefruit juice (Bergamottin) Cimetidine-H2-receptor antagonist
Aprepitant (Substance P antagonist, NK1 receptor antagonist)
Azole antifungals- fluconazole, ketoconazole ,itraconazole
Quercetin Calcium channel blockers- verapamil , Diltiazem
Terfenadine, a non-sedating antihistamine, is extensively cleared by extensive first-pass metabolism. It is highly protein bound and peak plasma concentrations are reached within 1 hour of administration. After a 60 mg dose the peak plasma concentration of terfenadine is ~ 1.5 ng/ml and its elimination half-life is around 20 hours. The metabolism of terfenadine is shown below.
13. Indicate on the diagram above what reactions are involved in terfenadine metabolism and which enzymes are likely to be involved (7 marks).
Terfenadine was widely prescribed, worldwide, until a low number of serious cardiovascular side effects were noted after which the drug was withdrawn from the market. These included QT prolongation, torsade de pointes leading to serious ventricular
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