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Glyceryl Trinitrate - page 4
Keywords: GTN, Glyceryl trinitrate, Nutrition and Energy
By Einstein10 on 30/12/2009
Level: Foundation Degree
Page Number: 4 of 6 pages: 1 2 3 4 5 6or small intracellular/Para cellular channels which mean that Suxamethonium is very poorly absorbed. Thirdly, Suxamethonium has a pH value of 4 with a pKa value of 8 making it a weak base. We can use the following equation to sow the dissociation of a weak base where the ionised form BH+ is impermeable.
B + H+ BH+
From the Henderson Hassel back equation it can be shown that:
pKa−pH log [BH+]
[B]
where [BH+] and [B] are the concentrations of the ionized and non-ionised forms and the pKa is the pH value when [BH+]=[B]. Therefore, after oral administration the pKa value of Suxamethonium would be 8 and the pH of the stomach would be 2 meaning that 100% of the Suxamethonium would be in the ionized form [BH+]. This would mean that 0% of Suxamethonium would be in its non-ionized form and therefore none of it would cross the cell membrane of the stomach. With the same equation and with regards to the pH of the small intestine (pH 5.5) only 3% would be in the non-ionized form and only 3% of the Suxamethonium would cross the cell membrane of the small intestine.
Finally the special transport system for Suxamethonium does not exist either so the Suxamethonium salts are not completely absorbed giving unwanted affects. If this drug is given orally it passes straight through the intestine and into the faeces. This is the reason why Suxamethonium is not absorbed after oral administration and is normally given intravenously.
3. Why has suxamethonium a short duration of action (around 2-3 minutes) in most patients (4 marks) but an increased half-life in 1 in 3000 patients (7 marks)?
4. Using CYP2C9 as an example, explain what is meant by genetic polymorphism of drug metabolising enzymes (10 marks)
5. Which other isoenzymes of Cytochrome P450 exhibit genetic polymorphism? For each case give an example of a drug that would normally be metabolised by each isozyme and the clinical implications of genetic polymorphism (5 marks).
The half-lives of the anti-asthmatic drug, theophylline, in different patients are given in Table 1:
Table 1 -
Patient Half-life of Theophylline (Hours)
Premature Infants 14-57
Newborn Infants 19-24
Young Children 2-4
Normal adults 4-6
6. Show the main metabolic pathways of theophylline which occur in adults including in your answer the major metabolites and important enzymes (5 marks) ?
Theophylinne (1,3 Di-methylxanthine)
3-methylxanthine 1-methylxanthine 1-methyluric acid 1,3- dimethyluric acid
CYP1A2 catalyses both hydroxylation and demethylation and it is the most important enzyme for Theophylinne metabolism.
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