Adverse reactions drug metabolising enzyme

Johnson TN. The development of drug metabolising enzymes and their influence on the susceptibility to adverse drug reactions in children. Toxicology. 2003 192 37-48. 

Overdose relative to a particular patient. Adverse reactions may be explained by the way drugs are metabolised in phenotypically different sub-sets the population. There are, for example, differences in the way that some drugs are metabolised by the liver microsomal enzymes (dealt with elsewhere), which alter the kinetics of the drug and its metabolites. Special care must be taken with such drugs and interactions with other drugs. 

The main problems with early, irreversible MAOIs were adverse interactions with other drugs (notably sympathomimetics, such as ephedrine, phenylpropanolamine and tricyclic antidepressants) and the infamous "cheese reaction". The cheese reaction is a consequence of accumulation of the dietary and trace amine, tyramine, in noradrenergic neurons when MAO is inhibited. Tyramine, which is found in cheese and certain other foods (particularly fermented food products and dried meats), is normally metabolised by MAO in the gut wall and liver and so little ever reaches the systemic circulation. MAOIs, by inactivating this enzymic shield, enable tyramine to reach the bloodstream and eventually to be taken up by the monoamine transporters on serotonergic and noradrenergic neurons. Fike amphetamine, tyramine reduces the pH gradient across the vesicle membrane which, in turn, causes the vesicular transporter to fail. Transmitter that leaks out of the vesicles into the neuronal cytosol cannot be metabolised because... 

The adverse effect profile of roflmnilast has been described previously. However, new data became available recently. A systematic review smnmarised the available data on adverse effects and drug reactions of roflmnilast. This systematic review was based on six clinical trials with a total population of 9102 COPD patients, with the study duration ranging between 24 and 52 weeks [89 ]. Roflmnilast is metabolised by CYP 3A4, CYP 2C19 and CYP 1A2. Inhibitors of these enzymes such as erythromycin or ketoconazole were shown to increase the activity and half-life of roflumilast. In contrast, drugs that induced these enzymes, like rifampicin, had the opposite effect, reducing the activity and half-life of roflumilast. Roflumilast did not significantly interact with montelukast, budesonide, or antacids. 

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