Interactions with other drugs

Compounds that may increase the hypoglycaemic effect of sulphonylureas and cause a reduction in their dosage requirement include antibiotics and 

Compounds that may diminish the hypoglycaemic effect and thus cause an increase in the dosage requirement of sulphonylurea include rifampicin (Syvalahti et al., 1974). There is a theoretical risk of a diminished hypoglycaemic effect with corticosteroids and with oral contraceptives. It has been stated that the absorption of glibenclamide from the gastrointestinal tract may be reduced if it is taken together with guar gum. 

The elimination of renally excreted sulphonylureas (e.g. carbutamide, chlorpropamide, glisoxepide) may be diminished by probenecide and salicylates. 

It is considered that any interaction between sulphonylureas and Ca2+-channel blockers such as nifedipine and verapamil is not significant. 

Instead of first-generation sulphonylureas, second-generation drugs must be preferred in cardiac glycoside-treated diabetics (Ballagi-Pordany et al., 1989). In rabbits and rats, glibenclamide decreased, while tolbutamide and carbutamide increased, strophantidin toxicity and myocardial ischaemia-induced transitory ventricular fibrillation in a dose-dependent manner (Pogatsa et al., 1988). 

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Clinical Particulars (therapeutic indications, administration, contraindications, special warnings and precautions, interaction with other drugs, use in pregnancy or lactation, effects on driving, undesirable effects, overdose)... 

There is no shortage of AEDs (Fig. 16.7) but it is not appropriate to consider them in detail in this text other than to see how their mechanisms of action comply with and illustrate those proposed above (Fig. 16.6) for the control of epileptic seizures (see Meldrum 1996 Upton 1994). The decision on which drug to use depends not only on their proven efficacy in a particular type of epilepsy (some drugs are inactive in certain forms) but also what side-effects they have—many are sedative — how they interact with other drugs and how often they need to be taken. Compliance is a problem over a long period if dosing is required more than once a day. It is probably acceptable in reality, if not scientifically, to divide the drugs into old-established AEDs and new AEDs. Only the latter have been developed chemically to modify the known synaptic function of the amino acids. 

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... 

Carbamazepine may interact with other drugs by inducing their metabolism. Valproic acid increases concentrations ofthe 10,11-epoxide metabolite without affecting the concentration of carbamazepine. The interaction of erythromycin and clarithromycin (CYP3A4 inhibition) with carbamazepine is particularly significant. 

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