True: Antacids taken within 2 hours of taking phenothiazines decrease their absorption, reduce their plasma concentrations and hence reduce their therapeutic effects (Kaplan et al 2000, p. 128; King 2004, p. 652).

True: Caffeine can cause and worsen anxiety and can precipitate panic attacks. Caffeine in high doses antagonizes the anxiolytic effects of benzodiazepines by reducing their receptor binding (Taylor et al 2005, p. 351).

True: Carbamazepine decreases serum concentrations of aripiprazole, clozapine, haloperidol, olanzapine, risperidone and ziprasidone by inducing cytochrome P450 3A4. This effect is particularly important for haloperidol (Sadock & Sadock 2005, p. 2734).

False: Cimetidine inhibits cytochrome P450 enzymes CYP 1A2, 2C19 and 3A. This inhibits the metabolism leading to increased plasma levels of tricyclic antidepressants, SSRIs, carbamazepine, valproate and antipsychotics (BNF 2005, Appendix 1; Cookson et al 2002, p. 58; King 2004, pp. 357, 640; Sadock & Sadock 2005, p. 2121).

False: Pharmacokinetic interactions occur when a drug alters the absorption, distribution, metabolism or elimination of a second drug.

In pharmacodynamic interactions, a target action is altered by a second drug operating on the same target receptor. Hence, the interaction between alcohol and diazepam resulting in increased sedation and impaired psychomotor performance is pharmacodynamic (Johnstone et al 2004, p. 303; King 2004, p. 60).

False: Disulfiram inhibits the enzyme acetaldehyde dehydrogenase resulting in the accumulation of acetaldehyde. Acamprosate (citrated calcium carbamide) is a GABA agonist and glutamate antagonist. Combined treatment with disulfiram and acamprosate may have better outcome than either treatment alone. Acamprosate does not interact with disulfiram (Gelder et al 2000, p. 501).

False: Enalapril and other angiotensin-converting enzyme inhibitors increase serum lithium levels by reducing lithium clearance. They increase the risk of lithium toxicity, especially in the elderly.

Thiazide and other diuretics which deplete sodium also raise lithium levels.

Nonsteroidal anti-inflammatory drugs such as indomethacin, and, to a lesser extent, ibuprofen, naproxen, aspirin and sulindac, increase lithium levels.

Osmotic diuretics, acetazolamide, triamterene, methylxanthines and drugs which raise the glomerular filtration rate lower lithium levels (Bazire 2005, p. 322; Kaplan et al 2000, p. 145).

False: Aminophylline, theophylline and caffeine increase lithium excretion and reduce lithium levels. Aminophylline and theophylline may reduce lithium levels by 20–30%. This effect has been used to treat lithium toxicity (Bazire 2005, p. 326; Kaplan et al 2000, p. 145).

True: Metronidazole causes a disulfiram-like reaction with alcohol. The symptoms include facial flushing, throbbing headache and palpitations (BNF 2005, 4.10, 5.1.11).

True: Halothane and enflurane may interact with MAOIs and cause muscle stiffness and hyperpyrexia. MAOIs can interact hazardously with general anaesthetics. Hence, MAOIs should ideally be stopped 2 weeks before surgery. However, general anaesthesia can be attempted in patients on MAOIs in an emergency (BNF 2005, Appendix 1; Stein & Wilkinson 1998, p. 188).

False: Non-nicotine chemicals, such as aromatic hydrocarbons in tobacco smoke, activate cytochrome P450 enzyme CYP 1A2 and thereby decrease the levels of clomipramine, clozapine, desipramine, doxepin, fluvoxamine, haloperidol, imipramine, nortriptyline, oxazepam and propranolol. The levels of haloperidol, clozapine and fluvoxamine increase 30–40% with abstinence (Cookson et al 2002, p. 58; Sadock & Sadock 2005, p. 1260; Stein & Wilkinson 1998, p. 160).

True: TCAs enhance antihypertensive effect of hydralazine and nitroprusside.

TCAs, however, inhibit the antihypertensive effects of adrenergic neuron blocking agents, e.g. guanethidine, by blocking their uptake into the sympathetic nerve terminal.

TCAs also inhibit the antihypertensive effects of methyldopa and clonidine. The mechanism remains unknown (BNF 2005, Appendix 1; King 2004, p. 210; Stein & Wilkinson 1998, p. 160).

True: Chronic use of alcohol induces hepatic isoenzymes and may lower tricyclic levels.

Acute ingestion of alcohol can reduce first-pass metabolism by competition, resulting in 2–3 times higher tricyclic levels.

Chronic heavy alcohol consumption can impair hepatic function and elevate blood levels (Johnstone et al 2004, p. 272; King 2004, p. 638; Sadock & Sadock 2005, p. 2963).

False: Tricyclic antidepressants enhance the depressant effects of alcohol, including sedation and impairment of psychomotor performance, by the mechanism of summation (Bazire 2005, p. 363; BNF 2005, Appendix 1; King 2004, p. 638).

True: Antidepressants, including TCAs, interact with sympathomimetics like adrenaline to cause hypertension and ventricular arrhythmias by summation (BNF 2005, Appendix 1; King 2004, p. 640).

True: Barbiturates induce cytochrome P450 CYP 3A4 and, consequently, increase the metabolism and hence reduce the serum levels of amitriptyline, desipramine, protriptyline and nortriptyline by 14–60%. Pentobarbital may affect nortriptyline metabolism within 2 days, both when starting (induction) and on discontinuation. Moreover, tricyclics lower seizure threshold (Bazire 2005, p. 292; Cookson et al 2002, p. 58).

True: Carbamazepine and phenytoin induce CYP 3A4 and 1A2, and increase the metabolism and decrease plasma levels of clozapine by up to 50%. When carbamazepine is stopped, clozapine levels may double.

Clozapine lowers seizure threshold and hence can compromise the antiepileptic effect of carbamazepine.

Both clozapine and carbamazepine can cause agranulocytosis and the combination is associated with an enhanced risk (Bazire 2005, p. 328; King 2004, p. 650; Sadock & Sadock 2002, p. 1073).

False: Fluoxetine inhibits CYP 2D6 markedly and 1A2 and 3A moderately. Clozapine is metabolized by CYP 1A2, 2D6 and 3A4. Therefore, fluoxetine increases clozapine levels. Fluvoxamine causes an even greater increase in clozapine levels (Bazire 2005, p. 284; BNF 2005, Appendix 1; King 2004, p. 635; Sadock & Sadock 2005, p. 2704).

True: Grapefruit juice is a powerful inhibitor of CYP 1A2 and 3A4 in the gut mucosa. It increases the plasma levels of buspirone and, possibly, benzodiazepine and sildenafil (BNF 2005, Appendix 1; Cookson et al 2002, p. 58; Sadock & Sadock 2005, pp. 2788, 2889; Stein & Wilkinson 1998, p. 177).

False: In patients treated with thiazide diuretics and chlorthalidone, the proximal tubules attempt to compensate for sodium loss by increasing the reabsorption of sodium. As the proximal tubule cannot differentiate between sodium and lithium, lithium reabsorption is also increased. This, coupled with fluid loss in diuresis, concentrates lithium in the blood and increases the risk of toxicity. They should be used only when other choices are not available and with strict monitoring.

The risk is much lower with frusemide, a loop diuretic, which inhibits the reabsorption of sodium and lithium in the proximal tubule as well as elsewhere in the nephron.

Potassium sparing diuretics such as spironolactone and triamterene may also increase lithium concentration. The risk is much lower with amiloride which, in fact, may be used to treat lithium-induced polyuria.

Carbonic anhydrase inhibitors such as acetazolamide, osmotic diuretics such as mannitol and urea, and xanthine alkaloids such as caffeine and theophylline all increase the excretion of lithium and hence lower serum lithium levels.

Frusemide may be the safest diuretic with lithium (Bazire 2005, p. 323; Cookson et al 2002, p. 335).

False: Unlike most antidepressants, reboxetine has little inhibitory effect on the cytochrome P450 system (Johnstone et al 2004, p. 280).

True: Fluoxetine and fluvoxamine inhibit cytochrome P450 enzymes CYP 3A4 and 2C9 respectively and increase the plasma concentration of carbamazepine (Bazire 2005, p. 634; BNF 2005, Appendix 1).

False: Chlorpromazine increases the level of TCAs by inhibiting CYP 1A2 and 2D6. TCAs do not increase the levels of chlorpromazine (Bazire 2005, p. 292; King 2004, p. 639; Stein & Wilkinson 1998, p. 160).

True: Clonidine is an a₂-adrenoceptor agonist. It is used to treat hypertension, migraine and menopausal flushing. TCAs antagonize the hypotensive effects of clonidine (Bazire 2005, p. 293; BNF 2005, Appendix 1; Kaplan et al 2000, p. 34).

True: Fluoxetine increases plasma levels of diazepam by inhibiting CYP 2C19 and CYP 3A3/4 (Cookson et al 2002, p. 58; Gelder et al 2006, p. 547; King 2004, p. 452).