Bisoprolol. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in hypertension and angina pectoris.

Bisoprolol is a beta 1-adrenoceptor antagonist with no partial agonist (intrinsic sympathomimetic) activity or membrane stabilising (local anaesthetic) activity. The oral bioavailability of bisoprolol is high (90%) and the drug has a long elimination half-life which allows once-daily administration; in addition, it is hepatically and renally cleared in equal proportions. In non-comparative studies, and comparative trials, bisoprolol proved effective, and as efficacious as atenolol, low doses of metoprolol, diuretics and nifedipine SR in hypertension, and atenolol and verapamil in stable angina pectoris. Bisoprolol has been well tolerated in most patients. Thus, bisoprolol is an effective alternative to other beta-adrenoceptor antagonists in patients with mild to moderate essential hypertension or stable angina pectoris. Furthermore, its unique pharmacokinetic properties may offer advantages in selected patients. However, the results of further comparative studies with established agents in the treatment of hypertension and angina pectoris are still awaited so that a final assessment of the relative place in therapy of bisoprolol in these disease states may be made.

Lisinopril. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in hypertension and congestive heart failure.

Lisinopril is an orally active angiotensin-converting enzyme (ACE) inhibitor which at dosages of 20 to 80 mg once daily is effective in lowering blood pressure in all grades of essential hypertension. It is at least as effective as usual therapeutic dosages of hydrochlorothiazide, atenolol, metoprolol and nifedipine while direct comparisons with other ACE inhibitors have not been reported. Many patients achieve an adequate blood pressure reduction with lisinopril alone, and in those who do not, most will with the addition of hydrochlorothiazide; lisinopril also attenuates hypokalaemia induced by thiazide diuretics. In patients with congestive heart failure resistant to conventional therapy, lisinopril 2.5 to 20 mg once daily improved indices of cardiac function and appeared to produce greater benefit than captopril in one controlled study. Lisinopril is well tolerated, with few serious adverse effects being reported. Thus, lisinopril is a suitable treatment for essential hypertension and shows promise in the treatment of congestive heart failure. If additional studies confirm these preliminary findings, then lisinopril will have a similar profile of indications to other ACE inhibitors, and like some other drugs in this class it offers the convenience of once daily administration.

Lofepramine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in depressive illness.

Lofepramine is a tricyclic antidepressant that is structurally similar to imipramine and is extensively metabolised to desipramine. In the absence of other major pharmacological effects it appears that its antidepressant activity stems from the facilitation of noradrenergic neurotransmission by uptake inhibition, and possibly by the additional facilitation of serotoninergic neurotransmission. The overall therapeutic efficacy of lofepramine is comparable to that of imipramine, amitriptyline, clomipramine, maprotiline and mianserin in patients with depression of varying severity, and coexisting anxiety. Dry mouth is the most commonly reported side effect of usual therapeutic doses of lofepramine, but the incidence of this and other anticholinergic side effects is less among patients treated with lofepramine than with imipramine. Lofepramine has not been associated with adverse effects on cardiac function even in cases of attempted suicide by overdose. Thus, providing its apparent favourable side effect profile is confirmed in practice, lofepramine may be a valuable alternative for treatment of the depressed patient where a tricyclic is indicated.

Dothiepin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in depressive illness.

Dothiepin is a tricyclic antidepressant that is structurally related to amitriptyline. It appears that the antidepressant activity of dothiepin is mediated through facilitation of noradrenergic neurotransmission by uptake inhibition and possibly also by enhancement of serotoninergic neurotransmission. The overall therapeutic efficacy of dothiepin is very similar to that of amitriptyline. In addition, dothiepin appears to be comparable to imipramine, doxepin, maprotiline, mianserin, fluoxetine, fluvoxamine and trazodone. Dry mouth is the most commonly reported side effect of therapeutic doses but the incidence of this and other anticholinergic side effects is less among patients treated with dothiepin than with amitriptyline. However, the sedative/anxiolytic activity of dothiepin is similar to that of amitriptyline. Dothiepin has not been associated with cardiotoxicity at therapeutic doses. Thus, many years of extensive clinical use have shown that dothiepin is now an established and effective antidepressant in both inpatients and outpatients with depressive symptoms of varying severity and coexisting anxiety. Its therapeutic equivalence to other tricyclics ensures its place as a treatment alternative in these disorders.