Tissue-type plasminogen activator. A review of its pharmacology and therapeutic use as a thrombolytic agent.

Coronary arterial thrombolysis is becoming an established treatment of acute myocardial infarction. If given early enough, it recanalises occluded coronary arteries, salvages myocardial function and reduces mortality. A reduction of mortality in patients with acute myocardial infarction has now been demonstrated for streptokinase, anisoylated plasminogen streptokinase activator complex (APSAC; anistreplase) and recombinant tissue-type plasminogen activator (rt-PA).

Probucol. A reappraisal of its pharmacological properties and therapeutic use in hypercholesterolaemia.

Probucol is a lipid-regulating agent structurally dissimilar to other known agents, with a unique pharmacodynamic and clinical profile. It is effective in the treatment of primary Type IIa and IIb hyperlipoproteinaemias, including polygenic (non-familial) hypercholesterolaemia and both heterozygous and homozygous forms of familial hypercholesterolaemia, with reductions in plasma total cholesterol and low density lipoprotein (LDL)-cholesterol levels of about 10 to 20% being attained. Marked effects on cutaneous and tendinous xanthomas have been observed, with significant regression often apparent after 2 or 3 months' therapy.

Labetalol. A reappraisal of its pharmacology, pharmacokinetics and therapeutic use in hypertension and ischaemic heart disease.

Since labetalol was first reviewed in the Journal (1978), its scope of therapeutic use has expanded and become better defined. Labetalol is an adrenoceptor blocking drug with combined alpha- and beta-blocking properties. These result in a more favourable haemodynamic profile for labetalol compared with 'pure' beta-blockers or pure alpha-blockers, but also contribute to a wider range, but not an overall increased incidence, of adverse effects.

Sultamicillin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use.

Sultamicillin is the tosylate salt of the double ester of sulbactam plus ampicillin. Sulbactam is a semisynthetic beta-lactamase inhibitor which, in combination with ampicillin, extends the antibacterial activity of the latter to include some beta-lactamase-producing strains of bacteria that would otherwise be resistant. The combination of sulbactam plus ampicillin for parenteral use has previously been shown to be clinically and bacteriologically effective in a variety of infections.

Tamoxifen. A reappraisal of its pharmacodynamic and pharmacokinetic properties, and therapeutic use.

Tamoxifen, a non-steroidal antioestrogen, represents a significant advance in treatment of female breast cancer. In trials of tamoxifen as postsurgical adjuvant treatment of early breast cancer, disease-free survival is consistently prolonged, representing an enhanced quality of life in association with tamoxifen's favourable adverse effect profile. Moreover, overview analysis indicates a survival benefit of approximately 20% at 5 years for all women, most clearly evident in women over 50 years, while a survival benefit independent of menopausal, nodal or oestrogen receptor status has been demonstrated in some individual trials.

Enalapril. An update of its pharmacological properties and therapeutic use in congestive heart failure.

Enalapril provides significant haemodynamic, symptomatic and clinical improvement when added to maintenance therapy with digitalis and diuretics in patients with congestive heart failure [NYHA (New York Heart Association) classes II to IV]. These effects are not attenuated during long term therapy. More significantly, a clinical study demonstrated that enalapril reduces mortality when added to established therapy in patients with severe congestive heart failure (NYHA class IV) refractory to digitalis, diuretics and other vasodilators.

Loratadine. A preliminary review of its pharmacodynamic properties and therapeutic efficacy.

Loratadine is a long acting antihistamine which has a high selectivity for peripheral histamine H1-receptors and lacks the central nervous system depressant effects often associated with some of the older antihistamines. Results from controlled clinical trials have shown that loratadine (usually 10mg once daily) is a well-tolerated and effective antihistamine which will be beneficial in patients with allergic rhinitis and chronic urticaria. It was found to be significantly superior to placebo, faster acting than astemizole and as effective as usual dosages of terfenadine, clemastine, mequitazine and azatadine in eliciting relief of symptoms.

Cisapride. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use as a prokinetic agent in gastrointestinal motility disorders.

Cisapride, a substituted piperidinyl benzamide chemically related to metoclopramide, is an orally administered prokinetic agent which facilitates or restores motility throughout the length of the gastrointestinal tract. Its novel mechanism of action is thought to involve enhancement of acetylcholine release in the myenteric plexus of the gut. Because of its specificity cisapride is devoid of central depressant or antidopaminergic effects; side effects such as diarrhoea or loose stools, which occur infrequently, are related to its primary pharmacological action.

Flumazenil. A preliminary review of its benzodiazepine antagonist properties, intrinsic activity and therapeutic use.

Flumazenil, a 1,4-imidazobenzodiazepine, is a specific benzodiazepine antagonist which is indicated for use when the effect of a benzodiazepine must be quickly attenuated or terminated. Following intravenous administration, the onset of clinically apparent benzodiazepine antagonism usually occurs within 1 to 5 minutes. Although flumazenil has a short elimination half-life of about 1 hour, a single intravenous dose of up to 1 mg is usually sufficient to attain and maintain for about 2 hours the desired level of consciousness after general anaesthesia or conscious to moderate sedation induced by benzodiazepines.

Clinical pharmacology and pharmacokinetic properties of topically applied corticosteroids. A review.

The development of topical corticosteroids since the 1950s has opened new doors for dermatologists previously faced with treating intractable dermatoses, so that the pharmacology of topically applied corticosteroids is now reasonably well described. Manipulation of the steroid molecule has produced compounds with greater lipophilicity, fewer mineralocorticoid properties and high potency. Potency is determined through various techniques, notably the vasoconstrictor assay as well as the mitotic index suppression method and atrophogenic potential assay.

Quazepam. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in insomnia.

Quazepam is a trifluoroethyl benzodiazepine hypnotic with a half-life of 27 to 41 hours, which has been shown to induce and maintain sleep in the short to long term (up to 4 weeks) treatment of patients with chronic or transient insomnia. Although its hypnotic efficacy has been well characterised against placebo, there are few clinical studies in comparison with established hypnotics, particularly over long term administration. However, preliminary evidence suggests that quazepam 15 to 30 mg is as effective as flurazepam and triazolam in usual therapeutic doses, and causes minimal rebound insomnia following its withdrawal, unlike rapidly eliminated benzodiazepines such as triazolam.

Enprostil. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in the treatment of peptic ulcer disease.

Enprostil, a synthetic analogue of prostaglandin E2, is effective in the treatment of patients with duodenal or gastric ulcers. As demonstrated in pharmacological studies in healthy volunteers and in patients with inactive ulcer disease, gastric acid secretion is suppressed by up to 80% for almost 12 hours after single doses of enprostil. The drug also reduces the secretion of pepsin, another 'aggressive' factor in peptic ulcer disease.

l-Carnitine. A preliminary review of its pharmacokinetics, and its therapeutic use in ischaemic cardiac disease and primary and secondary carnitine deficiencies in relationship to its role in fatty acid metabolism.

l-Carnitine occurs naturally as an essential cofactor of fatty acid metabolism which is synthesised endogenously or obtained from dietary sources. In patients with primary carnitine deficiencies, which may be life-threatening, and some secondary deficiencies such as organic acidurias, the exogenously administered compound is clearly beneficial: by abolishing hypotonia, motor skills are improved, as are muscle weakness and wasting. In preliminary clinical trials in patients with ischaemic cardiac disease, therapy with l-carnitine has shown beneficial effects on myocardial function and metabolism and has improved exercise tolerance in patients with angina pectoris-findings which require further substantiation in larger controlled studies.

Pentamidine isethionate. A review of its antiprotozoal activity, pharmacokinetic properties and therapeutic use in Pneumocystis carinii pneumonia.

Pentamidine isethionate, an aromatic diamidine, is an antiprotozoal agent proven to decrease mortality from Pneumocystis carinii pneumonia in debilitated infants and immunodeficient adults and children. Like the combination antimicrobial agent co-trimoxazole, pentamidine has been shown in retrospective studies to resolve episodes of pneumonia in approximately 41 to 87% of patients, including those with the acquired immunodeficiency syndrome (AIDS), when used alone or as sequential therapy. Although about 45% of all patients given pentamidine experience side effects--which may include nephrotoxicity, hypotension, hypoglycaemia or local reactions--in patients with AIDS the incidence of side effects is less with pentamidine than with co-trimoxazole.

Nitrendipine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in the treatment of hypertension.

Nitrendipine is a calcium entry blocker shown to inhibit the movement of calcium through the 'slow channel' of cardiac and vascular smooth muscle, thus inducing peripheral vasodilation with consequent reductions in elevated blood pressure. As evidenced by clinical trials, nitrendipine promptly lowers blood pressure in patients with mild to moderate hypertension, and sustains this effect during long term administration. Combining nitrendipine with other antihypertensive agents such as diuretics or beta-blockers often results in successful treatment in patients unresponsive to nitrendipine monotherapy.

Buspirone. A preliminary review of its pharmacological properties and therapeutic efficacy as an anxiolytic.

Buspirone hydrochloride (HCl)1 is a new anxiolytic with a unique chemical structure. Its mechanism of action remains to be elucidated. Unlike the benzodiazepines, buspirone lacks hypnotic, anticonvulsant and muscle relaxant properties, and hence has been termed 'anxioselective'.

Zopiclone. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy as an hypnotic.

Zopiclone is the first of the cyclopyrrolones, a new class of psychotherapeutic agents possessing a pharmacological profile of high efficacy and low toxicity similar to that of the benzodiazepines. Binding is thought to occur to the benzodiazepine receptor complex, or to a site closely linked to this complex. Although zopiclone exhibits anticonvulsant, muscle relaxant and anxiolytic properties in animals, it finds better use as an hypnotic because of marked sedating effects.