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Fenoprofen1 (dl-2-[3-phenoxyphenyl]propionic acid) is a new non-steroidal anti-inflammatory, antipyretic, analgesic agent advocated for use in rheumatoid arthritis, degenerative joint disease, ankylosing spondylitis and gout. Published data suggest that in rheumatoid arthritis, fenoprofen 2.4 g daily is comparable in effectiveness with moderate doses of aspirin (3.6 to 4 g daily), but generally causes fewer and milder side-effects at the dosages used. In published comparisons with other non-steroidal anti-inflammatory agents of the same chemical group, it is closely comparable with naproxen in effectiveness but tends to cause more minor side-effects than naproxen. However, as no one of the non-steroidal anti-inflammatory agents is the most suitable drug for all patients requiring such therapy, fenoprofen should be considered along with the other drugs of its type in the initial treatment of the arthritic patient. Fenoprofen has compared favourably with phenylbutazone in osteoarthrosis of the hips and with aspirin in osteoarthrosis of the shoulders, hips, knees and spine. Its exact place in the management of gout and ankylosing spondylitis remains to be determined.

Bufexamac2 is a new topically active non-steroidal anti-inflammatory agent incorporated into a cream base for use in eczema and other inflammatory dermatoses. Comparative studies have shown the efficacy of bufexamac 5% cream to be indistinguishable from that of commonly used topical fluorinated corticosteroids in eczema and various other inflammatory dermatoses, but its relative efficacy in psoriasis has yet to be determined. Bufexamac has not been compared with hydrocortisone but it would appear to be at least as effective in eczema (which responds readily to all topical steroids), and is perhaps without the problems associated with long-term or inappropriate use of the more potent fluorinated steroids. It is well tolerated by most patients.

Doxepin is closely related in structure and general pharmacological properties to other tricyclic antidepressant drugs such as amitriptyline and imipramine. It combines antidepressant activity with a sedative effect and in this respect resembles amitriptyline, with which it shares a similar profile of clinical action. The mood elevating effect of doxepin appears to be similar to that of amitriptyline but is probably less marked than that of imipramine and in some studies has been slower to take effect than imipramine. At dosages which have achieved a similar overall response rate, doxepin tends to cause fewer or less troublesome side-effects than imipramine, amitriptyline or amitriptyline-prephenazine. The more marked sedative properties of doxepin make it more useful than imipramine in depressed patients with sleep distrubances and in depression associated with anxiety. The benzodiazepines remain the drugs of choice in anxiety states. but when anxiety is accompained by significant depression, doxepin is more effective than chlordiazepoxide or diazepam. Doxepin is usually well tolerated, and in particular by the elderly and those with cardiovascular disease. Side-effects are similar in nature to those of other tricyclic antidepressants, with dry mouth, drowsiness and constipation being the most common. Postural hypotension is uncommon. Although doxepin appears to cause fewer cardiovascular side-effects in usual therapeutic doses, it has an intrinsic cardiotoxicity on overdosage similar to other tricyclics.

Dantrolene sodium or dantrolene1 is 1([5-(nitrophenyl)furfurylidend] amino) hydantoin sodium hydrate. It is indicated for use in chronic disorders characterised by skeletal muscle spasticity, such as spinal cord injury, stroke, cerebral palsy and multiple sclerosis. Dantrolene is believed to act directly on the contractile mechanism of skeletal muscle to decrease the force of contraction in the absence of any demonstrated effects on neural pathways, on the neuromuscular junction, or on the excitable properties of the muscle fibre membranes. Controlled trials have demonstrated that dantrolene is superior to placebo in adults or children with spasticity from various causes, as evidenced by clinical assessments of disability and daily activities, and by muscle and reflex responses to mechanical and electrical stimulation. It is somewhat less effective in patients with multiple sclerosis than in those with spasticity from other causes. There has been a general clinical impression in controlled trials that dantrolene caused less sedation than would have been expected from therapeutically comparable doses of diazepam. In 2 controlled trials, there was no significant difference between dantrolene and diazepam in terms of reductions in spasticity, clonus, and hyperreflexia, but side-effects such as drowsiness and inco-ordination occurred significantly more frequently on diazepam. Long-term studies have indicated continuing benefit for patients taking dantrolene, though the incidence of side-effects has often been high and there has been a suggestion of exacerbation of seizures in children with cerebral palsy. Dantrolene may be of value in the medical treatment of spasm of the external urethral sphincter due to neurological and non-neurological disease, and animal studies suggest a potential use in the management of malignant hyperpyrexia. Chemical evidence of liver dysfunction may occur in 0.7 to 1% of patients on long-term treatment with dantrolene, with symptomatic hepatitis in 0.35 to 0.5% and fatal hepatitis in 0.1 to 0.2%. The drug commonly causes transient drowsiness, dizziness, weakness, general malaise, fatigue and diarrhoea at the start of therapy. Muscle weakness may be the principal limiting side-effect in ambulant patients, particularly in those with multiple sclerosis, and therapy could be hazardous in patients with pre-existing bulbar or respiratory weakness. The dosage of dantrolene has been fixed in most controlled trials, though long-term studies have indicated the need for individualisation of dosage. The initial dose is usually 25mg once daily, increasing to 25mg two, three or four times daily, and then by increments of 25mg up to as high as 100mg two, three or four times daily. The lowest dose compatible with optimal response is recommended.

At doses similar to those used in the treatment of chronic bronchial asthma, intranasal beclomethasone dipropionate is effective in alleviating nasal symptoms of seasonal allergic and perennial rhinitis in about three-quarters of patients. Eye symptoms are not relieved. The carry-over effect of the evening dose is useful in preventing early morning attacks of sneezing. Intranasal beclomethasone dipropionate is useful in controlling symptoms persisting after polypectomy and may possibly delay or eliminate the need for the surgical removal of nasal polyps, which may shrink after several weeks or months of treatment.

Tinidazole1, a synthetic imidazole derivative, has been used in the oral treatment of several protozoal infections — trichomoniasis, giardiasis and amoebiasis. Among the protozoal organisms inhibited by tinidazole are Trichomonas vaginalis, Trichomonas foetus, and Entamoeba histolytica. In vitro, tinidazole has been shown to possess antiprotozoal activity at least comparable to, and in some cases greater than, metronidazole. Tinidazole also has activity against some Gram-negative anaerobic bacilli, including Bacteroides spp. Following oral administration of a 2g dose, like metronidazole serum levels peak in about 2 hours but persist for longer. Any clinical significance of the longer plasma half-life (tinidazole 12.5h; metronidazole 7.3h) has yet to be demonstrated. Tinidazole is approximately 20% bound to plasma proteins. Only unchanged drug has been found in the plasma and urine of tinidazole-treated subjects, although metabolites have been detected in animal studies. A single 2g dose of tinidazole has been shown to be effective therapy in vaginal trichomoniasis and in urogenital trichomoniasis in males. Single-dose therapy in general offers advantages in regard to convenience, and in the treatment of a sexually transmissible disease such as trichomoniasis, single-dose therapy facilitates compliance of patient and sexual partner. In comparative studies, tinidazole, in both single-dose and traditional multiple-dose regimens, has been shown to be equivalent and often superior to other anti-trichomonal agents, including metronidazole. In intestinal amoebiasis, tinidazole has been evaluated after both once-a-day and multiple daily dose regimens, with the former giving slightly better results. When both metronidazole and tinidazole were administered in multiple daily dose regimens, the two agents yielded similar cure rates; in one study fewer tinidazole-treated patients required a second course. Tinidazole has also been successful in some cases of amoebic liver abscess, but an advantage over metronidazole has not been demonstrated. Results in the treatment of giardiasis, especially with the single-dose regimen, are promising, and in one study, tinidazole proved effective in infections resistant to metronidazole. Even in large doses, tinidazole has been well tolerated, although rarely vomiting may occur and the patient may need to be re-treated with a multiple dose regimen.

Fenfluramine has been used for a number of years as a short-term adjunct to diet in the management of obesity. Controlled studies and clinical experience have shown that it possesses anorectic activity at least as good as that of other therapeutically useful drugs of its type, but like these drugs it has only a limited role in the overall management of obesity. Tolerance to the anorectic effects of fenfluramine may possibly develop more slowly than to other chemically related drugs in patients with refractory obesity. The mechanism of its anorectic action is probably by an effect on the appetite control centres in the hypothalamus, rather than by an effect on glucose and lipid metabolism. However, its effect in enhancing glucose uptake into skeletal muscle may be of advantage in diabetes mellitus, preliminary studies suggesting that it is of potential use in maturity-onset obese diabetics who cannot be adequately controlled by dietary measures alone. The starting dosage in obesity of 40mg daily should be increased gradually over 2 to 4 weeks to 60 to 120mg. In general, little extra benefit is gained by higher dosage. When a course of therapy is to be discontinued, fenfluramine dosage should be reduced gradually over a period of 2 to 4 weeks in order to avoid mood depression which has occurred in some patients on abrupt withdrawal of the drug. With these recommendations, the majority of patients tolerate fenfluramine satisfactorily, although some patients may have to discontinue the drug because of troublesome gastro-intestinal problems, diarrhoea, drowsiness or dizziness. Unlike other amphetamine-derived anorectics, fenfluramine is not a central stimulant in therapeutic doses, and it probably has little abuse potential.

Synopsis: Hexoprenaline1, N,N-[2-(3,4-dihydroxyphenyl)-2-hydroxyethyl] hexamethylenediamine, sulphate is a selective β2-adrenoreceptor agonist which is active in man as a bronchodilator by the oral or intravenous routes and by inhalation. It is indicated for use in the treatment of bronchospasm associated with obstructive airways diseases, including asthma, bronchitis and emphysema. Clinical experience and double-blind studies have established that hexoprenaline is an effective bronchodilator. Its major advantage over many other brochodilators of equal efficacy is its generally low production of side-effects, particularly tremor, palpitations, and tachycardia. In comparative trials, it has generally been rated as superior to orciprenaline or trimeto-quinol, but comparisons with salbutamol have provided equivocal results. Oral hexoprenaline was superior to fenoterol as long-term maintenance therapy in asthma, principally because its somewhat lesser bronchodilatory effects were more than compensated for by a lesser incidence of side-effects. Pharmacodynamic Studies: Both in animals and humans, hexoprenaline is markedly longer in action than other catechol-containing β2-agonists, such as isoprenaline and rimiterol. It protects asthmatic patients against bronchoconstriction induced by histamine, acetylcholine and allergens. Hexoprenaline is effective by inhalation and by the oral and intravenous routes, and is similar to salbutamol in onset and duration of action. Significant effects on the cardiovascular system are seen after oral or inhaled doses, only at levels several fold greater than those required for significant bronchodilatation, though a pronounced increase in heart rate occurs a few minutes after intravenous administration, and a moderate increase may occur after repeated oral dosage. Hexoprenaline has been given to asthmatic patients with hypertension of all grades of severity, and to others with cardiac disease, by all three routes of administration without causing adverse cardiovascular effects. Like other sympathomimetic amines, hexoprenaline has a lipolytic and glycogenolytic effect, but this does not apparently interfere significantly with glucose utilisation in diabetic patients inhaling the drug or receiving it intravenously. In general, hexoprenaline does not affect blood-gas values or acid-base status, though one trial reported a significant hypoxemia following inhalation of 400pg hexoprenaline. Its inhibition of uterine activity, which reflects activity at β2-adrenoreceptors, in the absence of significant cardiovascular effects, may have therapeutic application in the suppression of labour contractions, at least by the intravenous route. Pharmacokinetics Studies with tritium-labelled hexoprenaline in rats have shown that it is rapidly absorbed after intratracheal or intramuscular administration, and is also absorbed from the intestine. Hexoprenaline undergoes only slow O-methylation compared with isoprenaline, but its long duration of action may also be due to the initial 3-O-methyl metabolite being an effective bronchodilator. Excretion is mainly in the urine in the form of sulphates and glucuronides of the mono- and di-3-O-methyl derivatives, although unchanged hexoprenaline predominates initially. Therapeutic Trials: Single- and multiple-dose studies of oral hexoprenaline in asthmatic patients have shown the drug to have superior bronchodilator properties to placebo and tri-metoquinol, but to be not significantly different from orciprenaline. Direct, comparison suggests that hexoprenaline by metered aerosol is more selective than orciprenaline or salbutamol, producing less cardiac stimulation for a greater or similar degree of bronchodilatation. Inhaled solutions of hexoprenaline at concentrations of 0.025% and 1 % are at least as effective as orciprenaline or isoprenaline 2%, with fewer side-effects and a greater degree of bronchodilation. Intravenous hexoprenaline 5μg was as effective as orciprenaline at 100 times this dose, and produced significantly fewer side-effects and a lesser degree of tachycardia. In long-term studies, patients have usually been treated initially, and particularly in severe or hospitalised cases, by intravenous hexoprenaline. Oral hexoprenaline has then been substituted for maintenance therapy, supplemented in many patients by inhaled drug from metered aerosols. The average long-term improvement in pulmonary function has been about 20 to 25%. In a 1-year study, oral hexoprenaline was significantly better than fenoterol in terms of fewer side-effects, though fenoterol produced a greater degree of improvement in pulmonary function; hexoprenaline was particularly suitable in a sub-group of patients with cardiac disease, who experienced tachycardia, anginal pain and palpitations with fenoterol but not with hexoprenaline. Hexoprenaline alone is not recommended in status asthmaticus, by any route of administration, though it may be given intravenously together with aminophylline and corticosteroids for severe acute attacks of asthma. Subsequent maintenance therapy can then be carried out with oral and/or inhaled drug. Side-effects: There have been few reports of significant side-effects following the acute administration of hexoprenaline by inhalation. An initial transient mild tachycardia may occasionally occur, which is usually not subjectively apparent to the patient. After intravenous injection, and sometimes after inhalation, a transient reddening of the skin may be observed in particularly sensitive vascular areas. Palpitations and skeletal muscle tremor have been observed after high or cumulative doses of oral or inhaled hexoprenaline over a short period of time, and occur in a dose-dependent manner following intravenous administration. Over-dosage may produce fine tremor, general unrest, dizziness, and perspiration but gastrointestinal effects are rare. Contraindications and Precautions: There are no specific contraindications to hexoprenaline, though the same precautions as to its use apply as they do to other sympathomimetic substances. It should be used with caution in patients with thyrotoxicosis, hypertension, cadiac disease, diabetes mellitus, and renal or hepatic dysfunction, and in those who are hypersensitive to sympathomimetic drugs. Dosage and Administration: Hexoprenaline can be given by metered aerosol in doses of 200 to 400μg, up to 5 times daily. Children may receive half the adult dose. Frequent repetition of dosage should be avoided, in view of the long duration of action of inhaled hexoprenaline. The drug is also available for inhalation as a 0.02% solution, for use in compressed air or ultrasound aerohalers. Dosage of the undiluted solution is 1 to 20 breaths, several times daily, but inhalation may be continued for up to 10 minutes depending upon respiratory rate and quantity delivered by the inhaler. Hexoprenaline solution may also be used for damp inhalation with air-humidifying substances in a plastic tent. By the oral route, hexoprenaline should be given in doses of 0.5 to 1.0mg, 3 times daily, 30 minutes before meals, though some patients may require up to 1.0mg 4 times daily. Infants and babies should receive about 1/4 of the adult dose, preferably dissolved in milk, and older children about 1/2 of the adult dose. Symptoms of overdosage may only become apparent after several days of oral treatment, due to the prolonged action of the drug. Initial side-effects may subside with continuing treatment. The dose by the intravenous route is 5 to 10μg, injected slowly over 2 minutes. Up to 15 or 20μg may be given during 24 hours, though some patients may require 30μg. Infants and babies may receive 1 to 3μg, 1 to 3 times daily, with older children receiving 3 to 4μg, 1 to 3 times daily.

Sodium valproate1 has a broad spectrum of anticonvulsant activity, but is structurally unrelated to conventional antiepileptic drugs. Its proposed mode of action is mediated through effects on the function of brain γ-aminobutyric acid (GABA). However, the elevations in brain and cerebellar GABA, and the concomitant reductions in levels of cyclic guanosine monophosphate, occur in animals at dose levels which are unlikely to be achieved during the treatment of epileptic patients.

Metoclopramide, 4-amino-5-chloro-2-methoxy-N-(2-diethyl-aminoethyl) benzamide, is advocated for use in gastro-intestinal diagnostics, and in treating various types of vomiting and a variety of functional and organic gastro-intestinal disorders. Published data have indicated that metoclopramide assists radiological identification of lesions in the small intestine, facilitates duodenal intubation and small intestine biopsy, and eases emergency endoscopy in upper gastro-intestinal haemorrhage. Metoclopramide reduces post-operative vomiting and radiation sickness, and ameliorates some types of drug-induced vomiting. It may provide symptomatic relief in dyspepsia and possibly in vertigo, reflux oesophagitis and hiccups, but further controlled trials are needed to confirm the efficacy of metoclopramide in these proposed areas of use. It promotes gastric emptying prior to anaesthesia. Its effects in healing gastric ulcer and preventing relapse of duodenal ulcer remain unproven. Side-effects are few and transient, though alarming extrapyramidal reactions can occur in a small proportion of patients receiving therapeutic doses but more usually following excessive doses in young subjects. They respond rapidly to withdrawal of the drug.

Carbenoxolone sodium has been shown to accelerate the rate of healing of both gastric and duodenal ulcers, but its overall value in duodenal ulcer is probably less because of the high rate of natural remission of duodenal ulcers. Further studies are required to decide whether it should be used prophylactically to delay ulcer recurrence. Carbenoxolone may act by affecting both the proliferative activity of gastric epithelium and the differentiation of the epithelial cells to produce mucus (as well as favourably altering the physicochemical properties of mucus and by reducing peptic activity), factors which may be relevant ot the prevention of acute gastric ulcers. Some studies suggest that carbenoxolone adds to the effect of hospitalisation and bed rest on ulcer healing. Whether bed rest confers additional benefit to the drug's ulcer healing effect in outpatients is also uncertain. There is no evidence that accelerated healing by carbenoxolone is associated with improved overall prognosis. Carbenoxolone is of greatest benefit in accelerating the healing of gastric ulcers in patients for whom hospitalisation is not possible or desirable, but it should only be used in the ambulatory patient when careful and regular observation of serum electrolytes (particularly potassium), blood pressure and weight is possible and when it is known that the patient will attend regular follow-up. Patient must be educated in the proper use of the drug. If severe mineralocorticoid-like toxic effects such as sodium and water retention and hypokalaemia appear, as they do in a variable proportion of patients but most frequently in those receiving excessive doses, carbenoxolone should be stopped and the complication treated; they respond to thiazide diuretics and potassium supplements, and probably to amiloride given in conjunction with a low dose of a thiazide diuretic. Treatment with carbenoxolone can continue with concurrent diuretic therapy in patients with less severe side-effects. Optimum therapeutic effect in gastric ulcer with the least side-effects is achieved with a dosage of 100mg carbenoxolone tablets 3 times daily for the first week followed by 50mg 3 times daily thereafter, best taken before meals. A lower dosage is desirable in the elderly and in those with liver, cardiac or renal disease. Barium meal or preferably endoscopic examinations should be performed regularly and therapy continued until the ulcer is healed. Dosage for duodenal ulcer is 50mg 4 times daily, in special positioned-release capsules. These are best taken about 20 minutes before meals.

Beclomethasone dipropionate is a topically active corticosteroid used as an adjuvant in the control of chronic asthma when given by inhalation as an aerosol. It is not intended for treatment of acute attacks. It appears that the main difference between beclomethasone dipropionate and other corticosteroids previously used by inhalation is its high topical activity together with a lower systemic activity due to metabolic inactivation of the swallowed portion of the dose. Clinical experience has shown that at doses of 200 to 600mug daily, beclomethasone dipropionate inhaler is preferable to oral corticosteroids, because of lack of side-effects, when adult patients and children who are inadequately controlled by full doses of sodium cromoglycate and bronchodilators, are first considered to need maintenance corticosteroids. Inhaled beclomethasone dipropionate can allow a worthwhile reduction in maintenance doses of systemic corticosteroids in many patients already receiving these drugs and can replace systemic steroids entirely in some patients, particularly when their initial dose of steroids is less than 10mg daily of prednisone or its equivalent. Substitution should be attempted when the patient's asthma is well controlled on their usual doses of systemic steroids and full doses of other adjuvant therapy. Withdrawal of systemic corticosteroids should be performed slowly and carefully. Because recovery from impaired adrenocortical function caused by prolonged systemic steroid therapy is usually slow, special care is necessary for 9 to 12 months after transfer to beclomethasone dipropionate aerosol until the hypothalamo-pituitary-adrenal axis has sufficiently recovered to cope with emergencies such as trauma, surgery, severe infections or an acute attack of asthma. It is essential that additional therapy including high doses of systemic corticosteroids be used immediately to control any acute exacerbation of asthma which occurs during maintenance therapy with beclomethasone dipropionate aerosol. Tests of adrenal function suggest that beclomethasone dipropionate at dosages of 400 to 800 mug daily has little or no adverse effect. The most common side-effect associated with the continuous use of beclomethasone dipropionate inhaler has been oropharyngeal candidiasis, which appears to be dose-related and more common in women than in men. Systemic steroid withdrawal effects, like being generally unwell, and exacerbation of underlying allergic diseases such as allergic rhinitis, have been reported after substitution of beclomethasone dipropionate inhaler for systemic steroids. However, systemic withdrawal effects seldom occur if systemic steroids are withdrawn slowly.

Maprotiline1, 1-(3-methylaminopropyl) dibenzo(b,e) bicyclo (2.2.2) octadiene, is a tetracyclic drug, distinguished from conventional tricyclic antidepressants only by the rigid flexure of itsmolecular skeleton. In contrast to amitriptyline or imipramine, maprotiline has sedative and tranquillising properties in animals, appears to have negligible effects on the cardiovascular system in man, and does not influence the central metabolism of 5-hydroxytryptamine. It is indicated for use in the treatment of all types of mental depression or depressive mood disorders, but seems to offer no compelling advantages over the tricyclic antidepressants.

Naproxen2, (+)-6-methoxy-alpha-methyl-2-naphthalene acetic acid, is a new non-steroidal anti=inflammatory agent advocated for use in rheumatiod arthritis, degenerative joint disease and ankylosing spondylitis. Published data suggest that in rheumatiod arthritis, naproxen 500mg daily comparable in efficacy with moderate doses of aspirin (3.6 to 4g daily) or 150mg daily of indomethacin, but generally causes fewer and milder side-effects than these drugs at the dosages used and can be given less frequently (12-hourly). Encouraging intial results have been reproted from its use in other inflammatory joint disorders, including acute gout and juvenile rheumatiod arthritis. It has compared favourably with indomethacin in ostioarthrosis of the hip of knee. Its exact place in the management of ankylosing spondylitis remains to be determined.

Econazole1 is a recently introduced imidazole antifungal agent which is very closely related structurally to another imidazole derivative, miconazole. For local application the nitrate salt of econazole is used, while in preliminary investigations of systemic use in a few patients econazole base has been administered orally or intravenously. In uncontrolled studies in large numbers of patients, econazole nitrate has been administered topically in the treatment of dermatomycoses due to a wide variety of fungi, and vaginally in the treatment of vaginal candidosis; but it has not been compared with any other antifungal drug in controlled therapeutic trials in mycoses of the skin and has only been compared with nystatin in a few patients with vaginal candidosis. Until adequate comparative studies are done the relative place of econazole in the treatment of dermatomycoses and vaginal condidosis, compared with traditional antifungal agents and with other imidazole derivatives such as miconazole or clotrimazole, cannot be clearly stated. Nevertheless, econazole nitrate is an effective antifungal drug. In dermatological studies about 90% of a large number of patients were cured, often after a relatively short treatment period (2 to 6 weeks, as occurs with other imidazole antifungal agents). The cure rate was only slightly lower (about 85%) in patients with severe mycoses of many years' duration than in those whose infections were of more recent onset. In vaginal candidosis a 3-day treatment regimen using a 150mg suppository once daily was only slightly less effective (85% mycological cure rate) than a 15-day regimen using a 50mg dose (suppository or cream) once daily (90% cure rate). A 3 to 5 day 'higher' dose regimen was slightly more effective than a standard 15-day regimen of nystatin vaginal inserts in a small group of patients with vaginal candidosis. The convenience of the higher-dose shorter term regimen would likely be an important advantage to most patients. Whether other agents useful in vaginal candidosis would be as effective as econazole were they to be used in this way, has not been determined. Topical or intravaginal econazole nitrate has usually been well tolerated, side effects being limited to local irritation in about 1 to 4% of patients in most studies.

Synopsis: Fenoterol, the 4-hydroxyphenyl derivative of orciprenaline, is a resorcinol derivative with relatively high selectivity for β2-adrenoceptors. It is active in man after inhalation or oral administration and is indicated in the treatment of bronchospasm associated with asthma, bronchitis and other obstructive airway diseases.

Hydrocortisone 17-butyrate is a new non-fluorinated topical corticosteroid for use in psoriasis, eczema and other inflammatory dermatoses. In double-blind paired comparisons with other topical corticosteroids, the efficacy of hydrocortisone 17-butyrate 0.1% has generally been indistinguishable from that of triamcinolone acetonide 0.1%, fluocinolone acetonide 0.025% or betamethasone 17-valerate 0.1% in patients with eczema or psoriasis. When applied to the face of patients with atrophy superimposed on rosacea and perioral dermatitis resulting from prolonged use of fluorinated topical corticosteroids, hydrocortisone 17-butyrate 0.1% did not prevent the beneficial effect of systemic tetracycline nor the disappearance of telangiectasis, and tended to be more effective than hydrocortisone 1%. This result suggests that hydrocortisone 17-butyrate may be suitable for long-term use on facial lesions, although the occurrence of moderate rebound eruption in about 10% of patients indicates the need for caution. The findings suggest that hydrocortisone 17-butyrate may be less liable to cause skin atrophy and adrenal suppression than some other potent topical corticosteroids, but trials to date have been too short to allow definite conclusions regarding possible long-term effects and have not involved infants or children.

Clotrimazole 2, a synthetic imidazole derivative, is primarily used locally in the treatment of vaginal and skin infections due to yeasts and dermatophytes. In vitro, it is most active against Candida spp., Trichophyton spp., Microsporum spp. and Malazzesia fuffur (Pityrosporon orbiculare). In addition, it has some in vitro activity against certain Gram-positive bacteria, and at very high concentrations has activity against Trichomonas spp. In the treatment of vaginal candidiasis, clotrimazole vaginal tablets have produced cure rates comparable with those of conventional nystatin vaginal tablets. There have been no published comparisons with nystatin vaginal cream or foaming vaginal tablets - nystatin dosage forms preferred by some clinicians. Cootrimazole has also been successful in patients who had failed to respond to other antifungal agents such as nystatin and amphotericin B. Results in trichomonal vaginitis are not impressive. Skin infections caused by Candida or dermatophytes have been effectively treated with topical application of clotrimazole. In comparative trials, clotrimazole cream has been as effective as Whitfield's ointment and tolnaftate in the treatment of dermatophytoses, and as effective as nystatin in cutaneous candidiasis. Clotrimazole topical preparations are generally well tolerated, but local irritation has necessitated withdrawal of therapy in a few cases. Candidal septicemia and urinary and pulmonary candidiasis have been cured with oral clotrimazole therapy. Results in other types of serious fungal infections, including pulmonary aspergillosis, have been disappointing. A limiting factor in oral clotrimazole therapy is the high incidence of gastro-intestinal disturbances and neurological reactions.

Tobramycin is a new aminoglycoside antibiotic with a broad antibacterial spectrum in vitro, and pharmacokinetic properties similar to those for gentamicin. Tobramycin is more active than gentamicin against Pseudomonas aeruginosa and active against many gentamicin resistant strains, but is not active against enterobacteriaceae resistant to gentamicin. Theoretically, tobramycin has an advantage over gentamicin against infections caused by P. aeruginosa, but any advantage in clinical practice has yet to be adequately demonstrated. Clinical experience with tobramycin is considerably less than with gentamicin. Whilst tobramycin appears to offer no clear advantages over gentamicin against sensitive organisms it is indicated in infection caused by strains of P. aeruginosa which are resistant to gentamicin, but sensitive to tobramycin. Like gentamicin, tobramycin acts synergistically with corbenicillin and the cephalosporins. The efficacy of the tobramycin-carbenicillin combination has been shown in endocarditis caused by P. aeruginosa which was unresponsive to gentamicin plus carbenicillin. Ototoxicity and nephrotoxicity similar to that seen with other animoglycosides have been encountered in therapeutic trials with tobramycin and wider clinical experience is necessary to determine the relative incidence of these side-effects with gentamicin and tobramycin used under similar conditions. Antimicrobial activity: In comparative studies, in vitro, tobramycin is more active than gentamicin against clinical isolates of Pseudomonas aeruginosa. Similarly, the inhibitory index, which is the ratio between the serum concentration attained at usual therapuetic doses and the minimum inhibitory concentration, for Pseudomonas aeruginosa is higher for tobramycin than for gentamicin. Against Gram-negative bacteria other than Pseudomonas spp. the spectrum of activity of tobramycin is similar to that of gentamicin. For most species the activity of tobramycin is slightly less than that of gentamicin. Gentamicin is consistently more active than tobramycin against Serratia marcescens. Like other aminoglycoside antibiotics, tobramycin is active in vitro in low concentrations against Staphylococcus aureus. Tobramycin is essentially inactive against Streptococcus pyogenes, Streptococcus faecalis and Streptococcus pneumoniae (pneumococci). Maner aminoglycosides and of other antibiotics against various bacteria in vitro, but comparisons between studies cannot always be interpreted literally because the activity of many antibiotics in vitro, including tobramycin, is influenced by the nature of the culture media and the presence of certain salts. The sensitivity of P. aeruginosa to tobramycin is influenced by the magnesium, and calcium content of the culture media whilst that of all species is reduced by sodium ions. Wide variations in the concentration of these ions may result in divergent MIC values and an inappropriate choice of antibacterial agent to treat pseudomonas infection...

At doses similar to those used in the treatment of chronic bronchial asthma, intranasal beclomethasone dipropionate is effective in alleviating nasal symptoms of seasonal allergic and perennial rhinitis in about three-quarters of patients. Eye symptoms are not relieved. The carry-over effect of the evening dose is useful in preventing early morning attacks of sneezing. Intranasal beclomethasone dipropionate is useful in controlling symptoms persisting after polypectomy and may possibly delay or eliminate the need for the surgical removal of nasal polyps, which may shrink after several weeks or months of treatment.

The demonstration that long-term administration of relatively low doses of clonidine decreased the responsiveness of blood vessels to vasodilator and vasoconstrictor drugs in animals led to its investigation in the prevention of migraine in man. Results of placebo-controlled and open therapeutic trials have shown that clonidine in low dosages (75 to 150 mug daily) is useful in preventing migraine headaches in about 30%-50% of patients. A 50% or greater reduction in headache frequency or headache indices has been reported in 40% of patients in controlled and open studies. Thus clonidine, like other drugs used in the interval therapy of migraine, can be expected to be effective in only a proportion of patients. Although clonidine has not been compared directly with other drugs used in the prophylactic treatment of migraine, the general clinical impression is that it is less effective then pizotifen or methysergide. Because it is relatively well tolerated at dosages of 75 to 150 mug daily it is worthy of a trial, particularly in patients considered to need prophylactic migraine therapy for the first time, and when migraine occurs in association with hypertension. At the dosages used in migraine prophylaxis, which are almost invariably lower than used in hypertension, clonidine does not cause hypotension and can be used in patients with cardiovascular disease. The principal side-effects are drowsiness and dry mouth which tend to diminish as treatment continues.

Miconazole2, a synthetic imidazole derivative, is a new topical antifungal agent for use in the local treatment of vaginal, and skin and nail infections due to yeasts and dermatophytes. It is particularly active against Candida spp., Trichophyton spp., Epidermophyton spp., Microsporum spp. and Pityrosporon orbiculare (Malassezia furfur), but also possesses some activity against Gram-positive bacteria. In vaginal candidiasis, miconazole vaginal cream has produced higher cure rates than conventional nystatin vaginal tablets or amphotericin B vaginal cream. There have been no published comparisons with nystatin vaginal cream or foaming vaginal tablets - the nystatin dosage form preferred by some clinicians. The vaginal cream has also achieved a cure where previous nystatin or natamycin therapy had failed. Miconazole has proved equally effective in both Candida and dermatophyte infections of the skin, but as yet there have been no published comparisons with other antifungal agents. However, it has been successfully used in chronic skin infections which had not responded satisfactorily to other agents such as natamycin and pecilocin. Preliminary experience with oral and intravenous miconazole therapy in systemic candidiasis is promising. Miconazole preparations are well accepted and tolerated.

Pimozide 1-(1-[4,4-bis(4-fluorophenyl)butyl]-4-peperidinyl)-2-benzimidazolone, is the first of a new series of psychotropic drugs, the kiphenylbutylpiperidines. It is advocated for once-daily use as maintenance therapy in chronic schizophrenia and for the treatment of psychic and functional disorders induced by personality traits. Published data suggest that in chronic schizophrenia, pimozide 4 to 6mg daily is indistinguishable from maintenance doses of chlorpromazine, fluphenazine, flupenthixol, perphenazine, or thioidazine. Patient groups have usually been to small to allow statistically significant differences to be apparent, but in some trials pimozide was significantly superior to trifluoperzine and to haloperidol. On present evidence, pimozide has no place in the hyperactive, aggressive type of patient or in treating the acute phase of schizophrenia, probably because of its relative lack of sedative properties compared with many antipsychotic drugs. The incidence and severity of extrapyramidal reactions with pimozide are low, but suitably designed controlled studies are needed to determine whether its use leads to a reduction in the requirement for antiparkinsonian medication. In anxious patients, pimozide seems to offer no advantages over currently available anxiolytic agents, either in terms of efficacy or incidence of side-effects. Claims for a specific effect against anxiety associated with psychosis or disturbed personality traits remain unproven.