Bumetanide: A preliminary report of its pharmacological properties and therapeutic efficacy in oedema.

Bumetanide2 is a new diuretic with a rapid onset and short duration of action. It is advocated for the treatment of oedema of cardiac origin; that associated with cirrhosis of the liver and renal diseases, including the nephrotic syndrome oedema of pregnancy and in pulmonary oedema. Bumetanide produces a pattern of water and electrolyte excretion closely resembling that of frusemide although it differs structurally from frusemide and other diuretics. 1 mg of bumetanide produces a diuretic effect similar to that evoked by 40 to 60 mg of frusemide. Short-and long-term studies in oedema of varying aetiology have shown bumetanide to be an effective diuretic. Because it is chemically different from existing diuretics, bumetanide may be helpful in oedema resistant to other drugs. It is well tolerated, but like other natriuretics it causes hypericaemia and may cause hypokalaemia during long-term administration.

Amoxycillin: A review of its antibacterial and pharmacokinietic properties and therapeutic use.

Amoxycillin2 is an acid stable semisynthetic penicillin closely related to ampicillin. Unlike pivampicillin and hetacillin, amoxycillin is not converted to ampicillin in the body. The antibacterial spectrum and level of activity of amoxycillin is essentially the same as for ampicillin, and there is complete cross-resistance between the two drugs. After oral administration, amoxycillin is better absorbed than ampicillin. Mean peak serum levels of amoxycillin are generally twice those of ampicillin after an equal dose. The better absorption and penetration into certain body tissues and fluids of amoxycillin and its greater activity against experimental infections in mice, suggest that it might be preferred to ampicillin in the treatment of some infections, but any clear superiority over ampicillin in clinical practice has yet to be demonstrated. However, these properties have enabled amoxycillin to be given at half the dose of ampicillin without loss of therapeutic efficacy, and the princpal side-effects of skin rashes and diarrhoea have tended to be less frequent with amoxycillin than with ampicillin. Other side-effects are essentially similar in nature to those reported with ampicillin.

Minocycline: A review of its antibacterial and pharmacokinetic properties and therapeutic use.

Minocycline is a semi-synthetic tetracycline derivative which is well absorbed and distributed in body tissues and is suitable for twice daily administration. It appears to be as generally effective as other tetracyclines and analogues, but also to be effective in infections due to tetracycline-resistant staphylococci. Side-effects are typical of those of other tetracyclines, but minocycline has been associated with a high incidence of vertigo in some studies. On the other hand, minocycline appears to have little or no photosensitising potential. It is not yet clear whether minocycline can be safely used in patients with moderate or severe impairment of renal function, but if used in renal failure, the plasma urea concentration should be monitored.

Timolol: a preliminary report of its pharmacological properties and therapeutic efficacy in angina and hypertension.

Timolol (MK 950) is a new beta-adrenergic receptor blocking drug. It has little or no membrane stabilising ('quinidine-like') or partial agonist (intrinsic sympathomimetic) activity and thus resembles sotalol. On a weight for.weight basis, timolol is more potent than sotalol or propranolol. A 2.5 mg dose of timolol causes about the same reduction in resting heart rate as 20mg of propranolol. Results of placebo-controlled and of comparative trials with other beta-adrenergic receptor blocking drugs, have shown that timolol effectively lowers blood pressure without producing orthostatic or exercise hypotension. Findings of an international multicentre trial in angina pectoris, indicate that timolol is effective in reducing the frequency of anginal attacks and the consumption of glyceryl trinitrate for their relief.

Beclomethasone dipropionate: II: Allergic rhinitis and other conditions.

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.

Metoprolol: a review of its pharmacological properties and therapeutic efficacy in hypertension and angina pectoris.

Metoprolol is a beta1-selective adrenoceptor blocking drug. In hypertension, its duration of effect is longer than expected from its half-life and it is suitable for twice daily administration. There is some evidence that once daily administration may be possible in treating hypertension. It is similar in efficacy to other beta-adrenoceptor blocking drugs in angina pectoris and essential hypertension, when given in equiactive beta-blocking dosages. Metoprolol is well tolerated and side-effects have not proved a problem. It has some pharmacodynamic and pharmacokinetic differences from other beta-adrenoceptor blocking drugs and may prove useful in cases where these differences are shown to be clinically important.

Triazolam: a review of its pharmacological properties and therapeutic efficacy in patients with insomnia.

Triazolam is a triazolobenzodiazepine with hypnotic properties, advocated for use in acute or chronic insomnia, situational insomnia in hospitalised patients, and insomnia associated with other disease states. As triazolam has a relatively short half-life of about 2 to 3 hours in healthy subjects and has only 1 short acting active metabolite, alpha-hydroxytriazolam, it would seem more suitable as an hypnotic than longer acting drugs such as flurazepam, nitrazepam or flunitrazepam, particularly when residual sedative effects on the day after ingestion are undesirable. Thus, with usual hypnotic doses of triazolam (0.25 or 0.5 mg) impairment of psychomotor and cognitive function is generally not carried over into the day after ingestion, although at doses of 1 mg or greater, residual effects may appear. In short term comparative studies triazolam was clearly superior to a placebo, and was at lest as effective as flurazepam, or other benzodiazepines such as nitrazepam or diazepam, in hastening sleep onset, reducing nocturnal awakenings, and increasing sleep duration. In other studies it was often superior to chloral hydrate, methyprylone or quinalbarbitone (secobarbital). In a small number of patients with chronic insomnia receiving extended treatment with triazolam in a clinical setting or in some sleep laboratory studies, no evidence of tolerance occurred; however, some evidence of reduced effect with repeated administration has been reported in one sleep laboratory study. Thus, a definitive statement about the likelihood of tolerance occurring on repeated administration is difficult to make at this time.

Temazepam: a review of its pharmacological properties and therapeutic efficacy as an hypnotic.

Temazepam is a benzodiazepine drug which is a minor metabolite of diazepam. In clinical studies using subjective evaluation methods it was effective for maintaining sleep and increasing total sleep time. However, sleep laboratory studies did not show a significant effect on some sleep parameters, especially sleep induction. Temazepam has a relatively short half-life (about 5 to 11 hours, longer in some subjects and in the elderly), and no active metabolites of clinical importance, and thus may be considered more suitable for use as an hypnotic than longer acting drugs such as diazepam, nitrazepam or flurazepam when residual sedative effects the next day are not desirable. Indeed, few residual effects on morning performance appear to occur with usual single doses of temazepam, although at the upper end of the recommended dosage range (30 mg or more) some evidence of impaired psychomoter and cognitive function in the morning has been reported. Whether or not temazepam is likely to produce "hangover" with repeated night-time administration needs further clarification. While a call for a large number of controlled trials may not be justifiable in evaluating a new hypnotic, a few well designed additional comparative studies in insomniac subjects are needed to assess adequately the relative merits of temazepam (particularly with regard to sleep onset) compared with other benzodiazepine hypnotics, especially those which are short- or intermediate-acting.

Trifluridine: a review of its antiviral activity and therapeutic use in the topical treatment of viral eye infections.

Trifluridine (trifluorothymidine) is an antiviral agent for topical use in the eye, and is structurally related to idoxuridine. In vitro studies have shown that it effectively inhibits the replication of herpes simplex virus type 1, which causes primary keratoconjunctivitis and recurrent epithelial keratitis in man. In masked comparative studies, predominantly in patients with dendritic ulcers, trifluridine 1% solution was effective in over 90% of patients; in such studies it was comparable with vidarabine in treating dendritic ulcers, and was at least as effective as, and in some studies more effective than, idoxuridine. The drug was also effective in treating a small number of patients with geographic ulcers (sometimes associated with the usage of topical corticosteroids), and this could be an important advantage if confirmed in further well-designed studies. However, experience at present is too limited to reliably determine the usual response rate in this difficult therapeutic area. In open studies the drug proved to be particularly useful in treating ulcers previously unresponsive to idoxuridine or vidarabine, and in treating patients intolerant of idoxuridine, with a high success rate and minimal side effects being reported. The role of trifluridine in treating deep stromal disease, uveitis, or adenovirus kerato-conjunctivitis has not been established. The drug is well tolerated and cross-hypersensitivity and cross-toxicity between trifluridine, idoxuridine and vidarabine are rare. Thus, trifluridine is an effective alternative to the drugs available for treating herpetic keratitis, and seems especially useful in 'difficult' cases.

Nadolol: a review of its pharmacological properties and therapeutic efficacy in hypertension and angina pectoris.

Nadolol is a nonselective beta-adrenoceptor blocking drug without intrinsic sympathomimetic or membrane stabilising activity. Its inherently long duration of activity makes it suitable for once daily administration in both hypertension and angina pectoris, and in these conditions it has been as effective as propranolol given in a traditional regimen 4 times daily. However, other beta-blocking drugs can also be given with reduced frequency, especially in hypertension; and some, such as atenolol (a longer acting 'cardioselective' agent) or long-acting preparations of other beta-blockers, have also been given once daily in angina prophylaxis. Nevertheless, nadolol is one of a few beta-blocking drugs which have clearly been shown to be effective in both hypertension and angina with once daily administration. Other specific properties of nadolol, such as its excretion entirely in unmetabolised form, may offer advantages over other existing beta-blocking drugs in specific patients, while some properties (such as lack of 'cardioselectivity') may be disadvantageous in others. The choice of a beta-blocking drug should thus be based on a knowledge of the pharmacodynamic and pharmacokinetic properties of the different beta-blocking drugs, and a careful consideration of how such properties can best be applied to benefit the individual patient.

Nomifensine: A review of its pharmacological properties and therapeutic efficacy in depressive illness.

Nomifensine is a tetrahydoisoquinoline antidepressant which is chemically unrelated to the tricyclic or tetracyclic antidepressants, the monoamine oxidase inhibitors or the recently introduced agents. Nomifensine resembles the tricyclic antidepressants in many of its pharmacological effects in animal models of depressive illness, but differs from them in that it strongly inhibits the re-uptake of dopamine as well as noradrenaline and is a relatively weak inhibitor of serotonin uptake. It has an overall efficacy comparable with that of imipramine and amitriptyline in depressive illness, but at dosages which have achieved a similar overall clinical improvement, nomifensine causes little or no sedation, fewer and milder anticholinergic side effects, and also appears less likely than these drugs to cause serious cardiotoxicity on overdosage. Nomifensine may aggravate the psychopathology of patients with schizo-affective disorders and intensification of the psychosis may require neuroleptic therapy. Nomifensine also has antianxiety activity, but its role in treating anxiety associated with primary depression has still to be clarified. Nomifensine appears to be well tolerated by the elderly.

Ipratropium bromide: a review of its pharmacological properties and therapeutic efficacy in asthma and chronic bronchitis.

Ipratropium bromide is an anticholinergc bronchodilator administered by inhalation. Although producing bronchodilation in most patients with obstructive airways disease, it is somewhat less effective than beta 2-adrenoceptor agonist drugs such as salbutamol or fenoterol in patients with asthma, but is at least as effective as these agents in bronchitis. As with the beta 2-adrenoceptor agonists, the onset of maximum effect with ipratropium (about 1.5 to 2 hours) is slower than with isoprenaline (although significant bronchodilation usually occurs within seconds or minutes of ipratropium inhalation), and the duration of effect (about 4 to 6 hours) is longer. Studies of concomitant use of ipratropium and other agents such as beta 2-adrenoceptor agonists, theophylline, or sodium cromoglycate, have usually shown a greater response in many patients than with single drug therapy, as might be expected from the different mechanisms of action of these groups of drugs. Usual inhaled doses of ipratropium were well tolerated in all studies. Ipratropium thus appears to be a suitable alternative to beta 2-adrenoceptor agonist drugs in patients not fully responding to these agents, and combined therapy with ipratropium and other bronchodilating drugs may prove to be an important area of use in patients failing to respond adequately to a single drug regimen. (nevertheless, in asthma patients in whom a 'non-responsive' state is developing, initiation of corticosteroid therapy should not be delayed). Ipratropium may also be useful in the occasional patient in whom side effects such as palpitations or tremor are troublesome with usual inhaled doses of beta 2-adrenoceptor agonists.

Ticarcillin: a review of its pharmacological properties and therapeutic efficacy.

Ticarcillin is a semisynthetic penicillin for parenteral administration. The antibacterial activity of ticarcillin is similar to that of carbenicillin except that it is two to four times more active in vitro against Pseudomonas aeruginosa, generally less active against Gram-positive cocci and more active against most Gram-negative bacilli. As the pharmacokinetics of ticarcillin and carbenicillin are also similar, ticarcillin should theoretically be clinically effective when administered at a lower dosage than carbenicillin. There is some evidence that ticarcillin is comparable in efficacy with carbenicillin when given in half to two-thirds the dosage, when the drugs are given in combination with an aminoglycoside and in clinical situations where these drugs are agents of choice. Ticarcillin has been used successfully in the treatment of complicated urinary tract infection, pulmonary infection in cystic fibrosis and bacteraemia and is effective when combined with an aminoglycoside in severe infections in patients with granulocytopenia. The efficacy in anaerobic infections is at present poorly documented, although preliminary results are promising. Tolerability has generally been good with hypokalaemia being the most frequently reported side effect. At the dosages used, bleeding and fluid overload have seldom occurred.

Miconazole: a preliminary review of its therapeutic efficacy in systemic fungal infections.

Miconazole is an imidazole antifungal drug which has recently become available for systemic use. Its antifungal activity has been well studied and it is active in vitro against a wide range of fungi. Published and unpublished reports of the use of miconazole in conditions such as systemic or mucocutaneous candidosis, coccidioidomycosis, fungal meningitis, and paracoccidioidomycosis (which seems especially responsive) have often been encouraging, particularly in view of the serious, refractory nature of the conditions treated, but in most areas of use experience is limited. There are few effective drugs available for treating most systemic fungal infections, and if further studies confirm the encouraging results often seen to date, miconazole will be an important addition to the limited choices available for such conditions.

Colestipol: a review of its pharmacological properties and therapeutic efficacy in patients with hypercholesterolaemia.

Colestipol is an anion exchange resin with bile acid sequestering properties resembling those of cholestyramine, another lipid-lowering binding resin. In daily doses of 15 to 30g colestipol reduces total plasma cholesterol concentrations (primarily low density lipoprotein cholesterol) by about 15 to 30%, but plasma triglyceride concentrations may be unchanged or in some patients increased. Thus, like cholestyramine, colestipol is of benefit in patients with primary hypercholesterolaemia without associated hypertriglyceridaemia (type IIa hyperlipoproteinaemia). Colestipol is odourless and tasteless, and is said by some to be more readily tolerated by patients than cholestyramine, leading to improved compliance, but such data has not been documented in most studies. Side effects of colestipol treatment are primarily gastrointestinal in nature since the drug is essentially unabsorbed. As with cholestyramine, colestipol may bind with other concomitantly administered drugs reducing their absorption or enterohepatic recirculation; dosage intervals of other concurrent medications should be adjusted to minimise the potential for such an interaction.

Diflunisal: a review of its pharmacological properties and therapeutic use in pain and musculoskeletal strains and sprains and pain in osteoarthritis.

Diflunisal is a salicylic acid derivative with analgesic and anti-inflammatory activity. It has been studied in osteoarthritis, pain resulting from musculoskeketal sprains and strains and from minor surgery and cancer. The duration of its analgesic effect is longer than that of aspirin and diflunisal is effective when given twice daily. Diflunisal is not metabolised to salicylic acid and has a lesser effect than aspirin on platelet function in vivo. In osteoarthritis, diflunisal appears comparable in efficacy to moderate doses of aspirin (2 to 3g daily), but is better tolerated. It has not been compared with the most active phenylalkanoic acid derivatives such as naproxen in adequate numbers of patients. Diflunisal is comparable with glafenine in pain and with propoxyphene/paracetamol combinations and oxyphenbutazone in pain and in musculoskeletal strains and sprains. As with other non-steroidal agents, gastrointestinal complaints are the most frequently reported side effects.

Nefopam: a review of its pharmacological properties and therapeutic efficacy.

Nefopam is a non-narcotic analgesic not structurally related to other analgesic drugs. It is effective by the oral and parenteral routes, and when appropriate dose ratios were compared in short term studies it was shown to produce analgesia comparable to that with the oral analgesics aspirin, dextropropoxyphene and pentazocine, as well as that with 'moderate' doses of parenteral morphine, pethidine and pentazocine. However, when 'higher' dose ratios were compared, morphine and pethidine were usually more effective than nefopam, possibly due to a 'ceiling effect' for analgesia which may occur with higher doses of nefopam, as with other simple analgesics. Although a few patients with chronic pain have received nefopam for several weeks, further studies are needed to clarify its continued effectiveness and safety when used over long periods. In most patients nefopam has been relatively well tolerated, the most frequent side effects being sweating, nausea and in some studies sedation.

Piroxicam: a review of its pharmacological properties and therapeutic efficacy.

Piroxicam is an N-heterocyclic carboxamide of 1,2 benzothiazine 1,1 dioxide with analgesic and anti-inflammatory activity. It has an extended half-life of about 40 hours and is suitable for once daily administration. Published studies indicate that piroxicam 20mg daily is comparable with aspirin 3 to 6g. indomethacin 75 to 150mg, phenylbutazone 400mg, naproxen 500mg, ibuprofen 1200 to 2400mg and diclofenac 75mg in rheumatoid arthritis. In osteoarthritis, piroxicam 20mg daily is comparable in efficacy with aspirin 2.6 to 3.9g, indomethacin 75mg, naproxen 500mg and fenbufen 600mg but is generally better tolerated than aspirin or indomethacin in patients with arthritic diseases. Piroxicam 20mg was at least as effective as indomethacin 75mg in a study in ankylosing spondylitis. As with other non-steroidal anti-inflammatory drugs gastrointestinal complaints are the most frequently reported side effects and their frequency and severity appears to be dose-related.

Flunisolide: a review of its pharmacological properties and therapeutic efficacy in rhinitis.

Flunisolide, a derivative of fluocinolone acetonide, is advocated for intranasal inhalation for the treatment of perennial and seasonal allergic rhinitis. It is rapidly absorbed by all routes of administration, but it quickly undergoes extensive first-pass metabolism to a 6 beta-hydroxylated metabolite, which possesses only weak corticosteroid effects. Intranasal flunisolide relieves nasal symptoms (but not eye symptoms) in both perennial and seasonal allergic rhinitis, being most effective in patients who have an allergic component to their rhinitis; and like other corticosteroids it may reduce the need for systemic antihistamines in such patients, expecially during peak pollen periods. A few well designed comparative studies have shown flunisolide to be as effective as intranasal beclomethasone, and (in a single study) more effective than intranasal sodium cromoglycate solution. Only transient side effects have occurred, including nasal stinging and throat irritation. No Candida infections have been clinically apparent in short or longer term trials. Resting morning plasma cortisol levels have not been suppressed by usual therapeutic doses of intranasal flunisolide, but the drug's effects on hypothalamo-pituitary-adrenal (HPA) axis integrity during conditions of stress have not been evaluated.

Diclofenac sodium: a review of its pharmacological properties and therapeutic use in rheumatic diseases and pain of varying origin.

Diclofenac sodium, a phenylacetic acid derivative, is a non-steroidal, anti-inflammatory, analgesic agent advocated for use in rheumatoid arthritis, degenerative joint disease, ankylosing spondylitis and allied conditions, and in the treatment of pain resulting from minor surgery, trauma and dysmenorrhoea. Published data indicate that diclofenac 75 to 150mg daily (25 to 50mg 3 times daily) is comparable in efficacy with ordinary aspirin 3 to 5g daily and indomethacin 75 to 150mg daily in rheumatoid arthritis and with indomethacin in osteoarthritis. Available data suggest that in patients with osteoarthritis diclofenac sodium is comparable in efficacy and tolerability with naproxen, ibuprofen, sulindac and diflunisal. As oral diclofenac is generally given in 3 divided daily doses it may be at a disadvantage relative to less frequent administration with naproxen, diflunisal and sulindac in rheumatoid arthritis, although there is some evidence of diclofenac's efficacy when administered twice daily, or once daily as a slow release tablet. The drug is also available as suppositories and ampoules for intramuscular injection. No one of the non-steroidal anti-inflammatory agents is the most suitable drug for all patients requiring such therapy, and diclofenac should be considered along with other drugs of its type in the arthritic patient.