Azelastine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential

Azelastine is an antiallergic agent which demonstrates histamine H1-receptor antagonist activity and also inhibits histamine release from mast cells following antigen and non-antigen stimuli. Azelastine antagonises histamine- and leukotriene-induced bronchospasm in animal studies and reduces airway responsiveness to inhaled antigen or distilled water, and exercise challenge. In comparative studies, orally administered azelastine in doses up to 4 mg/day consistently relieved symptoms in patients with seasonal or perennial rhinitis - comparable to inhaled sodium cromoglycate (cromolyn sodium) 80 mg/day, oral chlorpheniramine (chlorphenamine) and oral terfenadine 120 mg/day. In addition, azelastine administered as an intranasal spray was as effective as oral terfenadine 120 mg/day and intranasal budesonide 0.4 mg/day in alleviating symptoms of rhinitis. Azelastine is also a potent antiasthmatic agent which produces significant and long lasting bronchodilation in patients with bronchial asthma. The drug is superior to placebo and comparable to oral ketotifen 2 mg/day and sustained release theophylline 700 mg/day when administered as a twice daily oral 4 mg dose. Azelastine is generally well tolerated: the most common adverse effects are altered taste perception and drowsiness. Adverse effects are mild and transient and result in withdrawal of treatment in less than 2% of patients. In a comparative study oral azelastine 2 or 4 mg/day produced no more sedation than terfenadine 120 mg/day. Thus, barring unexpected findings with wider clinical use, azelastine offers an effective and well tolerated choice of treatment for patients with allergic rhinitis and/or bronchial asthma, which may be particularly beneficial in patients in whom inhaled drug treatment is contraindicated.     

Ketorolac. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential

Ketorolac is a non-steroidal agent with potent analgesic and moderate anti-inflammatory activity. It is administered as the tromethamine salt orally, intramuscularly, intravenously, and as a topical ophthalmic solution. Clinical studies indicate single-dose efficacy greater than that of morphine, pethidine (meperidine) and pentazocine in moderate to severe postoperative pain, with some evidence of a more favourable adverse effect profile than morphine or pethidine. In single-dose studies ketorolac has also compared favourably with aspirin, paracetamol (acetaminophen) and a few other non-steroidal anti-inflammatory drugs. If further investigation confirms the initially favourable findings regarding efficacy and tolerability, ketorolac will be a useful alternative to opioid agents in postsurgical pain. It may well also find use in acute musculoskeletal pain, where it appears at least as effective as other agents with which it has been compared. From the limited clinical data available, ketorolac also seems promising in the treatment of ocular inflammatory conditions. Additional multiple-dose studies are required to evaluate fully the potential of ketorolac in the management of chronic pain states where it has shown superior efficacy to aspirin. In summary, ketorolac offers promise as an alternative to opioid and to other nonsteroidal analgesics in ameliorating moderate to severe postsurgical pain, and with wider clinical experience may find a place in the treatment of acute musculoskeletal and other pain states, and ocular inflammatory conditions.     

Acarbose. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential

Acarbose delays the production of monosaccharides (notably glucose) by inhibiting the alpha-glucosidases associated with the brush-border membrane of the small intestine which are responsible for the digestion of complex polysaccharides and sucrose. In healthy subjects acarbose 100 to 200 mg significantly inhibits postprandial glucose, insulin and triglyceride responses, with some evidence of carbohydrate malabsorption with the higher dose. Clinical trials in patients with non-insulin-dependent diabetes mellitus showed that acarbose improved diabetic control, especially postprandial blood glucose levels, independent of whether the patients were receiving concomitant oral antidiabetic drugs in addition to dietary management. In comparative studies acarbose was significantly superior to placebo, and comparable to biguanides, when used alone or as an adjuvant to sulphonylurea therapy. Trials in patients requiring insulin to control their diabetes demonstrated that acarbose significantly reduced postprandial blood glucose concentrations, resulting in a smoother diurnal blood glucose-time curve and improved symptoms associated with nocturnal hypoglycaemia. Daily insulin requirements were sometimes reduced. In large multicentre trials acarbose up to 600 mg/day for 3 to 12 months improved glycaemic control in approximately 55% of patients with non-insulin-dependent or insulin-dependent diabetes mellitus. Apart from its use in diabetes, encouraging preliminary results have been obtained with acarbose in other therapeutic areas such as dumping syndrome, reactive hypoglycaemia, and types IIb and IV hyperlipoproteinaemias--however, further clinical experience is needed in these settings before clear conclusions can be drawn. No serious side effects have been reported during treatment with acarbose, although it is associated with a high incidence of troublesome gastrointestinal symptoms such as flatulence, abdominal distension, borborygmus and diarrhoea. The incidence of these reactions usually decreases with time. Thus, acarbose represents the first of a new class of oral antidiabetic drugs--the alpha-glucosidase inhibitors. It has proven useful for improving glycaemic control when used as an adjunct to standard therapy involving dietary restriction, oral antidiabetic drugs and/or subcutaneous insulin. That being the case, acarbose should provide the clinician with an interesting treatment option which can be used in a broad range of patients with diabetes mellitus in whom 'traditional' management approaches produce suboptimal glycaemic control.     

Dilevalol. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in hypertension

Dilevalol, the RR-stereoisomer of labetalol, is a non-cardioselective beta-adrenoceptor antagonist with substantial partial beta 2-agonist and negligible alpha 1-blocking activity. Reduction in blood pressure during dilevalol administration is associated with peripheral vasodilatation, and heart rate remains essentially unchanged. Following oral administration, dilevalol is completely absorbed. Once-daily administration is possible, due to a long elimination half-life. Large well-controlled trials reveal that dilevalol is equivalent in antihypertensive efficacy to metoprolol, the ACE inhibitors captopril and enalapril, and the calcium antagonist nifedipine. Smaller noncomparative and comparative trials demonstrate the blood pressure-lowering effects of dilevalol and suggest an efficacy at least equivalent to that of the 'pure' beta-blockers atenolol and propranolol and the alpha 1-blockers urapidil and doxazosin. Dilevalol appears to be well tolerated, the most frequent adverse effects being dizziness, headache and diarrhoea in only about 7% of patients each. Unlike alpha 1-blockers and labetalol, dilevalol is not commonly associated with orthostatic hypotension. Thus, data suggest that dilevalol, with its distinctive pharmacological profile, is likely to be a useful addition to the options currently available for treating patients with mild to moderate essential hypertension.     

Remoxipride. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in schizophrenia

Remoxipride is a substituted benzamide of the same class as sulpiride, and has a pharmacodynamic profile consistent with central antidopaminergic activity. It is a weak, but relatively selective, central dopamine D2-receptor antagonist and appears to have preferential affinity for extrastriatal dopamine D2-receptors. It also has marked affinity for central sigma receptors. Clinical data from noncomparative and comparative studies show that remoxipride has antipsychotic acticvity in patients with chronic schizophrenia, and acute exacerbation of chronic schizophrenia, with activity on both positive and negative symptoms. Its overall efficacy in these studies was similar to that of haloperidol. Importantly, however, remoxipride produced a substantially lower incidence of extrapyramidal effects than haloperidol. Further long term comparative studies are required to ascertain the relative suitability of remoxipride for preventing relapse in psychotic patients, and to determine whether tardive dyskinesia occurs in remoxipride recipients--the latter has not been reported with remoxipride to date. Thus, while further experience (particularly of a long term comparative nature) is needed, at present remoxipride appears to offer an important tolerability advantage over haloperidol.     

Xipamide. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy

Xipamide is a diuretic derived from salicylic acid and has a structural resemblance to chlorthalidone. Its pharmacodynamic profile shows a diuretic efficacy is similar to that of frusemide (furosemide) at doses up to 40 mg, but the onset and duration of action are comparable to those of hydrochlorothiazide. Xipamide has been studied mostly in the treatment of mild to moderate essential hypertension, with few controlled studies of its use in oedematous states. The efficacy of xipamide 20 to 40 mg once daily in patients with mild to moderate hypertension is comparable to that of bendrofluazide 5 mg, bumetanide 1 mg or hydrochlorothiazide 50 mg when used alone in newly treated or previously treated patients. The addition of xipamide 20 to 40 mg daily to regimens containing beta-blockers, adrenergic neuron-blocking drugs and/or methyldopa has resulted in a further reduction in blood pressure. A few studies in oedematous states suggest that xipamide 40 to 80 mg is comparable in efficacy to equal doses of frusemide, and that the side effects of hypokalaemia, hyperuricaemia and increased blood glucose in diabetics or latent diabetics are similar to those of other diuretics. Thus, xipamide is a suitable alternative to other diuretics in the treatment of mild to moderate hypertension and combines the efficacy of frusemide with a less abrupt action in the treatment of oedema.     

Flunarizine. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use

Flunarizine is a 'selective' calcium entry blocker with a similar chemical structure and pharmacological profile to the related compound, cinnarizine. However, in contrast to cinnarizine it has a long plasma half-life and need only be given once a day. The majority of therapeutic trials in the prophylaxis of migraine, occlusive peripheral vascular disease and vertigo of central or peripheral origin have been placebo-controlled, and have shown that the drug produces significantly greater beneficial effects than placebo as evaluated by subjective and objective criteria. A small number of comparative studies have shown flunarizine to be at least as effective as pizotifen in migraine prophylaxis, and in a longer term study as effective as cinnarizine in vertigo of central origin. However, it has not been compared with other drugs which may be useful in these areas, such as methysergide in migraine prophylaxis, some antihistamines or phenothiazines in vertigo, or (understandably at this stage of its evolution) with surgical revascularisation in severe occlusive peripheral vascular disease. In preliminary placebo-controlled studies there was some evidence that flunarizine may improve impaired cognitive function in patients with cerebrovascular disorders, but such findings need further confirmation in additional carefully conducted studies. With a very long half-life, flunarizine may be given once daily; and drowsiness, the main side effect, can be minimised by taking the daily dose in the evening. Thus, it appears that flunarizine will offer a useful alternative in some therapeutic areas that can be difficult to manage with previously available therapy. However, a definitive statement on its relative place in therapy of such conditions must await a few well-controlled comparative studies.     

Bumetanide. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use

Bumetanide is a potent 'loop' diuretic for the treatment of oedema associated with congestive heart failure, hepatic and renal diseases, acute pulmonary congestion and premenstrual syndrome and in forced diuresis during and after surgery. Bumetanide may be given orally, intravenously or intramuscularly and produces a rapid and marked diuresis, and increased urinary excretion of sodium, chloride and other electrolytes (within 30 minutes) which persists for 3 to 6 hours. Its principal site of action is on the ascending limb of the loop of Henle, with a secondary action on the proximal tubule. Pharmacologically, bumetanide is about 40-fold more potent than frusemide (furosemide), with the exception of its effects on urinary potassium excretion where its potency is lower. Studies in patients with oedema due to congestive heart failure, pulmonary oedema or hepatic disease show that oral or intravenous bumetanide 0.5 to 2 mg/day produces results comparable to those with frusemide 20 to 80 mg/day. In acute pulmonary oedema, intravenous bumetanide produces a very rapid diuresis. Higher doses of bumetanide may be required (up to 15 mg/day) in patients with chronic renal failure or nephrotic syndrome. In these patients muscle cramps are not uncommon with bumetanide, but glomerular filtration rates are unaffected. In most studies, diuretic effects were accompanied by decreased bodyweight, abdominal girth and improvements in a variety of haemodynamic parameters. Comparison of bumetanide with frusemide at a dose ratio of 1 : 40 reveals no significant differences in clinical response with the exception of renal disease, where patients with oedema appear to respond better to bumetanide. Combination with thiazide diuretics enhances the clinical response to bumetanide. Potassium supplements and spironolactone may be beneficial additions to bumetanide where patients at risk of hypokalaemia can be identified. Clinically important side effects are infrequent, with audiological impairment occurring to a lesser extent than with frusemide. Bumetanide thus offers an important alternative to frusemide when a 'loop' diuretic is indicated.     

Meptazinol. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy

Meptazinol is a new opioid-type analgesic with mixed agonist/antagonist properties. It may be given orally, intravenously or intramuscularly. In studies in patients with moderate to severe pain of various aetiologies, usually following surgery or in obstetrics, the characteristics of analgesia with meptazinol were comparable to those seen with equianalgesic doses of pentazocine, pethidine or a combination of dextropropoxyphene and paracetamol. Preoperative use and use as a component of anaesthesia require further investigation before conclusions may be drawn on its effectiveness in these areas. Onset of action, recorded in a few studies, was faster than that with the other analgesics but duration was shorter than that of morphine, buprenorphine and pentazocine. Only a small number of patients with chronic pain have received long term therapy with meptazinol; in such patients there was no need for increased doses as treatment progressed. Respiratory depression has only been observed in patients receiving meptazinol as a premedication or while undergoing anaesthesia. Similarly any haemodynamic changes have been limited to preoperative patients or patients undergoing anaesthesia. Like other agonist/antagonist analgesic drugs, the abuse potential of meptazinol seems relatively low, but only wider clinical use for longer periods can establish this with certainty. The most commonly reported side effects have been gastrointestinal in nature, and although the incidence of central nervous system side effects has been relatively low, drowsiness and dizziness have caused occasional problems. Thus, meptazinol is a relatively potent but safe addition to the analgesics available for treatment of the patient with moderate to severe pain.     

Nimodipine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in cerebrovascular disease

Nimodipine is a dihydropyridine calcium antagonist which has been shown to dilate cerebral arterioles and increase cerebral blood flow in animals and humans. It has potential in the treatment of a range of cerebrovascular disorders. Major interest to date, however, has focused on its use in the prevention and treatment of the delayed ischaemic neurological deficits that frequently occur in patients with subarachnoid haemorrhages as a result of sustained cerebral vasospasm. Initial studies in which patients were treated with an intravenous infusion of nimodipine for up to 2 weeks, followed by oral treatment for 7 days, indicated that a higher proportion of patients than would normally be expected recovered with little or no permanent neurological damage. In a number of controlled studies oral nimodipine treatment for 3 weeks significantly decreased mortality rates and increased the number of patients who had a 'good' neurological outcome as compared with placebo treatment. In some of these trials fewer of the nimodipine-treated patients developed neurological deficits during the treatment period, but in none was there a significant effect on the incidence of angiographic vasospasm. It would seem that other pharmacological actions, such as increasing collateral blood flow to underperfused regions or a direct anti-ischaemic effect at the cellular level, may contribute to the clinical benefits obtained with nimodipine treatment. Preliminary results suggest that nimodipine is potentially useful in other cerebrovascular disorders, particularly ischaemic stroke. To date, nimodipine has been well-tolerated, the only adverse effects of any significance being reductions in the blood pressure of some patients and reversible increases in liver enzymes during intravenous therapy. Thus, nimodipine has significant potential in the treatment of patients with subarachnoid haemorrhage. Wider clinical use should confirm its value as a significant addition to the very limited range of therapeutic choices currently available for patients with this disorder.     

Fosinopril. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in essential hypertension.

Fosinopril is a phosphinic acid prodrug which, after oral administration, undergoes rapid hydrolysis to its active diacid, the angiotensin converting enzyme (ACE) inhibitor fosinoprilat. Unlike other ACE inhibitors, fosinoprilat has a compensatory dual route of elimination and is cleared by the liver and kidneys. Thus, in patients with diminished renal function increased hepatic clearance of fosinoprilat is noted and, similarly, in patients with diminished hepatic function increased renal clearance seems to occur. Because of this compensatory elimination, fosinopril therapy for all patients can begin with the same recommended dosage. Fosinopril 10 to 40mg administered once daily is an effective antihypertensive regimen that has shown efficacy similar to that of enalapril 5 to 10 mg/day, propranolol 80 to 160 mg/day, hydrochlorothiazide 25 to 50 mg/day and sustained release nifedipine 40 mg/day in preliminary clinical trials. Generally, fosinopril is well tolerated and adverse events associated with the drug are usually mild and similar to those associated with other ACE inhibitors. Thus, fosinopril appears to be a useful alternative to certain 'established' agents used for treating patients with essential hypertension.     

Terbinafine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in superficial mycoses.

Terbinafine is an orally and topically active allylamine antifungal agent with a primarily fungicidal action in vitro. Its spectrum of in vitro activity includes a broad range of dermatophyte, filamentous, dimorphic and dematiaceous fungi, and some yeast species. In clinical trials, mycological and overall efficacy rates of around 90 and 80%, respectively, have been achieved in cutaneous dermatophyte infections (tinea corporis/cruris and tinea pedis) with terbinafine, administered either orally (250 or 500 mg/day) or topically (a 1% cream applied twice daily). Similar rates of cure have been obtained with oral terbinafine in dermatophyte nail infections after relatively short treatment periods ranging from 3 to 12 months. Topical terbinafine has been effective in approximately 80% of patients with cutaneous candidiasis or pityriasis versicolor. Few comparative data have been published, but generally oral terbinafine appeared to be at least as effective as oral griseofulvin or ketoconazole in tinea corporis/cruris and more effective than griseofulvin in tinea pedis. Both oral and topical terbinafine have been very well tolerated in clinical trials to date, with only minor adverse effects reported. Although further research is required to establish the efficacy of terbinafine in comparison with other available therapies, as well as to fully clarify its tolerability profile, the early results obtained with terbinafine in superficial fungal infections are very encouraging. Terbinafine appears likely to become a first-line therapy for dermatophyte infections, particularly those affecting the nails.     

Cilazapril. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in cardiovascular disease.

Cilazapril is an orally active angiotensin converting enzyme (ACE) inhibitor which lowers peripheral vascular resistance without affecting heart rate. Like enalapril and ramipril it is a prodrug, and is hydrolysed after absorption to cilazaprilat, which has a long terminal phase elimination half-life permitting once daily administration. Given once daily at doses between 2.5 and 5 mg, cilazapril reduces arterial blood pressure in patients with mild to moderate essential and renal hypertension. Patients who do not respond adequately to cilazapril monotherapy usually respond with the addition of a diuretic such as hydrochlorothiazide. Preliminary data suggest that cilazapril is of comparable antihypertensive efficacy to usual therapeutic dosages of hydrochlorothiazide, slow release propranolol, nitrendipine, captopril and enalapril. In small studies cilazapril has produced sustained beneficial haemodynamic effects in patients with congestive heart failure. Cilazapril has been well tolerated and exhibits tolerability typical of ACE inhibitors as a class, including their lack of detrimental effect on glucose or lipid metabolism. Cilazapril should provide an effective alternative in the treatment of hypertension and, if preliminary data are confirmed, in congestive heart failure.     

Paroxetine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in depressive illness.

Paroxetine is a potent and selective inhibitor of the neuronal reuptake of serotonin, thereby facilitating serotoninergic transmission; this action appears to account for the antidepressant activity observed with this drug. A mean terminal elimination half-life of approximately 24 hours permits once daily administration. Results of short term clinical trials have shown paroxetine to be significantly superior to placebo, and comparable to amitriptyline, clomipramine, imipramine, dothiepin and mianserin in relieving symptoms associated with major depressive disorders. Paroxetine has shown some preliminary promise in the treatment of depressive illness resistant to tricyclic antidepressant therapy but further studies are required before any conclusions can be drawn. Paroxetine in therapeutic doses has been very well tolerated, and the favourable tolerability profile of this agent appears to be its primary advantage over traditional antidepressant agents. Paroxetine causes minimal anticholinergic-type adverse effects, and unlike tricyclic antidepressants, it does not precipitate cardiovascular effects or provoke cardiac conduction disturbances. Nausea has been the most frequently reported adverse event during short term use of paroxetine, but it is generally mild and transient and subsides with continued use. With longer term use headache, sweating and constipation were the most frequently reported side effects but the incidence rate was not significantly different from that noted for comparator antidepressants. Furthermore, the frequency of withdrawal due to adverse effects is less with paroxetine than with tricyclic antidepressant agents. Overall, available data appear to indicate that while the efficacy of paroxetine is similar to that of traditional antidepressant drugs, the newer agent possesses much improved tolerability. In addition, the wide therapeutic index of paroxetine may be beneficial when treating patients with an increased risk of suicide. Thus, paroxetine clearly looks to become a valuable addition to the range of drugs currently available to treat depressive illness. Future research may help to further define the relative place of this newer agent in antidepressant therapy and determine how its overall therapeutic efficacy compares with that of other related antidepressant agents such as fluoxetine.     

Bopindolol. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy.

Bopindolol is a nonselective beta-adrenoceptor antagonist [corrected] with partial agonist activity which is used in the treatment of hypertension. The drug is rapidly metabolised to an active hydrolysed form. The antihypertensive effects of bopindolol 0.5 to 4 mg are sustained for more than 24 hours after once daily dosing, and the drug appears similar in efficacy to propranolol, metoprolol, atenolol, pindolol and slow release nifedipine in the treatment of mild to moderate forms of this disease. In limited trials bopindolol has also successfully reduced symptoms in patients with angina pectoris, anxiety and essential tremor. Thus, bopindolol is an effective and well-tolerated beta-adrenoceptor antagonist.     

Citalopram. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in depressive illness.

Citalopram is an antidepressant belonging to a new class of drugs which enhance serotoninergic neurotransmission through potent and selective inhibition of serotonin reuptake. Preliminary trials suggest that its short term therapeutic efficacy is significantly greater than that of placebo and mianserin, and comparable to that of amitriptyline, maprotiline and imipramine. It appears to be a weaker antidepressant agent than clomipramine, but better tolerated. Its elimination half-life of 33 hours permits once daily oral administration. Symptomatic improvement obtained with short term treatment has been maintained when therapy has been extended for up to 1 year; in the few patients studied for this extended period, the relapse rate was lower than with fluvoxamine, fluoxetine or imipramine. Compared to standard antidepressant agents, citalopram is well tolerated. It does not appear to be cardiotoxic, has not been associated with seizures in humans, and is relatively nonsedating. Unlike the tricyclic antidepressants, citalopram has minimal anticholinergic effects. Mild and transient nausea, with or without vomiting, is the most frequent adverse effect--occurring in 20% of patients--and increased perspiration, headache, dry mouth, tremor and insomnia are experienced by 15 to 18% of patients. Citalopram thus offers similar therapeutic efficacy and a more favourable tolerability profile than the tricyclic antidepressants. Preliminary data suggest that it may be particularly useful in patients who cannot tolerate the anticholinergic or cardiovascular side effects of tricyclic antidepressants and in those for whom sedation is not indicated.     

Pentoxifylline. A review of its pharmacodynamic and pharmacokinetic properties, and its therapeutic efficacy

Pentoxifylline (oxpentifylline) is an orally active haemorheological agent for the treatment of peripheral vascular disease, cerebrovascular disease and a number of other conditions involving a defective regional microcirculation. Pentoxifylline acts primarily by increasing red blood cell deformability, by reducing blood viscosity and by decreasing the potential for platelet aggregation and thrombus formation. Extensive open and placebo-controlled studies have shown that pentoxifylline 600 to 1200 mg/day for at least 6 weeks is associated with subjective and objective improvements in 60 to 100% of patients with peripheral vascular disease. The most commonly assessed clinical parameter, walking distance, is usually improved by about 100%, although much greater improvements have also been documented. Other parameters which have been clearly improved include lower limb rest pain, paraesthesia, muscle blood flow, cramps and leg ulcers. Pentoxifylline has produced consistently better results than placebo, and in those studies using comparative drugs, better results than nylidrin, adenosine and naftidrofuryl. In patients with cerebrovascular disorders, open studies with pentoxifylline, usually at a dosage of 600 to 1200 mg/day (300 to 600 mg/day in Japan), have shown marked overall clinical improvements in about 85% of patients. Symptomatic improvements in rehabilitation psychometric tests, neuromotor and speech deficits and other subjective symptoms have accompanied increased cerebral blood flow, particularly to ischaemic areas. Pentoxifylline would appear to be useful in most types of cerebrovascular disease including transient ischaemic attacks, sequelae of cerebral thrombosis and haemorrhage, and chronic ischaemic disorders. In patients with chronic cerebrovascular disease pentoxifylline 600 to 1200 mg/day conferred significant clinical benefit compared with placebo and in isolated studies proved to be superior to drugs such as co-dergocrine mesylate, adenosine and pyrithioxine. Preliminary studies indicate that pentoxifylline may also prove useful in vaso-occlusive crises of sickle cell disease, some hearing disorders, disorders of eye circulation, high altitude sickness and asthenozoospermia. Pentoxifylline is usually well tolerated when administered as the conventional controlled release formulation, gastrointestinal symptoms (about 3%) being the most common complaint, although these and other adverse effects have not occurred to a significantly greater extent than with placebo. Thus, pentoxifylline offers a well-tolerated and effective alternative to the treatment options available for patients with peripheral vascular disease.(ABSTRACT TRUNCATED AT 400 WORDS)     

Dopexamine hydrochloride. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in acute cardiac insufficiency

Dopexamine hydrochloride is a novel synthetic catecholamine, structurally related to dopamine, with marked intrinsic agonist activity at beta 2-adrenoceptors, lesser agonist activity at dopamine DA1- and DA2-receptors and beta 1-adrenoceptors, and an inhibitory action on the neuronal catecholamine uptake mechanism. The drug is administered by intravenous infusion, and is characterized by a rapid onset and short duration of action. Short term haemodynamic studies in volunteers and patients with severe chronic heart failure have indicated that dopexamine hydrochloride reduces afterload through pronounced arterial vasodilatation, increases renal perfusion by selective renal vasodilation and evokes mild cardiac stimulation through direct and indirect positive inotropism. Preliminary small-scale noncomparative studies indicate that dopexamine hydrochloride displays beneficial haemodynamic effects in patients with acute heart failure and those requiring haemodynamic support following cardiac surgery, and that these effects are substantially maintained during longer term administration (less than or equal to 24 hours). Dopexamine hydrochloride appears to be generally well tolerated. Nausea and vomiting are the most frequently reported adverse effects, and respond to dosage reduction. Occasional reports of chest pain/angina pectoris precipitated by tachycardia indicates the need for caution in the use of dopexamine hydrochloride in patients with ischaemic heart disease. Thus, dopexamine hydrochloride may prove to be a useful alternative to dopamine and dobutamine in the treatment of acute heart failure and the postoperative management of low cardiac output states, although controlled studies are required to establish its efficacy and tolerability with respect to that of established therapies.     

Pirprofen. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy

Pirprofen is a non-steroidal anti-inflammatory drug, related structurally to drugs such as ibuprofen, ketoprofen and naproxen. Published clinical trials indicate that pirprofen 600 to 1200 mg/day as 2 or 3 divided doses is a suitable alternative to usual therapeutic dosages of aspirin, flurbiprofen, ibuprofen, indomethacin, ketoprofen, naproxen, piroxicam and sulindac in the treatment of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, musculoskeletal disorders and non-articular rheumatism. More studies are required to evaluate its potential relative to other commonly used drugs in the treatment of gout, juvenile rheumatoid arthritis and dysmenorrhoea. In patients with acute postsurgical, trauma or cancer pain, single oral or intramuscular doses of pirprofen 200 to 400mg provide equivalent analgesic activity to usual therapeutic doses of aspirin, diflunisal, ketoprofen, noramidopyrine, paracetamol and pentazocine. As with other non-steroidal anti-inflammatory drugs, gastrointestinal complaints are the most frequently reported side effects. At equivalent analgesic or anti-inflammatory dosages, pirprofen probably causes fewer side effects than aspirin and appears to be as well tolerated as the other agents with which it has been compared. Long term tolerability, particularly compared with some of the newer, purportedly less gastrotoxic agents or formulations, needs to be investigated further. Pirprofen does not appear likely to offer any particular advantage with respect to efficacy and tolerability over other non-steroidal anti-inflammatory drugs, except aspirin. However, as no one agent is the most suitable drug for all patients requiring such therapy, pirprofen may be considered along with other drugs of this type in the therapy of arthritic conditions and acute pain states.     

Zidovudine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy

Zidovudine (azidothymidine) is a thymidine analogue antiretroviral drug active against human immunodeficiency virus (HIV). In acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC) patients, orally and intravenously administered zidovudine is effective in reducing the incidence of opportunistic infections and neoplasms, increasing helper T lymphocyte numbers, and improving survival rates and quality of life. Adverse effects include serious haematological abnormalities and severe headache, abdominal discomfort, nausea, myalgia and insomnia. In addition, neutropenia and other anaemias frequently limit zidovudine therapy and may result in a need for multiple blood transfusions, dose reductions or withdrawal of the drug. However, despite these problems and the lack of information about some aspects of zidovudine use, zidovudine provides a major hope for HIV-infected patients, and it has rapidly become the standard therapy for improving the quality and duration of the lives of AIDS and ARC patients.