Heparan sulphate and hyaluronic acid components of the glycocalyx do not play a role in flow-mediated dilation of the iliac in the anaesthetized pig.

The shear-stress sensor function of vascular glycocalyx heparan sulphate and hyaluronic acid was investigated in vivo by assessing flow-mediated dilation before and after their removal. Heparinase III exposure (100 mU·mL-1 for 20 min;n = 6) did not significantly affect flow-mediated dilation of the iliac, from 0.42 ± 0.08 mm (mean ± SEM) to 0.34 ± 0.07 mm after (P = 0.12; paired Student's t test) for a statistically similar increase in shear stress; 18.24 ± 4.2 N·m-2 for the control and 15.8 ± 3.6 N·m-2 for the heparinase III experiment (P = 0.18). Hyaluronidase exposure (0.14-1.4 mg·mL-1 for 20 min; n = 8) also did not significantly reduce flow-mediated dilation of the iliac, which averaged 0.39 ± 0.08 mm before and 0.38 ± 0.09 mm after (P = 0.11) for a statistically similar increase in shear stress; 11.90 ± 3.20 N·m-2 for the control and 9.8 ± 3.33 N·m-2 for the hyaluronidase experiment (P = 0.88). Removal of both heparan sulphate and hyaluronic acid was confirmed using immunohistochemistry. Neither the heparan sulphate nor the hyaluronic acid components of the glycocalyx mediate shear-stress-induced vasodilation in conduit arteries in vivo.

In vivo neutralization of IL-6 receptors ameliorates gastrointestinal dysfunction in dystrophin-deficient mdx mice.

BACKGROUND: Duchenne muscular dystrophy (DMD) is a fatal disease characterized by progressive deterioration and degeneration of striated muscle. A mutation resulting in the loss of dystrophin, a structural protein which protects cells from contraction-induced damage, underlies DMD pathophysiology. Damage to muscle fibers results in chronic inflammation and elevated levels of proinflammatory cytokines such as interleukin-6 (IL-6). However, loss of cellular dystrophin also affects neurons and smooth muscle in the gastrointestinal (GI) tract with complaints such as hypomotility, pseudo-obstruction, and constipation reported in DMD patients. METHODS: Using dystrophin-deficient mdx mice, studies were carried out to examine colonic morphology and function compared with wild-type mice. Treatment with neutralizing IL-6 receptor antibodies (xIL-6R) and/or the corticotropin-releasing factor (CRF) 2 receptor agonist, urocortin 2 (uro2) was tested to determine if they ameliorated GI dysfunction in mdx mice. KEY RESULTS: Mdx mice exhibited thickening of colonic smooth muscle layers and delayed stress-induced defecation. In organ bath studies, neurally mediated IL-6-evoked contractions were larger in mdx colons. In vivo treatment of mdx mice with xIL-6R normalized defecation rates and colon lengths. Uro2 treatment did not affect motility or morphology. The potentiated colonic contractile response to IL-6 was attenuated by treatment with xIL-6R. CONCLUSIONS & INFERENCES: These findings confirm the importance of dystrophin in normal GI function and implicate IL-6 as an important regulator of GI motility in the mdx mouse. Inhibition of IL-6 signaling may offer a potential new therapeutic strategy for treating DMD-associated GI symptoms.

Oral idarubicin. A review of its pharmacological properties and clinical efficacy in the treatment of haematological malignancies and advanced breast cancer.

Idarubicin is an anthracycline agent available as both oral and intravenous formulations. The oral formulation has demonstrated efficacy in the treatment of advanced breast cancer, low-grade non-Hodgkin's lymphoma, myelodysplastic syndromes and as first-line induction therapy of acute myelogenous leukaemia where intravenous anthracycline treatment is precluded. It also has potential in ameliorating blast crisis of chronic myelogenous leukaemia and in multiple myeloma. The most frequent adverse effects associated with oral idarubicin are those commonly found with anthracyclines, namely myelosuppression, nausea and vomiting, diarrhoea and mucositis. There appears to be minimal significant cardiotoxicity with oral idarubicia. In summary; available data concerning oral idarubicin in haematological malignancies and advanced breast cancer are sufficiently encouraging to warrant further research. To maximise the use of oral idarubicin, future studies should define the optimal dose for elderly patients, its comparative efficacy with other available regimens and address quality-of-life and pharmacoeconomic issues associated with the substitution of oral for intravenous chemotherapy.

Eutectic lidocaine/prilocaine cream. A review of the topical anaesthetic/analgesic efficacy of a eutectic mixture of local anaesthetics (EMLA).

Eutectic lidocaine/prilocaine cream 5% is a eutectic mixture of the local anaesthetics lidocaine (lignocaine) 25 mg/g and prilocaine 25 mg/g that provides dermal anaesthesia/analgesia following topical application. The principal indication in which eutectic lidocaine/prilocaine cream has been studied is the management of pain associated with venipuncture or intravenous cannulation, where significantly greater pain relief than placebo, with equivalent efficacy to ethyl chloride spray and lidocaine infiltration, has been demonstrated. In dermatological surgery, eutectic lidocaine/prilocaine cream offers effective pain relief in children undergoing curettage of molluscum contagiosum lesions, and in adults undergoing split-skin graft harvesting. Particular benefit has also been shown with use of eutectic lidocaine/prilocaine cream in association with treatment of condylomata acuminata in both men and women, and it appears to provide a useful alternative to lidocaine infiltration in this context. Further research in such indications as paediatric lumbar puncture, minor otological surgery, and minor gynaecological, urological and andrological procedures is likely to further broaden the profile of clinical use for eutectic lidocaine/prilocaine cream. Eutectic lidocaine/prilocaine cream has a very favourable tolerability profile, transient and mild skin blanching and erythema being the most frequent adverse events to occur in association with its application to skin. The potential for inducing methaemoglobinaemia, attributed to a metabolite of the prilocaine component of the formulation, prohibits its use in infants younger than 6 months. In summary, eutectic lidocaine/prilocaine cream is a novel formulation of local anaesthetics that has proven to be effective and well-tolerated in the relief of pain associated with various minor interventions in adults and children.

Nabumetone. A reappraisal of its pharmacology and therapeutic use in rheumatic diseases.

Nabumetone is a nonsteroidal anti-inflammatory drug (NSAID) used to treat rheumatic and inflammatory conditions. It is absorbed as a nonacidic prodrug and is rapidly converted in the liver to an active metabolite which is responsible for its anti-inflammatory and analgesic effects. Published data from earlier comparative studies indicate that nabumetone, administered in a single dose of 1 to 2g daily, is as effective as aspirin, diclofenac, ibuprofen, indomethacin, naproxen and sulindac for the symptomatic treatment of rheumatoid arthritis, osteoarthritis, various nonarticular rheumatic conditions and acute soft tissue injury. Adverse events with nabumetone occur less frequently than with aspirin, and the incidence of gastrointestinal adverse events with nabumetone compares favourably with that of other NSAIDs. Rates of gastrointestinal ulceration and bleeding with nabumetone are low, apparently less than 1% annually. More recently, data from large-scale clinical trials and postmarketing surveillance studies have further confirmed the efficacy and tolerability of nabumetone. Thus, the drug should now be considered a well established member of this group of agents for the treatment of painful rheumatic and inflammatory conditions.

Nadroparin calcium. A review of its pharmacology and clinical applications in the prevention and treatment of thromboembolic disorders.

Nadroparin calcium is a low molecular weight heparin with a mean molecular weight of 4.5 kD. Compared with unfractionated heparin, nadroparin calcium has a greater ratio of anti-factor Xa/anti-factor IIa activity. Nadroparin calcium has a longer half-life and greater bioavailability than unfractionated heparin and can be administered by subcutaneous injection once daily for prophylaxis and twice daily for treatment. In clinical trials, nadroparin calcium has been shown to be at least as effective as unfractionated heparin in preventing deep venous thrombosis (DVT) after various surgical procedures including major orthopaedic and abdominal surgery, and in maintaining the patency of the extracorporeal circulation in adults and children undergoing haemodialysis. Nadroparin calcium is well tolerated, the most common adverse event associated with its use being the development of minor haematoma at the operative incision site. In postmarketing surveillance data to date, the incidence of major haemorrhage related to nadroparin calcium use has been very low (< 1%). Nadroparin calcium has also been associated with a very low incidence of thrombocytopenia (< 0.001%). Thus, nadroparin calcium is an effective alternative to unfractionated heparin in the prophylaxis or treatment of thromboembolic venous events, with the advantages of more convenient administration and a lower incidence of thrombocytopenia.

Cefpodoxime proxetil. A review of its antibacterial activity, pharmacokinetic properties and therapeutic potential.

Cefpodoxime proxetil is an orally administered prodrug which is absorbed and de-esterified by the intestinal mucosa to release the third generation cephalosporin, cefpodoxime. Cefpodoxime is stable towards the most commonly found plasmid-mediated beta-lactamases and the drug has a broad spectrum of antibacterial activity encompassing both Gram-negative and Gram-positive bacteria, rendering it a possible option for empirical use in a wide range of community acquired infections in both adult and paediatric patients. The extended plasma half-life of cefpodoxime (1.9 to 3.7 h) permits twice daily administration. In comparative trials, twice daily cefpodoxime proxetil (dose equivalent cefpodoxime 100 to 400 mg) was as effective as a 3- to 4-times daily regimen of phenoxymethylpenicillin in pharyngotonsillitis, as well as thrice daily amoxicillin (with or without clavulanic acid) or cefaclor against infections of the ear, the upper and lower respiratory tract, the urinary tract and those of the skin and soft tissues. The latter reflects the enhanced antistaphylococcal activity of cefpodoxime, which distinguishes it from other orally active third generation cephalosporins such as cefixime. Most notably, an oral regimen of cefpodoxime proxetil was as efficacious as parenterally administered ceftriaxone for the treatment of bronchopneumonia in hospitalised patients at risk due to the presence of underlying diseases, addictions or advancing age. A single oral dose of cefpodoxime was also as efficacious as ceftriaxone in uncomplicated anogenital gonococcal infections. Cefpodoxime proxetil is generally well tolerated, with mild to moderate gastrointestinal disturbances occurring in 4 to 15% of patients treated with therapeutic doses. Thus, a convenient twice daily oral regimen of cefpodoxime proxetil can be prescribed as an effective alternative to established beta-lactam therapies in the empirical outpatient treatment of infections of the respiratory and urinary tracts as well as those of the skin and soft tissues.

Nicorandil. A review of its pharmacology and therapeutic efficacy in angina pectoris.

Nicorandil belongs to the class of compounds known as potassium channel activators which are characterised by their arterial vasodilator properties. In addition, nicorandil has venodilating properties which are attributable to a nitrate group in its chemical structure. Therefore, by combining these two vasodilator mechanisms, nicorandil represents a novel type of compound for use in the treatment of angina pectoris. Furthermore, increasing experimental evidence suggests that potassium channel activation may also exert a direct cytoprotective effect by augmenting normal physiological processes which protect the heart against ischaemic events. Comparative studies of up to 3 months' duration suggest that nicorandil is equivalent in efficacy to isosorbide dinitrate, propranolol, atenolol, nifedipine or diltiazem in the treatment of stable angina. Preliminary evidence suggests that an improvement of anginal and ischaemic symptoms is maintained for up to 1 year. Whilst the efficacy of nicorandil in other types of angina has not been extensively studied, preliminary results indicate that intravenous nicorandil is as effective as isosorbide dinitrate in the treatment of unstable angina and is also effective in patients with variant angina. In addition, the limited data available indicate that nicorandil may be effective in patients with unstable and variant angina who are refractory to therapy with conventional antianginal agents, a potentially important area for further study. Headache, mostly of mild to moderate intensity was the most commonly reported adverse event, occurring in one-third of patients receiving the recommended therapeutic regimen of nicorandil 10 to 20mg twice daily. In comparative trials involving a total of 84 patients who received nicorandil, the incidence of headache was similar to that produced by isosorbide mononitrate and isosorbide dinitrate. Headache was most frequent on initiating therapy but declined with continued treatment. To date, approximately 5% of patients participating in European trials have withdrawn due to headache, although this rate may be reduced by using a lower starting dose of nicorandil (5 mg twice daily). In summary, clinical experience thus far indicates that nicorandil, with its novel combination of two distinct vasodilator mechanisms, offers an effective alternative to established vasodilator therapy with conventional nitrates and calcium antagonists in the long term treatment of stable angina pectoris. Further studies are warranted to establish whether the unique pharmacodynamic profile of nicorandil is advantageous for the treatment of other types of angina and/or the ischaemic myocardium.

Imipenem/cilastatin. A reappraisal of its antibacterial activity, pharmacokinetic properties and therapeutic efficacy.

Imipenem is an antibacterial agent of the carbapenem class of beta-lactams, with a very broad spectrum of activity that includes most Gram-negative and Gram-positive pathogens, aerobes and anaerobes, and with marked activity against species producing beta-lactamases. It is coadministered with cilastatin, a renal dehydropeptidase inhibitor that prevents renal metabolism of imipenem. As initial monotherapy, imipenem/cilastatin provides effective and well-tolerated treatment of moderate to severe infections in various body systems, including intra-abdominal, obstetric and gynaecological, lower respiratory tract, skin and soft tissue, and urinary tract infections, and also in bacteraemia and septicaemia, and in patients with malignancy-related febrile neutropenia. It is likely to be of particular benefit in cases where bacterial pathogens have not yet been identified, such as in the treatment of serious infections in immunocompromised patients, or in an intensive care setting. Thus, imipenem/cilastatin is effective as initial monotherapy of a variety of infections, including infections in neutropenic patients, with a clear role in empirical treatment of mixed infection.

Indobufen. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in cerebral, peripheral and coronary vascular disease.

Indobufen is an inhibitor of platelet aggregation which acts by reversibly inhibiting the platelet cyclo-oxygenase enzyme. Improvements in walking distances and microcirculatory parameters have been achieved during therapy with indobufen in patients with peripheral vascular disease and intermittent claudication. Indobufen has been shown to be as effective as aspirin plus dipyridamole in preventing the reocclusion of coronary and femoro-popliteal artery bypass grafts and has been shown to significantly reduce platelet deposition on haemodialysis membranes. Initial studies have also indicated that indobufen may have a prophylactic effect on the incidence of secondary thrombotic events following transient ischaemic attack or mild stroke and may be effective in the prophylaxis of migraine. Indobufen is well tolerated following oral administration and has been associated with a low incidence of adverse effects rarely requiring withdrawal of treatment. Thus, available evidence indicates that indobufen may be an effective alternative to aspirin for the treatment of cerebral, peripheral and coronary vascular diseases with the advantage of a lower incidence of gastrointestinal effects compared to high dose aspirin, rendering indobufen more suitable for longer term therapy.

Enoxaparin. A review of its pharmacology and clinical applications in the prevention and treatment of thromboembolic disorders.

Enoxaparin (PK 10169) belongs to the group of low molecular weight heparins which have a greater bioavailability and longer half-life than unfractionated heparin, permitting less frequent subcutaneous administration. In well controlled trials in surgical patients at high risk of deep venous thrombosis (DVT), enoxaparin has demonstrated prophylactic efficacy against venographically confirmed DVT at least equal to that observed with unfractionated heparin. Efficacy has also been demonstrated in patients at moderate risk and in limited investigations using 125I-fibrinogen scanning in nonsurgical patients at risk of DVT; in addition, enoxaparin appears to provide effective treatment of established DVT. In clinical studies, enoxaparin has also prevented coagulation of extracorporeal circulation, maintaining the patency of the circuit in patients undergoing haemodialysis. Thus, enoxaparin represents an effective alternative in the prophylaxis and treatment of thrombosis, with the convenience of less frequent administration than unfractionated heparin and the possible advantage of a lesser propensity for bleeding complications.

Transdermal Nicotine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy as an aid to smoking cessation.

Transdermal nicotine delivery systems are a cigarette smoking cessation aid designed to deliver nicotine into the systemic circulation via the skin. The partial replacement of plasma nicotine, which would have otherwise been obtained from cigarettes, reduces the severity of nicotine withdrawal symptoms, and so allows the smoker to abstain from smoking more easily. The systems are available in 16- and 24-hour application regimens, and are recommended for daily use for up to 20 weeks, including a series of 'weaning-off' courses. Clinical trials have shown that abstinence rates of 30 to 41% can be achieved during the first 6 weeks of application of transdermal nicotine systems, compared with 4 to 21% with placebo systems. The use of concomitant behavioural therapy may increase the success of treatment, with initial abstinence rates of up to 86% reported. However, long term abstinence rates (greater than 6 months) are considerably lower with or without behavioural therapy, often falling to less than half of the initial rates. Transdermal nicotine systems have been well tolerated in clinical trials, with local irritation at the site of application being the most common adverse event. Mild gastric, central nervous system (CNS) and sleep disturbances have also been reported. The ease of use and unobtrusive nature of the systems have resulted in a high degree of patient compliance. Thus, transdermal nicotine systems offer a convenient form of nicotine replacement therapy which are well tolerated and, due to their pharmacokinetic profile, probably have a low dependency potential. The short term abstinence rates achieved with this therapy are encouraging; however, the maintenance of abstinence in the long term is harder to achieve. Transdermal nicotine replacement therapy, therefore, represents an important advance in the difficult area of smoking cessation management.

Etodolac. A reappraisal of its pharmacology and therapeutic use in rheumatic diseases and pain states.

Etodolac is a nonsteroidal anti-inflammatory drug (NSAID) effective in the treatment of rheumatoid arthritis, osteoarthritis and ankylosing spondylitis, and in the alleviation of postoperative pain. Etodolac also provides relief of other types of pain, including that arising from gouty conditions and traumatic injury. In all indications, etodolac appears to be at least as effective as other NSAIDs. The incidence of clinical adverse effects other than abdominal pain and dyspepsia is similar to that observed with placebo, and etodolac has been associated with a low rate of gastrointestinal ulceration and other serious events. Data from preliminary animal studies have suggested that etodolac may provide more selective inhibition of prostaglandin synthesis at sites of inflammation than some other currently available NSAIDs. Thus, available evidence indicates that etodolac, with its low incidence of gastrointestinal events, is an effective and well tolerated alternative to other NSAIDs in the treatment of arthritic diseases and pain of various aetiologies and should be considered a first-line therapy.

Omeprazole. An updated review of its pharmacology and therapeutic use in acid-related disorders.

Omeprazole is the first of a new class of drugs, the acid pump inhibitors, which control gastric acid secretion at the final stage of the acid secretory pathway and thus reduce basal and stimulated acid secretion irrespective of the stimulus. In patients with duodenal or gastric ulcers, omeprazole as a single 20 mg daily dose provides more rapid and complete healing compared with ranitidine 150 mg twice daily or 300 mg at nighttime, or cimetidine 800 or 1000 mg/day. Patients poorly responsive to treatment with histamine H2-receptor antagonists respond well to omeprazole--most ulcers healed within 4 to 8 weeks of omeprazole 40 mg/day therapy. Omeprazole 20 or 40 mg/day has been administered as maintenance therapy for peptic ulcer disease for up to 5.5 years with very few ulcer recurrences. In patients with erosive or ulcerative oesophagitis, omeprazole 20 or 40 mg/day produces healing in about 80% of patients after 4 weeks, and is superior to ranitidine with respect to both healing and symptom relief. Healing rates of greater than 80% are achieved after 8 weeks in patients with severe reflux oesophagitis unresponsive to H2-receptor antagonists. Maintenance therapy with a daily 20 mg dose prevents relapse in about 80% of patients over a 12-month period. Omeprazole is considered to be the best pharmacological option for controlling gastric acid secretion in patients with Zollinger-Ellison syndrome. Daily dosages of 20 to 360 (median 60 to 70 mg successfully reduce basal acid output to target levels (less than 10 mmol/h or less than 5 mmol/h in patients with severe oesophagitis or partial gastrectomy) during treatment for up to 4 years. Omeprazole is well tolerated in short term studies (up to 12 weeks); the reported incidence of serious side effects (about 1%) being similar to that seen in patients treated with an histamine H2-receptor antagonist. The longer term tolerability of omeprazole has been investigated in patients treated for up to 5.5 years. Slight hyperplasia, but no evidence of enterochromaffin-like (ECL) cell dysplasia or neoplasia or ECL cell carcinoids has been reported. ECL cell carcinoids have been observed in rats after life-long treatment with high doses of omeprazole or ranitidine, or in rats with partial corpectomy; the weight of experimental evidence indicates that this is a result of prolonged hypergastrinaemia.(ABSTRACT TRUNCATED AT 400 WORDS)

Celiprolol. An updated review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in cardiovascular disease.

Celiprolol is a hydrophilic, beta 1-selective adrenoceptor antagonist with mild selective beta 2-agonist as well as weak vasodilator properties. Celiprolol 200 to 400mg once daily by mouth is similar in antihypertensive efficacy to usual doses of propranolol, atenolol, metoprolol and pindolol in patients with mild to moderate systemic hypertension. Similar doses of celiprolol are as efficacious as propranolol and atenolol in improving exercise tolerance and reducing the frequency of anginal attacks in patients with angina pectoris. Further clinical experience suggests that celiprolol does not produce bronchoconstriction and may have mild bronchodilating activity in asthmatic patients; it may also enhance the effects of bronchodilator drugs. Celiprolol has a slightly beneficial effect on serum lipid profiles, and does not appear to exert adverse effects on carbohydrate metabolism. If the apparent pharmacodynamic advantages of celiprolol translate into clinical benefits and are confirmed in well designed long term clinical trials, then celiprolol should represent a definite advance in beta-blocker therapy.

Adenosine. An evaluation of its use in cardiac diagnostic procedures, and in the treatment of paroxysmal supraventricular tachycardia.

Adenosine (adenine riboside), administered either as the free base or as the 5'-triphosphate (ATP) by rapid intravenous bolus, depresses atrioventricular (AV) nodal conduction, resulting in transient AV block. Adenosine is the active agent and ATP is rapidly converted to adenosine after exogenous administration. By blocking the anterograde AV nodal limb of a re-entrant circuit, adenosine 6 to 12 mg (or ATP 10 to 20 mg) converts almost all episodes of paroxysmal supraventricular tachycardia (PSVT) involving the AV node within 30 seconds of administration. This is at least equivalent in efficacy to verapamil in adults, and superior to lanatoside C in children, with a considerably more rapid onset of action. Furthermore, if a dose of adenosine is ineffective, the exceptionally short plasma half-life of the adenyl nucleosides (less than 10 sec) allows rapid upward dosage titration until PSVT is terminated. Because the induced conduction block primarily affects the AV node, adenosine is a useful diagnostic tool in patients with broad or narrow QRS complex tachycardia; it terminates arrhythmias dependent on the AV node, unmasks other supraventricular mechanisms during transient AV block, but almost always has no effect on ventricular tachycardia. Noncardiac adverse effects, i.e. flushing, dyspnoea and chest pain, may occur during acute arrhythmia termination or diagnosis with adenosine, and arrhythmias may develop; however, these effects are usually transient (lasting less than 1 minute). Adenosine has also been used to induce coronary vasodilation in patients undergoing thallium-201 single photon emission computed tomography (201Tl SPECT), 2-dimensional echocardiography or positron emission tomography to evaluate suspected coronary artery disease. Intravenous infusion of adenosine 140 micrograms/kg/min for 6 minutes was generally associated with only mild adverse effects. These usually resolved within 1 to 2 minutes of discontinuing adenosine, although occasionally patients required aminophylline and/or nitroglycerin (glyceryl trinitrate). Diagnoses based on the results of scintigraphy were of a sensitivity, specificity and predictive accuracy comparable to those achieved with exercise- or dipyridamole-201Tl SPECT. Adenosine is therefore particularly suitable for the diagnosis of tachycardias and the acute management of PSVT involving the AV node in all age groups, without the risks of cardiac arrest and hypotension associated with verapamil. Furthermore, intravenous adenosine infusion may be used to induce coronary vasodilation in patients unable to perform exercise stress tests for 201Tl scintigraphy, and is well tolerated.

Torasemide. A review of its pharmacological properties and therapeutic potential.

Torasemide (torsemide) is a high-ceiling loop diuretic which acts on the thick ascending limb of the loop of Henle to promote rapid and marked excretion of water, sodium and chloride. Like furosemide (frusemide), its major site of action is from the luminal side of the cell. Torasemide is at least twice as potent as furosemide on a weight-for-weight basis, produces equivalent diuresis and natriuresis at lower urinary concentrations and has a longer duration of action, allowing once-daily administration without the paradoxical antidiuresis seen with furosemide. Torasemide also appears to promote excretion of potassium and calcium to a lesser extent than furosemide. In trials of up to 48 weeks' duration in patients with mild to moderate essential hypertension, torasemide, administered as a single daily dose, has been shown to achieve adequate blood pressure control reaching steady-state within 8 to 12 weeks. Those patients not responding initially have generally responded to a doubling of the dose. Comparative trials of up to 6 months show torasemide is as effective as indapamide, hydrochlorothiazide or a combination of triamterene/hydrochlorothiazide in maintaining control of blood pressure. Torasemide has also been used successfully to treat oedematous states associated with chronic congestive heart failure, renal disease and hepatic cirrhosis. In short term trials control of blood pressure, bodyweight and residual oedema has been sustained. Torasemide appears to be a useful alternative to furosemide in these patients, providing potent and long-lasting diuresis while being relatively potassium and calcium sparing. In clinical trials to date torasemide has been well tolerated with adverse effects of a mild, transient nature reported by only small numbers of patients. Changes in biochemical parameters have been common, including decreases in plasma sodium and potassium levels and increases in plasma creatinine and uric acid levels. These changes are typical of loop diuretics. No changes were clinically significant nor were clinically relevant changes noted in glucose metabolism, cholesterol or triglyceride levels or in haematological values. Thus, torasemide is an interesting new loop diuretic with potential use in the treatment of mild to moderate essential hypertension and of oedematous states in which diuretic therapy is warranted. Preliminary studies suggest it to be as efficacious as other diuretics in common use and to have some advantage over furosemide in duration of action and in effects on potassium and calcium. However, further long term trials in larger groups of patients are needed to delineate the place of torasemide in therapy fully, both as a single agent and in combination with other currently accepted drug regimens.

Cetirizine. A review of its pharmacological properties and clinical potential in allergic rhinitis, pollen-induced asthma, and chronic urticaria.

Cetirizine, a piperazine derivative and carboxylated metabolite of hydroxyzine, is a potent histamine H1-receptor antagonist with antiallergic properties. It has marked affinity for peripheral histamine H1-receptors and, at the standard dose of 10mg daily, lacks the CNS depressant effects of standard antihistamines. In addition, it inhibits histamine release and eosinophil chemotaxis during the secondary phase of the allergic response. Results from controlled clinical trials indicate that cetirizine is an effective and well tolerated treatment of seasonal and perennial allergic rhinitis and chronic idiopathic urticaria. Cetirizine appears to be as effective as conventional dosages of terfenadine, chlorpheniramine and hydroxyzine in relieving symptoms associated with these disorders and produces a markedly lower incidence of sedation than chlorpheniramine, hydroxyzine and several other standard antihistamines. Thus, cetirizine appears to provide a useful alternative to other 'nonsedating' antihistamines; cetirizine may also have a future role in the treatment of allergic asthma and certain forms of physical urticaria.

Ocular betaxolol. A review of its pharmacological properties, and therapeutic efficacy in glaucoma and ocular hypertension.

Betaxolol is a lipophilic beta-adrenoceptor antagonist relatively selective for beta 1-adrenoceptors with only weak beta 2-blocking activity. Used topically in glaucoma and ocular hypertension, betaxolol 0.5% solution produces a reduction in intraocular pressure of between 13 and 30%, an effect comparable with that of ocular timolol. It may usefully be combined with other types of anti-glaucoma agents. The most notable feature of its adverse effect profile is transient local stinging or irritation, occurring in 25 to 40% of patients. Following ocular administration, betaxolol appears to be largely devoid of adverse bronchopulmonary or cardiac effects, in comparison with nonselective ocular beta-adrenoceptor antagonists, which may be more likely to exert systemic effects. Betaxolol has negligible local anaesthetic activity, so that corneal desensitisation does not occur with its use. Thus, betaxolol is an alternative therapeutic option available to the physician for the management of chronic open-angle glaucoma and ocular hypertension. Its apparently lower propensity to affect the cardiopulmonary system represents a significant advantage over other ocular beta-adrenoceptor antagonists.

Diltiazem. A reappraisal of its pharmacological properties and therapeutic use.

Diltiazem is a calcium antagonist effective in the treatment of stable, variant and unstable angina pectoris and mild to moderate systemic hypertension, with a generally favourable adverse effect profile. It is also effective in terminating supraventricular tachycardia and in controlling the ventricular response to atrial fibrillation/flutter. Atrioventricular block, the risk of which may be exacerbated by concomitant beta-adrenoceptor antagonist therapy, occurs rarely as an adverse effect of diltiazem treatment. Diltiazem appears to exert complex cardioprotective effects which have been of benefit after intracoronary administration to patients undergoing coronary angiography and bypass procedures. In addition, long term diltiazem treatment has produced a significant reduction in subsequent cardiac events in patients with non-Q wave myocardial infarction. Thus, diltiazem is an effective and well-tolerated first-line or alternative treatment of patients with ischaemic heart disease, systemic hypertension, and supraventricular arrhythmias, with possible potential in limiting ischaemia-induced myocardial damage.