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Biomedical subjects

R N Brogden

Publications and source records attributed to R N Brogden.

At least 73 records · Page 4Linked to original sources
PubMed1991

Flutamide. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in advanced prostatic cancer.

Flutamide, a nonsteroidal antiandrogenic drug devoid of hormonal agonist activity, is used in the treatment of advanced prostate cancer. In previously untreated patients, flutamide 750 mg daily given alone is of comparable efficacy to diethylstilbestrol (stilboestrol) 1 or 3 mg daily and estramustine 560 or 840 mg daily, but has the potential advantages of fewer cardiovascular effects and maintenance of some sexual potency. Its greatest therapeutic potential is as a component of combination androgen blockade, where administration with an agonist analogue of gonadotrophin-releasing hormone (GnRH) [luteinising hormone-releasing hormone (LH-RH)] in both initial uncontrolled and randomised studies increased survival time relative to GnRH agonist monotherapy or orchidectomy. Subsequent multicentre trials, however, have been unable to confirm an improvement in survival time. Thus, while there seems to be little doubt that flutamide prevents the initial disease flare caused by GnRH agonists, an improvement in remission rate and survival remains contentious. Flutamide is generally well tolerated and is suitable monotherapy in patients with previously untreated advanced prostatic cancer who wish to preserve sexual potency. However, full assessment of the role of combination androgen blockade awaits publication of the final results of ongoing multicentre trials.

Animals↗
PubMed1991

Quinapril. A review of its pharmacological properties, and therapeutic efficacy in cardiovascular disorders.

Quinapril is a monoethyl ester which is hydrolysed after absorption to form an active metabolite, quinaprilat, which is a more potent angiotensin converting enzyme (ACE) inhibitor than the parent drug. Quinaprilat has a short elimination half-life but a potent binding affinity for ACE which enables once daily administration. Data from clinical studies indicate that quinapril 10 to 40 mg daily, given as a single dose, is an effective antihypertensive agent, suitable as monotherapy for reducing high blood pressure and maintaining satisfactory control during long term treatment of mild to severe hypertension. Dosages of 80 mg daily have been used in some patients. Concomitant diuretic therapy usually elicits a response in patients who fail to respond adequately to monotherapy. Initial studies suggest that quinapril also has a role in the treatment of mild to severe congestive heart failure. In the few long term studies conducted the beneficial acute haemodynamic effects were maintained during long term treatment and were accompanied by symptomatic and functional improvement. The majority of these patients responded to twice daily administration. Adverse effects associated with the antihypertensive action of quinapril are generally mild, well tolerated and are similar to those of other ACE inhibitors. Thus, quinapril appears to be a useful alternative ACE inhibitor for the treatment of mild to severe hypertension and congestive heart failure.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

Sustained release nifedipine formulations. An appraisal of their current uses and prospective roles in the treatment of hypertension, ischaemic heart disease and peripheral vascular disorders.

Nifedipine antagonises influx of calcium through cell membrane slow channels, and sustained release formulations of the calcium channel blocker have been shown to be effective in the treatment of mild to moderate hypertension and both stable and variant angina pectoris. Preliminary findings also indicate that these formulations are effective in the treatment of Raynaud's phenomenon and hypertension in pregnancy, and that they reduce the frequency of ischaemic episodes in some patients with silent myocardial ischaemia. The exact mechanism of action of nifedipine in all of these disorders has not been defined. However, its potent peripheral and coronary arterial dilator properties, together with improvements in oxygen supply/demand, are of particular importance. A major goal of sustained release therapy is to permit reductions in the frequency of nifedipine administration, preferably to once daily, and thus improve patient compliance. Two new once-daily formulations--the nifedipine gastrointestinal therapeutic system (GITS) and a fixed combination capsule comprising sustained release nifedipine 20 mg and atenolol 50 mg--have exhibited marked antihypertensive efficacy. The GITS preparation has also been used effectively in the treatment of stable angina pectoris, and both formulations appear to be well tolerated. Sustained release nifedipine formulations are generally better tolerated than their conventionally formulated counterparts, particularly with regard to reflex tachycardia. Adverse effects seem to be dose related, are mainly associated with the drug's potent vasodilatory action, and include headache, flushing and dizziness. Generally, these effects are mild to moderate in severity and transient, usually diminishing with continued treatment. Thus, sustained release nifedipine formulations are useful and established cardiovascular therapeutic agents which have demonstrable efficacy in various forms of angina, mild to moderate hypertension and Raynaud's phenomenon. Further, promising results shown by the nifedipine GITS formulation, with its advantage of once daily administration suggest that it is likely to become one of the preferred nifedipine formulations for the treatment of hypertension and the various forms of angina.

Coronary Disease↗
PubMed1991

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.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

Acrivastine. A review of its pharmacological properties and therapeutic efficacy in allergic rhinitis, urticaria and related disorders.

Acrivastine is a short acting histamine H1-receptor antagonist with a rapid onset of action. Double-blind clinical trials have shown acrivastine (usually 8mg three times daily) to be an effective and well tolerated antihistamine in the treatment of chronic urticaria and allergic rhinitis. Acrivastine was more effective than placebo and similar in efficacy to clemastine or terfenadine in the treatment of seasonal allergic rhinitis. In the treatment of dermatoses in which histamine has a pathogenetic role, the efficacy of acrivastine was superior to that of placebo and similar to that of usual dosages of clemastine, hydroxyzine, chlorpheniramine, cyproheptadine or terfenadine. Acrivastine caused less drowsiness than clemastine, the incidence of adverse effects being indistinguishable from that with placebo or terfenadine. Thus, acrivastine is an effective addition to drugs currently available for the treatment of patients with allergic diseases in whom a histamine H1-receptor antagonist is indicated. Because of its rapid onset of action acrivastine will be particularly useful for 'on demand' therapy in patients with intermittent symptoms.

Dermatitis, Atopic↗
PubMed1991

Ifosfamide/mesna. A review of its antineoplastic activity, pharmacokinetic properties and therapeutic efficacy in cancer.

Ifosfamide is an oxazaphosphorine alkylating agent with a broad spectrum of antineoplastic activity. It is a prodrug metabolised in the liver by cytochrome P450 mixed-function oxidase enzymes to isofosforamide mustard, the active alkylating compound. Mesna, a uroprotective thiol agent, is routinely administered concomitantly with ifosfamide, and has almost eliminated ifosfamide-induced haemorrhagic cystitis and has reduced nephron toxicity. Therapeutic studies, mostly noncomparative in nature, have demonstrated the efficacy of ifosfamide/mesna alone, or more commonly as a component of combination regimens, in a variety of cancers. In patients with relapsed or refractory disseminated nonseminomatous testicular cancer, a salvage regimen of ifosfamide/mesna, cisplatin and either etoposide or vinblastine produced complete response in approximately one-quarter of patients. As a component of both induction and salvage chemotherapeutic regimens, ifosfamide/mesna has produced favourable response rates in small cell lung cancer, paediatric solid tumours, non-Hodgkin's and Hodgkin's lymphoma, and ovarian cancer. Induction therapy with ifosfamide/mesna-containing chemotherapeutic regimens has been encouraging in non-small cell lung cancer, adult soft-tissue sarcomas, and as neoadjuvant therapy in advanced cervical cancer. As salvage therapy, ifosfamide/mesna-containing combinations have a palliative role in advanced breast cancer and advanced cervical cancer. Ifosfamide/mesna can elicit responses in patients refractory to numerous other antineoplastic drugs, including cyclophosphamide. With administration of concomitant mesna to protect against ifosfamide-induced urotoxicity, the principal dose-limiting toxicity of ifosfamide is myelosuppression; leucopenia is generally more severe than thrombocytopenia. Reversible CNS adverse effects ranging from mild somnolence and confusion to severe encephalopathy and coma can occur in approximately 10 to 20% of patients after intravenous infusion, and the incidence of neurotoxicity may be increased to 50% after oral administration because of differences in the preferential route of metabolism between the 2 routes of administration. Other adverse effects of ifosfamide include nephrotoxicity, alopecia, and nausea/vomiting. In general, intravenously administered mesna is associated with a low incidence of adverse effects; however, gastrointestinal disturbances are common following oral administration. Thus, ifosfamide/mesna is an important and worthwhile addition to the currently available range of chemotherapeutic agents. It has a broad spectrum of antineoplastic activity and causes less marked myelosuppression than many other cytotoxic agents. At present, the role of ifosfamide/mesna in refractory germ cell testicular cancer is clearly defined; however, its overall place in the treatment of other forms of cancer awaits delineation in future well-controlled comparative studies.

Drug Evaluation↗
PubMed1991

Atenolol. A reappraisal of its pharmacological properties and therapeutic use in cardiovascular disorders.

Atenolol is a selective beta 1-adrenoceptor antagonist with a duration of activity of at least 24 hours. The scope of therapeutic use of the drug has been expanded and become better defined since it was first reviewed in the Journal in 1979. Atenolol is effective and generally well tolerated in patients with all grades of hypertension. Data from comparative studies show that when administered orally, atenolol reduces blood pressure to a similar extent, and in a similar proportion of patients, as usual therapeutic doses of other beta-adrenoceptor antagonists (such as acebutolol, celiprolol, betaxolol, indenolol, metoprolol, nadolol, pindolol, propranolol, tertatolol), angiotensin converting enzyme (ACE) inhibitors (e.g. captopril, enalapril and lisinopril), calcium antagonists (e.g. amlodipine, diltiazem, felodipine, isradipine, nitrendipine, nifedipine, verapamil), doxazosin, ketanserin and alpha-methyldopa. Atenolol effectively lowers blood pressure in elderly patients with hypertension and in women with hypertension associated with pregnancy, and improves objective and subjective indices in patients with stable angina pectoris. Oral atenolol is used for preventing recurrence of supraventricular arrhythmias once control is achieved by intravenous administration of atenolol. Early intervention with intravenous atenolol followed by oral maintenance therapy reduces infarct recurrence and cardiovascular mortality in patients with known or suspected myocardial infarction. There is also encouraging evidence of reduced mortality from cardiovascular disease during long term therapy with atenolol in patients with hypertension. Atenolol is well tolerated in most patients. Increases in plasma levels of both total triglycerides and very low density lipoprotein (VLDL) triglycerides have accompanied atenolol therapy although the clinical relevance, if any, of longer term metabolic effects has yet to be determined. Its low lipid solubility and limited brain penetration results in a lower incidence of central nervous system effects than that associated with propranolol. After many years of clinical usage atenolol is a well established treatment option in several areas of cardiovascular medicine such as mild to moderate hypertension and stable angina pectoris. Furthermore, it has also shown potential in the treatment of some cardiac arrhythmias and has been associated with reduced cardiovascular mortality in patients with hypertension and in patients with myocardial infarction.

Arrhythmias, Cardiac↗
PubMed1991

Naftifine. A review of its antimicrobial activity and therapeutic use in superficial dermatomycoses.

Naftifine is an allylamine derivative for topical administration with a mechanism of action distinct from that of other classes of antifungal agents. It inhibits squalene epoxidase and may have certain anti-inflammatory properties, but its precise mechanism of action is as yet unclear. In vitro, naftifine has potent fungistatic and fungicidal activity against dermatophytes. This correlates well with its clinical and mycological activity in patients with dermatophytoses. There is improvement in clinical symptoms and overall therapeutic success after a 2- to 5-week course of therapy in a high percentage of patients (usually over 80%) with tinea cruris or corporis, and in a slightly smaller percentage of those with tinea pedis. Naftifine is moderately active in vitro against moulds, but is generally less active against yeasts, including Candida albicans. However, it has proved reasonably effective in the treatment of patients with cutaneous candidiasis, although further studies are necessary to establish its place in therapy for this indication. In view of its good local tolerability, absence of systemic adverse effects, novel mechanism of action and effectiveness with once-daily application, naftifine offers a useful addition to available pharmaceutical options in patients with dermatomycoses.

Allylamine↗
PubMed1991

Salmeterol xinafoate. A review of its pharmacological properties and therapeutic potential in reversible obstructive airways disease.

Salmeterol xinafoate, like salbutamol (albuterol), is a saligenin derivative, and a selective beta 2-adrenoceptor agonist. It produces bronchodilation for at least 12 hours following inhalation of a single 50 micrograms dose. Salmeterol is intended for regular twice-daily treatment of reversible airways obstruction and not for immediate symptomatic relief, and when used in this manner, 50 micrograms twice daily is more effective than salbutamol 200 micrograms or terbutaline 500 micrograms administered 4 times daily, or individually titrated oral doses of theophylline in improving objective and subjective criteria of efficacy in patients with mild to moderate asthma. Salmeterol 100 micrograms inhaled twice daily may provide better control than the lower dose in patients with severe asthma. The long duration of effect of salmeterol makes it particularly suitable for treating patients with nocturnal asthma in whom it improves sleep quality. The place of salmeterol, like that of other beta 2-adrenoceptor agonists used regularly in the treatment of asthma, is being debated. Patients in need of regular beta 2-agonist therapy should also be regarded as candidates for inhaled corticosteroids to counteract underlying inflammation. Thus, salmeterol may be particularly useful in patients requiring regular treatment with beta 2-agonists for nocturnal asthma and results of trials in progress involving large numbers of patients are awaited with interest.

Administration, Inhalation↗
PubMed1991

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

Enoximone is an imidazolone derivative currently undergoing trials in patients with congestive heart failure refractory to conventional therapy. It is a phosphodiesterase inhibitor with both positive inotropic and vasodilator properties, and is active by both oral and intravenous routes of administration. While pharmacodynamic studies have documented beneficial haemodynamic effects after short term oral administration, and objective and subjective improvement relative to placebo during some short term trials, its clinical efficacy during continuous longer term therapy remains uncertain. Enoximone is of potential benefit as an adjunct in short term management of patients with end-stage cardiac failure awaiting cardiac transplantation. In the usually small studies reported to date enoximone was generally better tolerated at oral dosages of less than 2 mg/kg than at higher dosages. Thus, while its pharmacodynamic profile holds potential promise in a difficult therapeutic area, the long term clinical efficacy and tolerability of enoximone remain yet to be determined in controlled trials of adequate size and duration.

Animals↗
PubMed1991

Flumazenil. A reappraisal of its pharmacological properties and therapeutic efficacy as a benzodiazepine antagonist.

Flumazenil is a specific benzodiazepine antagonist which is indicated when the central effects of a benzodiazepine need to be attenuated or terminated. Following intravenous administration of up to 1 mg, flumazenil effectively reverses sedation and improves psychomotor performance following administration of short and longer acting benzodiazepines used for sedation, or general anaesthesia supplemented with benzodiazepines. The duration of action is short at generally 30 to 60 minutes and supplemental doses of flumazenil may be needed to maintain the desired level of consciousness in some patients. After poisoning with high dosages of benzodiazepines alone or combined with other drugs, the initial single dose of flumazenil will require supplementing with repeated low intravenous doses or an infusion to maintain wakefulness. In such patients, flumazenil also facilitates differential diagnosis and reduces the necessity for interventions. Flumazenil thus enhances recovery and allows more rapid discharge of patients sedated with benzodiazepines for diagnostic procedures and facilitates management of patients during the initial recovery period following general anaesthesia supplemented with benzodiazepines, but does not preclude normal monitoring during the recovery period. Flumazenil is clearly very useful in treating drug poisoning when benzodiazepines are a major component. By virtue of its specific benzodiazepine antagonist effects, flumazenil provides an innovative and well tolerated approach in clinical situations requiring rapid reversal of benzodiazepine-induced central nervous system depressant effects.

Animals↗
PubMed1990

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.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1990

Buserelin. A review of its pharmacodynamic and pharmacokinetic properties, and clinical profile.

The gonadotrophin releasing hormone (GnRH) [luteinising hormone-releasing hormone (LHRH); gonadorelin] agonist buserelin is a promising new agent in the treatment of a variety of disorders in gynaecology and andrology, paediatrics and oncology. While a single dose of buserelin stimulates the release of pituitary gonadotrophins, multiple doses produce reversible pituitary desensitisation, and this specific blockade of gonadotrophin support to the gonads provides the basis for the drug's efficacy in conditions dependent on sex hormone secretion. Thus, buserelin provides comparable efficacy to orchidectomy or high dose estrogens in the treatment of hormone-sensitive prostate cancer and exhibits a lower incidence of adverse effects. During the early phase of treatment it may be particularly useful in combination with antiandrogens. Buserelin also appears promising in hormone-sensitive premenopausal breast cancer. Extensive studies have proven the value of buserelin in endometriosis, where it produces a transient remission with gradual recurrence of the disease on cessation of treatment. Surgical intervention is necessary in severe disease after buserelin-induced involution of the lesions. In patients with uterine leiomyoma, preliminary data suggest that buserelin may be beneficial in rendering surgery more conservative by reducing fibroid size, although it appears unlikely to preclude surgical intervention. The use of buserelin to induce a state of reversible hypogonadotrophism before administration of exogenous gonadotrophins is a promising strategy in the treatment of infertility associated with polycystic ovary syndrome and other conditions of infertility with underlying ovarian dysfunction; such a strategy also clearly enhances the efficiency of in vitro fertilisation programmes. Initial studies suggest its potential usefulness as a female contraceptive when administered intermittently in conjunction with a progestogen. Buserelin represents a first-line treatment of central precocious puberty. In endometriosis the adverse effect profile of buserelin is generally favourable, with hypoestrogenic effects such as hot flushes and vaginal dryness, and decreased libido, predominating. There is no apparent detrimental effect on lipid metabolism. The potential for adverse hypoestrogenic effects on bone mineral content with long term administration remains to be clarified. Thus, the GnRH agonist buserelin represents an advance in the treatment of a variety of gynaecological and andrological as well as paediatric and oncological conditions, infertility and other sex-hormone dependent conditions, with a low incidence of adverse treatment effects.

Animals↗
PubMed1990

Acecainide (N-acetylprocainamide). A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in cardiac arrhythmias.

Acecainide (N-acetylprocainamide), the N-acetylated metabolite of procainamide, is a Class III antiarrhythmic agent. It can be given either intravenously or orally, and is eliminated primarily by renal excretion. In a small number of noncomparative and placebo-controlled short term therapeutic trials acecainide markedly reduced premature ventricular beats and prevented induction of ventricular tachycardia in more than 70% of patients following intravenous administration and in about 50% after oral administration. Acecainide was effective in about one-quarter of patients refractory to other antiarrhythmic drugs. Interpretation of its effectiveness following long term oral therapy is complicated by the limited number of patients, and patients discontinuing due to adverse effects or lack of efficacy. However, about 40% of the small number treated for extended periods were controlled for periods of 6 months to 3 to 4 years. Comparative studies with other antiarrhythmic drugs have not been undertaken apart from a small study in atrial flutter where acecainide was better than quinidine plus digoxin. Thus, although further clinical experience is required before the relative place of acecainide in therapy can be determined, the drug nevertheless appears to offer advantages over procainamide, particularly with respect to the reduced formation of antinuclear antibodies.

Acecainide↗
PubMed1990

Pinacidil. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in the treatment of hypertension.

Pinacidil is an orally administered antihypertensive drug that acts via direct relaxation of vascular smooth muscle to produce peripheral vasodilatation and a reduction in blood pressure without significant direct effects on cardiac electrophysiology. Pinacidil is unrelated to other antihypertensive drugs in clinical use, either in structure or mechanism of action. It belongs to a new class of agents called 'potassium channel openers' which act via potassium efflux to hyperpolarize cell membranes, indirectly causing a net reduction in intracellular calcium that leads to relaxation of vascular smooth muscle. Pinacidil is indicated in the management of essential hypertension. In clinical trials of up to 1 year duration, pinacidil administered twice daily in a controlled release capsule formulation has been shown to achieve adequate blood pressure control both in previously untreated patients and in those with blood pressure inadequately controlled by beta-adrenoceptor blocking drugs or thiazide diuretics. In long term (up to 1 year) comparative studies pinacidil was at least as effective as hydralazine, prazosin or nifedipine in maintaining blood pressure control. Pinacidil may also have a potential use in the treatment of patients with secondary renal hypertension. Clinical trials to date have usually allowed the addition of a thiazide diuretic and/or beta-adrenoceptor blocking drug to enhance the efficacy of pinacidil and/or to reduce the incidence of adverse effects. The main adverse effects of pinacidil treatment, which result from its peripheral vasodilator activity, are headache, oedema, palpitations and tachycardia. Although the overall incidence of adverse effects is quite high, they are usually mild, transient in nature and respond to a reduction in dose. Nevertheless, these effects may occasionally be severe, necessitating withdrawal from therapy. Thus, pinacidil is an effective antihypertensive drug for the treatment of mild to moderate essential hypertension. Despite its novel mechanism of action pinacidil causes adverse effects typical of peripheral vasodilators; during long term use with twice daily administration of the controlled release capsule formulation, the addition of a diuretic is often necessary to attenuate peripheral oedema and maintain adequate control of blood pressure. Further long term controlled trials are needed to determine the precise role of pinacidil relative to that of the angiotensin converting enzyme (ACE) inhibitors and calcium channel blocking drugs.

Animals↗
PubMed1990

Mexiletine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in the treatment of arrhythmias.

As a member of the class Ib antiarrhythmic drugs mexiletine's primary mechanism of action is blocking fast sodium channels, reducing the phase 0 maximal upstroke velocity of the action potential. It increases the ratio of effective refractory period to action potential duration, but has little effect on conductivity. Unlike quinidine it does not prolong QRS and QT (QTc) intervals. In the dosage range 600 to 900 mg daily mexiletine effectively suppresses premature ventricular contractions (PVCs) in 25% to 79% of patients, with or without underlying cardiac disease. In comparative studies the response rate was comparable to that with quinidine or disopyramide. However, the use of antiarrhythmic therapy in patients with asymptomatic arrhythmias is controversial. More importantly, mexiletine abolishes spontaneous or inducible ventricular tachycardia or fibrillation in the short term in 20% to 50% of patients with refractory arrhythmias. Arrhythmia suppression is maintained in 57% to over 80% of these early therapeutic successes in the long term, with mexiletine alone or in combination with another antiarrhythmic drug. As with other antiarrhythmic drugs, there is no substantial evidence that administration of mexiletine after acute myocardial infarction improves long term prognosis. Although the incidence of adverse effects associated with mexiletine is high, the majority are minor gastrointestinal or neurological effects which can be adequately controlled through dosage adjustment. Furthermore, mexiletine has minimal effects on haemodynamic variables, or on cardiac function in patients with or without pre-existing deterioration of left ventricular function, and it appears to have a low proarrhythmic potential. Thus, while the therapeutic efficacy of mexiletine for the prevention or suppression of symptomatic ventricular arrhythmias may be no greater than that of other antiarrhythmic drugs, and less than that of some (e.g. amiodarone), it is effective in a significant proportion of patients refractory to other treatments and can be administered without causing adverse haemodynamic effects to patients with complicating factors such as acute myocardial infarction or congestive heart failure.

Animals↗
PubMed1990

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

Teicoplanin is a glycopeptide antibiotic with a molecular structure which is related to that of vancomycin. Gram-positive bacteria such as staphylococci (including methicillin-resistant strains), streptococci, enterococci and many anaerobic Gram-positive bacteria are susceptible to teicoplanin in vitro. Teicoplanin has an exceptionally long half-life, allowing once-daily intramuscular or intravenous administration. Teicoplanin is clinically and bacteriologically effective against a wide variety of Gram-positive infections such as septicaemia, endocarditis, skin and soft tissue infections and infections associated with venous catheters. The drug is equally efficacious against methicillin-resistant and -susceptible staphylococci. Adverse effects with teicoplanin are generally limited to local effects or hypersensitivity reactions. While teicoplanin has the potential for ototoxicity and nephrotoxicity, the incidence appears to be quite low when recommended serum concentrations are maintained. Teicoplanin is a valuable alternative to vancomycin, and providing controlled comparative studies prove equivalent safety and efficacy between the 2 glycopeptides the more easily administered teicoplanin should become the preferred antibacterial agent.

Anti-Bacterial Agents↗