Transient ischaemic attacks. Current treatment concepts

Transient ischaemic attacks are common, having an incidence of at least 50 per 100,000 population per annum, and the risk of stroke and/or death is about 10% per annum. Death is more often due to the complications of coronary artery disease than cerebrovascular disease. The most important issues in management are distinguishing transient ischaemic attacks from several other causes of 'transient focal neurological attacks', and managing the risk factors for vascular disease in general, particularly hypertension. The utility of specific 'antithrombotic' treatments is still uncertain, but for long term use aspirin seems to be the most promising. The only dose so far tested in clinical trials has been about 600mg twice daily but lower doses may theoretically be as, or more, effective. Trials of aspirin and other antiplatelet agents, and also of carotid endarterectomy and extracranial-to-intracranial bypass surgery are continuing and should be strongly encouraged. Although transient ischaemic attacks recover - by definition - in 24 hours, the pathophysiology, natural history, and treatment of focal cerebral ischaemia which recovers in a matter of days or weeks is probably rather similar.     

Menorrhagia. Current drug treatment concepts.

Since menorrhagia occurs in 9 to 14% of populations of healthy women, many general practitioners will encounter menorrhagia-related problems. Menorrhagia is difficult to objectify and the choice of treatment between the available drugs is not always an easy one. In this survey, the available knowledge on menorrhagia diagnosis, underlying pathophysiology and treatment, especially medicinal treatment, are discussed. Overall, a practical approach is emphasised. The desire for contraception as well as the underlying cause of menorrhagia determine the drug of choice in the treatment of menorrhagia. If contraception is desired, oral combination contraceptives and continuously dosed progestogens, orally or as a medicated intrauterine device (IUD), are the first choice drugs for essential menorrhagia, and for fibroid- and bleeding disorder-associated menorrhagia. If no contraception is desired, the first choice treatments are drugs that need to be administered only during menstruation, such as prostaglandin synthesis inhibitors or antifibrinolytics. Of these, antifibrinolytics reduce menstrual blood loss to the greatest extent, whereas prostaglandin synthesis inhibitors have the lowest incidence of side effects. Prostaglandin synthesis inhibitors also have the extra advantage of diminishing dysmenorrhoea. There is no place for ergometrine in the treatment of menorrhagia. No studies are available as yet on the combination of various drug treatment modalities, although such an evaluation would be desirable.     

Current concepts in the treatment of prostate cancer

Carcinoma of the prostate is one of the most common cancers in men over 50 years of age and is the second leading cause of cancer death in men over 75. As a general rule, symptoms usually are not apparent until the tumor is far advanced. Between 80 to 90 percent of patients have metastatic disease at the time of presentation and are not curable by surgery. Endocrine manipulation remains the most effective and commonly used treatment for metastatic carcinoma of the prostate.     

Current concepts in the treatment of immune thrombocytopenia

Platelet destruction by antibodies is a common cause of thrombocytopenia. In this review, various treatments for immune thrombocytopenia are discussed, with emphasis on corticosteroids, splenectomy, danazol, high-dose immunoglobulin G, anti-Rhesus globulin, colchicine and cytotoxic, immunosuppressive agents such as cyclophosphamide and azathioprine. An approach to the treatment of adult idiopathic thrombocytopenic purpura (ITP) is reviewed in detail and the treatments for several other immune thrombocytopenic disorders are summarised.     

Current concepts in the treatment of rheumatoid arthritis

The treatment of RA is complex and often frustrating. The pathologic process of RA is composed of acute inflammation, chronic immunologic phenomenon, and chronic connective tissue degradation. It is important to understand not only the pathophysiology of RA but also the mechanism of action of our therapeutic drugs so that treatment can be tailored to affect the important aspects of the process leading to end-organ damage. Despite the many drugs available, therapy is still unsatisfactory. Many drugs work in only certain patients. This could be secondary to variability in the disease state or to difference in drug metabolism. A better understanding of both disease and therapeutic agents may lead to better use of our present agents and development of new, more effective treatment modalities.     

Current concepts in the treatment of disorders of micturition

Disorders of micturition may be divided into disturbances of the storage function of the bladder, and disturbances of the emptying function. The main symptoms of disturbances of storage function are frequency, urgency and incontinence. Hyperactivity of the bladder may lead to urge incontinence, and incompetence of the urethral closure mechanism to stress incontinence. There are many drugs available for treating bladder hyperactivity, but their efficacy as judged from controlled clinical trials (when available) is often limited. Bladder contraction in man is mediated by stimulation of muscarinic receptors, and when given parenterally anticholinergic drugs have been shown to depress bladder hyperactivity irrespective of the underlying cause. Clinically, however, treatment of urge incontinence with anticholinergic drugs is often unsatisfactory. Lack of effect of oral treatment and systemic side effects limit the use of available agents. Drugs with "mixed" actions (anticholinergic and 'direct' muscle effects), for example oxybutynin and terodiline, have well-documented efficacy in bladder hyperactivity. Side effects are common with oxybutynin; terodiline seems to be well tolerated. The aim of drug treatment of stress incontinence is to increase outflow resistance. Although there is only limited possibility of improving the condition with drugs, beneficial effects can be obtained in some patients by use of orally active alpha-adrenoceptor agonists (e.g. phenylpropanolamine) and/or oestrogens. The main symptom of disturbed bladder emptying is urinary retention. Drug therapy is aimed at improving the contractile activity of the detrusor or reducing urethral outflow resistance. Drugs used for improving bladder contractility include parasympathomimetic agents, e.g. bethanechol or carbachol, and intravesical instillation of prostaglandins. Although the efficacy of both types of treatment is open to question, bethanechol seems to be widely used. Increased outflow resistance may be seen in patients with parasympathetic decentralization of the lower urinary tract or in patients with benign prostatic hypertrophy. These patients may respond favourably to alpha-adrenoceptor blockers such as phenoxybenzamine or prazosin.     

Pruritus. Current concepts in pathogenesis and treatment

Pruritus is an unpleasant sensation that provokes an urge to scratch. Many stimuli (notably histamine) are able to induce pruritus. The neural conduction of the itch sensation from the free unmyelinated nerve endings to the central nervous system mainly occurs on unmyelinated C fibres and the anterolateral spinothalamic tract. Pruritus is a common symptom in many skin or systemic diseases, but very little is known about the mechanism of the condition. Treatment evaluation is difficult; many methods do not evaluate the pruritus, but only the scratching, which is a consequence of pruritus. A number of asymptomatic treatments are only partially effective and we know little about their mechanism of action. Antihistamines remain the treatment of first choice for pruritus without known cause, but generally give incomplete relief. Whenever possible it is best to treat the underlying disease.     

Current concepts and treatment options in eosinophilic esophagitis

Eosinophilic esophagitis (EE) is an inflammatory disorder of the esophagus that affects both children and adults, and is different from gastro-esophageal reflux disease. The immunopathogenesis of EE involves an allergic response to environmental and food allergens, and the proinflammatory cytokines IL-5 and IL-13. EE may be associated with atopic disorders and peripheral eosinophilia, and may be familial in distribution. The most common presentation is dysphagia and food impaction in adults, with additional manifestations of epigastric pain, emesis, weight loss and failure to thrive in children. Typical endoscopic findings include ringed esophagus, linear furrows, strictures and narrow esophagus. Diagnosis is confirmed by the presence of 20 or more eosinophils per high power field in the esophagus. The available treatment options include elemental diet, avoidance of specific food allergens, topical and systemic corticosteroids, and humanized monoclonal antibodies against IL-5. This review summarizes the etiopathogenesis, clinical, endoscopic and histopathological findings in EE, and describes current available treatment options.     

Diabetic neuropathies. Current concepts in prevention and treatment

Diabetic nerve damage leads to a wide variety of unpleasant problems: painful sensations, muscle weakness, numb feet predisposing to ulcers, impotence, and a series of distressing effects due to autonomic dysfunction. At present, there is no single effective treatment for the many clinical syndromes--each of which may well have a different cause. Improved blood glucose control must remain the first line of treatment, hopefully to improve nerve structure and function but also to raise the pain threshold. A variety of sedatives and analgesics may also help some patients. Inhibition of the enzyme aldose reductase with resultant interference with neural sorbitol and myo-inositol metabolism would seem to have a good theoretical basis in therapy, and detailed results of long term clinical trials of aldose reductase inhibitors such as sorbinil and tolrestat are awaited with interest. Their role in the future could be more important in prevention of nerve damage than in attempting to reverse gross end-stage nerve destruction. In diabetic subjects with loss of pain sensation in the foot due to neuropathy or in the more advanced state of foot ulceration, intensive educational and clinical efforts should be exerted to prevent this distressing and common problem. In the future, a more detailed understanding of the biochemical abnormalities occurring in nerves and their effect on nerve function, structure and vasculature may lead to more satisfactory and logical treatments for this the commonest single complication of diabetes.     

The urticarias. Current concepts in pathogenesis and treatment

Urticaria is a very common disease which is often associated with angioedema. Release of histamine and perhaps other mediators from the cutaneous mast cells is believed to be the likeliest cause for the development of these wheals in most instances, but there may be both non-immunological as well as immunological inputs into this final common pathway. The former include trauma, cholinergic mechanisms and non-immunological histamine release by drugs. Immune mechanisms most commonly are of the IgE-mediated type, but occasionally the activation of complement or other mediators of hypersensitivity may be involved. Drug and food allergy are among the most common causes of acute urticaria, but there are numerous other possibilities which mandate a thorough general medical history and physical examination (including ruling out infection, connective tissue disease and neoplasms). In cases of chronic urticaria, when the lesions have persisted for longer than about 2 months, no cause for the disease is discernable in most instances. However, in these cases, as well as in acute urticaria, symptomatic treatment generally can provide substantial symptom relief, with emphasis on the astute use of various types of antihistamines.     

Anthelmintics. Current concepts in the treatment of helminthic infections

This article discusses the anthelmintics now in common use and describes their mode of action and toxic side effects. The drugs reviewed include: pyrantel pamoate, mebendazole, piperazine, thiabendazole, niclosamide, praziquantel, niridazole, oxamniquine and diethylcarbamazine. Most of the common roundworm intestinal infections respond to treatment with pyrantel pamoate, which has the advantage of single-dose therapy. Trichuriasis requires therapy with mebendazole, while the filariases are treated with diethylcarbamazine. There is no specific therapy for trichinellosis, but its symptoms can be alleviated. Intestinal cestode infections respond to treatment with niclosamide and cerebral cysticercosis to praziquantel, but echinococcal hydatid disease still requires surgical intervention in certain cases, although prolonged treatment with mebendazole shows promise. The greatest recent advance in the therapy of helminthiases is the development of praziquantel which effectively treats the most severe of these infections.     

Current concepts in the prevention and treatment of ventilator-associated pneumonia

Ventilator-associated pneumonia (VAP) is one of the most common causes of infection in intensive care unit (ICU) patients. Efforts to prevent VAP have focused on both pharmacologic and nonpharmacologic strategies. Two of the more controversial pharmacologic approaches included selective decontamination of the digestive tract (SDD) and decontamination of the oropharynx using topical antimicrobials or antiseptics including chlorhexidine (CHX). Additionally, avoidance of pharmacotherapy-related risk factors is hypothesized to reduce VAP rates. Successful treatment of VAP is becoming increasingly difficult in the era of antibiotic resistance. Utilization of local antibiograms, implementation of standardized treatment pathways, and optimization of pharmacodynamic-based dosing offer methods to improve empiric therapy selections. De-escalation of therapy should be a constant focus in an attempt to reduce overall antibiotic consumption and the selection pressure on ICU flora, thus minimizing the development and spread of antimicrobial resistance in the ICU.     

Current and historical concepts of opiate treatment in psychiatric disorders

In recent years psychiatric research has rediscovered the theoretical and clinical importance of opiates, especially for the understanding of depressive disorders. However, opiate treatment is not a new therapeutic concept in psychiatry. The use of opium for "melancholia" and "mania" may be traced to ancient classical medicine. After Paracelsus and Sydenham, the psychiatry of the German Romantic Era widely discussed therapeutic opium use with the Engelken family going on to develop a structured opium treatment of depression in the first half of the nineteenth century. Although the underlying scientific problems of psychiatric opium therapy were never solved, it gained an outstanding position as a practical treatment for over 100 years.     

Current concepts in the pathogenesis and treatment of reflux esophagitis

The etiology, pathogenesis, diagnosis, and treatment of reflux esophagitis are reviewed. Reflux esophagitis is the subjective or objective response to gastroesophageal reflux (GER), which is defined as the entrance of gastroduodenal contents into the esophagus not associated with vomiting or belching. The pathogenesis of reflux esophagitis may involve a number of mechanisms, including changes in lower esophageal sphincter pressure, gastric volume, composition of the refluxate, esophageal acid clearance, and esophageal tissue resistance. The most common symptom of reflux esophagitis is heartburn. Regurgitation of fluid into the mouth, usually after bending or during the night, is an unequivocal symptom of GER. Treatment can be divided into three phases. Phase 1 involves the avoidance of certain foods and habits, elevation of the bed head, antacid, and alginic acid-antacid therapy. Phase 2 involves drug therapy with agents not yet approved by the FDA for this indication: bethanechol chloride, cimetidine, and metoclopramide hydrochloride. Bethanechol chloride 25 mg is generally given four times daily. Cimetidine is given in doses of 300-400 mg after meals and at bedtime. Metoclopramide hydrochloride is administered in doses of 10 mg before meals and at bedtime. Phase 3 is antireflux surgery. Clinical experience has shown that phase 1 therapy is successful for about 75% of all patients. Of the 25% that do not respond to phase 1 therapy, about 90% will respond to phase 2 therapy, leaving only 5-10% of all patients with this disorder who will require phase 3 treatment. Current data favor cimetidine and bethanechol over metoclopramide. The least proof of efficacy and the most frequent adverse side effects are seen with metoclopramide. Cimetidine and bethanechol appear to have similar efficacy and relatively infrequent side effects. Evidence confirming the superiority of cimetidine over bethanechol is lacking. Further research is needed to determine the optimal pharmacologic combinations and treatment regimens.     

Current concepts in the pharmacological treatment of obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a chronic and often disabling disease. OCD is characterised by intrusive, unwanted and persistently recurring mental events (obsessions) that usually evoke discomfort or anxiety, and/or repetitive ritualistic behaviours (compulsions) that are aimed at reducing discomfort and anxiety. However, the compulsions succeed only in achieving transient relief, followed by a growing sense of pressure. 10 years ago, OCD was considered a rare and treatment-refractory disorder. Recent well designed studies document a lifetime prevalence rate for OCD of more than 2% in the general population. The outlook for patients with OCD has changed in the last decade, with many well controlled studies showing that OCD patients respond to specific behavioural and pharmacological treatments. The specific form of behavioural therapy is in vivo exposure coupled with response prevention. Only serotonin reuptake inhibitors, such as clomipramine, fluoxetine and fluvoxamine, are effective in the treatment of both depressed and not depressed OCD patients. Fluoxetine and fluvoxamine lack the anticholinergic side effects of clomipramine and, thus, provide an alternative treatment for patients who cannot tolerate clomipramine. Other nonserotonergic antidepressants (tricyclics and monoamine oxidase inhibitors) and anxiolytic agents have not been found to be consistently effective in this disorder. Insufficient data on the efficacy of neuroleptics and their potentially irreversible side effects limit their use in OCD patients. Behavioural and the pharmacological treatment are complementary, and a combination of the 2 therapies is apparently more effective than either modality alone.