Drugs

Guslandi, Mario

doi: 10.2165/00003495-199753010-00001pmid: 9010645

Low-dose aspirin is widely employed as antiplatelet therapy for cardiovascular disorders. However, even in the dosages usually employed for that purpose (75 to 325mg daily), the drug maintains its ability to damage the gastric mucosa by inducing bleeding ulcers and/or erosions. Pharmacological protection is therefore necessary. Specific long term studies with histamine H2 receptor antagonists or sucralfate are lacking, but data from trials on the prevention of gastric damage by other nonsteroidal anti-inflammatory drugs (NSAIDs) are discouraging. Recent preliminary data suggest that misoprostol, in keeping with its ability to protect both gastric and duodenal mucosa from long term NSAID treatment, seems to be effective also against long term low-dose aspirin therapy in this setting.

Haller, Hermann

doi: 10.2165/00003495-199700531-00003pmid: 9034750

The endothelium is involved in both the physiological regulation of vascular tone and the structural transformation of the vessel under pathological conditions. Under physiological conditions, endothelial cells continuously secrete nitric oxide (NO), which relaxes smooth muscle cells and ensures vessel patency. Damaged or excessively activated endothelial cells can also secrete vasoconstrictor factors, the best known of which is endothelin-1 (ET-1), as well as factors that affect the differentiation and growth of vascular smooth muscle cells.

Champion, G.; Feng, Pao; Azuma, Takeshi; Caughey, David; Chan, Ka; Kashiwazaki, Sadao; Liu, Hwa-Chang; Nasution, Achmad; Nobunaga, Masasni; Prichanond, Surawut; Torralba, Tito; Udom, Visitsunthorn; Utis, Deesomchok; Wang, Soo; Wong, Woon; Yang, Dah-Jung;

Rabelink, Ton; Koomans, Hein

doi: 10.2165/00003495-199700531-00004pmid: 9034751

Endothelial dysfunction is emerging as an important factor in the early development of acute and chronic renal disease. Drugs aimed specifically at rectifying this aberration are being developed, although other established agents such as calcium antagonists, angiotensin converting enzyme (ACE) inhibitors and HMG CoA reductase inhibitors also have beneficial effects in this setting. Calcium antagonists are particularly effective at ameliorating acute renal ischaemia associated with endothelial dysfunction. Combination therapy with a calcium antagonist and an ACE inhibitor might optimise the beneficial effects of calcium channel blockade on the sequelae of endothelial dysfunction in chronic renal failure.

Greenshaw, Andrew; Silverstone, Peter

doi: 10.2165/00003495-199753010-00003pmid: 9010647

The discovery of multiple subtypes of the serotonin 5-HT receptor has generated enormous interest over the past few years. Possibly the most exciting, in terms of psychiatric clinical practice, appeared to be the 5-HT3 receptor. Early animal studies suggested that the 5-HT3 receptor antagonists, in addition to their well recognised antiemetic use, might be clinically useful in a number of areas. These included anxiety disorders, psychotic disorders, drug and alcohol abuse disorders, depressive disorders, cognitive disorders, the treatment of pain and the treatment of irritable bowel syndrome. With the exception of antiemetic actions, this review examines these potential therapeutic areas carefully, paying particular attention not only to the animal literature, but to the clinical studies which have resulted from these initial findings. Unfortunately, studies in many of these therapeutic areas have not lived up to their initial promise. Indeed, no clinical studies have yet clearly demonstrated the usefulness of 5-HT3 receptor antagonists in the treatment of CNS disorders. Nonetheless, in view of the absence of published results from double-blind, placebo-controlled studies in many of these therapeutic areas, further research would be useful in confirming the effectiveness, or otherwise, of this group of compounds.

Burnett, John

doi: 10.2165/00003495-199700531-00005pmid: 9034752

The endothelium participates in the control of coronary vascular tone and growth through the release of vasodilating and growth-inhibiting factors such as nitric oxide (NO) and C-type natriuretic peptide (CNP), and vasoconstricting and growth-promoting substances such as endothelin-1 (ET-1). Abnormalities in NO and/or CNP generation or actions have been demonstrated in various cardiovascular pathophysiological states, specifically atherosclerosis, congestive heart failure, hypertension and hypercholesterolaemia. Moreover, an increase in plasma ET-1 levels has also been reported in these disease states. When these observations are considered together, these states may be characterised by an attenuated release or action of NO and/or CNP, together with an augmented release of ET-1. Thus, an imbalance between these opposing factors may contribute to the alteration in vascular tone and the vascular remodelling characteristics of cardiovascular disease. The following article summarises the present knowledge of endothelial control of the coronary circulation and derangements associated with coronary endothelial dysfunction.

Ferro, Charles; Webb, David

doi: 10.2165/00003495-199700531-00006pmid: 9034753

Vascular endothelial cells play a key role in cardiovascular regulation by producing a number of potent vasoactive agents, including the vasodilator molecule nitric oxide (NO) and the vasoconstrictor peptide endothelin (ET)-l. A dysfunction of the vascular endothelium has been implicated in the pathophysiology of a number of cardiovascular diseases, important among which is essential hypertension. Impairment of NO synthesis, or increased inactivation of NO by superoxide radicals, may account for the increased peripheral vascular tone associated with hypertension, as well as contribute to the clinical consequences of this condition, which include vascular hypertrophy, increased platelet and monocyte adhesion to the endothelium, atherosclerosis, myocardial infarction and stroke. Similarly, increased ET-1 synthesis, or increased smooth muscle sensitivity to ET-1, could account for many of the features of hypertension, including increased peripheral vascular tone and vascular hypertrophy. Modulation of endothelial function is, therefore, an attractive therapeutic option in the treatment of hypertension.

Klepser, Michael; Klepser, Teresa

doi: 10.2165/00003495-199753010-00004pmid: 9010648

The AIDS epidemic has led to the emergence of several disease entities which in the pre-AIDS era were rare or seemingly innocuous. Experience of treating these diseases varies. In some instances, such as Pneumocystis carinii pneumonia, there is an abundance of published literature to direct our course of action. However, for many of these newly recognised diseases our treatment experience is limited. Furthermore, in many instances, well controlled trials evaluating treatment modalities in the AIDS population are lacking. We have identified 13 disease entities (P carinii pneumonia, toxoplasmosis, cryptococcosis, histoplasmosis, Mycobacterium tuberculosis, Mycobacterium avium complex, cytomegalovirus, coccidioidomycosis, isosporiasis, candidosis, Kaposi’s sarcoma, herpes simplex virus, and varicella zoster virus) and have reviewed the current literature with regard to their treatment.

doi: 10.2165/00003495-199700531-00007pmid: N/A

Saracco, Giorgio; Rizzetto, Mario

doi: 10.2165/00003495-199753010-00005pmid: 9010649

The recommended interferon dosage for patients with chronic hepatitis and typical hepatitis B virus (HBV) infection is 10MU 3 times weekly for 4 to 6 months; with such a regimen sustained alanine aminotransferase (ALT) normalisation, liver histology improvement, clearance of HBV DNA and serocon version from hepatitis B e antigen (HBeAg) to anti-HBe are obtained in about 40% of treated patients. Patients with elevated disease activity (high ALT values, active chronic hepatitis, low HBV DNA levels) tend to respond better to therapy; Oriental patients and immunocompromised patients are not ideal candidates for interferon. Patients with chronic hepatitis B and the HBeAg-negative variant should be given intermediate dosages (6 to 9MU thrice weekly) of interferon for prolonged periods (12 months); however, even with this approach, the relapse rate is high (>60%) during the follow-up.