Important pharmacogenomic aspects in the management of HIV/AIDS

In managing HIV/AIDS with highly active antiretroviral agents, the historical therapeutic aim remains to maintain the plasma concentrations at a level above the half maximal inhibitory concentration (IC50) required for 50% inhibition in viral replication. Concentration dependent toxicity is often observed in patients with elevated drug exposure and high peak plasma levels in lieu accurately calculated drug dosages. Similarly low plasma concentrations are frequently witnessed in individuals receiving adequate dosage regimens. Pharmacogenetic variations in drug metabolizing enzymes may contribute to this phenomenon. Over the last decade, knowledge about the role of pharmacogenetics in the treatment and prediction of ARV plasma levels have increased significantly. However, the extent of these genetic variations remain largely unknown in the South African population,which has sparked a renewed enthusiasm for local pharmacogenetic studies

Important pharmacogenomic aspects in the management of HIV/AIDS

In managing HIV/AIDS with highly active antiretroviral agents, the historical therapeutic aim remains to maintain the plasma concentrations at a level above the half maximal inhibitory concentration (IC50) required for 50% inhibition in viral replication.Concentration dependent toxicity is often observed in patients with elevated drug exposure and high peak plasma levels in lieu of accurately calculated drug dosages. Similarly lowplasmaconcentrationsarefrequently witnessed in individuals receiving adequate dosage regimens. Pharmacogenetic variations in drug metabolizing enzymes may contribute to this phenomenon.Over the last decade, knowledge about the role of pharmacogenetics in the treatment and prediction of ARV plasma levels have increased significantly. However, the extent of these genetic variations remain largely unknown in the South African population,which has sparked a renewed enthusiasm forlocalpharmacogenetic studies

To clot, or not to clot ­ Antithrombotic therapy is the question

Haemostasis and thrombosis rely on three components namely the vascular endothelial wall, blood platelets and the coagulation cascade. Non-physiologic excessive thrombosis occurs when haemostatic processes are dysfunctional, causing undue clot formation or reduced clot lysis. Antithrombotic agents including antiplatelet, anticoagulation and fibrinolytic agents are essential for the prophylaxis and pharmacological management of venous thromboembolism and arterial thrombosis. Anticoagulation treatment options have expanded steadily over the past few decades, providing a greater number of agents. Anticoagulants that directly target the enzymatic activity of thrombin and factor Xa have recently been developed to address the inadequacies of traditional vitamin K antagonists. Appropriate use of these agents requires knowledge of their individual characteristics, risks, and benefits

The sore throat: a clinical approach to tonsillopharyngitis

Acute sore throat is a common complaint encountered by medical practitioners and health care workers routinely. The disease is mostly caused by viral infections of the upper respiratory tract and is usually self limiting. Symptoms rarely exceed two weeks, irrespective of the cause. Group A beta-haemolytic streptococci accounts for the majority of bacterial instances of tonsillopharyngitis. Clinical examination is not always adequate to diagnose bacterial infections, resulting in the irrational and over-prescribing of antibiotics, especially in upper respiratory tract infections, contributing to communal antimicrobial bacterial resistance. A few scoring systems are available to assist physicians in deciding on the aetiology without resorting to unnecessary laboratory investigations. This article briefly reviews the scoring systems and antimicrobial management of streptococcal throat infections

Severe Hypertriglyceridaemia as a Result of familial Chylomicronaemia : the Cape Town Experience

Lipoprotein lipase deficiency causes severe hypertriglyceridaemia due to chylomicronaemia and leads to recurrent and potentially life-threatening pancreatitis. This disorder can only be managed by dietary fat restriction as drugs are ineffective.We review the experience with familial chylomicronaemia in patients who attended the lipid clinics at Groote Schuur Hospital and the Red Cross Children's War Memorial Hospital in Cape Town. The criteria for inclusion were an initial plasma triglyceride concentration of 15 mmol/L and a typical type I Fredrickson hyperlipidaemia pattern on plasma lipoprotein electrophoresis. A total of 29 patients were seen over 25 years. The mean age of presentation was 10 years; but ranged from from 0 to 43 years. The modes of presentation differed: pancreatitis (n=16); eruptive xanthomata (n=2); coincidental detection of hypertriglyceridaemia (n=2); screening relatives (n=7) and after death from pancreatitis (n=1). Plasma triglycerides responded rapidly and dramatically to dietary fat restriction and some patients sustained good control of the hyperlipidaemia.. The onset of pancreatitis was earlier in patients of Indian ancestry suggesting a genotype/phenotype interaction within this disorder. Genetic work-up indicated founder effects in the Afrikaner and Indian patients. Lipaemic plasma should be taken seriously at all ages and necessitates work-up at specialised clinics where the diagnosis of chylomicronaemia or type I hyperlipidaemia facilitates appropriate dietary management that can prevent pancreatitis

Effect of Compression Force; Humidity and Disintegrant Concentration on the Disintegration and Dissolution of Directly Compressed Furosemide Tablets using Croscarmellose Sodium as Disintegrant

PURPOSE: The effect of compression force; relative humidity and disintegrant concentration on furosemide dissolution in directly compressed furosemide/Avicelr-tablets was studied. METHODS: Mixtures of furosemide (12.5 percent w/w); Ac-Di-Solr (0; 0.625 percent to 10 percent w/w) and Avicelr PH200 (qs to 100 percent w/w) were prepared in a Turbularmixer at 69 rpm for 10 min. Tablets were stored for 6 months under conditions similar to the four climatic zones recognized by ICH. Tablet hardness; disintegration time and dissolution were measured. RESULTS: At the same compression force; disintegration time decreased as the disintegrant concentration increased above 0.625 percent w/w but an increase in compression force resulted in increased tablet crushing strength and apparent density; both of which prolonged the disintegration time. This effect was less significant when the disintegrant concentration was above 1.25 percent. However; storage under high relative humidity conditions (mediterranean or subtropical; hot and humid climate) caused softening of tablets leading to the spontaneous disintegration of tablets containing high concentrations of Ac-Di-Solr . CONCLUSION: Fast disintegration of tablets within 1-2 min is a prerequisite for improving the dissolution of furosemide. This was attributed to an increase in the speed at which the maximum surface area of the sparingly water-soluble drug is exposed to the dissolution medium. Ac-Di-Solr was an efficient disintegrant for furosomide tablets at low concentrations of 1.25 percent -10 percent because it rapidly released the hydrophobic drug particles from tablets. However; tablets containing 10 percent disintegrant must be protected from atmospheric moisture because storage at 60-70 percent relative humidity led to softening of tablets