Vishal R. Tandon

Pleiotropic effects of statins

The lipid-lowering actions of statins are well known. However, recent studies provide compelling evidence that the clinical benefits of statin therapy may also be attributed to mechanisms independent of their cholesterol-lowering effects. These non-lipid-lowering (pleiotropic) effects of statin therapy are believed to include antiinflammatory actions, property to reverse endothelial dysfunction by decreasing LDL oxidation and increasing nitric oxide bioavailability. Their antioxidant actions, ability to provide plaque stability, favorable coagulation profile, ability to prevent platelet aggregation and normalize sympathetic outflow as well as their antiproliferative and immunosuppressive properties also contribute to the non-lipid-lowering effects. These pleiotropic effects shown by statin therapy offer many advantages over the currently available drugs for dyslipidemias. These additional benefits not only find therapeutic application in cardiovascular disorders but also in many other disease states.

Hepatoprotective activity of Vitex negundo leaf extract against anti-tubercular drugs induced hepatotoxicity

Hepatoprotective (HP) activity of Vitex negundo (VN) leaf ethanolic extract was investigated against hepatotoxicity (HT) produced by administering a combination of three anti-tubercular drugs isoniazid (INH)-7.5 mg/kg, rifampin (RMP)-10 mg/kg and pyrazinamide (PZA)-35 mg/kg for 35 35 days by oral route in rats. V. negundo leaf ethanolic extract was administered in three graded doses of 100, 250 and 500 mg/kg orally, 45 min prior to anti-tubercular challenge for 35 days. HP effect of V. negundo leaf ethanolic extract was evident in the doses of 250 and 500 mg/kg as there was a significant decrease in TB, AST, ALT and ALP levels in comparison to control. Histology of the liver section of the animals treated with the V. negundo leaf ethanolic extract in the doses of 250 and 500 mg/kg further confirms the HP activity.

Preliminary screening of osteoporosis and osteopenia in urban women from Jammu using calcaneal QUS

BACKGROUND Osteoporosis is a major public health problem, associated with substantial morbidity and socio-economic burden. An early detection can help in reducing the fracture rates and overall socio-economic burden in such patients. AIM The present study was carried out to screen the bone status (osteopenia and osteoporosis) above the age of 25 years in urban women population in this region. MATERIALS AND METHODS A hospital based study was carried out in 158 women by calculating T-scores utilizing calcaneal QUS as diagnostic tool. RESULTS The result suggested that a substantial female population had oesteopenia and osteoporosis after the age of 45 years. The incidence of osteoporosis was (20.25%) and osteopenia (36.79%) with maximum number of both osteoporosis and osteopenic women recorded in the age group of (55-64 years). After the age of 65 years, there was an almost 100% incidence of either osteopenia or osteoporosis, indicating that it increases with age and in postmenopausal period, thereby suggesting lack of estrogenic activity might be responsible for this increasing trend. Religion, caste and diet had an influence on the outcome of osteopenic and osteoporosis score in present study, but still it has to be substantiated by conducting larger randomized clinical trials in future. CONCLUSION A substantial female population was screened for osteoporosis and osteopenia using calcaneal QUS method utilizing same WHO T score criteria that otherwise shall remain undiagnosed and face the complications and menace of osteoporosis.

Obesity: Friend or foe for osteoporosis

Osteoporosis and obesity are worldwide health problems. Interestingly, both are associated with significant morbidity and mortality. Both the diseases have common linkage as bone marrow mesenchymal stromal cells are the common precursors for both osteoblasts and adipocytes. Aging may shift composition of bone marrow by increasing adipocytes, osteoclast activity, and decreasing osteoblast activity, resulting into osteoporosis. Adipocytes secret leptin, adiponectin, adipsin, as well as proinflammatory cytokines, that contributes in pathogenesis of osteoporosis. This new concept supports the hypothesis, that the positive correlation of weight and body mass index (BMI) with bone mineral density (BMD) is not confirmed by large population-based studies. Thus, the previous concept, that obesity is protective for osteoporosis may not stand same as bone marrow fat deposition (adipogenesis) seen in obesity, is detrimental for bone health.

P-glycoprotein: pharmacological relevance

P-glycoprotein (P-gp) is a 170 kDa membrane-bound protein, an energy-dependent efflux transporter driven by ATP hydrolysis. It is responsible for multidrug resistance of many drugs. Physiologically, it is involved in limiting the harmful exposure of toxins, drugs, and xenobiotics to the body by extruding them out of cells. It is increasingly recognized to play an important modulating role in the pharmacokinetic properties of many clinically important therapeutic agents and because of its importance in pharmacokinetics, its screening has to be incorporated into the drug discovery process. The modulation of drug transporters through inhibition or induction by various drugs or herbs can lead to significant drug-drug or drug-herb interactions by affecting various pharmacokinetic parameters of the drug. In addition, genetic polymorphism of P-gp has also been reported, which may affect drug disposition, produce variable drug effects, and may change disease risk susceptibility. As drug interactions and genetic polymorphism are important factors to be considered during drug development, P-gp may have an impact on drug development in future.

Pregnancy and rheumatoid arthritis.

Pregnancy in most cases, is associated with remission of rheumatoid arthritis (RA), but a quarter of patients continue to have active disease or even worsening of the disease and most patients who improve, relapse in the postpartum period. The pathophysiology of this improvement in disease activity during pregnancy remains unknown, but hormonal, cell-mediated immunological and humoral immunological changes during pregnancy, have been proposed responsible for this. Most of the pregnant women with RA have an uneventful course, with no significant complications. In general, no significant increase in maternal or fetal morbidity seems to be attributable to RA. Patients with RA do not have decreased fertility. A majority of patients with RA may go in remission and anti-rheumatic treatment may not be required as soon as women become pregnant. But other patients who continue with the disease activity require treatment. The preferred disease-modifying agents during pregnancy are sulfasalazine and hydroxychloroquine. Azathioprine and cyclosporine can be used if the benefits outweigh the risks. Paracetamol and low dose prednisone are preferred and considered safe, both for mother and fetus. Methotrexate and lefunomide are contraindicated and must be prophylactically withdrawn before a planned pregnancy. Biologics generally should be stopped when pregnancy is discovered. An overall rational approach is highly warranted to treat RA during pregnancy.

Prevalence of tuberculosis, hepatitis B, hepatitis C and syphilis co-infections among HIV/AIDS patients.

Co-infections of tuberculosis (TB), hepatitis-B (HBV), hepatitis-C (HCV) and syphilis are a major concern in HIV/AIDS patients. TB remains an important public health problem in the world that has been exacerbated by the HIV epidemic, resulting in increased morbidity and mortality wordwide.[1] HIV, HBV and HCV share modes of transmission and hence co-exist in the same host at signiÞ cantly high rates.[2] Enormous evidences are available indicating that syphilis increases the risk of HIV infection.[3]

Antihypertensive drug prescription patterns, rationality, and adherence to Joint National Committee-7 hypertension treatment guidelines among Indian postmenopausal women

Aim of Study: The aim of this study is to evaluate antihypertensive drug prescription patterns, rationality and adherence to Joint National Committee (JNC-7) hypertension (HT) treatment recommendations among Indian postmenopausal women (PMW). Materials and Methods: An observational and cross-sectional prospective prescription audit study was carried over a period of 1 year. A total of 500 prescriptions prescribed to PMW for diagnosed HT, were identified for one point analysis. Drug prescription patterns/trends, and their adherence to JNC-7 report as well as rationality using WHO guide to good prescribing was assessed. Results: In the monotherapy, category angiotensin receptor blockers (ARBs) accounted (24.8%), calcium channel blockers (CCBs) (19.4%), angiotensin converting enzyme inhibitors (ACEIs) (11%), beta blockers (BBs) (2.8%), and diuretics (2%) of the total prescription. Individually, amlodipine was maximally prescribed in 16.4%. 31.6% had double combination, whereas 2.2% and 1% had triple and four drug combinations, respectively. About 3.6% of the prescription contained antihypertensive combination along with other class of drug. ARBs + diuretic were observed in 11%, CCBs + BB 10% and ACEI + diuretic in 2.6% of the total prescriptions. Among the combination therapy amlodipine + atenolol (8.4%), telmisartan + hydrochlorothiazide (6%) and losartan + hydrochlorothiazide (4.4%) were maximally prescribed. 84.21% (P < 0.001) of the prescription showed nonadherence as per recommendations for pre-HT. 100% and 43.25% adherence rates were noticed for Stage 1 HT (P < 0.001) and Stage 2 HT (P > 0.05) patients. Conclusion: Antihypertensive prescription trends largely adhere to existing guidelines and are rational except polypharmacy, generic and fixed dose combinations prescribing, were some of the common pharmacologically considered irrationality noticed.

Adverse Drug Reaction Profile in Patients on Anti-tubercular Treatment Alone and in Combination with Highly Active Antiretroviral Therapy.

BACKGROUND AND OBJECTIVES Adverse drug reactions are very common among patients on anti-tubercular treatment alone or in combination with highly active antiretroviral therapy but comparatively studied very less. Hence, the current study was done to evalaute the adverse drug reaction (ADR) profile in patients receiving anti-tubercular treatment (ATT) and ATT with highly active antiretroviral therapy (HAART). MATERIALS AND METHODS A one year prospective, cross-sectional observational study was undertaken using suspected adverse drug data collection form available under Pharmacovigilance Programme of India. RESULTS Seventy four patients receiving ATT & 32 patients on both ATT & HAART presented with 74 and 45 adverse drug events (ADE) respectively. Males were more affected than females in both the groups. DOTS category- 1 regimen was mostly responsible for ADE in both the groups. Epigastric pain was the most common ADE in TB patients, while anaemia was the most common presentation in TB with HIV group. On comparison, ADE rate of TB with HIV co-morbid patients was more (55.8%) than TB patients (0.36%) (p < 0.001). Urban population presented more with ADR in TB/HIV group unlike rural population in TB group (p<0.0001). Whereas, illiterate were more involved in TB group unlike literate in TB/HIV group (p<0.05). Type A reactions were more common in TB group (p < 0.001). Addition of drugs for the management of ADR events was more in TB/HIV group (p < 0.001) as compared to TB group. Rest all the parameters were comparable. CONCLUSION The study underscores that concomitant HAART and ATT, result in more ADRs in comparison to ATT alone demanding collaboration & integration of National AIDS Control programme and PvPI to enhance drug safety in this field.

Comparative evaluation of efficacy, safety and haemostatic parameters of enoxaparin and fondaparinux in unstable coronary artery disease.

AIM To compare the safety and efficacy of Enoxaparin (EX) and Fondaparinux (FD) in patients with Unstable Coronary Artery Disease (UCAD). MATERIALS AND METHODS A prospective, open label, randomized comparative study was designed to study the comparative efficacy and safety of EX and FD in UCAD patients. Recovery, recurrence, major and minor bleeding and biochemical investigations were evaluated and compared among two arms. RESULTS The baseline demographic characteristics were similar in both groups, with mean age of 56.05 and 56.05 years in EX and FD group respectively. Recovery was equal in two arms. Recurrent MI or angina was seen numerically more in EX group, but it did not statistically vary from that in the FD group. Incidence of haemorrhage was similar in both groups at 9 days, but at 30 days, EX showed a higher incidence (p<0.05). Deaths were prevented in both the treatment arms. Bleeding parameters such as BT, CT and platelet count were not altered in both groups. CONCLUSION FD appeared to be better than EX in efficacy, as was indicated by a numerically more decrease in recurrence of angina or MI. FD regimen group also had better safety profile, as there was no incidence of haemorrhage at 30 days Therefore, we conclude that FD is an attractive option than EX in UCAD patients.