An evaluation of the effect of atorvastatin on memory and psychomotor functions in hypertensive patients.

BACKGROUND: The effect of statins on memory and psychomotor function has been controversial and needs further evaluation. AIMS: To evaluate the effect of atorvastatin on memory and psychomotor functions in hypertensive patients treated with enalapril or amlodipine. SETTINGS AND DESIGN: Prospective, comparative, non-randomized, before-after, open-label clinical study conducted at a tertiary care hospital in Western India. MATERIALS AND METHODS: Memory was evaluated with PGI (Post Graduate Institute, Chandigarh) Memory Scale, while psychomotor functions were evaluated with Digit Letter Substitution test, Six Letter Cancellation test, and Finger Tapping test at baseline, 1 week, 1 month, and 3 months of starting atorvastatin in 74 hypertensive patients who were prescribed either enalapril or amlodipine with or without atorvastatin 10 mg/day. Scores obtained in patients receiving enalapril or amlodipine were compared with those receiving these drugs along with atorvastatin. Memory and psychomotor functions of 12 healthy volunteers were also evaluated and compared with those of the patients at respective time periods. STATISTICAL ANALYSIS: Student's t test, Wilcoxon Signed Rank test, and Mann Whitney U test were used to compare the pre- and post-treatment scores of memory and psychomotor functions in various groups. Statistical significance was considered at P<0.05. RESULTS: A statistically significant improvement in scores of memory and psychomotor functions was observed in both healthy volunteers (P=0.009 and P=0.016) and hypertensive patients (P=0.008 and P=0.031) throughout the study period. Memory and psychomotor function in hypertensive patients remained significantly inferior to those of healthy volunteers (P=0.01 and P=0.018). There was no significant difference in the scores of memory and psychomotor functions between patients receiving atorvastatin and those not receiving this drug. CONCLUSION: Atorvastatin, at 10 mg/day dose, does not have any significant effect on memory and psychomotor functions in hypertensive patients treated with enalapril or amlodipine.

Effect of tobacco consumption on semen quality of a population of hypofertile males.

Effect of tobacco use (by chewing or smoking) on semen quality has been seen. Semen analysis of 119 tobacco chewers and 219 smokers was compared with those of 288 control patients. Some decrease in the ejaculate volume, sperm density, and total count was observed in tobacco users, but it was statistically insignificant. No difference was found in other parameters, like motility and morphology. It is concluded that tobacco use by chewing or smoking is not associated with impaired semen quality in males selected from an idiopathically hypofertile population.

Effect of calcium salts & related substances on the motility & viability of ejaculated human spermatozoa in vitro.

Effect of four calcium salts, three calcium antagonists, calcium ionophore (A 23187) and calmodulin was studied in vitro on the motility and viability of ejaculated normal human spermatozoa at different time intervals. Effect of calcium salts was also studied on the oligoasthenospermic samples with an original motility of 10 to 30 per cent. Calcium salts were found to improve the sperm motility by 6 to 16 per cent and this may be due to a direct excitatory influence and a protective action of calcium on the spermatozoa since the viability was also improved by 4 to 11 per cent in these cases. A similar improvement in motility (8 to 11%) and viability (5 to 9%) was observed in hypokinetic samples also, Calcium antagonists inhibited the sperm motility and viability significantly. Diltiazem was the most potent drug in this respect, the reduction in motility being by 11 to 22 per cent and in viability by 6 to 14 per cent, after 30 sec of incubation. Calcium ionophore and calmodulin were found to be more potent than calcium antagonists to produce a dose-dependent decrease in sperm motility and viability. The results confirm that ionized calcium plays an important role in the regulation of sperm motility. Although intracellular concentration of calcium may be a better determinant physiologically, the manipulation of extracellular levels in a critical range may promote the sperm motility, viability and other vital functions. This has a potential use in situations like artificial insemination, in vitro fertilization and semen banking. Calcium ionophores and calmodulin need further investigation for a possible use as vaginal spermicides.

Effect of certain volatile oils on ejaculated human spermatozoa.

PIP: The effect of 7 volatile oils -- oils of clove, peppermint, ajowan, dill, basil, cinnamon, and eugenol -- and 4 fixed oils -- groundnut, coconut, vegetable, and pure clarified butter -- on human spermatozoa in vitro were studied. Fresh ejaculates were obtained from male partners of infertile couples. Semen samples from 6 different donors were used for each dilution. Percent change in motility over control was calculated. All the volatile oils studied revealed a potent spermicidal action. This was confirmed by a supra-vital staining. The oils differed in the potency of their action. In decreasing order of immediate spermicidal activity, the oils could be graded as follows:oil of cinnamon, eugenol, clove oil, oil of basil, oil of ajowan, oil of peppermint, and dill. Higher dilutions of volatile oils also were spermicidal when they were incubated with semen samples for a longer period. The fixed oils were devoid of action on spermatozoa.^ieng

The calcium channel antagonist, verapamil, potentiates the inhibitory action of morphine on intestinal and biliary motility.

The effects of morphine and verapamil have been assessed on the gastrointestinal propulsion of charcoal meal and egg yolk-induced gall bladder emptying in mice. Each drug significantly inhibited these functions. In combination, an additive effect was seen on the inhibition of gastrointestinal transit, whilst verapamil potentiated the morphine-induced inhibition of gall bladder emptying. It is concluded that calcium ion channel antagonists may potentiate the activity of opiate drugs.

Effect of nifedipine, a calcium channel inhibitor, on sedation produced by reserpine, clonidine and propranolol in mice.

Spontaneous motor activity, rotarod test and observational rating of sedation were employed to study effect of nifedipine on sedation produced by reserpine, clonidine and propranolol. Reserpine (2 mg kg-1), clonidine (4 mg kg-1), and propranolol (40 mg kg-1) significantly reduced spontaneous motor activity and staying capacity of animals on accelerating rotarod (P < 0.01). Observational sedation was also caused significantly as indicated by a higher score in test. Nifedipine (2 mg kg-1) produced no sedation or excitation on its own. Reduction in spontaneous motor activity produced by reserpine and clonidine was partially reversed in animals treated with nifedipine (P < 0.01). A similar effect of nifedipine was also evident on the observational sedation induced by reserpine and clonidine. Effect of these drugs on rotarod times was nearly totally antagonised by nifedipine. Nifedipine did not oppose the sedation produced by propranolol which actually became significantly greater in the animals pretreated with nifedipine in all three tests. It is concluded that nifedipine antagonizes the sedation produced by reserpine and clonidine, probably by blocking central alpha 2-adrenoceptors. The sedative effect of propranolol can be potentiated by nifedipine possibly because of a pharmacokinetic interaction.

Comparative evaluation of anticonvulsant activity of calcium channel blockers in experimental animals.

Pentylenetetrazole (PTZ)-induced convulsions and the maximal electroshock (MES) seizure test were employed to study the anticonvulsant effects of nifedipine (2, 3.5 and 5 mg kg-1), flunarizine (10, 20 and 40 mg kg-1) and diltiazem (10, 15 and 30 mg kg-1). Nifedipine and flunarizine prolonged the latent period and reduced the mean duration of PTZ induced seizures. They also reduced the severity of convulsions and the number of deaths due to PTZ significantly. Nifedipine was more potent in this regard (P < 0.01). All these drugs prolonged the latent period and reduced the duration of tonic extensor phase of MES seizures in a significant manner. Flunarizine was most potent in this test. Complete protection from tonic extensor phase was observed in 10-50% animals pretreated with nifedipine and flunarizine in a dose dependent manner. The response of diltiazem was weak in both these tests. It is concluded that all three calcium channel blockers possess an important but different anticonvulsant effect and their significant clinical use can be made while keeping in view the characteristics of their pharmacological action.

Early outcome of second line antiretroviral therapy in treatment-experienced human immunodeficiency virus positive patients.

PURPOSE AND AIM: Multi-drug resistance in treatment-experienced human immune deficiency virus (HIV) patients has been a major cause to first line antiretroviral therapy (ART) failure, necessitating a switch to second line therapy. In India, the second line treatment program is still relatively new with little experience and unclear outcomes. It is therefore, critical to assess the clinical, virological and immunological effectiveness and treatment outcome over the 1(st) year of follow-up in the patients' switched to the second line ART at public sector tertiary care center. MATERIALS AND METHODS: A prospective, observational study was carried out on HIV positive patients switched on second line ART from January 2010 to December 2010 at ART Centre, Civil Hospital, Ahmedabad. Demographic details, symptoms, adverse drug reactions (ADRs), second line ART regimens, CD4 count, and plasma viral load (PVL) were recorded in a case record form. Patients were followed-up monthly for 12 months. The data was analyzed by t-test, z-test, and Fisher-exact test. RESULTS: Out of 126 patients, 82 received regimen V [zidovudine (ZDV) + lamivudine (3TC) + tenofovir (TDF) + boosted lopinavir (LPV/r)] and 44 received regimen Va [3TC + TDF + LPV/r]. A significant (P < 0.0001) increase in mean body weight and marked reduction in number of patients (7) categorized as WHO stage III/IV was observed at 12 months of second line ART. Moreover, a significant immune reconstitution with increase in mean CD4 count and viral suppression (PVL < 400 copies/ml) in 103 (82%) patients (P < 0.0001) was also observed. A total of 83 ADRs were observed in 69 (55%) patients, the most common being dyslipidemia (57) followed by anemia (9). CONCLUSION: Early treatment outcome with second line ART was good with 82% success rate in treatment experienced HIV patients. Dyslipidemia and anemia were the common ADRs observed.

Efficacy and safety of anti-tuberculosis drugs in HIV-positive patients: a prospective study.

OBJECTIVES: To assess the efficacy and safety of anti-tuberculosis drugs in HIV-positive patients at a tertiary care teaching hospital. MATERIALS AND METHODS: As a part of an ongoing study of opportunistic infections (OIs) in HIV-positive patients, drug treatment in patients suffering from tuberculosis was assessed to determine its efficacy and safety. Based on prevalence data for last three years, a purposive sampling of study population was carried out in this observational, prospective, single centre study. Tuberculosis (TB) was the most common OI observed. The selected patients were followed up for a period of one year to evaluate the clinical course and outcome of OIs, and the efficacy and safety of drugs used was checked. RESULTS: Tuberculosis was observed in 89 out of 134 enrolled patients. These included 79 adults and 10 children. Males (66.2%) were commonly affected. Extra pulmonary TB (73%) was the most common manifestation with abdominal TB observed in 55 (61.7%) patients. All patients were treated in accordance with the Revised National Tuberculosis Control Programme (RNTCP) guidelines as recommended by National AIDS Control Organization (NACO), India. Outcome of TB was assessable in 70 patients. Majority (82.8%) of the patients were cured, while 12 patients (17.1%) died during the course of treatment. A total of 149 ADRs were observed in 67 (75.2%) patients. Majority of ADRs (n = 147) were non-serious and did not warrant a change in therapy. Discoloration of urine was the most common ADR observed. CONCLUSION: TB is the most common opportunistic infection in HIV-positive patients with abdominal TB being the most common manifestation. RNTCP and NACO guidelines are adhered to in these patients. Anti-tuberculosis drugs are well tolerated and effective in majority of the patients.

Tenofovir induced Fanconi syndrome: a possible pharmacokinetic interaction.

Tenofovir was introduced as a second line drug for the treatment of human immunodeficiency virus (HIV) infection in India in December 2009. Although rare, renal toxicity is a recognized adverse drug reaction (ADR) of this drug, especially when administered with boosted lopinavir-ritonavir. In this case, an HIV positive patient receiving tenofovir based antiretroviral therapy (ART) for last 1 year developed albuminuria, glycosuria and hypophosphatemia. Renal function tests and random blood sugar were within normal limits. He was diagnosed as a case of tenofovir induced Fanconi syndrome. Tenofovir was discontinued and patient was prescribed an alternate regimen. Five months later clinical symptoms and renal functions returned to normal. A pharmacokinetic interaction between tenofovir and ritonavir may have resulted in the toxicity. A periodic monitoring of renal functions is desirable in patients on tenofovir based ART.

Antiretroviral drugs: critical issues and recent advances.

Human immunodeficiency virus (HIV) infection is now recognized as a chronic illness. Although the success of highly active antiretroviral therapy is beyond question, several issues still persist. Since the drugs cannot eradicate the virus, cure is not yet possible, and patients have to maintain a lifelong adherence with the risk of toxic effects, drug-drug interactions and drug resistance. A clear understanding of the viral replication and its interaction with host cell factors has led to the development of a large number of effective antiretroviral drugs (ARVs). New drugs in the existing class such as apricitabine, elvucitabine and etravirine have shown promising results against HIV isolates resistant to first line drugs. These drugs have offered a new choice for patients with drug resistant disease. However, the impact of their long term use on safety is yet to be assessed. Novel drugs with unique mechanism of action such as CD4 receptor attachment inhibitors, maturation inhibitors, pharmacokinetic enhancers, capsid assembly inhibitors and lens epithelium derived growth factor inhibitors are still under development. Currently, ARVs, especially tenofovir and emtricitabine, are also being evaluated for prevention of sexual transmission of HIV-1. The initial results of an HIV prevention trial network are encouraging and have recommended the use of ARVs for pre-exposure prophylaxis. Thus, ARVs form the key component of HIV prevention and treatment strategy. This article discusses the challenges associated with HIV-1 treatment and updates several major advances in the development of ARVs.

Steroid-induced central serous retinopathy.

A-24 year-old male was prescribed prednisolone (60 mg/day) for left sided facial palsy. After three days of therapy, the patient complained of black spots in his vision in right eye. Fluorescein angiography of right eye showed evidence of central serous retinopathy (CSR). Prednisolone dose was withdrawn gradually and the patient improved within a week. There were no other systemic or ophthalmic diseases reported by the patient, which could have caused this condition. An improvement after dechallenge confirmed steroid-induced CSR. Recurrent CSR is known to cause permanent loss of vision. Hence, awareness regarding this adverse drug reaction (ADR) with steroids and its reporting can minimize this complication and help in better patient management.

An evaluation of knowledge, attitude, and practice of adverse drug reaction reporting among prescribers at a tertiary care hospital.

OBJECTIVES: Spontaneous reporting is an important tool in pharmacovigilance. However, its success depends on cooperative and motivated prescribers. Under-reporting of adverse drug reactions (ADRs) by prescribers is a common problem. The present study was undertaken to evaluate the knowledge, attitude, and practices (KAP) regarding ADR reporting among prescribers at the Civil Hospital, Ahmedabad, to get an insight into the causes of under-reporting of ADRs. MATERIALS AND METHODS: A pretested KAP questionnaire comprising of 15 questions (knowledge 6, attitude 5, and practice 4) was administered to 436 prescribers. The questionnaires were assessed for their completeness (maximum score 20) and the type of responses regarding ADR reporting. Microsoft Excel worksheet (Microsoft Office 2007) and Chi-Square test were used for statistical analysis. RESULTS: A total of 260 (61%) prescribers completed the questionnaire (mean score of completion 18.04). The response rate of resident doctors (70.7%) was better than consultants (34.5%) (P < 0.001). ADR reporting was considered important by 97.3% of the respondents; primarily for improving patient safety (28.8%) and identifying new ADRs (24.6%). A majority of the respondents opined that they would like to report serious ADRs (56%). However, only 15% of the prescribers had reported ADRs previously. The reasons cited for this were lack of information on where (70%) and how (68%) to report and the lack of access to reporting forms (49.2%). Preferred methods for reporting were e-mail (56%) and personal communication (42%). CONCLUSION: The prescribers are aware of the ADRs and the importance of their reporting. However, under reporting and lack of knowledge about the reporting system are clearly evident. Creating awareness about ADR reporting and devising means to make it easy and convenient may aid in improving spontaneous reporting.

Atorvastatin-induced pancreatitis.

Drugs account for 1-2% of all cases of pancreatitis. A 58-year-old man was prescribed atorvastatin 10 mg for 6 months for hyperlipidemia. He developed acute abdominal pain and vomiting with epigastric tenderness. Serum lipase and CT scan of the patient suggested the presence of acute pancreatitis. The patient was hospitalized; atorvastatin was stopped and treated symptomatically. He recovered completely within 10 days of drug withdrawal. The causality of the adverse drug reaction according to Naranjo and WHO-UMC Scale was probable. The exact mechanism of pancreatitis due to atorvastatin is not known. It may be a class effect of HMG CoA reductase inhibitors as it had been reported with other statins too. The definite causal relationship is difficult to establish, as rechallenge with the suspected drug was not done due to ethical consideration.