In vivo anticonvulsant activity of 2-propanone-1,3,5,5-trimethyl-2-cyclohexen-1-ylidine in pilocarpine and strychnine induced-seizure models.

An imbalance between inhibitory (GABA) and excitatory (Glutamate) neurotransmission contribute to the development of epilepsy. Earlier studies reported that dysregulation of GABA and glutamatergic activities resulted in status epilepticus (SE) and ultimately support the development of temporal lobe epilepsy (TLE), a type of resistant epilepsy. In the earlier work, 2-propanone-1,3,5,5-trimethyl-2-cyclohexen-1-ylidine demonstrated anticonvulsant activity against pentylenetetrazole (PTZ)-induced seizures. Apart from the PTZ-induced TLE, the dysregulation muscaranic receptors and glycine receptors are also widely reported phenomena in the development of temporal lobe epilepsy. Keeping the role of these two receptors in epilepsy, the present work investigated the effect of 2-propanone-1,3,5,5-trimethyl-2-cyclohexen-1-ylidine in pilocarpine-induced and strychnine-induced seizure models. Our results demonstrated that 2-propanone-1,3,5,5-trimethyl-2-cyclohexen-1-ylidine significantly delayed the onset of seizure with maximum protection from SE in pilocarpine-induced seizure model. However, the test compound did not revealed any effect on strychnine-induced seizures in mice. Based on these observations, we suggest that 2-propanone-1,3,5,5-trimethyl-2-cyclohexen-1-ylidine could be a potential candidate in reduction of SE and treatment of temporal lobe epilepsy (TLE) in future.

A prevalence study of potentially inappropriate medications use in hospitalized Pakistani elderly.

BACKGROUND: Inappropriate prescribing in elderly patients is a widespread health problem. It is associated with increased drug-related problems and health expenditure. AIMS: To determine the prevalence and types of potentially inappropriate medications (PIM) prescribed to elderly patients with polypharmacy and the factors associated with their use in these patients. METHODS: A cross-sectional study conducted among 228 elderly hospitalized patients with polypharmacy. Elderly patients were defined as patients ≥65 years of age, and polypharmacy was defined as taking ≥5 drugs. Based on previously published criteria (Beers and STOPP), a list of 32 PIM was developed using a Delphi technique, which was used as a tool to detect the prevalence of PIM. Age, gender, comorbidity, patients' functional status, and complete medication history were recorded to evaluate as variables related to PIM. The association between PIM used and independent variables was also assessed. RESULTS: The prevalence of PIM used among the hospitalized elderly patients was 64%. PIM use according to STOPP criteria was identified in 44% of patients, whereas Beers-listed PIM were identified in 50% of patients. The most frequently observed PIM were the combination of nonsteroidal anti-inflammatory drugs (NSAIDs) with antihypertensives and long-term NSAIDs, which account for more than 90 and 75% of the total observed PIM, respectively. Patients with age ≥85 years were more likely to be prescribed PIM. High comorbidity was found to be an independent predictor of PIM use. Polypharmacy with ≥10 drugs prescribed to patients predicted the presence of PIM. DISCUSSION: The study showed a high prevalence of PIM use among hospitalized elderly patients. The consensus-validated list of PIM was a useful tool for screening inappropriate prescribing in this particular patient population. CONCLUSION: Our findings support the need for measures to improve the quality of drug treatment in the elderly Pakistani population, especially among dependent patients with polypharmacy.

Current Status and Future Suggestions for Improving the Pharm. D Curriculum towards Clinical Pharmacy Practice in Pakistan.

Objectives & Background: Good curriculum is reflected as the backbone for standard universities to develop competitive professionals having great potential. Pharmacy education in Pakistan has gone through the same developmental stages as in other countries, but is still striving for improvement. In the present study, we want (i) to know the opinion on whether the current pharmacy curriculum requires any improvement in order to meet the training needs of pharmacy professionals regarding clinical knowledge and pharmacy practice; and (ii) to present some humble suggestions to decision-making authorities in order to improve it with respect to patient-focused programs (PFP). Methods: The study was conducted in two sessions. In first session, a questionnaire was distributed to pharmacy students of eight public/private sector universities of Karachi (N = 354) offering Pharm. D degrees. The second session dealt with the pharmacy teachers, deans, and practicing pharmacists in health care facilities (who are in any ways also related to academia), in order to take their opinions on and suggestions for the development of a better Pharm. D curriculum (N = 135). Results: Our results showed that 75.2% of respondents agree that the Pharm. D curriculum does not meet the international standards of practice, and 88.4% of respondents support the addition of more clinical aspects than industrial ones, as Pharm. D could be both clinically and industrially oriented, according to the needs of the Pakistani people. Furthermore, 80.2% of respondents are of the view that an apprenticeship should be included in last two years, while 88.4% demand a 'paid residency program' to facilitate the hospital, clinical and compounding areas of pharmacy. In addition, we also received a number of verbal suggestions for improving the Pharm. D curriculum being followed in Pakistan. Discussion & Conclusions: We conclude that our Pharm. D curriculum needs additions in terms of clinical practice by providing residencies and electives in health care settings. Accordingly, the need for a clinically oriented curriculum is highlighted in Pakistan, keeping in mind the continuing importance of the industrial viewpoint. Various studies have criticized the pharmacy curriculum in Pakistan in the past. Conversely, we suggest some changes in the curriculum, as change is always needed for a better tomorrow.

Adverse drug reactions (ADRS) reporting: awareness and reasons of under-reporting among health care professionals, a challenge for pharmacists.

OBJECTIVES: To measure awareness about adverse drug reaction (ADRs) reporting among doctors, pharmacists and nurses and to determine reasons of ADRs under-reporting in Pakistan. METHODS: In present study, a self-administered questionnaire was used to measure the awareness level about ADRs reporting among health care professionals (HCPs) of Pakistan. This was a cross sectional study. RESULTS: Out of the respondents 51 % were physicians, 29.7 % pharmacists and 19.3 % were nurses. 65.5 % of HCP population observed ADRs, out of which only 57.4 % reported these in their respective hospitals. About 77.3 % of population understood the importance of reporting ADRs while 67.3 % of population agrees that pharmacists are chief personnel for the development of system. 71.8 % of HCPs agrees that ADRs are not reported because Community pharmacy lacks legally qualified pharmacists. Only 14.3 % of HCPs population knows that there is any ADR reporting organization in Pakistan. CONCLUSION: The study recommends the need of such reporting system and more than half of the studied population agreed that pharmacists are required in developing such system.

Modulation of c-Fos and BDNF protein expression in pentylenetetrazole-kindled mice following the treatment with novel antiepileptic compound HHL-6.

Brain-derived neurotrophic factor (BDNF) and c-Fos are shown to promote epileptogenesis and are taken as a marker of neuronal activity. The present study investigated the expression of BDNF and c-Fos in mice brain with pentylenetetrazol- (PTZ-) induced generalized seizure and evaluated the effect of novel tryptamine derivative HHL-6 on the expression of these two markers. The subconvulsive dose of PTZ (50 mg/kg) was administered on alternate days in the experimental groups until the seizure scores 4-5 developed in the PTZ-control group. At the end of each experiment, animals were sacrificed, brain samples were collected and cryosectioned, and immunohistochemical analysis of BDNF and c-Fos protein was performed. Data obtained from two sections per mouse (n = 12 animals/group) is presented as means ± S.E.M. The test compound HHL-6 demonstrated a potent anticonvulsant activity in the PTZ-induced seizure in mice. Significant reduction in the BDNF (P < 0.003) and c-Fos (P < 0.01) protein expression was observed in the HHL-6 treated group. Based on these results we suggest that one of the possible mechanisms of HHL-6 to inhibit epileptogenesis might be due to its controlling effect on the cellular and molecular expression of the factors that contribute to the development of epileptogenic plasticity in the CNS.