An overview of structurally diversified anticonvulsant agents

There are several limited approaches to treat epilepsy in hospitals, for example, using medicines, surgery, electrical stimulation and dietary interventions. Despite the availability of all these new and old approaches, seizure is particularly difficult to manage. The quest for new antiepileptic molecules with more specificity and less CNS toxicity continues for medicinal chemists until a new and ideal drug arrives. This review covers new antiseizure molecules of different chemical classes, the exact mode of action of which is still unidentified. Newer agents include sulfonamides, thiadiazoles, semi- and thiosemicarbazones, pyrrolidine-2,5-diones, imidazoles, benzothiazoles and amino acid derivatives. These new chemical entities can be useful for the design and development of forthcoming antiseizure agents

Pharmacokinetic studies of drug absorption into human skin

PhDOptimum therapeutic outcomes require not only proper drug selection but also effective drug delivery and monitoring. The aim of this thesis was to A) study drug delivery through the skin with a liquid formulated to promote absorption, B) develop and validate methods to analyze the drug in the samples obtained, C) assess appropriate methods to measure the transdermal delivery of drug, and D) apply to pharmacodynamics. The stability of a rectal formulation of diazepam, Diastat®, and a quality control of a topical form, TDS® diazepam, were studied using high performance liquid chromatography (HPLC) with ultraviolet absorption detection (UV). It was found that diazepam at 10 mg/mL was stable in solution at various temperatures for at least 4 weeks. A pharmacokinetic study of diazepam delivery from the TDS® delivery system was compared with delivery of the drug following rectal administration of Diastat® in 12 healthy volunteers. The TDS® diazepam was evaluated for safety and no adverse effects or events were observed. The preparation was found to be able to deliver diazepam systemically in humans, the confidence interval (CI) of the ratios for Cmax and AUC of diazepam from the two formulations A (TDS®): B (rectal) were not contained within the bioequivalence limit 80–125%, Cmax (0–72h): 7.3–14% and AUC0-72h: 20–38%. In addition, the 90% CI of desmethyldiazepam (A:B) ratio were not contained within the bioequivalence limit, Cmax (0–72h): 38–54% and AUC0-72h: 33–58%. Although not bioequivalent to Diastat® these finding suggest that skin may be an alternative method of diazepam delivery but further developments and studies would be required. The development and validation of fast, high throughput methods to evaluate tetracaine from skin tape samples was another challenge. Sensitive and reliable capillary electrophoresis with UV and HPLC-UV methods were developed and validated to measure tetracaine in skin using tape samples from volunteers given 1 mL Ametop gel (4% w/w of tetracaine) to support a pharmacokinetic drug delivery study of Ametop. The results from these validation studies demonstrated an equal ability of the two methods to measure tetracaine concentrations reproducibly and accurately. The Bland Altman test was in a range of ± 1.96 SD from the mean (SD = ± 8.02, Mean = 2.23), and percentage error (± 20%.), which show an acceptable difference. The assays were found to possess both the sensitivity and specificity necessary to measure the analyte in the skin tape stripping at the concentrations range in these tapes. Finally, observation of appropriate methods to measure the transdermal drug in vivo techniques, such as microdialysis (MD) and tape stripping (TS) have been employed by plotting a concentration time profile to investigate the capability of measuring tetracaine (pharmacokinetics) in local tissue, instead of measuring tetracaine by conventional systemic measurements. The results showed that the tetracaine Cmax concentration was higher in the stratum corneum compared with the major metabolites of tetracaine, 4- butylaminobenzoic acid (BABA) by 3 and 10 times in MD and plasma, respectively. TS samples reached the maximum concentration quicker than BABA in dialysate and plasma samples (p = 0.002). The median tmax was higher in plasma (IQR -53minutes, 95% CI: - 30– -105) compared with tape samples. The AUC and Cmax for tetracaine were higher in TS compared with BABA in MD and plasma (Mean AUC0-4h: 88582, 55594 and 13208 nM.min: Mean Cmax (0–4h), 850, 459, 110 nM, respectively). In addition, the AUC and Cmax values demonstrated that data from the TS study showed less variability compared with the data from plasma. The most variable data were for MD (CV%; AUC0-4h, 24, 63, and 85%: Cmax (0–4h), 42, 60, 80%, respectively). AUC and Cmax (Bartlett’s test, p = 0.004 for AUC; and Levene’s test, p = 0.042, and 0.028, respectively) This thesis has demonstrated that 1) diazepam was successfully delivered through the skin into the systemic circulation by the TDS® system, 2) novel methods have been developed for the measurement of tetracaine and its metabolite, and 3) the methods have been successfully applied to three different sample types employed in pharmacokinetic studies

DRUG UTILIZATION BASED ADRS MONITORING OF ANTIHYPERTENSIVE AGENTS PRESCRIBED IN AL-QUWAYIYAH GENERAL HOSPITAL, SAUDI ARABIA

Objective: To monitor drug utilization based adverse drug reactions (ADRs) of antihypertensive agents prescribed in Al-Quwayiyah general hospital, Saudi Arabia.Methods: An open, non-comparative, observational study was conducted on hypertensive patients attending the medicine outpatient department of Al-Quwayyah general hospital, Al-Quwayyah, Saudi arabia. Data were collected by conducting patient interviews. Data were captured for adverse drug reaction monitoring based on Narinjo scale and WHO format.Results: 25 ADRs were observed out of 212 hypertensive patients. Incidence was found to be higher in patients more than 40 y age, and females experienced more ADRs (n = 16, 7.54%) than males, 9 (4.62%). Combination therapy was associated with more number of ADRs (64.0%) as against monotherapy (36.0%). Calcium channel blockers were found to be the most frequently associated drugs with ADRs (n = 8), followed by diuretics (n = 6), and β-blockers (n = 5). Among individual drugs, amlodipine was found to be the commonest drug associated with ADRs (n = 8), followed by torasemide (n = 4). ADRs associated with the central nervous system was found to be the most frequent (48.0%) followed by musculoskeletal complaints (20.0%) and respiratory system disorders (16.0%).Conclusion: ADRs were experienced by taking the antihypertensive drugs prescribed in Al-Quwayyah general hospital, Saudi arabia. The findings would be useful for physicians in rational prescribing. Calcium channel blockers were found to be the most frequently associated drugs with ADRs

Prevalence of tobacco use and its socio-demographic determinants among Saudi female school adolescents in Jeddah

Tobacco use among females is a rising public health issue. Further insight into the smoking epidemic can be gained from studying a specific subgroup of interest within the population. Determining predictors of each tobacco smoking type is necessary for planning tobacco specific intervention programmes. The aim of this study was to determine the prevalence of ever tobacco use and its associated socio-demographic factors among Saudi female adolescents aged 12 to 19 in Jeddah. A cross-sectional analytical study was conducted among female students from intermediate and high secondary schools in Jeddah during the academic year 2012-2013. Sampling with probability proportionate to size was used to select a sample of 5,150 students from 40 schools. The data were collected using validated self-administrated questionnaire that required information on tobacco use behaviours and selected socio-demographic characteristics. A total of 5,073 students participated in this study of whom 51.6% were from intermediate grades, and 83.1% from public schools. The prevalence of ever tobacco use was 44.2% (36.2% water pipe and 30.9% cigarettes). The significant predictors of ever tobacco use were student’s age, mother’s education, family structure, residence location and monthly student’s allowance. In conclusion, ever tobacco used is highly prevalent among female adolescents in Jeddah. Designing intervention programmes aimed at preventing Saudi female adolescents from smoking should include all forms of tobacco use

Stuttered swallowing: Electric stimulation of the right insula interferes with water swallowing. A case report

<p>Abstract</p> <p>Background</p> <p>Various functional resonance imaging, magnetoencephalographic and lesion studies suggest the involvement of the insular cortex in the control of swallowing. However, the exact location of insular activation during swallowing and its functional significance remain unclear.</p> <p>Case presentation</p> <p>Invasive electroencephalographic monitoring was performed in a 24-year-old man with medically intractable stereotyped nocturnal hypermotor seizures due to a ganglioglioma. During stimulation of the right inferior posterior insular cortex with depth electrodes the patient spontaneously reported a perception of a "stutter in swallowing". Stimulation of the inferior posterior insular cortex at highest intensity (4 mA) was also associated with irregular and delayed swallows. Swallowing was not impaired during stimulation of the superior posterior insular cortex, regardless of stimulation intensity.</p> <p>Conclusions</p> <p>These results indicate that the right inferior posterior insular cortex is involved in the neural circuitry underlying the control of swallowing.</p

Determination of the intrinsic kinetics of decomposition of hydrates formed from mixtures of nitrogen and carbon dioxide using in-situ particle size analysis

Bibliography: p. 84-89Some pages are in colour

Kinetic studies of gas hydrate formation using in situ particle size analysis and raman spectroscopy

Bibliography: p. 151-16