A Contemporary Exploration of Traditional Indian Snake Envenomation Therapies.

Snakebite being a quick progressing serious situation needs immediate and aggressive therapy. Snake venom antiserum is the only approved and effective treatment available, but for selected snake species only. The requirement of trained staff for administration and serum reactions make the therapy complicated. In tropical countries where snakebite incidence is high and healthcare facilities are limited, mortality and morbidities associated with snake envenomation are proportionately high. Traditional compilations of medical practitioners' personal journals have wealth of plant-based snake venom antidotes. Relatively, very few plants or their extractives have been scientifically investigated for neutralization of snake venom or its components. None of these investigations presents enough evidence to initiate clinical testing of the agents. This review focuses on curating Indian traditional snake envenomation therapies, identifying plants involved and finding relevant evidence across modern literature to neutralize snake venom components. Traditional formulations, their method of preparation and dosing have been discussed along with the investigational approach in modern research and their possible outcomes. A safe and easily administrable small molecule of plant origin that would protect or limit the spread of venom and provide valuable time for the victim to reach the healthcare centre would be a great lifesaver.

Curriculum for pharmacology in pharmacy institutions in India: opportunities and challenges.

The curriculum of pharmacy institutions in India is regulated by the All India Council for Technical Education (AICTE) and the Pharmacy Council of India (PCI) at degree and diploma levels. However, it has been over two decades that the syllabi have been revised by these regulatory agencies. Considering the dynamic character of pharmacology, it is essential to prepare a syllabus that caters to the contemporary needs of the academic institutions and pharmaceutical industry, the community. Pharmacists are also witnessing a greater role in community pharmacy practice as well as in several healthcare sectors. Considering these facts, a panel discussion was held at IPSCON 2013, (the Annual Conference of Indian Pharmacological Society) at Bangalore. The discussion saw several recommendations for syllabi for institutions offering various pharmacy courses to meet the objectives of teaching, learning and research in Pharmacology. This article documents a summary of the discussion. For B. Pharm. course, a balance between industry-oriented pharmacology and clinical pharmacy has been recommended. Redundant animal experiments should be replaced with the simulation experiments or those which are feasible in the light of stringent regulations of the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA). It is recommended that the M. Pharm curriculum should focus on preclinical research with the inclusion of molecular biology and experiments on gene expression, proteomics, pharmacogenomics, cell culture and tissue culture. In general, at all levels, exposure of students to hospitals and clinicians is needed. Pharm. D., syllabus too should lay lesser emphasis on experimental pharmacology. Present experiments in the D. Pharm. course have no relevance to the program objectives and hence, only experiments through demonstrations or simulated preparations or interactive videos maybe undertaken. Regulatory bodies as well as universities should design a comprehensive syllabus and plan an effective pedagogy to prepare graduates who are competent and capable of bringing positive changes in the community and healthcare in India.

Physicochemical investigations and stability studies of amorphous gliclazide.

Gliclazide (GLI), a poorly water-soluble antidiabetic, was transformed into a glassy state by melt quench technique in order to improve its physicochemical properties. Chemical stability of GLI during formation of glass was assessed by monitoring thin-layer chromatography, and an existence of amorphous form was confirmed by differential scanning calorimetry and X-ray powder diffractometry. The glass transition occurred at 67.5°C. The amorphous material thus generated was examined for its in vitro dissolution performance in phosphate buffer (pH 6.8). Surprisingly, amorphous GLI did not perform well and was unable to improve the dissolution characteristics compared to pure drug over entire period of dissolution studies. These unexpected results might be due to the formation of a cohesive supercooled liquid state and structural relaxation of amorphous form toward the supercooled liquid region which indicated functional inability of amorphous GLI from stability point of view. Hence, stabilization of amorphous GLI was attempted by elevation of T(g) via formation of solid dispersion systems involving comprehensive antiplasticizing as well as surface adsorption mechanisms. The binary and ternary amorphous dispersions prepared with polyvinylpyrrolidone K30 (as antiplasticizer for elevation of T (g)) and Aerosil 200® and/or Sylysia® 350 (as adsorbent) in the ratio of 1:1:1 (w/w) using kneading and spray-drying techniques demonstrated significant enhancement in rate and extent of dissolution of drug initially. During accelerated stability studies, ternary systems showed no significant reduction in drug dissolution performance over a period of 3 months indicating excellent stabilization of amorphous GLI.

Evaluation of antidiarrheal and in vitro antiprotozoal activities of extracts of leaves of Alocasia indica.

CONTEXT: Alocasia indica Schott (Araceae) is used in several regions of India, especially in rural communities, by traditional medicine practitioners to treat diarrhea. However, no scientific data are available to justify the traditional potentials of the plant species in gastrointestinal disorders. OBJECTIVE: To evaluate the antidiarrheal and in vitro antiprotozoal activities of extracts of leaves of Alocasia indica using various pharmacological models. MATERIALS AND METHODS: In vitro antidiarrheal activity of aqueous and ethanol extracts of Alocasia indica was evaluated against Escherichia coli, Salmonella typhimurium, Shigella flexneri and Staphylococcus aureus by agar well diffusion method. In vivo antidiarrheal activity of the extracts was studied against recinolic acid-induced diarrhea and magnesium sulfate-induced diarrhea. The effect of the extracts on normal intestinal transit, recinolic acid-induced intestinal transit, recinolic acid-induced intestinal fluid accumulation (enteropooling) and gastric emptying was assessed. In vitro antiprotozoal activity of aqueous and ethanol extracts of Alocasia indica was studied against Entamoeba histolytica and Giardia intestinalis. RESULTS: The aqueous and ethanol extracts exhibited significant in vitro antidiarrheal activity compared to the standard drug ciprofloxacine (10 µg/mL). The plant extracts showed significant (P <0.05) and dose-dependent antidiarrheal activity comparable to that of the reference drug, loperamide (10 mg/kg). The plant extracts exhibited significant in vitro antiprotozoal activity against both protozoa compared to the standard amebicidal and giardicidal drugs, metronidazole and emetine. DISCUSSION AND CONCLUSION: The results showed that the extracts of Alocasia indica have significant antidiarrheal and in vitro antiprotozoal activities which support its use in traditional herbal medicine practice.

Tailored release drug delivery system for rifampicin and isoniazid for enhanced bioavailability of rifampicin.

The front line antitubercular drugs rifampicin (RMP) and isoniazid (INH), when co-administered, face the problem of reduced bioavailability of RMP. Stabilization of RMP in the presence of INH under acidic environment may improve the bioavailability of RMP. In vitro degradation studies showed around 15-25% degradation of RMP under the aforesaid conditions if the ratio of RMP: INH is above 1:0.5.This degradation is reduced to less than 10% when the ratio of RMP: INH is below 1:0.25. Based on these findings, an innovative drug delivery system was designed with the immediate release of RMP and tailored prolonged release of INH. The bilayer tablets prepared with this concept were subjected to relative bioavailability studies in healthy human volunteers in an open label, balanced, randomized, single-dose, cross-over study under fasted state. A validated LC-MS/MS bioanalytical method was employed for estimation of RMP and INH in plasma. Bioavailability studies revealed that C(max) and AUC for RMP increased by 18 and 20%, respectively, confirming the above innovative concept. Even in the case of INH, AUC increased significantly by around 30% and thus time above minimum inhibitory concentration (MIC) would also increase, which may result in further improved clinical outcome.

Formulation and in vitro evaluation of rifampicin loaded porous microspheres.

Rifampicin (RIF) is a major component in fixed dose combination therapy for the treatment of tuberculosis. RIF has low solubility and high permeability with high dose and hence it is classified as class II drug in Biopharmaceutical Classification System (BCS). RIF has poor and variable bioavailability because of its poor solubility, acid decomposition and, drug and food interaction. The present investigation was aimed to develop RIF loaded porous microspheres as a controlled release dosage form. Eudragit based porous microspheres of RIF were prepared by emulsion solvent diffusion method. Prepared porous microspheres were evaluated for its entrapment efficacy, morphology, thermal behavior, crystalline nature, in-vitro drug release and stability in simulated gastric fluid. The entrapment efficacy of drug loaded microspheres was found to be in the range of 19.04â74.57%. Surface morphology revealed the porous and spherical structure of microspheres. Differential scanning calorimetric studies confirmed that formulation process altered the crystalline nature of RIF. In vitro drug release studies indicated that drug to polymer ratio of 2:1 showed more than 85% drug release over the period of 3 h. Stability studies in simulated gastric fluid (SGF) indicated that low relative decomposition of 18.5% was achieved with high drug to low polymer ratio of 1:4. The results obtained from the present investigation concluded that RIF loaded porous microspheres are suitable for developing oral controlled release dosage form of RIF that can prevent acid decomposition and provide better biopharmaceutical properties. Further more the microspheres can be evaluated for preventing the interaction with isoniazid, other drugs and foodstuffs.

Hepatoprotective activity of hydroalcoholic extract of leaves of Alocasia indica (Linn.).

Oral administration of hydroalcoholic extract of A. indica (250 and 500 mg/kg) effectively inhibited CCl4 and paracetamol induced changes in the serum marker enzymes, cholesterol, serum protein and albumin in a dose-dependent manner as compared to the normal and the standard drug silymarin-treated groups. Hepatic steatosis, fatty infiltration, hydropic degeneration and necrosis observed in CCl4 and paracetamol-treated groups were completely absent in histology of the liver sections of the animals treated with the extracts. The results suggests that the hydroalcoholic extract of leaves of A. indica possess significant potential as hepatoprotective agent.

Effect of erythromycin and rifampicin on monoethylglycinexylidide test.

BACKGROUND: The dynamic liver function test based on the hepatic conversion of lidocaine to monoethylglycinexylidide (MEGX) provides a direct measure of the actual functional state of the liver. Cytochrome P450 (CYP) 3A4 has been proposed as the main CYP isoform responsible for MEGX formation. The concomitant use of either CYP3A4 inducer rifampicin or CYP3A4 inhibitor erythromycin may influence the results of MEGX test. Hence, the objective of this study was to evaluate the effect of a CYP3A4 inhibitor erythromycin and inducer rifampicin on the MEGX test. MATERIALS AND METHODS: The study included 20 healthy male volunteers whose routine laboratory tests were normal. As per study protocol, MEGX test was carried out in all the participants after an overnight fast. All the participants were given 1 mg/kg lidocaine dose intravenously and MEGX concentration at 30 and 60 min after IV dose was measured using HPLC. These MEGX values served as control values. Ten subjects received 600 mg/day erythromycin orally for six days while remaining ten participants received 600 mg/day rifampicin orally for six days. On the sixth day, MEGX test was carried out two hours after the last dose. RESULT: Rifampicin increased the mean plasma concentration of MEGX(30) from 93.94 ± 26.31 to 98.54 ± 24.94 µg/ml (P = 0.085) and MEGX(60) from 134.34 ± 35.42 to 136.36 ± 33.14 µg/ml (P = 0.051). Erythromycin lowered the serum concentration of MEGX(30) from 101.37 ± 39.39 to 96.67 ± 36.09 µg/ml (P = 0.128) and MEGX(60) from 142.52 ± 42.65 to 138.98 ± 40.23 µg/ml (P = 0.159). CONCLUSION: It can be concluded from this study that the MEGX test is not affected by concomitant administration of CYP3A4 modifiers rifampicin and erythromycin.

Monoethylglycinexylidide (MEGX) as a liver function test in cirrhosis.

AIMS: To compare the performance of monoethylglycinexylidide (MEGX) test and conventional liver function tests (LFT) in differentiating between healthy volunteers and patients with different severity of liver cirrhosis, as judged using Child-Pugh (CP) classification. METHODS: One hundred and four patients with cirrhosis (CP class A, 47; B, 32; C, 25) and 25 healthy volunteers were studied between January 2005 to June 2006. In these subjects, conventional LFT were done, and serum specimens collected 15, 30 and 60 minutes after lidocaine injection were analyzed for MEGX. RESULTS: Conventional liver function tests showed minor differences between healthy volunteers and patients with Child class A, whereas these discriminated well between patients with Child class C and healthy volunteers. The changes in ALT, AST, bilirubin, albumin, AP and PT values were statistically significant in CP class B and C but not in class A when compared with healthy volunteers. MEGX concentration at 60 min was significantly higher in healthy volunteers (131.2 ng/mL) as compared to patients with cirrhosis (CP A - 51.3 ng/mL; CP B - 37.1 ng/mL; CP C - 17.3 ng/mL). There were significant differences (p <0.001) among all four groups (healthy volunteers and patients with CP classes A, B and C) for MEGX concentrations at each time point. MEGX test correlated well with CP scores (p <0.0001). CONCLUSION: MEGX test is a useful marker to stratify patients with liver cirrhosis based on liver function.

Prognostic value of the monoethylglycinexylidide test in alcoholic cirrhosis.

BACKGROUND: The existing conventional liver function tests (LFTs) are indirect, inferior and have limited prognostic value. Therefore, the monoethylglycinexylidide (MEGX) test, which provides a direct measure of the actual functional state of the liver, is proposed as a real-time liver function test. The objective of this study was to assess the prognostic value of the MEGX test in cirrhosis by comparing it with Child-Turcotte-Pugh (CTP), the Mayo end stage liver disease (MELD) and discriminant function (DF) scores. MATERIALS AND METHODS: The study was carried out in Satara, India during the period of January 2005 to June 2006 and included 79 adult alcoholic cirrhotic patients. The serum specimen from each patient was analyzed using conventional LFTs and the MEGX test. The prognostic scores-CTP, MELD and DF scores were calculated and statistical analyses was performed. RESULTS: Based on receiver operating characteristic (ROC) curves, the MELD score and MEGX60 showed excellent sensitivity and specificity. The comparison of area under ROC curves showed that MELD and MEGX60 had superior prognostic accuracy when compared to other scores. Kaplan-Meier survival curves for corresponding cutoff values clearly differentiated between patients with different survival times. CONCLUSION: The MEGX test has shown more sensitivity, specificity and accuracy than CTP and DF scores in determining cases with the possibility of three- and six-month survival. Thus, it can be concluded that MEGX test along with MELD, is an effective prognostic tool in the hands of clinicians for predicting short-term survival.