Nonnutritive sweeteners (NNS) have become an important part of everyday life and are increasingly used nowadays in a variety of dietary and medicinal products. They provide fewer calories and far more intense sweetness than sugar-containing products and are used by a plethora of population subsets for varying objectives. Six of these agents (aspartame, saccharine, sucralose, neotame, acesulfame-K, and stevia) have previously received a generally recognized as safe status from the United States Food and Drug Administration, and two more (Swingle fruit extract and advantame) have been added in the recent years to this ever growing list. They are claimed to promote weight loss and deemed safe for consumption by diabetics; however, there is inconclusive evidence to support most of their uses and some recent studies even hint that these earlier established benefits regarding NNS use might not be true. There is a lack of properly designed randomized controlled studies to assess their efficacy in different populations, whereas observational studies often remain confounded due to reverse causality and often yield opposite findings. Pregnant and lactating women, children, diabetics, migraine, and epilepsy patients represent the susceptible population to the adverse effects of NNS-containing products and should use these products with utmost caution. The overall use of NNS remains controversial, and consumers should be amply informed about the potential risks of using them, based on current evidence-based dietary guidelines.

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Objectives: Xanthones are flavonoids with numerous activities, including antioxidant, antidepressant., or anxiolytic-like. Therefore, the aim of our study was to determine antidepressant- and anxiolytic-like properties of four xanthone derivatives (3-chloro-5-[(4-methylpiperazin-1-yl)methyl]-9H-xanthen-9-one dihydrochloride [HBK-5], 6-methoxy-2-[(4-methylpiperazin-1-yl) methyl]-9H-xanthen-9-one dihydrochloride, 2-[(4-benzylpiperazin-1-yl) methyl]-6-methoxy-9H-xanthen-9-one dihydrochloride, 2-{[4-(2-methoxyphenyl) piperazin-1-yl] methyl}-9H-xanthen-9-one hydrochloride), as well as the influence on cognitive and motor function of active compounds, using animal models. Materials and Methods: To determine the antidepressant-like activity, we used forced swim test (FST) and tail suspension test (TST) in mice. We evaluated anxiolytic-like properties in the four-plate test in mice. We studied the influence on cognitive and motor function in passive avoidance step.through and chimney tests, respectively. Results: The antidepressant-like activity (in both FST and TST) showed only HBK-5. Moreover, the compound was also active in the four-plate test, which suggests that it possessed anxiolytic-like properties. HBK-5 did not cause any cognitive and motor deficits in mice at antidepressant- and anxiolytic-like doses. Conclusions: HBK-5 may have potential in the treatment of depression or anxiety disorders, but this issue needs further studies.

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Objective: The objective of this study was to investigate the prophylactic and curative effect of the ethanol leaf extract of Ipomoea eriocarpa (Convolvulaceae) (IEE) in ethylene glycol-induced urolithiasis in rats. Materials and Methods: Thirty male Wistar rats were divided into five groups (n = 6). All the groups received stone-inducing treatment till 28^th day, comprising 1% ethylene glycol (v/v) with 1% ammonium chloride (w/v) for 4 days, followed by 1% ethylene glycol alone in water, except Group I (Control). Group II received only stone-inducing treatment till 28^th day. Group III (Standard) received cystone (500 mg/kg) from 15^th day till 28^th day. Group IV (Prophylactic) received IEE (200 mg/kg) from 1^st day till 28^th day and Group V (Curative) received IEE (200 mg/kg) from 15^th day till 28^th day. Various biochemical parameters such as phosphorus, calcium, magnesium, urea, and creatinine levels were evaluated using urine, serum, and kidney homogenate. The kidneys were also sectioned and examined histopathologically under light microscope to study the kidney architecture and calcium oxalate deposits. Results: The IEE treatment (prophylactic and curative) significantly (P < 0.001) restored the parameters in urine, serum, and kidney homogenate to near-normal level. The histopathological examinations revealed that calcium oxalate crystal deposits in the renal tubules and congestion and dilation of the parenchymal blood vessels were significantly reverted after IEE treatment. Conclusions: The leaf extract of I. eriocarpa reduces and inhibits the growth of urinary stones showing its effect as an antiurolithiatic agent.

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Objective: Bruguiera gymnorrhiza (BRG) (L.) Lamk (Rhizophoraceae), a mangrove species, is widely distributed in the Pacific region, eastern Africa, Indian subcontinent, and subtropical Australia. The leaves of this plant are traditionally used for treating burns and inflammatory lesions. This study isolates the bioactive compound from the methanol extract of BRG leaves and evaluates the possible mechanisms of anti-inflammatory activity involved. Materials and Methods: Bioassay-guided fractionation of BRG was performed to identify the bioactive fraction (displaying inhibition of cyclooxygenase 2 [COX2] - 5-lipoxygenase (5-LOX) activities and tumor necrosis factor-alpha (TNF-α) production at the tested concentrations of 100 and 10 μg/ml). The fractionation was performed by solvent extraction and preparative high-performance liquid chromatography. The bioactive compound was characterized by ultraviolet–visible, liquid chromatography–mass spectrometry and nuclear magnetic resonance spectroscopy. The antioxidant potential was evaluated by electron spin resonance spectrum of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical at 250 μM. The effect of the compound was also studied on TNF-α converting enzyme and nuclear factor kappa B (NF-κB) activities at the concentrations 100, 10 and 1 μg/ml. Results: Bioassay-guided purification of BRG revealed the presence of a flavone (5,7-dihydroxy-2- [3-hydroxy-4,5-dimethoxy-phenyl]-chromen-4-one) of molecular weight 330Da. It demonstrated more than 80% inhibition against COX2, 5-LOX activities and TNF-α production at 100 μg/ml. It also displayed 40% inhibition against DPPH radical at the tested concentration along with 23.1% inhibition of NF-κB activity at 100 μg/ml. Conclusions: The isolated methoxy-flavone may play a predominant role in the anti-inflammatory properties displayed by BRG leaves. Such activity may involve multiple mechanisms, namely (a) modulation of oxidative stress (b) inhibition of arachidonic acid metabolism and (c) downregulation of pro-inflammatory cytokines probably through NF-κB inhibition.

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Black hairy tongue (BHT) is a benign disease characterized by elongated filiform lingual papillae, with a carpet-like appearance of the dorsum of the tongue. It is has been reported to occur with a prevalence ranging from 0.6% to 11.3%. Although its etiology is not fully understood, BHT may be triggered by smoking, excessive coffee or black tea drinking, poor oral hygiene, trigeminal neuralgia, general debilitation, dry mouth as well as certain drugs. We present here a case of a patient with psychosis, depression, and benign prostatic hyperplasia, who developed BHT following treatment with a fixed dose combination (FDC) of olanzapine and fluoxetine and recovered within 3 months after withdrawal of treatment with FDC.

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Dystonia is sustained muscle contraction, which may be primary or secondary to other causes. Drugs comprise one of the most important causes for the secondary dystonia, the usual mechanism being a dopaminergic blockade. There are very few reports describing dystonia resulting from carbamazepine (CBZ) administration. In this case report, a 16-year-old male with mental retardation and seizure disorder developed dystonia at therapeutic blood levels of CBZ.

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Objective: Equisetum arvense has been used to treat bone diseases. The traditional supplementation of calcium and Vitamin D for osteoporosis patients is insufficient considering the rise in patients every year. We have observed that extending the calcium and Vitamin D supplement with L-lysine, L-proline, L-arginine, and L-ascorbic acid (N) positively affects bone mineralization in ovariectomized rat. Here, we report a further extension of the above supplement with E. arvense. Materials and Methods: The changes in serum biomarkers, bone mineral content, and femur bone histology were studied and compared to the standard drug for osteoporosis, namely raloxifene (RAL). Results: We report a significant change in formation and resorption markers of bone as well as in cortical bone thickness and trabecular width in N and N + EA groups. The treatment N + EA also restored lipid profile near to normal level compared to ovariectomized group. Conclusions: Treatment N + EA was found to be as effective as RAL in reversing the osteoporotic changes.

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Finasteride and dutasteride are commonly used 5-alpha reductase inhibitors. While finasteride is a selective inhibitor of 5-alpha reductase Type II, dutasteride inhibits 5- alpha reductase Type I and II. The United States Food and Drug Administration approved the use of finasteride for benign prostatic hypertrophy (BPH) as well as androgenic alopecia (AGA) while dutasteride is approved only for BPH. Off-label use of dutasteride is not uncommon in AGA as well. Although the postfinasteride syndrome (PFS) is a well-established entity, its symptomatology is quite variable. Here, we describe a case of an atypical PFS in a patient treated with dutasteride and finasteride for AGA. The multisystem involvement and irreversible nature of this case warrant its reporting.

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Objective: Treatment of chronic urticaria (CU) can be difficult in many patients. Achieving long-term remission and reducing the requirement of antihistamines are vital in CU. The objective of this study was to assess the effectiveness of injection histaglobulin, a complex of histamine and human immunoglobulin, in producing relief in patients with CU. Materials and Methods: Fifty-one patients with CU were enrolled into this prospective clinical study. Patients were administered 1 ml of injection histaglobulin subcutaneous for 8 consecutive weeks. They were also prescribed tablet levocetirizine 5 mg to be taken when required (but not more than the permitted dosage). Efficacy was assessed using urticaria activity score (UAS) which has a maximum score of 33/day, during each weekly visit. Final assessment was done after 24 weeks. Results: Twenty-nine patients had completed the entire 8-week drug regimen. Mean basal UAS was 18.9 ± 6.3 and it reduced to 80.4% by 8 weeks. The angioedema sub-score reduced by 89.8%. Anti-histamine pill burden also reduced significantly. By 24 weeks of starting the therapy, 23 patients (45%) had attained complete remission. No adverse effects to the drug were observed. Conclusions: Histaglobulin was found to be effective in producing long-term remission and it reduced the antihistamine requirement as well. Thus, it can serve as an effective alternative to existing treatment modalities.

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Objective: The study was conducted to develop the glucocorticoid-induced osteoporosis (GIO) model in Sprague-Dawley weanling rats using different doses of methylprednisolone (MP) and evaluate the antiosteoporotic effect of a classical ayurvedic formulation, Panchatikta Ghrita (PG), in this model. Materials and Methods: Institutional Animal Ethics Committee approval was obtained. Development of model was done by subcutaneous injection of 2 doses of MP (14 and 28 mg/kg/week) for 4 weeks in 21-day old weanlings. Following confirmation of the dose of MP that induced osteoporosis, the antiosteoporotic effect of PG was tested in this model in comparison to a known antiosteoporotic agent, alendronate. Both alendronate (2.9 mg/kg/day) and PG (1.35 g/kg/day) were administered orally 2 weeks after MP - 14 mg/kg/week injection and continued for 4 weeks. Serum and urine calcium and inorganic phosphate were analyzed at weekly intervals. Animals were sacrificed after 6 weeks, and femur bones were processed to measure bone hardness and elasticity and for histological studies. Results: Rats treated with MP - 14 mg/kg/week showed optimum osteoporotic effect with no mortality as compared to MP - 28 mg/kg/week; hence, this dose of MP was used further for the efficacy study. Osteoporotic rats treated with PG 1.35 g/kg showed increase in serum calcium and inorganic phosphate levels, whereas urine calcium and phosphate levels were significantly reduced. A significant decrease in a number of osteoclasts, whereas an increase in bone hardness and elasticity was observed as compared to diseased group demonstrating antiosteoporotic effect of PG. Conclusion: PG has an antiosteoporotic effect in GIO rat model.

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Objective: The underlying mechanisms for the analgesic action of paracetamol (PCT) are still under considerable debate. It has been recently proposed that PCT may act by modulating the Serotonin system. This study was conducted to verify the influence of Serotonin modulating drugs (buspirone, ondansetron, and fluoxetine) on the analgesic effect of PCT. Materials and Methods: Thirty adult albino mice were assigned to five groups: Normal saline, PCT, fluoxetine selective serotonin reuptake inhibitor (SSRI) + PCT, buspirone (5-HT_1AAgonist) + PCT, and ondansetron (5HT₃antagonist) + PCT. Hot-plate and formalin test were used to determine pain threshold, tests being conducted 60 min after the last treatment. Statistical analysis was done using analysis of variance followed by Dunnet's test. Results: Coadministration of buspirone with PCT attenuated the antinociceptive activity of PCT (P < 0.001), whereas fluoxetine + PCT increased pain threshold in the hot-plate and formalin test (P = 0.0046). Analgesic effect of PCT was not affected by ondansetron in formalin models. It attenuated analgesic action of PCT in hot-plate test (P = 0.0137). Conclusion: The results suggest that 5-HT₁receptors could also be responsible for the analgesic effect of PCT. Also, higher analgesia is produced by co-administration of SSRI (fluoxetine) + PCT.

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Neurological disturbances caused by lithium range from simple side effects such as benign tremor to acute reversible neurotoxicity. Rarely, lithium is reported to cause irreversible, permanent neurological sequelae most commonly manifested as cerebellar dysfunction, although other presentations have also been described. We report two cases of persistent cerebellar syndrome following acute lithium toxicity and discuss them in the light of existing literature on the subject.

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Objective: Intestinal mucositis is a significant problem haunting clinicians for decades. One of the major reasons for its occurrence is high-dose chemotherapy. The study is aimed at investigating effect of intestinal mucositis on pharmacokinetics, organ distribution, and bioavailability of azathioprine (AZA) (6-mercaptopurine). Materials and Methods: Intestinal mucositis was induced with methotrexate (MTX) (2.5 mg/kg). The oral absorption of AZA and 6-mercaptopurine (metabolite) levels were determined in control and MTX-treated rats: ex vivo (noneverted sac technique) and in vivo (pharmacokinetics and organ-distribution) using high-performance liquid chromatography. Immunohistochemistry was conducted to evaluate peptide transporter expression on luminal membrane of small intestine. Results: Intestinal permeation of AZA into systemic circulation of rats was lower after MTX administration, widely found in intestinal segments of mucositis-induced rats leading to decline in systemic bioavailability of AZA. Immunohistochemistry findings indicated diminution of peptide transporter expression representing hampered absorption of drugs absorbed via this transporter. Conclusion: Study outcome has thrown light on altered fate of AZA when administered to individuals with mucositis which suggests modified drug therapy. These findings can further be investigated in different drug classes which might be administered concomitantly in mucositis and study outcome can be further confirmed in mucositis patients in clinical practice also.

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Objective: This study aims to screen and validate five individual warfarin dosing models (four Asian model algorithms, namely, Ohno, Wen, Miao, Huang, and the algorithm of International Warfarin Pharmacogenetic Consortium, namely IWPC algorithm) with the aim of evaluating their accuracy, practicality, and safety. Materials and Methods: Patients' CYP2C9*3 and VKORC1–1639G >A genes were genotyped, and patient-related information and steady warfarin doses were recorded. The difference between the predicted dose and actual maintenance dose of each model was compared. Results: The prediction accuracies of the Huang and Wen models were the highest. In terms of clinical practicality, the Huang model rated the highest for the low-dose group, whereas the Ohno and IWPC models rated the highest for the middle-dose group. The models tended to markedly overpredict the doses in the low-dose group, especially the IWPC model. The Miao model tended to severely underpredict the doses in the middle-dose group, whereas no model exhibited severe overprediction. Conclusions: Since none of the models ranked high for all the three criteria considered, the impact of various factors should be thoroughly considered before selecting the most appropriate model for the region's population.

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A 77-year-old male patient developed acrocyanosis and pain after treatment with amphotericin B liposome 150 mg daily intravenously for disseminated histoplasmosis, and subsequently developed elevated serum creatinine. Amphotericin B liposome was discontinued, and anisodamine was used intravenously to treat acrocyanosis and pain induced by amphotericin B liposome for 9 days and patient was cured. Naranjo adverse drug reaction probability scale score was 5, the World Health Organization-Uppsala Monitoring Centre criteria: Probable, indicating a probable adverse reaction to amphotericin B liposome.

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The Indian Pharmaceutical Industry is undergoing rapid development and expansion. Critical to this process, and the future of drug discovery in India is the continued education and training of integrative or in vivo pharmacologists, equipped with the knowledge, skills and expertise to undertake studies using laboratory animals. Modern in vivo pharmacologists not only require manual or technical skills, but a much broader education including in animal welfare, ethics, the principles of the replacement, refinement and reduction of animals in research, and nonanimal alternative techniques. This education, training, and continued professional development throughout their careers can be provided, in part, through the use of online e-learning resources. While many excellent resources exist, they are hard to locate and not widely known to the community. To address this issue, Education and Training Resources in In vivo Sciences, a free website which provides access to free open access e-learning resources in in vivo pharmacology was developed. Use of this resource by researchers and educators will result in better-trained researchers and members of ethical review committees, which in turn will raise animal welfare standards, minimize the pain, suffering and distress of laboratory animals, and enhance scientific research.

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Objectives: Tramadol is a centrally acting synthetic analgesic. It has a cardioprotective effect against myocardial ischemia-reperfusion (I/R) injury in isolated rat heart. We hypothesized that tramadol may exert a similar protective effect on hepatic I/R injury. Hence, the current investigation was designed to study the possible protective effects of tramadol on experimentally-induced hepatic I/R injury in rats. Materials and Methods: Tramadol was administered 30 min before ischemia following which the rats were subjected to 45 min of ischemia followed by 1 h of reperfusion. Results: Tramadol attenuated hepatic injury induced by I/R as evidenced by the reduction of transaminases, structural changes, and apoptotic cell death. It decreased the level of inflammatory markers such as tumor necrosis factor-alpha (TNF-α), TNF-α/interleukin-10 (IL-10) ratio, and nuclear factor-κB gene expression. It also increased the anti-inflammatory cytokine, IL-10 levels in hepatic tissues. Furthermore, it reduced oxidative stress parameters except manganese superoxide dismutase activity. Conclusion: The results suggest that tramadol has hepatoprotective effects against hepatic I/R injury via anti-inflammatory, antiapoptotic, and antioxidant effects.

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Objectives: Guaifenesin possesses expectorant, muscle relaxant, and anticonvulsive properties. To the best of our knowledge, the promising data regarding the developmental toxicity of guaifenesin are scarce. The current study investigates the developmental toxic effects of guaifenesin in detail using female rats. Materials and Methods: Twenty-five dams were divided into five groups. Group 1 served as a control, while Group-2, -3, -4, and -5 were administered with 250, 350, 500, and 600 (mg/kg b.w.) doses of guaifenesin, respectively, starting from gestation day 6 to day 17. Half of the total recovered fetuses was subjected to morphologic and morphometric analysis, while other half was subjected to skeletal examination. Results: A significant reduction in maternal weight, and food/water intake, was observed, however, no mortality and morbidity were observed. About 14 dead fetuses were found in Group-3 and -4 each, while 26 in Group 5. Morphological analysis revealed 21.2%, 45.4%, 67.2%, and 86.9% of total fetuses having hemorrhagic spots in Group-2, -3, -4, and -5, respectively. Dropping wrist/ankle and kinky tail were found in Group-4 and -5 only. Morphometric analysis showed a significant decline in fetal weight, full body length, skull length, forelimb length, hindlimb length, and tail length in all guaifenesin treated groups. Skeletal examination displayed that only Group 5 fetuses had increased intercostal space between 7^th and 8^th rib. We also observed improper development of carpals, metacarpals, tarsals, and metatarsals of the Group 5 fetuses. Conclusion: Guaifenesin showed a significant developmental toxicity at selected test doses; therefore, a careful use is suggested during pregnancy.

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Erlotinib belongs to the targeted cancer treatments acting through epidermal growth factor receptor inhibition. Papulopustular eruption is the most common cutaneous toxicity. The pathogenesis of the rash is not clear. There is no consensus on treatment. In this report, we describe a 73-year-old female patient who was referred to our outpatient clinic for evaluation and treatment of a widespread acneiform eruption. She was put on erlotinib therapy for 3 months for the treatment of lung adenocarcinoma. The patient has developed nonpruritic papules and pustules widespread over the body except the face for the past 2 weeks. Bacterial culture obtained from a pustule on the back grew methicillin-sensitive Staphylococcus aureus (SA). Histopathological examination of a papule demonstrated vacuolar degeneration of basal layer, prominent walls of vessels, a mixed infiltration of eosinophils, and lymphocytes and erythrocyte extravasation. The eruption was successfully treated with two weekly pulses of azithromycin 500 mg for 3 consecutive days. This case demonstrated that erlotinib may cause purpuric papular eruption secondarily infected with SA. Routine bacterial culture should be performed from pustules before any treatment.

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Oral sodium phosphate (OSP), an effective bowel purgative, is available over the counter (OTC) and requires a substantially lower volume than polyethylene glycol-based preparative agents. Rarely, OSP consumption has been associated with acute hypocalcemia and hyperphosphatemia. We describe a case of chronic kidney disease patient developing symptomatic hypocalcemia following OTC OSP.

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Objectives: Cytochrome P450 2C9 (CYP2C9) is a member of cytochrome P450 (CYP) family that accounts for nearly 18% of the total CYP protein content in the human liver microsomes and catalyzes almost 15–20% of the drugs. Considering the paucity of data on the polymorphisms of CYP2C9 in Western Indian population, the present study was conducted to evaluate the prevalence of CYP2C9 polymorphisms (*1, *2 and *3) and correlate it with the activity using flurbiprofen (FLB) as a probe drug. Materials and Methods: A 100 mg FLB capsule was administered to 298 healthy adult participants. Venous blood samples were analyzed at 2 h postdose for the estimation of FLB and 4-hydroxy FLB. Metabolic ratio (MR) was calculated to determine the extent of poor metabolizer (PM) and rapid metabolizer status using probit plot. Genotyping of CYP2C9 polymorphism was performed using polymerase chain reaction-restriction fragment length polymorphism technique. Results: Of the total 298 participants, phenotype was assessable in 288 and genotype was performed in 289 participants. The median (range) MR of the study population was 6.6 (1.65–66.05). Five participants were found to be PMs by phenotype. Of the total 289 participants, 209 (72.3%) (66.7, 77.2) had CYP2C9*1/*1, 25 (8.7%) (5.8, 12.7) with CYP2C9*1/*2, 55 (19%) (14.8, 24.1) had CYP2C9*1/*3, 3 (1%) (0.3, 3.3) had CYP2C9*2/*3 genotype. A significant association between phenotype and genotype was observed. Conclusion: To conclude, the present study found significant association of CYP2C9 activity by both phenotype and genotype and these findings have to be corroborated in different kinds of patients.

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Objectives: To assess pharmacotherapeutics (PT) knowledge of second professional medical undergraduates. Materials and Methods: It is a questionnaire-based cross-sectional study. The questionnaire was designed to objectively assess the current level of knowledge of PT acquired by the second MBBS students in a medical college in India. Thirty Type-A multiple choice questions (MCQs) related with the PT of common and important medical conditions and some emergency conditions were administered to 125 participants. Grading of knowledge was also done as poor, average, and good both subjectively and objectively. Descriptive statistics were used to analyze responses. Association of PT knowledge with respect to mode of admission in a medical college was analyzed with Chi-square test. Results: MCQs related with PT of nonemergency conditions were responded correctly by 9.8–77.7% of participants. MCQs related with PT of some emergency conditions were responded correctly by 17–66.1% of participants. No statistically significant association was observed in PT knowledge with respect to mode of admission. Conclusion: Gross deficiency in the PT knowledge can potentially and adversely affect future rational prescribing skills. PT knowledge about common medical conditions should be emphasized during undergraduate training program.

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