Anti-inflammatory, antinociceptive, and vasorelaxant effects of a new pyrazole compound 5-(1-(2-fluorophenyl)-1H-pyrazol-4-yl)-1H-tetrazole: role of NO/cGMP pathway and calcium channels.

Molecular modification of compounds remains important strategy towards the discovery of new drugs. In this sense, this study presents a new pyrazole derivative 5-(1-(2-fluorophenyl)-1H-pyrazol-4-yl)-1H-tetrazole (LQFM039) and evaluated the anti-inflammatory, analgesic, and vasorelaxant effects of this compound as well the mechanisms of action involved in the pharmacological effects. For this, mice were orally treated with LQFM039 (17.5, 35, or 70 mg/kg) prior acetic acid-induced abdominal writhing, formalin, tail flick, and carrageenan-induced paw edema protocols. In addition, vascular reactivity protocols were made with aortic rings contraction with phenylephrine and stimulated with graded concentrations of LQFM039. Abdominal writhing and licking time in both neurogenic and inflammatory phases of formalin were reduced with LQFM039 without altering latency to nociceptive response in the tail flick test. Carrageenan-induced paw edema showed that LQFM039 reduces edema and cell migration. In addition, the mechanism of action of LQFM039 involves NO/cGMP pathway and calcium channels, since this new pyrazole derivate elicited concentration-dependent relaxation attenuated by Nω-nitro-l-arginine methyl ester and 1H-[1,2,4] oxadiazolo [4,3-alpha]quinoxalin-1-one, and blockade of CaCl2-induced contraction. Altogether, our finding suggests anti-inflammatory, antinociceptive, and vasorelaxant effect of this new pyrazole derivative with involvement of NO/cGMP pathway and calcium channels.

Patient Case Report: Gabapentin-Induced Hypoglycemia.

PURPOSE: Gabapentin is an analog of gamma-aminobutyric acid (GABA), but its complete mechanism is not well understood. Common adverse effects from gabapentin include somnolence, sedation, and dizziness. Hyperglycemia is listed as a possible adverse drug reaction in the labeling. Case reports describe hypoglycemia in patients with diabetes, peritoneal dialysis, and/or incomplete medication records. The following case report details a hypoglycemia episode as a potential result of a gabapentin use in a patient without diabetes. SUMMARY: A 47-year old, 68 kg, white female presented to the emergency department with altered mental status. Her blood glucose level was 33 mg/dL. Gabapentin was started 1 week prior to the hypoglycemia episode. Her past medical history, concomitant medications, and other laboratory findings were not likely causes of her severe hypoglycemia. CONCLUSION: Gabapentin appears to have effects on several voltage-gated calcium channels. Hypoglycemia may be due to gabapentin binding to the alpha2delta subunit of the calcium channels in the pancreas. Future research should investigate gabapentin and the potential for hypoglycemia.

Orthostatic hypotension in a cohort of hypertensive patients referring to a hypertension clinic.

The prevalence of orthostatic hypotension (OH) in hypertensive patients ranges from 3 to 26%. Drugs are a common cause of non-neurogenic OH. In the present study, we retrospectively evaluated the medical records of 9242 patients with essential hypertension referred to our Hypertension Unit. We analysed data on supine and standing blood pressure values, age, sex, severity of hypertension and therapeutic associations of drugs, commonly used in the treatment of hypertension. OH was present in 957 patients (10.4%). Drug combinations including α-blockers, centrally acting drugs, non-dihydropyridine calcium-channel blockers and diuretics were associated with OH. These pharmacological associations must be administered with caution, especially in hypertensive patients at high risk of OH (elderly or with severe and uncontrolled hypertension). Angiotensin-receptor blocker (ARB) seems to be not related with OH and may have a potential protective effect on the development of OH.

Medicamentos reguladores de los canales de calcio: revisión de los posibles efectos secundarios

Los medicamentos reguladores de los canales de calcio tienen en la actualidad usos específicos en entidades cardiológicas y en otras áreas de la medicina interna como la neurología y la gastroenterología. La comunidad científica internacional ha acumulado abundante evidencia adicional sobre efectividad y seguridad desde su introducción en el mercado. Recientemente, y a propósito de las interpretaciones de algunos de los estudios existentes sobre nifedipino, se ha generado un especial interés por su seguridad y efectividad, por las diferencias entre sus formas de acción corta y prolongada y en general sobre la utilización de los anticálcicos en hipertensión arterial y en infarto agudo del miocardio (IAM) y angina inestable (AI). Algunas publicaciones aparecidas en importantes revistas médicas internacionales han revisado los aspectos mencionados y han merecido la atención científica y del público en general. El Comité de Investigaciones de la Academia Colombiana de Medicina se reunió para revisar los posibles efectos secundarios de los medicamentos anticálcicos dihidropiridínicos. El doctor Roberto de Zubiría, vicepresidente de la Academia Nacional de Medicina coordinó una reunión con los cardiólogos doctores Luis Moya, Enrique Melgarejo R. y Ricardo Rozo U. y el internista Alvaro Ruiz M