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Safety

 Non-Clinical Safety Pharmacology Profile of Verapamil: Analysis of Core and Supplementary Studies in Animal Models 1. Executive Summary and Non-Clinical Risk Classification Verapamil, a phenylalkylamine L-type calcium channel blocker, has a highly predictable non-clinical safety pharmacology profile defined by its mechanism of action. Comprehensive evaluation across the ICH S7 core battery (Cardiovascular, Respiratory, and Central Nervous Systems) and supplemental toxicology studies confirms that the primary functional effects are systemic vasodilation, profound depression of atrioventricular (AV) nodal conduction, and direct negative inotropy at elevated concentrations. The integrated risk assessment derived from non-clinical models reveals three critical liabilities that necessitate specific safety monitoring during human clinical development. Firstly, the acute cardiovascular risk is localized to dose-dependent AV block and subsequent myocardial depression, which becomes signif...
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Final try

 Verapamil Hydrochloride: A Comprehensive Review of its Pharmacodynamics, State-Dependent Electrophysiology, and Stereochemical Activity I. Introduction and Initial Pharmacological Classification A. The Genesis of Verapamil: Discovery as a Smooth Muscle Relaxant and Vasodilator Verapamil hydrochloride, a prototypical phenylalkylamine (PAA) and the first calcium channel blocker utilized clinically , was initially studied for its effect on vascular smooth muscle. Investigations in experimental animals established its primary mechanical action as a smooth muscle relaxant, conferring significant vasodilator properties. This classification stems from the fundamental principle that the influx of calcium ions is requisite for the contraction of vascular smooth muscle cells. By inhibiting this transmembrane \text{Ca}^{2+} influx, verapamil promotes the relaxation and dilation of blood vessels throughout the peripheral circulation. This inherent vasodilatory action reduces systemic vascular...
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Pharmacodynamics Nitin

Pharmacodynamic Analysis of Verapamil in Non-Human Animal Models: Mechanisms, Systemic Effects, and Species Variability I. Introduction to Verapamil Pharmacodynamics in Comparative Models Verapamil, a foundational agent in cardiovascular pharmacotherapy, belongs to the phenylalkylamine class of non-dihydropyridine calcium channel blockers. Its efficacy across diverse cardiac pathologies is predominantly attributed to the blockade of the L-type voltage-gated calcium channel (I_{\text{Ca, L}}). Unlike dihydropyridines (e.g., nifedipine), which exhibit greater affinity for vascular smooth muscle, verapamil preferentially targets myocardial and nodal L-type channels, resulting in pronounced negative chronotropic and dromotropic actions. The pharmacodynamic profile of verapamil in non-human animal models is essential for translational medicine and veterinary practice. Research utilizing dogs, cats, horses, mice, rats, and guinea pigs reveals significant variability in response, which dictat...
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QUALITY CONTROL AND QUALITY ASSURANCE Ridwan Islam. - ppt download

QUALITY CONTROL AND QUALITY ASSURANCE Ridwan Islam. - ppt download
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Andamans: 7 days, 7 islands (Episode 2)

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Shark tank | Kevin's desperation for this offer is too much .

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The 5 LESSONS In Life People Learn TOO LATE

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