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Pharmacological screening with reference to Antiarrythmic drugs

Need of drug screening


NEW DRUGS Conventional anti arrhythmic drugs risk of proarrhythmias. Dronedrone - analogue of amiodrone LESS TOXIC. (proarrhythmic risk) Ranolazine anti-anginal atrial selective

Procedure and protocol


Pre clinical testing of drugs in 1. Experimental animals or 2. In vitro for their biological and toxic effects 3. potential clinical applications The screening of anti-arrhythmics is done by two different methods. 1. In-vitro models 2. In-vivo models

IN-VITRO MODELS LAGENDROFF TECHNIQUE:


Animal Guinea pig (300-500g) Animal selected Sacrificed (stunning) heart removed placed in Ringers solution (37C) Aorta located and cut cannulated with Ringers solution (perfused at 40 mm Hg) Ligature

Test /std/control - administered. Occluded for 10 minutes reperfusion ECG electrode pulsatile stimulation, control of arrhythmia Heart rate and contractile force measured

evaluation
Heart rate (chronometer) Contractile force (force transducer) Incidence and duration of ventricular fibrillation or ventricular tachycardia is recorded in the control as well as test group.

In vivo models
In vivo models used to screen anti arrhythmic drugs can be divided into five groups: 1. 2. 3. 4. 5. Chemically induced arrhythmia Electrically induced arrhythmia Exercise induced ventricular fibrillation Mechanically induced arrhythmia Genetically induced arrhythmia

Example chemical induced


A large number of agents are capable of inducing arrhythmias. Administration of anesthetics like chloroform, ether, halothane (sensitizing agents) followed by a precipitating stimulus such as adrenaline, ouabain alkaloids cause arrhythmia.

Mechanically induced arrhythmia


Arrhythmias induced directly by ischemia and reperfusion Coronary artery ligation in anesthetized dog results in: in HR in heart contractility in BP Ventricular arrhythmias

Preclinical studies of medicinal plants


History With the tremendous increase in the global use of medicinal plants, several concerns regarding efficacy and safety of the herbal medicines have also been raised. Hence it has become necessary to standardize the efficacy and safety measures so as to ensure supply of medicinal plant materials with good quality.

Procedure
Collection of medicinal plants 1. The season 2. Correct part 3. Non contaminated 4. Climate conditions Botanical identification Proper drying of medicinal part Drying is important to maintain the pharmacological activity and to enhance the shelf life of medicine.

Importance of preclinical screening of medicinal plants


To establish the therapeutical efficacy of medicinal plants Validate the historical use by medicinal healers Chronic toxicological screenings are dead important for their safety evaluations After preclinical screenings, the phytochemical analysis of medicinal plants is also very important to salt out agent for pharmacological activity.

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