screening of analgesics

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Evaluation of analgesic Agents Screening of Analgesics:

Evaluation of analgesic Agents Screening of Analgesics Prepared by :- Kuldeep Kinja M.Pharma 2 nd Year Pharmacology

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BIOLOGICAL EVALUATION Process by which Toxicological study Absorption, Distribution, Metabolism, Elimination, etc is determined through clinical assessment in humans or veterinary animals by drug or group of drug

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Analgesics A drug that selectively relive pain by acting in the CNS and Peripheral pain mechanism without significantly altering consciousness. Act by Depressing sensory nerve centers Reducing conductivity of nerve fibers Analgesics divided in to two group Opioid/Narcotic Non opioid/Non narcotic

Analgesics:

Analgesics Narcotics The class - Opioids (morphine & morphine like drugs) Examples 1- Natural (as codeine) 2- Semi synthetic e.g. di-hydromorphine & diacetylmorphine (heroin) 3- Synthetic e.g. pethidine 4- Endogenous opiates as endorphins & encephalins

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Narcotics Antagonist Naloxone, nalorphine & levallorphan Uses Deep pain e.g. cancer, MI & anginal pain Potency High Side effect Addiction, Respiratory depression MOA ‡ of opiates receptors ( m, k ,s, d) and relief the pain.

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Non - narcotics The class Examples -NSAID 1- Aspirin 2- Paracetamol 3- Diclofenac 4- Piroxicam 5- Ketoprofin

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Uses Potency Side effect MOA Dull pain e.g. headache, toothache & backache Low No addiction. ↑in bleeding tendency & ulcer Inhibits prostaglandin synthesis by inhibition of cycloxygenase enzyme Non - narcotics

Screening of Narcotic Analgesic :

Screening of Narcotic Analgesic Principle:- Record the response of an animals to a painful stimulus before and after administration of analgesics. Thermal Method Radiant heat method Hot plate method Tail - flick method Chemical method Formalin test Mechanical method Tail – clip method

Hot plate method:

Hot plate method Requirement: - Drugs Morphine Test drug Instrumentations Cages Stop watches Thermostatically controlled hot plate Animals 10 mice

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Purpose: - The paws of mice are very sensitive to heat at temperature. So the response are jumping, withdrawal of paws and licking of the paws. The time until this response occur is prolonged after administration of centrally acting analgesics.

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Procedure:- Group of 10 mice with weight of about 25 gm. The hot plate consist of electrically heated surface with controlled temperature 55±1°C. Animals are place on hot plate and time of flicking or jumping is recorded by stop watch, before drug administration. The latency time is recording after 15,30,60,90 minutes following oral or subcutaneous administration of the standard or the test compound

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Evaluation:- Shows the prolongation of latency time by comparing value before and after administration of test compound. Comparison done by statistical analysis using t-test. The value which is exceed the value before administration for 50% or 100% can be regarded as positive response. ED 50 value can be calculated.

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Dose :- 7.5 mg/kg Morphine HCl s.c. 30 mg/kg Codeine HCl s.c. 30 mg/kg Pethidine HCl Where found to be effective. Where as Aspirin showed no effect even at high dose.

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Requirement:- Drugs Test drug chemical Formalin Animals Rat Formalin test

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Purpose: - The formalin test in Rats has been proposed as a chronic pain model which is sensitive to centrally active analgesic agent.

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Procedure:- Rats weighing 180-300 gm are administer 0.05 ml of 10% Formalin into the Dorsal portion of the front paw. The test drug is administered simultaneously either s.c. or orally Each individual Rat is placed into a clear plastic cage for observation. Reading are taken at 30 minute interval

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Pain response are indicated by elevation or favoring of paw Analgesic response is indicated if both paws are resting on the floor with no obvious favoring of injected paw

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Evaluation: - Using various doses ED 50 value for protection can be calculated. Dose :- 1.7 mg/kg Morphine s.c. 15 mg/kg Pethidine s.c.

Screening of Non-narcotic Analgesic :

Screening of Non-narcotic Analgesic methods:- Writhing method / Chemical method Electrical method / RANDALL-SELITTO test

Writhing Method:

Writhing Method Principle : The painful stimulus is induced by injection of an irritant substance (e.g. acetic acid) Writhing : Stretching of the body, withdrawing of the limb, retraction of the abdomen & the stomach touches the ground

Writhing method:

Writhing method REQUIREMENTS Animal : Mice Painful stimulus : Chemicals e.g. Acetic acid , Phenyl quinone Drug used : NSAID e.g. Na salicylate

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Procedure :- Mice with weight between 20 – 25 gm are used. Phenylquinone in concentration of 0.02% is suspended in a 1% suspension of CMC. 0.25 ml of this suspension is injected intraperitoneally . 2 Group of 6 animal are used for controlled and test.

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Test animals are administer the drug. The test animal are administered the drug at various pretreatment time prior to Phenylquinone administarion. The mice are placed individually in the glass beakers and 5 min. allow to elapse. The mice are than observed for appeared period of 10 min. and no. of writhes is recorded for each animal.

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Evalution:- The formula for computing percent inhibition is average writhes in the control group minus writhes in the drug group diveded by writhes in control group. The time period with the greatest percent of inhibition is considered the pick time.

REFENCES:-:

REFENCES:- Tripathi K.D. “ Essentials of Medical Pharmacology”, 5 th edition, Published by Jaypee Brothers. 2. Gerard J.T. “Principle of Anatomy and Physiology”,11 th edition, Willy International Publishers. .

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3. Thomas L.D. “ Medicinal Chemistry”,6 th edition, Published by Lippincott Williams and Wilkins 4. Vogel H.G. “Drug Discovery and Evaluation” 2 nd edition, Springer publishers. 5. http://Googel.com

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THANK YOU