1. DR. MOHD NAZAM ANSARI

2.  Analgesics: Painkillers, A drug that selectively relive pain by acting in the CNS and Peripheral pain mechanism without significantly altering consciousness.  Types of Analgesics  Opioid/Narcotic analgesics: Relive visceral pain. Uses: Deep pain e.g. Cancer, Myocardial Infarction, Anginal pain Examples: 1- Natural (as morphine, codeine) 2- Semi synthetic (heroin) 3- Synthetic (pethidine) 4- Endogenous opiates (endorphins & encephalins)  Non opioid/non-narcotic analgesics: Relieve somatic pain. Uses: Dull pain e.g. headache, toothache, backache Examples: Aspirin, Paracetamol, Diclofenac, Piroxicam

3. Non-Narcotic AnalgesicsNarcotic Analgesics Act peripherallyAct centrally Do not cause addictionCause addiction Do not produce CNS depressionProduce CNS depression Produce gastric irritationDo not produce gastric irritation Has anti-inflammatory effectHas no anti-inflammatory effect

5. Membrane phospholipid Phospholipase A 2 Arachidonic Acid Cycloxygenase Cyclic endoperoxides PGG 2 PGH 2 Isomerase Thromboxane synthetase ProstaglandinTXA 2 (PGE 2, PGD 2, PGF 2 α ) TXB 2

6. COX enzymes COX-1 enzyme Responsible for protecting body’s stomach lining and kidneys COX-2 enzyme Responsible for causing pain and inflammation

7. NSAIDs Inhibit COX-1 enzyme Inhibit prostaglandin that Protect the stomach lining COX-2 enzyme Inhibit prostaglandin that causes pain and inflammation Gastric ulceration and colitis anti-inflammatory & analgesic action

8.  Chemical  Electrical  Thermal  Mechanical

9.  It is very important method for screening of non- narcotic analgesics like aspirin.  Acids (pH 11), K + (10mEq/Lit)  Hypotonic or Hypertonic solutions  Neurohumors : Acetylcholine (10µg/ml), Histamine (10µg/ml), 5-HT (0.1µg/ml)  Polypeptides : Substance P and Plasma kinins (0.1µg/ml)  Prostaglandins potentiate activity of pain producers

10.  Pododolorimeter cage has metallic floor, voltage required to make animal to cry and struggle is noted before and after administration of drug.  Rectodolorimeter: A small electrode is inserted into rectum of animal and crying or jumping is noted before and after administration of drug.  Advantage: voltage required is very less.

11.  Most widely used 1.Eddy’s Hot Plate: Animal is placed on hot plate and time for jumping from plate is noted before and after administration of drug. Hind paw licking (4-6 sec) or jump response (2-3 sec) 2.Davies Test or Tail flick method: only for narcotic analgesics 3.Immersion of tail of rat in hot water

12. 1.Pressure on tail is given by a forceps, clamps, and hemostats. 2.Screw dense method 3.Tail clip method

15.  The Tail Flick assay is a pain receptive assay in which a mouse is placed within a restraining tube with its tail protruding.

16.  The method is based on the reaction of the rat to heat stimulus applied to a small area of the tail.  The time until this response occur is prolonged after administration of analgesics.

17. Albino rats of either sex weighing between 100-150 g are used. The rat is held and its tail is placed on a level surface, a radiant heat is applied to the tail at a point not more than 3 cm from its tip. After an interval the animal withdraws its tail with a sudden and characteristic flick. Time of flicking is recorded, before drug administration. The reaction time are thereafter recorded after 15, 30, 45 and 60 minutes after administration of the test drug

18. Reaction time in second Minutes after drug administrationControlRat No. 60453015 1. 2. 3. 4. 5. 6.

19.  Shows the prolongation of latency time by comparing value before and after administration of test compound.  Comparison done by statistical analysis using t-test.