Screening of antipyretic drugs

Screening of antipyretic drugs

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  Screening of Antipyretic Drugs Presenter:- Dr ArunSingh 3rd Year Resident Doctor Department of Pharmacology SMS Medical College,Jaipur
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  Outliner's Introduction Antipyretic Drugs Screening Models AntipyreticActivity-yeast Induced Pyrexia Method Antipyretic activity of Bauhinia Racemose Lam in Rat Antipyretic activity of Gracilaria Corticataj Antipyretic activity in Rabbits
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  Introduction • An antipyreticis a type of medication that will prevent or reduce fever by lowering body temperature from a raised state. • They will not affect normal body temperature if the patient does not have a fever. • Generally, most non-steroidal anti-inflammatory drugs (NSAIDs) work by inhibiting prostaglandin synthetase within the hypothalamus. • Fever, or pyrexia, occurs when the body reaches a temperature above what is considered "average". • Bear in mind, however, that this "average" temperature can vary from person to person within certain parameters.
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  • It isgenerally accepted fever exists at a temperature above 37 degrees Celsius when the thermometer is placed under the armpit, or over 37.5 degrees Celsius when measured orally or rectally. • Fever usually results from microbes such as bacteria or viruses triggering the body's defense mechanisms. • Antipyretics (literally "against the fire") are drugs that reduce fever.
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  Antipyretic Drugs • Thedrugs which lowers the elevated body temperature to the normal . • Drugs used are : 1. Aspirin (Non-selective COX Inhibitor) 2. Paracetamol (Inhibitor of PG’s synthesis)
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  Mechanism of action •Antipyretic drugs resets the thermostat toward normal and rapidly lowers the body temp of febrile patients by increasing heat dissipation as a result of peripheral vasodilation and sweating. • Inactivation of COX enzyme.
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  Screening models Brewer’s yeast suspension method Antipyretic activityin rabbits Antipyretic activity in rats
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  Antipyretic activity-yeast inducedpyrexia method • The body temperature of each albino Wistar rats was recorded by measuring rectal temperature at predetermined intervals. • Albino wistar rats are grouped into four containing six in each group. • The rats are trained to remain quiet in a restraint cage. • A thermistor probe is inserted 3 to 4 cm into the rectum and fastened to the tail by adhesive tape. • Temperature is recorded on a thermometer.
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  • After measuringthe basal rectal temperature, animals are given subcutaneous injections of 10 ml/kg of 15% w/v yeast suspended in a 0.5% w/v methylcellulose solution. • At the 19th hr after yeast injection the rectal temperature of the rats were recorded. • After yeast injection the test drug is administered with dose 250, 500 mg/kg to III & IV group animals. • Propylene glycol at dose of 5ml/kg was injected to the control group. • The II group of rats received the standard drug paracetamol at the dose of 150 mg/kg at the 19th hr after yeast injection.
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  • Subcutaneous injectionof yeast suspension markedly increased the rectal temperature 19th hr after its administration. • Rectal temperature of all the rats was recorded again on the 20th, 21st and 22nd hr after yeast injection. Group Category Drug Solution Group-I Control Propylene glycol (5ml) Group-II Standard drug Paracetamol (150mg) Group-III Methanolic extract of Tephrosia purpurea (250mg) Group-IV Methanolic extract of Tephrosia purpurea (500mg)
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  Evaluation • A decreaseof body temperature for at least 0.5°C for more than 30 min as compared with the temperature value before administration of the test compound is regarded as positive effect.
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  Antipyretic activity ofBauhinia Racemose Lam in rat • The plant Bauhinia racemose Lam belongs to the “Caesalpiniaceae” Family. • It is popularly known as “Apta” in Marathi, “Kanchnal” in Hindi. • Dhar et al, (1968) reported the antipyretic activity in mice from the hydro alcoholic extracts of Bauhinia racemose. • The plant Bauhinia racemose Lam. Belongs to the “Caesalpiniaceae” Family. It is popularly known as “Apta” in Marathi, “Kanchnal” in Hindi.
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  Dhar et al,(1968) reported the antipyretic activity in mice from the hydro alcoholic extracts of Bauhinia racemose. Thirty-six healthy Wistar Albino rats of 200- 250gms were divided into six groups of six animals each, with 50% sex ratio. The initial rectal temperature of each animal was recorded by digital thermometer and its hourly variation was noted for 3 and their average was recorded The pyrexia was induced by injecting a suspension of 15% of brewer’s yeast and 2% gum acacia in normal saline subcutaneously below the nape of neck in the volume of 1ml/100gm of animal weight.
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  The aqueous extractwas given orally to group 1& 2 of 100,200mgkg The alcoholic extract was given orally to group 3& 4 of 100,200mgkg. The 5 group is given with paracetamol of 100,200mgkg/ Sixth group is given with saline sol of 0.5 ml serve as negative control. Rectal temperature was recorded at 1,2&3 hour. The difference in temperature between 0 hour and at the end of 3 hr it is compared.
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  Aqueous and alcoholicextracts of Bauhinia racemose Lam. produced significant antipyretic activity in rats, which was induced by brewer’s yeast. The temperature was brought back to normal after 4 hrs of post administration of extracts. The aqueous extract @200mg/kg body weight and alcoholic extract @100mg/kg and 200mg/kg body weight was found to have significant effect and was found significant at 5% level of significance.
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  Antipyretic activity ofGracilaria Corticataj Gracilaria corticata J.Agardh is red seaweed belonging to Rhodophyceae member shows much attention in the present study for antipyretic activity. Gracilaria corticata J.Agardh were collected from Hare island, Thoothukudi in the southeast coast of Tamil Nadu. The shade dried samples were grounded to fine powder & 3g powdered sample was packed in Soxhlet apparatus and extracted with methanol for 8 hrs. The excess amount of methanol was evaporated, and fine methanol crude powder was prepared and stored in the refrigerator for the antipyretic activity.
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  Swiss albino ratswere weighing (150-240 gm) and male albino rats (15-18 gm) were used. The animals were housed in the departmental animal house under standard conditions (26±2°C and relative humidity 30-35%) in 12 hours light and 12 hours dark cycle respectively for 1 week before the experiment.
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  The experimental treatmentwas carried out as; Group I: Control group animals Normal saline 5ml/kg Group II: Animals were treated with Paracetamol (10mg/kg) Group III: Animals were administered with 200mg/kg methanol extract Group IV: Animals were administered with 400mg/kg methanol extract
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  Results • Antipyretic activityof methanol crude extract of Gracilaria corticata J. Ag. was studied by determining the effect on yeast- induced pyrexia in albino rats. • The result expressed that methanol extract of different doses caused lowering of the body temperature up to 4h following its administration. • The effect of methanol extract on yeast-induced pyrexia showed that the rectal temperature was markedly elevated to 41.7°C, after 18h the subcutaneous injection of yeast suspension decreased to 40.7°C within 1h of 200mg/kg methanol extract of Gracilaria corticata J. Ag.
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  • Treatment followedby 39.6°C at 2h and further reduced to 38.2°C at 4h showing a considerable decrease in compared to paracetamol. • 400mg/kg methanol extract also showed the decreased in temperature from 41.4°C to 39.6°C after 1h of treating with the administration of the methanol crude extract of Gracilaria corticata J. Ag. • When the time was increased up to 4hr,the results were observed significant reduced temperature to 37.2°C. • Both 200 and 400mg/kg marked antipyretic activity detected were significantly different than the controls (p<0.05).
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  Generally, for allconcentration of methanol crude extract of Gracilaria Corticata J. Ag. Showed marked antipyretic activities, hence, 400mg/kg methanol extract was highly effective than 200mg/kg. This result revealed that the methanol extract of Gracilaria Corticata J. Ag. Have detectable antipyretic activity as compared with standard paracetamol.
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  Antipyretic activity inrabbits Purpose and Rationale:  Lipopolysaccharides from Gram- negative bacteria ,e.g., E.coli, induce fever in rabbits after i.v. injection.  Body weight of 150 g are used.  Initial temperature is noted down.  Fevered by injection of 10mlkg Brewer's yeast suspension by s.c. .  The room temperature is kept at 22-24c.̊
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  The animals arereceiving the test and standard drug by oral The rectal temperature are recorded in 30-, 60-, 120- and 180-min post dosing Evaluation : • The difference between the actual values and the starting values are registered for each time interval. • The maximum reduction in rectal temperature in comparison to the control group is calculated.
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  • Results arecompared with effect of the standard drug ,e.g., aminophenazone 100 mg/kg.