Sec 2 Pharmacology PDF

Prepared By; GENERAL PHARMACOLOGY Dr. Aya Abd EL-Salam Demonstrator of Pharmacology Department at Faculty of Veterinary Medicine Cairo University Posology: It the Science dealing with studying of doses of drugs. Dose: The amount of drug required to produce desired therapeutic effect...

Prepared By; GENERAL PHARMACOLOGY Dr. Aya Abd EL-Salam Demonstrator of Pharmacology Department at Faculty of Veterinary Medicine Cairo University Posology: It the Science dealing with studying of doses of drugs. Dose: The amount of drug required to produce desired therapeutic effect in patient. Dosage: refers to determination & regulation of doses. Types of doses (4): 1.Therapeutic(medicinal) dose. 2.Effective dose (ED) 3.Toxic dose (TD) 4.Lethal dose (LD) 1.Therapeutic (medicinal) dose: it is the dose Given in a safe amount to adult diseased Animal To produce desired medicinal effect. 2.Effective dose: the dose which given to produce desired effect ,Given experimentally to lab animal 3 types of effective dose according to % of population : ED1 / ED50 / ED100 1.Median effective dose (MED) (ED50): the dose which produce desired Reaction in 50% of population 2.ED1: the dose which produce desired Reaction in 1% of population. 3.ED100: the dose which produce desired Reaction in 100% of population 3.Toxic dose (TD): It is the excessive dose which produce some harmful and toxic effects to the animal but not kill the animal. 3 types of Toxic dose according to % of population : 1.TD1: excessive dose which produce toxic effects to 1% of population. 2.TD50: excessive dose which produce toxic effects To 50% of population. 3.TD100: excessive dose which produce toxic effects to 100% of population. 4.Lethal dose (LD): The amount of drug which kill the animal. 4 types of Lethal dose according to % of population : 1.LD0: the maximum toxic dose but not kill animal “non fatal” 2.LD1:Minimum lethal dose: the dose which kill one animal in the group(MLD) 3.LD50: Median lethal dose:the dose (mg/kg bwt) which expected to kill 50% of population of the same species and strains 4.LD100: the lowest lethal dose which kill 100% of population. Minimum Lethal Dose (MLD) (LD1) Median Effective dose (MED) (ED50) ED1 ED100 TD1 TD50 TD100 LD0 LD50 LD100  Therapeutic index (TI) or safety margin an approximate assessment of the safety of the drug expressed as follow: LD50 TI = ED50  Wide ratio give high value of TI indicates that the drug of wide safety margin as Penicillin and sulphonamides ,atropine ,fenbendazole  10:1 20:1 30:1 40:1 50:1 Narrow ratio indicates low TI and narrow safety margin as Digitalis & strychnine 1:1 2:1 3:1 4:1  Factor affecting (influencing) doses Animal (6) Drug (7) Both (4) Species Form Idiosyncrasy Age Route Drug fastness Body weight Time of admin. Tolerance Sex Frequency of admin. cummulation Presence of disease Objective of medication Animal Condition Synergism antagonism  Factors related to animal 1.Species: Rabbit resist large doses of Atropine Emetics produce excitation in cats, rats and quiets man, dogs. Ruminants resist large oral doses more than simple stomach animals. 2.AGE: Adult animal require larger doses than young and aged animal Young animals more sensitive to drugs than adults Aged animals with weak, impair organs (liver, kidney). 3.BODY WEIGHT: Indicate amount of tissues to be affected by dose Dose expressed by unit/ Kg Body weight  4.SEX: No significant difference in drug response between males and females but special care must be taken in: 1)Pregnancy: avoid abortifacient drugs (drastic purgatives, ergot alkaloids, quinine) and drugs which cross placental barrier (Ab, morphine) affect fetus 2)Milking animal: avoid drugs which cross milk barrier as volatile oils as it change milk color, odor, taste and produce bad effect on neonate & humane health 5. PRESENCE OF DISEASE : Constipation: increase absorption, delay passage of drugs. Diarrhea, vomation: decrease absorption, decrease transit time. Hepatic disease: prolong effect of drug metabolized mainly in liver (chlorpromazine, barbiturates) Kidney disease; toxic effect of drug excreted by kidney (streptomycin, neomycin)  6.CONDITION OF THE ANIMAL: Some drugs not act on normal individuals: 1)Antipyretic : not decrease body temperature in normal animals only in febrile conditions. 2)Stomachic : not affect on animals with normal appetite but, increase appetite in animals with loss of appetite. 3)Digitalis : act only in animals with heart failure.  Factors related to Drug 1. Drug Form: Liquid drugs more absorbed than Solids Alcoholic drugs more absorbed than Aqueous Powder drugs more absorbed than Tablet Concentrated soln. more absorbed than Diluted soln. 2. Route of administration: In IV administration the dose reduced than in oral administration 3. Time of administration: On full stomach (after meal) On empty stomach To reduce gastric irritation, Prevent dilution with food (anthelmintic) vomation (iron, voltarine) Immediate action (antacids, appetizer) Enhance absorption (grisofulvin) Prevent inactivation (tetracycline not used Delay action of drugs with milk as it form insoluble chelates with aluminum, ca, mg salts )  Factors related to Drug 4. Frequency of administration:  Rapidly excreted drug repeated with frequent interval to keep effective drug level in Circulation & visa versa.  Drugs which are slowly excreted as Na.penicillin given every 6 days while procaine penicillin give once/day to produce the same effect.  Penicillin is considered as time dependent killers because it's antibacterial effect depend on time of contact with microorganisms. 5. Objective of medication:  Lpechacuanha root (emetine) act as expectorant in small dose & emetic in large dose  Quinine in small dose act as stomachic & in large dose act as antipyretic  Factors related to Drug 6. Synergism:  From Greek word (ergo) (work) & (syn) with Mean (pharmacological co-operation)  Occur when 2 drugs having the same effect giving together & the effect of their combination is greater than the sum of their independent when both given alone. E AB = 1 + 1 > 2 Ex:  Sulphonamides & Trimethoprim  Chloralhydrate & Bromide  barbiturates & aspirin  Factors related to Drug 7. Antagonism: Occur when 2 drugs having the opposite effects 1- Pharmacological Competitive Noncompetitive Agonist compete with antagonist on Agonist & antagonist act on the same receptor different sites of action. Reversible; atropine & acetylcholine Acetylcholine & papaverine on on muscarinic receptor. smooth muscles of intestine Irreversible; adrenaline & alpha adrenergic blockers.  Factors related to Drug 7. Antagonism: 2- Physiological: Two endogenous substance act on 2 different receptors producing opposite effect. Ex. Acetylcholine (parasympathetic NS) decrease heart rate , vasodilatation & adrenaline (sympathetic NS) increase heart rate , vasoconstriction 3- Chemical: Antagonism by neutralization of gastric acidity by alkaline drugs as : sod bicarbonate  Reversible competitive antagonism Can be overcome by increasing the dose of the agonist and increase its conc. on the receptor to overcome the blockage effect of the antagonist  Irreversible competitive antagonism (non-equilibrium) Increasing the conc. of the agonist on the receptor does not overcome the blockage effect of the antagonist  Noncompetitive antagonism Ca intestine papaverine channel Ach Ach act on muscarinic receptors on intestine smooth muscles cause stimulation Papaverine act on ca channels cause inhibition  Importance of antagonism 1.Correct side effect of drugs (ephedrine & phenobarbitone) 2.Treat drug toxicity as: 1.Treatment of organophosphorus compound toxicity with atropine 2.Treatment of morphine toxicity by nalorphine. 3.To know undesirable combinations which may decrease drug efficacy : Tetracycline's & Penicillin's  Factors related to BOTH 1.Idiosyncrasy (Drug allergy): Abnormal response to certain drugs in some individuals Sulphonamides --------- Skin rashes Penicillin----------------- Anaphylactic shock, Death in G.pig Some broad spectrum antibiotics …….Fatal colitis in Horse 2. Drug fastness (Bacterial resistance): Resistance of M.O. to some drugs to which it was previously sensitive due to admin. of sub inhibitory doses. Antibiotic & Sulphonamides , Penicillins 3.Tolerance: Unusual condition of the body in which larger dose than therapeutic one required to produce the same therapeutic effect.  3.Tolerance: 1)True tolerance :-  Species tolerance (natural, congenital): Certain Species Tolerate some drugs Ex: Rabbit tolerate atropine due to atropinase in liver invertebrates tolerate large doses of strychnine  Acquired tolerance: Occur only by repeated administration Of some drugs after period the therapeutic dose become Ineffective Ex: Morphine, Alcohol, Barbiturate & Caffeine ,Nitrates ,Xanthine 2)Cross tolerance: Occur to one drug after administration Of another related one Ex: Alcohol & Volatile Anesthesia, Member of Aminoglycosides  3)Pseudo tolerance or Apparent tolerance :-  As in case of diarrhea drug pass through intestine rapidly so not completely absorbed  As in case of ingesting small doses of poisons orally then GIT develop immunity against poisons…..prevent absorption of poisons into systemic circulation then poisoning can occur by another route except orally. Mechanism of development of tolerance 1)Slow absorption……Pseudo tolerance 2)Rapid metabolism…. Belladonna tolerance …enhancing of detoxification by stimulating microsomal enzymes in liver. 3)Rapid excretion...phenylbutazone is rapidly excreted in rodents, dogs more than man. 4)cellular changes: the most accepted mechanism The cells of C.N.S develop tolerance to morphine, barbiturates with normal physiological functions in the presence of very high concentrations which are toxic to non-tolerant cells of other systems.  4. Cummulation (undesirable phenomenon):  Def.: Condition in which drug is given repeatly and slowly excreted so the drug may accumulate in body to level of toxicity & may cause death  Ex.: Digitalis , emetine , Sodium bromide , heavy metals , Strychnine , Long acting sulphonamide  Advantages : immobilize some poisons in body depots  Types: 1)Apparent Cummulation: occur when insoluble Substances in the form of suspension injected into the body with slow absorption as Bismuth salts which treat Syphilis in man 2)Passive Cummulation: substance as lead can remain deposited in bones without producing toxic effects but ,toxic effects appear when released to blood  How to Overcome 1.Knowledge about kinetics of the drug 2.Start with initial dose followed by small maintenance one 3. Period of rest during treatment course 4. Diuretics Which help excretion of cumulative drug. 5. Stop treatment once toxic symptoms appear. 6. Check Liver and kidney function before and during drug administration 7. Know if the drug is rapidly or slowly eliminated from the body Estimation of doses according to: Route of administration Species Oral 1 part Horse 1 part Rectal 2 parts Camel 2 part IM & SC ½ part Cattle 1½ part IV ¼ part Sheep 1/5 part Pig 1/8 part Dog 1/16 part Cat 1/32 part