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Basic Pharmacology

By: Dhshan Hassan Dhshan

Basic Pharmacology By Dhshan Hassan Dhshan

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Basic Pharmacology By: Dhshan Hassan Dhshan Introduction (General Pharmacology) 2 .

: The study of drug  . 3: Non irritant. 2: More safe. 6: Potable. 4: Easy of Administration.(decrease activity and absorption of drug) Stomach Drug Stomach Drug 3 Liver Intestine Intestine Not First Pass Effect . 5: Economic.  Disadvantage:1: Not suitable for: -Emergency -Irritant -Vomiting -Diarrhea 2: Affected by PH.e.How they work . or treatment of disease  Sources of drugs:-Natural -Synthetic -Semisynthetic -----------------------------------------------------------------------------------------------------------------Pharmacology Pharmacokinetics Pharmacodynamics Pharmacotherapeutics What the body does to drug ADME What the drug does to body The result of drug and body action -Absorption Mechanism of Uses of Drug Action -Distribution (Therapeutic (Drug receptor -Metabolism effect) interaction) -Elimenation ------------------------------------------------------------------------------------------------------------------ Route of administration 1: Oral rout:  Advantage: 1: The most common.Basic Pharmacology By: Dhshan Hassan Dhshan  What is Pharmacology? It is the science that deals with chemical substance (drugs) on the function of living system. 3: First Pass Effect.what they do  Drugs (Therapeutic agent):Any substance other than food can be used in the prevention. i.What they are . diagnosis.

B 4 . Blood-Brain Barrier B. -Digoxin In Emptying rate  absorption. .  lipid solubility  Absorption. -Acidic drugs  absorbed in acidic medium (Stomach). (Like dissolve like) -Means polar drug (water soluble drug) not totally absorbed in the cell in tissue due to high amount of lipid content and not pass through B. -presence of disease  absorption 3: Gastric Emptying rate. 6: First pass effect. 5: PH of GIT.B. 4: Motility of GIT. -Amino acid compete for the same carrier of l-dopa. 2: State of health in the stomach.  Absorption. -may be or absorption depend on drugs e.g.Basic Pharmacology By: Dhshan Hassan Dhshan  Factors affecting oral absorption:1: Presence of food in the stomach.Motilityin case of diarrhea absorption. Blood-Brain Barrier B. e.B. Atropine motility of GIT  Emptying rate.B N.g. -Basic drugs  absorbed in basic medium (Intestine). N.B.B (Blood Brain Barrier) but lipid Soluble drug highly absorbed and Pass B. -Calcium from milk absorption of Tetracyclin. -Paracetamol In Emptying rate  absorption.B.B. -Tannic acid and tetracycline absorption of Iron.B.B. 7:Related to the drug.

Nicotine patches. 5: Suitable for Acid labile drugs.intrabone marrow .g.Basic Pharmacology By: Dhshan Hassan Dhshan 2: Parentral rout (injection):A-Intravenous (IV) injection: Advantage: 1:100% bioavailability (amount of drug reached to blood ) 2: No first pass effect. 4: Suitable in emergency. ----------------C-Subcutaneous (SC) injection: Absorption rate is slower than IV and IM  It is suitable for drugs that are non-irritant in aqueous soln. 5 . -e.Systemic delivery of drug -highly absorbed (high bioavailability) after parental high blood supply. 3: Suitable for irritant drug.  Better absorption than SC but less than IV. ------------------------------------ 4: Transdermal:. 5: Not suitable for oily and Suspended drugs.g. -Many drugs make lung irritants. or fine susp. susp. 3: Spreading of infection. 4: Required professional person. And oily drugs. 2: Must be Sterile. .intacardial .Systemic and Local delivery of drug.intrathecal . Disadvantage: 1: low safety.intraperitoneal ------------------------------------ 3:Mucosal rout:Buccal or Sublingual Nasal Ocular Systemic delivery of Local delivery Local delivery of drug of drug drug Vaginal Rectal Local delivery Systemic and of drug Local delivery of drug ------------------------------------ 4: Inhalation:. ----------------D-Other injection: e. ----------------B-Intramuscular (IM) injection: Suitable for soln..

Glucose 2: Active diffusion. 4: PH at the site of absorption. -Need Carrier and not need energy.  Factors affecting simple diffusion 1: increase dose concn. e.C 3: Pinocytosis. -Frome low concn. 6 .: Effect of the boy on the drug. 3: increase ionization  water soluble drug  Decrease absorption. e.From high concn.g. to high concn.  Special transfer. gradient. .g. -From low concn. to high concn. B12 intrinsic factor complex. -Need carrier and need energy. gradient.g. Increase absorption. to low concn. -The drug must be lipid soluble and small in Mwt. Vit. with concn.: the transfer of drug from the site of administration into the blood stream depend on Route of Administration  Mechanism of Absorption  Passive diffusion (simple diffusion) . with concn. -Need carrier and need energy. Vit. 2: increase Mwt. 1: Facilitate Diffusion. to low concn.  Consist of 4 process (ADME) 1: Absorption  Def. with concn.Basic Pharmacology By: Dhshan Hassan Dhshan Pharmacokinetics  Def. gradient.No needed energy and carrier. e. -From high concn. and size  Decrease absorption.

Basic Pharmacology By: Dhshan Hassan Dhshan  Factors affecting absorption 1: Patient-Related factors:  Route of Administration.g.>S.: the amount of administration drug reached to systemic circulation. 2: drug-Related factors:  Water and lipid solubility. I. = 100% Oral <100%  Example: Cyclosporine Bioavailability IV = 100% Bioavailability Oral = 25%  Oral dose = 4 x IV dose  Factors affecting Bioavailability  First pass effect  decrease Bioavailability  Efflux from introcytes.>Oral>Skin  Absorbing surface.>I. Non ionized  More lipid soluble high absorption. Solution > Suspension > Tablet ------------------------------------------------------------- Bioavailability  Def. Inorganic (small molecules) > Organic (Big molecules)  Pharmaceutical preparation.C. Vasoconstriction (V. Ferrous iron > Ferric iron.  Specific factors e. I.C. High lipid solubility Drug  high absorption  Ionization.V.)  absorption. intrinsic factor for Vit. Of drug 7 .V. (Solution > Suspension > Tablet).B12.C.  Valency.  Physicochemical properties of the drug. (Polarity – solubility – Particle size)  Nature of formulation.M. Adrenaline S.  Nature. Shok and heart failure  decrease absorption  Presence of other drugs. Increase Surface  increase Absorption  Systemic circulation.

: -If the drug has Vd higher than 42L / 100Kg  the drug has low affinity to binding to PP. ( polarity and size of drug) Degree of binding to plasma protein (PP) (increase binding  decrease Distribution) N. -Amount of free drug can be increase by: 1: Displacement by other drugsReplacement of one drug by another.B. .g. .: the apparent volume of fluid into which an administrated drug is dispersed.If the drug has Vd lower than 42L / 100Kg  the drug has high affinity to binding to PP.) : ‫ خاص بة‬volume of distribution‫كم دواء نه‬  e. .  The binding drug converted to free drug  to give the same action.Aspirin Vd =16L / 100Kg. e.: .‫يرتبط انذواء ببروتيه انبالزما ويصبح غير فعال وعىذما يصبح تركيس انذواء انحر قهيم يىفصم انذواء عه انبروتيه نيحافظ عهى وفس انتركيس‬ 2: decrease in albumin or plasma protein liver disease. Depend on: Blood flow  increase increase distribution (lung > liver > Bran) Ability of the drug to pass biological membrane. Aspirin and warfarin (anticoagulant) is binding in the samesite of PP increase aspirin intake increase free drug (Active drug)of warfarin increase toxicity .B. Vd (volume of distribution) = Q (Total amount of drug in the body) /Cp (Plasma concn.Basic Pharmacology By: Dhshan Hassan Dhshan 2: Distribution      Def.Digoxin  Vd =2290L / 100Kg. Volume of distribution Def.: Drug + Plasma Protein (PP) (Drug Complex and PP) Active form inactive from -When the free drug concn.  N.g. Cp = Q / Vd 8 .: the transfer of drug from the blood stream into the tissue.

reduction and hydrolysis.Hepatic microsomal biotransformation (located in the hepatic smooth endoplasmic reticulum ) -Non Hepatic microsomal biotransformation (located lung.  Can’t be induced and inhibited.Basic Pharmacology By: Dhshan Hassan Dhshan Half-life (t1/2)  Def. and other Oxidation. .: is the time pass for the plasma concn. 9  Responsible for Oxidation by Cytocrome P450.. and kidney)  Responsible for conjugation.  Activity is stable. Skin. (t1/2) Max. . or the amount of drug in the body to be reduced by 50%.  Activity is low. concn. 50% (t1/2) Onset time Elimination time Time     t1/2 can be increase by : decrease renal blood flow decrease Metabolism rate decrease Protein binding  t1/2 can be decrease by :  increase renal blood flow  increase Metabolism rate  increase Protein binding ------------------------------------------------------------------------------------------------------------------------------------- 3: Metabolism  Metabolism or Biotransformation usually conversion of drug from non-polar polar more polar Polar Group ‫ وهى عمهية اخراج انذواء عه طريق ادخال‬Metabolism ‫معظم االدوية تخرج مه انجسم بعذ امتصاصها ورنك وتيجة نعمهية‬ Non lipid soluble ‫ انى‬Lipid soluble ‫فيتحىل انذواء مه‬  Site of Metabolism.  Can be induced and inhibited. Glucuronidation. Drug blood concn.reduction and hydrolysis.

g. Chloral hydrate tri-chloro ethanol 3: Hydrolysis e.g.Chloramphenicol.: the process which involve excretion of drug out side of the body.  Age: deficiency of liver microsomal enzyme specially in child prolonged action of drug Increase toxicity e.  Sex differences : metabolism rate of certain drug faster in male than female e. ------------------------------------------------------------------------------------------------------------------------------------- 4: Excretion      Def.g.  Inhibition of microsomal enzymes: certain drug inhibit the activity of microsomal enzyme leading to prolongation the action of drug increase activity and toxicity of drug  e. Conjugation with glycine Aspirin Phase I Phase II  Results of metabolism.Active drug (Adrenalin)  Inactive (Vanil mandilic acid (VMA)).g. Paracetamol 2: Acetylation e. If drug acid  we used alkaline to increase excretion. Phenancetin paracetamol 2: Reduction e.  Toxification .  Maintain activation .g. Erythromycin and Ketoconazole.g. Omeprazole. Major drug excreted path way by  -Urinary excretion -Biliary excretion.  Inactivation . Chloramphenicol.g.  State of health: Presence of disease alter in the normal metabolism.Inactive drug (Imipramine)  Active (Desipramine). Carbamazepine.g.  Factors affecting metabolism.g. Isnoniazide 3: Methylation e.g. diazepam  Genetic factor: Absence of specific gene responsible for syntheses of special enzyme essential for normal metabolism. Noradrenalin 4: Conjugation e.  Activation .Drug (Methyl alcohol) Toxic (Formaldehyde). If drug alkali  we used acid to increase excretion.Basic Pharmacology By: Dhshan Hassan Dhshan  Divided into :- 1: Oxidation e.  Induction of microsomal enzymes:certain drug increase the activity of microsomal enzyme leading to increase metabolism rate decrease activity ( plasma concn.g. of drug)of drug  e. Cemitidine.Active drug (Phenacetin)  Active (Paracetamol). Minor drug excreted path way by  -Saliva -Skin -Milk -Gastric excretion -Bile salt. Heroin  HAC + Morphine 1: Glucuronidation e. 10 . Phenobarpitone and Imipramine.

 Endogenous receptor (ligand activated transcription factors). . Voltage-gated ion channels Tyrosine Kinase-Linked Receptor G-protein-coupled receptor 11 .Basic Pharmacology By: Dhshan Hassan Dhshan Pharmacodynamics  Def.DRDrug Receptor complex. . Ligand-gated ion channels. D + R = DR .Receptor called Ligand.  Enzyme linked receptor (Tyrosine Kinase-Linked Receptor).  G-protein-coupled receptor. -Biological effect increase when the drug receptor complex increases.D  drug .  What is a Receptor? -Any biological molecule to which a drug binds and produces  Response.: the study of the relationship of drug concn.R  Receptor . to drug effect.‫نكى يعطى انذواء تأثيرداخم انجسم البذ ان يرتبط بانهذف انمراد انىصىل إنية‬  Major classes of receptors  Ligand-gated ion channels.  Voltage-gated ion channels.

Gq Stimulatory  increase Phospholipase C (PLC)increase Insitol tri-phosphate (IP3) and increase DAG (Di-Acyl Glycerol).Go  decrease post synaptic Potential  decrease vomiting.: protein between receptor and effector organs.Gs  Stimulatory  increase Adenylcyclase  increase cAMP (cyclic Adenosine MonoPhosphate ) increase Ca++ influx from Sytoplasmic Reticulam (SR). interacts with actin  Contraction. .Gi  Inhibitory  decrease Adenylcyclase  decrease cAMP decrease Ca++ influx. Gq Vasoconstrictors Drugs Mechanism of Gq in Vasoconstrictors Drugs : Agonist binding to receptor Stimulate receptor  stimulate Gq  increase PLC PIP2(Phospho Insitol di-phosphate) IP3 + DAG Increase IP3 Increases intracellular Ca++Activates myosin light chain kinase Phosphorylates myosin. 12 .p Cell  Types:. . GPCRs Agonist Receptor G. . interacts with actin Cardiac muscle Contraction. Cardiac cell Blood Vessel Gs B-agonist in Cardiac Muscle Mechanism of Gs in Cardiac Muscle Constrictor Drug: Agonist binding to receptor  Stimulate receptor  stimulate Gs  increase A cyclase  increase cAMP increase Ca++ from SR  increase Ca++ in the Cardiac Muscle  Activates myosin light chain kinase  Phosphorylates myosin.Basic Pharmacology By: Dhshan Hassan Dhshan G-protein-coupled receptor (GPCRs)  G-protein  Def.

Bmax B Cd 13 .Basic Pharmacology By: Dhshan Hassan Dhshan  What is a Ligand? Any substance combines with receptor. [D] = Concentration of drug. Bmax =Maximum binding with receptor. Cd or Kd = dissociation constant.  types of Ligand:- Ligand has affinity and efficacy to Receptor ‫لدية القدرة على االرتباط بالمستقبل ليعطى تأثير‬ Agonist Antagonist Ligand has affinity and not have efficacy to Receptor ‫لدية القدرة على االرتباط بالمستقبل ولكن ال يعطى تأثير‬ Ligand-receptor interaction (Lock and Key theory) Receptor Ligand --------------------------------------------- Relationship between drug concn. and receptor binding: Increase Concentration of drug [D]  increase ability of binding to receptor. Bmax x [D] B= [D] x Cd B = Fraction of available receptors bound.

: the amount of drug given to the patient at a time. ------------------------------------------------------------------------------------------------------------------ Agonist types B C D  A : full agonist :  Maximum efficacy  Maximum Potency  B : full agonist :  Maximum efficacy  Reduced Potency  C : Partial agonist :  Reduced efficacy  Maximum Potency  D : Partial agonist :  Reduced efficacy  Reduced Potency ----------------------------------------------------------------------------------------------------------- Dose  Def.  Types of dose:  Therapeutic dose: The average dose that produce therapeutic effect.  Lethal dose or Fetal dose: The dose that produce death.  Initial dose: The dose used at start of treatment.  Maximum tolerated dose: The largest dose of a drug that can be taken safely. ED50 ED50: The dose that produce 50% of Emax.Basic Pharmacology By: Dhshan Hassan Dhshan Dose Response Curve Emax: the lowest dose produce maximum response.  Maintenance dose: The dose required to maintain the therapeutic effect. 14 .

3: Route of administration:  IV < Inhalation < IM < SC < Oral 4: Time of administration:  Irritant drugs are better taken after meals e.  Some drug avoided during Pregnancy.Basic Pharmacology By: Dhshan Hassan Dhshan  Factors affecting the dosage and action of drug. Aspirin. Ephedrine. weight and body surface area. 1: Age.  Calculation of child dose from adult dose.g. lactation and menstruation.  E.  Young’s formula : Adult dose X age in years Child dose = (Age + 12)  Dilling’s formula : Child dose =  Clark’s formula : Infant dose = Adult dose X age in years 20 Adult dose X Wt. 5: Genetic abnormality (Drug Idiosyncrasy)  Idiosyncrasy  Abnormal reaction to drug due to genetic abnormality.g.  Adult dose (20 – 60 years of age) and weight about 70 kg.  CNS (Central Nervous System) stimulant drugs should be not given at night they may cause insomnia e.  Effect of sex hormone on liver enzyme.  Children required small dose. in pounds 150 2: Sex:  Female need smaller dose than male due to  High fat content  increase fate in the body  slow rate of oxidation  decrease metabolism.  Primaquine may induce hemolytic anemia in Patient with Glucose-6phosphate dehydrogenase  deficiency in red blood cells (Hemolysis) 15 .g.

Basic Pharmacology By: Dhshan Hassan Dhshan 6: Hypersusceptibility (Supersensitivity drug intolerance) .  Acquired Tolerance . .g.The greater response to adrenaline in thyrotoxic patient . ------------------------------------------------------------------------------------------------------------- 16 . urtecaria and oedema) 2: Fever 3: Asthmatic attack 4: anaphylactic shock e.  Tachyphylaxis  effect increase gradual  decrease e.g. Penicillin 8: Tolerance  Def. Ephedrine  Increase Blood Pressure then decrease.Antibody-antigen interaction  increase release of histamine  Symptoms 1 : skin reaction (Skin rash.Mechanism of acquired tolerance (Drug Desensitization) Receptor Medicated Non-Receptor Medicated -loss of receptor Function -Physiological adaptation -Reduction of Receptor No.  Bacterial resistance to antibiotic. -reduction of receptor-coupled signaling component -Reduction of drug concn.  Types :  Congenital Tolerance  Racial  Ephedrine is not mydriatic in Negroes )‫)زوىج‬  Species  Rabbits is tolerated large amount of Belladonna due to Atropinesterase enzyme in rabbit liver and Plasma which rapidly detoxicate atropine.Drug intolerance is commonly observed in infant  because metabolism and excretion not fully developed 7: Hypersensitivity (Drug allergy) .Increase the dose to obtain the original effect  Cross Tolerance  between Nicotine and Lobeline.: Failure of responsiveness to the usual dose.  Individual  Genetic factors are possibly involved.

e. Smoking and Coffee.When drug stopped  develop some . Morphine     17 .Psychological and Physical dependence. .e.:( Measure of drug safety) it is the ratio of the dose that produces toxicity to the dose that produce effective response in population individual. It involves a certain degree of tissue adaptation.When drug stopped Withdrawal emotional distress for a relative short symptoms  reverse the normal period.Mild degree of drug dependence.g. pharmacological action .More serious form of drug dependence. . . .g. ED50 = Drug dose that produces therapeutic effect in 50% of population.Basic Pharmacology By: Dhshan Hassan Dhshan Therapeutic Index  Def. TD50 = Drug dose that produces toxic effect in 50% of population. Is a phenomena related to tolerance. . ---------------------------------------------------------------------------------------------------------------- Drug dependence It usually occurs after administration of CNS acting drugs.Psychological dependence. Types Habituation Addiction . LD50 (or TD50) TI = ED50 TI = Therapeutic index LD50 = Drug dose that produces death in 50% of population. Withdrawal of the drug could produce certain unpleasant symptoms.

and Ether When Decrease in Drug effect Antagonism Chemical antagonism Chemical interaction between 2 drug  decrease absorption Physiological antagonism Decrease physiological function of 2 drugs act on 2 different receptor different effects Competitive Pharmacological antagonism 2 drugs act on the same receptor but one of them is agonist and the other antagonist 18 Acetylcholine and atropine Non competitive Acetylcholine and organophosphate .g. Acetyl alc.Basic Pharmacology By: Dhshan Hassan Dhshan Drug-Drug Interaction  Def.: Drug interact with another drug when presence of both in the body. When Increase in Drug effect Addition Algebraic sum of the 2 Drugs effect 1+1=2 Synergism The combination effect more than algebraic sum 1 + 1 = > 2 e. and barbiturates Potentiation One of the drug is active and another is inactive 1 + 0 = > 1 e.  Decrease in drug effect. Ethyl alc.  May be   Increase in drug effect.g.