Pharmacokinetics and Pharmacodynamics Lecture Notes PDF

The National Ribat University Faculty of Dentistry Batch (2o) Lecture (2): Pharmacokinetics and pharmacodynamic...

The National Ribat University Faculty of Dentistry Batch (2o) Lecture (2): Pharmacokinetics and pharmacodynamic By: Dr.Sara Bushra Mahdi Abdelrazig Sept 2024 2 4 20 2 3/ S A RA BUS HRA 1 1 0/  2 4 20 2 3/ S A RA BUS HRA 2 1 0/  PHARMACOKINETICS: Pharmacokinetics is the study, which determines the rapidity and concentration of the drug in the body and its duration of appearance at the target organ, i.e. onset, time of peak action and duration of action and by these also determine the route(s) and frequency of administration of drug. 2 4 20 2 3/ S A RA BUS HRA 3 1 0/  2 4 20 2 3/ S A RA BUS HRA 4 1 0/  ABSORPTION: Absorption is the entry of drug with blood via the biological membrane from the site/ route of administration. 2 4 20 2 3/ S A RA BUS HRA 5 1 0/  BIO PHARMACEUTICS: It is the study of factors influencing the extent and rate of absorption and release of a drug from its various physicochemical properties and dosage forms and the therapeutic response obtained after its administration. 2 4 20 2 3/ S A RA BUS HRA 6 1 0/  FACTORS AFFECTING DRUG ABSORPTION: Biological factors Physiochemi cal properties Pharmaceuti cal properties 2 4 20 2 3/ S A RA BUS HRA 7 1 0/  BIOLOGICAL FACTORS: 1. Passage or Drug Through Body Membranes. 2. Site of Absorption. 3. Presence of Food and Other Salts. 4. Routes of Administration. 2 4 20 2 3/ S A RA BUS HRA 8 1 0/  PHYSICO-CHEMICAL FACTORS: 1. Lipid Solubility Dissociation Constant and pH. 2. Dissolution Rate. 3. Viscosity. 4. Crystal form. 5. The complexion e.g. the barbiturates and sulfonamides. Presence of EDTA increases the absorption of Mannitol. 2 4 20 2 3/ S A RA BUS HRA 9 1 0/  2 4 20 2 3/ S A RA BUS HRA 10 1 0/  PHARMACEUTICAL FACTORS: These factors are mainly related to the various dosage form of pharmaceuticals. Their absorption depends upon their physical nature like aqueous solution, suspension, powder, tablets, capsules etc. 2 4 20 2 3/ S A RA BUS HRA 11 1 0/  DIAGRAM REPRESENTS FACTORS AFFECTING DRUG ABSORPTION: 2 4 20 2 3/ S A RA BUS HRA 12 1 0/  BIOAVAILABILITY: The bioavailability of any drug is defined as its rate and extent of absorption. This is mainly used to describe the biological availability of a drug from a preparation and is calculated/determined in terms of amount or rate of presence of drug in various body fluids like blood, urine etc. It is also used to indicate a measurement of rate and relative amount of an administered drug in general circulation. 2 4 20 2 3/ S A RA BUS HRA 13 1 0/  CALCULATION: 2 4 20 2 3/ S A RA BUS HRA 14 1 0/  DISTRIBUTION: After absorption, the drug may be distributed into various body fluids like intestinal fluid, transcellular fluids e.g. fluids in the gastrointestinal tract, CSF etc. 2 4 20 2 3/ S A RA BUS HRA 15 1 0/ 15  FACTORS AFFECTING DRUG DISTRIBUTION: 1. Plasma binding protein. 2. Redistribution. 3. Blood brain barrier. 4. Placental barrier. 2 4 20 2 3/ S A RA BUS HRA 16 1 0/  DIAGRAM REPRESENTS DRUG METABOLISM 2 4 20 2 3/ S A RA BUS HRA 17 1 0/  METABOLISM Metabolism of drugs means chemical alteration of the drug in the body. The main site of metabolism is liver. Other sites: 1. Intestine. 2. Kidney. 3. Lung. 4. Plasma. 2 4 20 2 3/ S A RA BUS HRA 18 1 0/  PHASES OF DRUG METABOLISM: Phase 1 phase2 Oxidation-reduction and Conjugation or stage II reaction. hydrolysis. generated by a common chemical combination of the hydroxy-lating enzyme reactive group with a molecule system (cytochrome P450 provided by the body e.g. system; CYP). glucuronic acid, sulfate, glycine. endoplasmic reticulum of the liver cells. Assigment CYP3A4/5, CYP2C19, 2CYP2D6, CYP2C8/9, CYP2E1 and CYP1A1/2. Oxidation Acetylation Reduction Methylation hydrolysis Sulfate Conjugation Glucuronide Conjugation Glutathione Conjugation 2 4 20 2 3/ S A RA BUS HRA 19 1 0/  FACTOR AFFECTING DRUG METABOLISM: age sex Hormon al effect nu trition Gen etic factor ics' D isease cond ition Ph armacod yn am factor preg nancies ra In testin al micro flo 2 4 20 2 3/ S A RA BUS HRA 20 1 0/  EXCRETION Routes mainly kidneys, skin, lungs and alimentary tract. Volatile drug like chloroform eliminated through the lung. 2 4 20 2 3/ S A RA BUS HRA 21 1 0/  MECHANISM OF RENAL EXCRETION: Glomerular filtration Tubular Passive secretio diffusion n 2 4 20 2 3/ S A RA BUS HRA 22 1 0/  Glomerular filtration: The rate of drug filtration is determined by the glomerular filtration rate (GFR). The highly protein bound drugs like phenylbutazone, digoxin etc. are excreted slowly. Tubular secretion: The active secretory systems can rapidly remove the protein bound drugs from the blood and transport them into tubular fluid as the drugs that are bound to proteins are not readily available for excretion by filtration eg. salicylate and penicillin. Passive diffusion: Passive diffusion can occur in both the ways in proximal and distal convoluted tubules. The pH of the urine can affect the rate of passive diffusion and hence drug excretion. 2 4 20 2 3/ S A RA BUS HRA 23 1 0/  Type of excretion Example Pulmonary general anaesthetics, ethyl alcohol BILIARY erythromycin, novobiocin Sweat and Saliva lithium, potassium iodide and heavy metals Milk Tetracycline and sulfonamide 2 4 20 2 3/ S A RA BUS HRA 24 1 0/  Clearance: the rate of urinary excretion divided by the average concentration of excreted substance in the plasma. Biological half life (t½): the time takes the drug concentration to reduce by 50%. 2 4 20 2 3/ S A RA BUS HRA 25 1 0/  PHARMACODYNAMICS: Pharmacodynamics is the study of drug effects (biochemical and physiological) and their mechanism of action. Pharmacological effect Toxicity/adverse effects 2 4 20 2 3/ S A RA BUS HRA 26 1 0/  RELATIONSHIP BETWEEN PHARMACOKINETIC AND PHARMACODYNAMIC: 2 4 20 2 3/ S A RA BUS HRA 27 1 0/  2 4 20 2 3/ S A RA BUS HRA 28 1 0/ 28 28  TYPES OF DRUG ACTION: The drug may produce their effects by: I. Stimulation. II. Irritation. III. Depression. IV. Replacement. V. Bactericidal or cytotoxic effects. 2 4 20 2 3/ S A RA BUS HRA 29 1 0/  SITE OF ACTION: The site of drug action means where a drug acts and mechanism means how the drug acts. Drug which act only at the site of application (i.e. localized region) are termed as local or topical action for example, The local anaesthetics like lignocaine, procaine produce anaesthesia (local) in a localized region only. The second type of action is systemic or general action which produce their action after absorption, for example, general anaesthetics act centrally after absorption. 2 4 20 2 3/ S A RA BUS HRA 30 1 0/  FACTOR MODIFYING DRUG ACTION: 1. Age 2. Sex 3. Body size/weight 4. Species or racial difference. 5. Genetic 6. Route and time of adminstration 7. Pathological conditions ( renal, hepatic, gastrointestinal diseases, head injury, congestive heart failure and hyperthyroidism). 8. Tolerance. 9. Drug resistance. 10. medications 2 4 20 2 3/ S A RA BUS HRA 31 1 0/  DRUG TOLERANCE VS. ADDICTION VS. TACHYPHYLASIS: Tolerance: Tolerance is a condition when there is a requirement of higher dose of a drug to produce a given response. Drug resistance: It is tolerance of micro-organisms to inhibitory action of antimicrobials e.g. staphylococci to penicillin. Tachyphylaxis is the rapid development of tolerance in which there is a marked reduction in response even after repeated doses of a drug.. 2 4 20 2 3/ S A RA BUS HRA 32 1 0/  LOADING DOSE It is a single or many quickly repeated doses given in the beginning of treatment to achieve target concentration rapidly. DOSAGE INTERNAL Most of the drugs are given in divided dose daily, the dosing interval is determined by the plasma half life. The drugs with long half lives may be given once 2 4 20 2 3/ S A RA BUS HRA 33 1 0/  Cross tolerance is development of tolerance to pharmacologically related drugs e.g. morphine and barbiturates. 2 4 20 2 3/ S A RA BUS HRA 34 1 0/  CHEMICAL CHARACTER OF THE DRUG SAR DOSE- DRUG RESPONSE RECEPTORS RELATIONSHIP COMBINED DRUG EFFECT OF THE ANTAGONISM DRUG 2 4 20 2 3/ S A RA BUS HRA 35 1 0/  STRUCTURE-ACTIVITY RELATION: The effect of certain structural compounds in relation to its activity, duration of action and mechanism can be altered by changing the structure of drugs of known activity. A new product can show different reactions, different relation between the drugs and cell constituents and perhaps even new mechanism of action. 2 4 20 2 3/ S A RA BUS HRA 36 1 0/  RECEPTORS: The drug receptors are macromolecular sites which are situated on the surface or inside the effector cells with which specific agonist combines to produce its response. 2 4 20 2 3/ S A RA BUS HRA 37 1 0/  TYPES OF DRUG RECEPTORS: 2 4 20 2 3/ S A RA BUS HRA 38 1 0/  The ability of a drug to get bound to a receptor is termed as the ‘affinity of the drug’ for the receptor. The ability of the drug to produce a pharmacological response after its interaction with the receptor is known as ‘intrinsic activity of the drug’. 2 4 20 2 3/ S A RA BUS HRA 39 1 0/  CLASSIFICATION OF DRUG Agonists Antagonist Inverse agonist Partial agonist or affinity affinity Full affinity Full affinity High intrinsic No intrinsic Negligble or Lower intrinsic activity activity zero or minus activity intrinsic activity Mimic No mimic or endogenous block substances endogenous substances. methacholine g. atropine block e.g. pentazocine produces the the effect of is a partial effect of acetylcholine on agonist at µ acetylcholine at cholinergic receptor cholinergic muscarinic (subtype of receptors receptors opioid receptor) 2 4 20 2 3/ S A RA BUS HRA 40 1 0/  COMBINED EFFECT OF DRUGS SYNERGISM: When two drugs are given simultaneously, and the action of one drug is in creased by the other. Synergism can be addictive or super addictive ADDITIVE When the effect of two drugs are in the same direction. For example when aspirin is combined with paracetamol the combined effect is analgesic/antipyretic. SUPRADDITIVE In this the effect of combined therapy is greater than the individual effect of the one drug eg. Sulfonamide and trimethoprim (well known preparation ‘Septrin’) as antibacterial. 2 4 20 2 3/ S A RA BUS HRA 41 1 0/  DRUG ANTAGONISM: Antagonism describes the situation, when one drug decreases or inhibits the action of another. Either physical (affect the absorption)or chemical(drugs react chemically and form a biologically inactive). May used in the treatment of drug poisoning. Antagonists are competitive or non competitive antagonist. 2 4 20 2 3/ S A RA BUS HRA 42 1 0/  2 4 20 2 3/ S A RA BUS HRA 43 1 0/  I. Deadline of submission of assignments is 24 hours. II. Are included in the exam. III. Submitted in group. 2 4 20 2 3/ S A RA BUS HRA 44 1 0/