pharmacokinetics & pharmacodynamics- seminar- magdum sir.pptx
- 1. Sneha Anil Pachore M.Pharmacy Sem-II Pharmaceutics Dept. A.B.C.P. Sangli 1/14
- 2. INTRODUCTION The purpose of studying pharmacokinetics and pharmacodynamics is to understand the drug action, therapy, design, development and evaluation. PHARMACOKINETIC: It is a branch of Pharmacology which deals with the study of Absorption, Distribution, Metabolism, Excretion / Elimination. Pharmacokinetics is the study of What the body does to the drug PHARMACODYNAMIC: Pharmacodynamics is the study of biochemical and physiologic effect of drug. It is the study of What the drug does to the body 2/14
- 3. PHARMACOKINETICS It involves Four Processes: 1. Absorption 2. Drug distribution 3. Metabolism 4. Drug elimination 3/14
- 4. 1.ABSORPTION It is the process of entry of drug from site of administration into systemic circulation. The bioavailability of the drug depends on the extent of the absorption. Bioavailability is the percentage of drug that reaches the systemic circulation in an unchanged form and becomes available for biological effect following administration by any route. Bioequivalence occurs when two formulations of the same compound have the same bioavailability and the same rate of absorption. FACTORS INFLUENCING ABSORPTION: 1. FACTORS RELATED TO DRUG: a) Physicochemical properties - Degree of ionization, Degree of solubility, Chemical nature, valence. -High lipid / water partition coefficient increases absorption b) Pharmaceutical form of drug - e.g., Absorption of solutions is better than suspensions or tablets. 4/14
- 5. 2. FACTORS RELATED TO PATIENT: a) Route of administration - absorption is faster from i.v.> inhaled >i.m. > oral > dermal Administration. b) Area and vascularity of absorbing surface - Absorption is directly proportional to both area and vascularity. Thus absorption of the drug across the intestine is more efficient than across the stomach, as Intestine has more blood flow and much bigger surface area than those of the Stomach. c) State of absorbing surface - e.g. atrophic gastritis and mal-absorption syndrome decrease rate of absorption of drugs. a) Rate of general circulation - e.g. in shock, peripheral circulation is reduced and I.V. route is used. b) Presence of other drugs and other Specific factor - e.g. intrinsic factor of the stomach is essential for vitamin B12 absorption from lower ileum and adrenaline induces vasoconstriction so delay absorption of local anaesthetics. 5/14
- 6. 3. FIRST-PASS EFFECT (pre-systemic metabolism): Where drugs must pass through gut mucosa and liver before reaching systemic circulation. a) Gut first-pass effect: e.g. benzyl penicillin is destroyed by gastric acidity, insulin by digestive enzymes b) Hepatic first-pass effect: e.g. lidocaine (complete destruction so not effective orally) and propranolol (extensive destruction) 6/14
- 7. 2.DISTRIBUTION Distribution is the movement of drug from the central compartment (blood) to peripheral compartments. Here the concentration gradient is being the driving force for the movement from plasma to tissues. It depends on : - Ionization - Molecular size - Binding to plasma proteins - Differences in regional blood flow Presence of tissue - specific transporters. VOLUME OF DISTRIBUTION(Vd): It is defined as the volume of fluid required to contain the total amount of drug Q in the body at the same concentration as that present in the plasma, Cp Vd = Q/Cp IMPORTANCE OF Vd: 1. It helps in estimating the total amount of drug in body at any time. Amount of drug = Vd x plasma concentration of drug at certain time 2. Vd is important to determine the loading dose. Loading dose = Vd x desired concentration 7/14
- 8. 3. METABOILISM (BIOTRANSFORMATION) Biotransformation means chemical alteration of the drug in the body. It is needed to render non-polar (lipid-soluble) polar (lipid insoluble) compounds so that they are not reabsorbed in the renal tubules and are excreted. The primary site for drug metabolism is liver; others are-kidney, intestine, lungs and plasma. Phases of biotransformation: - - Phase I (Non-synthetic) reactions - A functional group is generated or exposed- metabolite may be active or inactive. - Phase II (Synthetic) reactions Mostly a conjugation reaction - Metabolite is mostly inactive (except few drugs). 8/14
- 9. FACTORS AFFECTING DRUG METABOLISM a) DRUGS: One drug can competitively inhibit the metabolism of another if it utilizes the same enzyme or cofactors either by Enzyme induction or by Enzyme inhibition. b) GENETIC VARIATION: The most important factor is genetically determined polymorphisms. e.g., Isoniazid is metabolized in the liver via acetylation. There are two forms (slow and fast) of the enzyme responsible for acetylation (N-acetyl transferase), thus some patients metabolize the drug quicker than others. Slow acetylators are prone to peripheral neuritis while fast acetylators are prone to hepatic toxicity. c) NUTRITIONAL STATE: Conjugating agents are sensitive to body nutrient level. e.g., low protein diet can decrease glycine. d) DOSAGE: High dose can saturate metabolic enzyme leading to drug accumulation. If metabolic pathway is saturated due to high dose or depletion of endogenous conjugate, an alternative pathway may appear. e.g. paracetamol may undergo N- hydroxylation to hepatotoxic metabolite. e) AGE: Drug metabolism is reduced in extremes of age (old patients and infants) 9/14
- 10. 4. ELIMINATION OR EXCRECTION Elimination-Termination of Drug Action by which a drug or metabolite is eliminated from the body. Drugs and their metabolites are excreted in Urine, Faeces, Exhaled air, Saliva and sweat. -Two-stage kidney process (filter, absorption) -Metabolites that are poorly reabsorbed by kidney are excreted in urine. -Some drugs have active (lipid soluble) metabolites that are reabsorbed into circulation (e.g., pro- drugs) -Other routes of elimination: lungs, bile, skin 10/14
- 11. PHARMACODYNAMICS Pharmacodynamics refers to the relationship between drug concentration at the site of action and the resulting effect, including the time course and intensity of therapeutic and adverse effects. The effect of a drug present at the site of action is determined by that drugs binding with a receptor. The concentration at the site of the receptor determines the intensity of a drugs effect. Drug Action: Four major types of bio- macromolecular targets of drug action is there, (A) Enzyme (B) Transmembrane ion channel (C) Membrane bound transporter (D) Receptor 11/14
- 12. FACTORS AFFECTING DRUG RESPONSE: Density of receptors on the cell surface. The mechanism by which a signal is transmitted into the cell by second messengers. Regulatory factors that control gene translation and protein production may influence drug effect. DOSE-RESPONSE CURVES: Individual responses to varying doses: -Threshold: Dose that produces a just-noticeable effect. -ED50: Dose that produces a 50% of maximum response. -Ceiling: Lowest dose that produces a maximal effect. DOSE-RESPONSE FUNCTIONS: Efficacy ED50 = median effective dose Lethality LD50 = median lethal dose Therapeutic Index = LD 50 /ED 50 = toxic dose/effective dose This is a measure of a drugs safety -A large number = a wide margin of safety -A small number = a small margin of safety 12/14
- 13. DURATION OF EFFECT: Duration of effect is determined by a complex set of factors, including : -The time that a drug is engaged on the receptor -Intracellular signalling -Gene regulation. Time Course Studies important for : -Predicting dosages/dosing intervals -Maintaining therapeutic levels -Determining time to elimination TOLERANCE: The effectiveness can decrease with continued use is referred to as tolerance. Tolerance may be caused by : -The pharmacokinetic factors, such as increased drug metabolism, that decrease the concentrations achieved with a given dose. -The pharmacodynamic factors like when the same concentration at the receptor site results in a reduced effect with repeated exposure. 13/14
- 14. THANK YOU 14/14