Pharmacodynamics(1) PDF

Pharmacodynamics(1) ILOs 1- what is pharmacology? 3- Meanning of the drug 4- Sources of the drugs 5- Mechanisms of action of drugs- Pharmacology: The science that deals with the study of drugs Subdivisions of Pharmacology: It is divided into: 1) Pharmacokinetic: What the body does to the drug or...

Pharmacodynamics(1) ILOs 1- what is pharmacology? 3- Meanning of the drug 4- Sources of the drugs 5- Mechanisms of action of drugs- Pharmacology: The science that deals with the study of drugs Subdivisions of Pharmacology: It is divided into: 1) Pharmacokinetic: What the body does to the drug or movement of the drug in the body. It studies: "ADME " Absorption Distribution Metabolism Excretion). 2)Pharmacodynamics: What the drug does to the body or the effect of the drug.It studies the mechanism of drug action and pharmacological effects. Chemical substances stimulate or inhibit an existing cell function (but do not create a new function in the cell). They are used in diagnosis, treatment & prevention of disease or in prevention of pregnancy 1-Physical: Osmosis: osmotic diuretics. Figure for demonstration only 2-Chemical: Antacids neutralize HCL in peptic ulcer 3-Acting on the Genetic Apparatus: Antibiotics and anticancer drugs Figure for demonstrarion only 4-Altering the enzyme activity: Drugs as enzyme inhibitors: Acetylcholine esterase inhibitor (physostigmine). 5- Interacting with carrier molecules: e.g. glucose uptake increased by antidiabetic drugs(thiozolidinediones) 6-Action on voltage gated ion channels: Local anesthetic as procaine blocks Na+ channel leading to membrane stabilization. Action on receptors: The most common mechanism of drug action. Protein macromolecule that interact specifically with a ligand (drug, transmitter or hormone) to produce a biological response  Affinity Ability of the drug to bind with the receptor to form a drug-receptor (D/R) complex. Intrinsic activity Ability of the drug to activate the receptor. It varies from -1 to +1.  Efficacy Ability of the D/R complex to produce a response. Drug receptor interaction Agonist Partial agonist Antagonist Inverse agonist  Agonist A drug interacts with the receptor, activating it, resulting in a pharmacological effect i.e. it has affinity, intrinsic activity +1 and efficacy e.g. ACh.  Antagonist A drug interacts with the receptor without activating it i.e. it only occupies the receptor to prevent the agonist from binding to the receptor. It has affinity but no efficacy and intrinsic activity is 0.e.g. atropine.  Partial agonist An agent which activates a receptor to produce submaximal effect but antagonizes the action of a full agonist. Intrinsic activity between 0 and +1. e.g. pindolol , succinylcholine  Inverse agonist An agent which activates a receptor to produce an effect in the opposite direction to that of the agonist. Intrinsic activity is negative e.g. β-carboline is an inverse agonist at benzodiazepine receptors so they produce insomnia and convulsions while benzodiazepines produce hypnosis and anticonvulsant effect. Dose response relationship There are two curves to study the relation between drug concentrations or doses and response Graded dose- response curve Quantal dose- response curve Graded dose-response curve A graph of the increasing response to increasing drug concentration or dose  It expresses an individual’s response to increasing doses of a given drug. The magnitude of a pharmacologic response is proportional to the number of receptors with which a drug effectively interacts  Importance 1-The efficacy of a drug: is the ability of a drug to elicit the pharmacologic response. It is measured by Emax (maximal response). NB: Potency? 2-Potency of a drug: is the relative measure of the amount of a drug required to produce a specified level of response (e.g., 50%) compared with other drugs that produce the same effect i.e. A potent drug induces the same response at a lower dose. 3-ED50: is the dose that produces the half maximal response ED50 3-Slope: is measured at the mid-portion of the dose– response curve. Steep dose–response curves indicate that a small change in dose produces a large change in response Disadvantages of graded dose response curve: Cannot be consulted if the effect of the drug is a quantal event i.e. prevention of convulsion or arrhythmias  Quantal dose-response curve Graph of the increasing fraction of a population that shows a specified response at progressively increasing doses This curve relates the dosage of a drug to the frequency with which a designated response will occur within a human or animal population. The response may be an “all-or-none” phenomenon (e.g., individuals either do or do not fall asleep after receiving a sedative).  Importance 1-Calculation of the ED50: the dose at which 50% of the population attains the desired response. 2-Calculation of the LD50: the dose that kills 50%of the population. 3-Determination of the therapeutic index of the drug: Therapeutic index of a drug is the ratio of the LD50 to the ED50. It is a rough index of drug safety it must be > 1 Therapeutic index LD50/ED50 LD50