Pharmacology I - Pharmacodynamics PDF

Pharmacology I Dr. Qasem Abdallah Chapter 3: Pharmacodynamics 1  Subdivisions of Pharmacology Pharmacokinetics: Describes the action of the body on a drug, including the principles of ADME Pharmacodynamics: Describes the action of a drug on the bo...

Pharmacology I Dr. Qasem Abdallah Chapter 3: Pharmacodynamics 1  Subdivisions of Pharmacology Pharmacokinetics: Describes the action of the body on a drug, including the principles of ADME Pharmacodynamics: Describes the action of a drug on the body, including the mechanism of action, toxic effects and dose response relations. Pharmacotherapeutics or Medical Pharmacology: Describes the uses of dugs for prevention, diagnosis and treatment. Toxicology: Describes the adverse effects of chemicals including drugs and other radiation. 2  Pharmacodynamics Pharmacodynamics: Describes the action of a drug on the body, including the mechanism of action, toxic effects and dose response relations. Mechanism of action: Understanding how drugs work. 3  Drug Pharmacodynamics The ideal drug is the drug that has: 1) Selective effect on a specific biological process. 2) Dose dependent effect. 3) Temporary effect. Why is it important to have selective drug? 1) Less side effects. 2) Less opportunity to have drug-drug interaction. 4  A Blood Eyes Kidneys vessels Eyes Skeletal A muscles Heart Kidneys Liver Blood Endocrine vessels glands Brain Bone Skeletal marrow muscles Heart B Liver Endocrine Bone glands Brain marrow B 5  Side effect and unwanted effects, is there any difference? How drugs work? The majority of drugs binds to macromolecules found in the surface or inside the cells. These macromolecules called Receptors. In some other cases drugs can show there action by binding to enzymes (neostigmine), DNA (nitrogen mustards) or other chemicals (antacids). 6 Factors influencing drug specificity Finding the disease specific regulatory molecule (Molecular target) which can be a receptor, enzyme or etc. Drug size. Drug Drug shape. Electrical charge of the drug. _ + Receptor + Liver cell Receptor Receptor Kidney Heart cell 7 cell  Drug Receptors Receptors are specialized target macro- molecules, present on the cell surface or intracellular, that binds a drug and mediates its pharmacologic actions. Functions of receptors 1. The ability to recognize a drug 2. Binding to a drug 3. Translating this binding into response 8  Major receptor families 1. Ligand-gated ion channels (nicotinic receptors). 2. G protein coupled receptors (adrenergic alpha receptors). 3. Enzyme-linked receptors (Tyrosine kinase receptors). 4. Intracellular receptors (oestrogen receptors). 9 10  Types of Drug-Receptor Bonds 1. Covalent bonds. 2. Electrostatic/ Ionic bonds. 3. Hydrogen bonds. 4. Hydrophobic/Van der Waals bonds. 11 12 Type of Drug-Receptor bindings Reversible Binding: Example: Atropine is an example of a reversible antagonist binds to the acetylcholine receptors. Irreversible Binding: Example: Phenoxybenzamine is an example of an irreversible alpha blocker — it permanently binds to α adrenergic receptors, preventing adrenaline and noradrenaline from binding. 13  Drug-Receptor Interaction Both drug and receptor are required in order to induce the drug response. 14 Drug-Receptor Interaction…. continue 1. When the number of Drug-receptor complex increases, the response increases. 2. Receptors are responsible for selectivity of drug action. 3. Receptors mediate the response of either starting or stopping the pharmacologic action. 4. Receptors do not induce their action without being stimulated by a drug/ligand. 15  Dose-response relationship When the binding of the receptor is increases, the effect increases. The maximal response is induced when a) When drug bind all receptors b) All second messengers are occupied 16  What is efficacy Efficacy: is the maximal response produced by a drug. 17 Factors influencing drug efficacy 1. Affinity of the drug: which is the ability of the drug to bind to the receptor. the concentration of drug required to occupy a specific number of receptors. 2. Potency of drugs: the concentration of drug required to induce a specific biological action. 18  What is Potency Potency is a measure of how much drug is required to cause biological response. The less drug is required to cause response the more is the potency. 19 Receptor affinity to drugs 20  Therapeutic window/index: It is the ratio of the dose that produces the minimal toxicity to the dose that produces a clinically effective response. Therapeutic index = minimal toxic dose/minimal effective dose 21  Drug-receptor interaction Agonism:  Full agonist.  Partial agonist. Antagonism:  Chemical antagonism:  Functional antagonism:  Competitive antagonism:  Non- Competitive antagonism: 22  Agonism  Full agonist: Its defined as an agent that can bind to a receptor and cause a response.  Partial agonist: Binds to the agonist binding site but cause less response than full agonist. 23  Antagonism 1) Chemical antagonism: Chemical antagonism involves a direct chemical interaction between the agonist and antagonist in such a way as to make the agonist pharmacologically in active. 2) Functional antagonism: happens between two different agonists that cause opposite effective. 24 Antagonism … continue 3) Competitive antagonism: This is the most frequent type of drug antagonism. Here the antagonist binds to the same site as the agonist but cause no activation on the receptor. 4) Non- Competitive antagonism: Here the antagonist binds to a different site from the agonist binding site and prevent the activation of the receptor. 25  Some Characteristics of Receptors Spare Receptors: There is no need to activate all receptors to achieve maximal response. Desensitizing of receptors: when repeated administration of a drug the receptors become less responsive. Up-regulation and Down-regulation of receptors: the cells may produce more receptors after continuous blocking by a drug. Also, cells may reduce the number of receptors after continuous stimulation by a drug. 26