Introduction to Autonomic Pharmacology (PDF)

‫ميحرلا نمحرلا هللا مسب‬ Introduction to Autonomic Pharmacology Mohammed Ali Khalifa Assistant Professor of Pharmacology July 2024 Course contents 1. Introduction to autonomic Pharmacology. 2. Cholinergic agonists. 3. Cholinergic antagonists....

‫ميحرلا نمحرلا هللا مسب‬ Introduction to Autonomic Pharmacology Mohammed Ali Khalifa Assistant Professor of Pharmacology July 2024 Course contents 1. Introduction to autonomic Pharmacology. 2. Cholinergic agonists. 3. Cholinergic antagonists. 4. Adrenergic Agonists. 5. Adrenergic antagonists. 6. Drugs acting on renal system. Course contents 7. Antihistamine drugs. 8. Drugs target on serotonin receptors. 9. Ergot alkaloids. 10. Vasoactive Peptides and related drugs. 11. Eicosanoids targeting drugs. Lecture Objectives After end of this lecture each student should able to know and analyze: 1. Pharmacodynamic definitions and principles. 2. Basic types and classes of drug receptors. 3. Definition and types of agonist. 4. Definition and types of antagonist. 5. Major classification of drugs targeting on autonomic nervous system. Pharmacodynamics Pharmacodynamics: describes the actions of a drug on the body, and the magnitude of the response. Most drugs exert their effects by interacting with receptors. The drug–receptor complex initiates alterations in biochemical and/or molecular activity of a cell by a process called signal transduction. Drug Receptors Receptors may be divided into four families: Ligand-gated ion channels, G protein–coupled receptors, Enzyme-linked receptors and Intracellular receptors. Relationship of drug- receptor binding to pharmacologic effect: is classified as graded or quantal dose-response relationship. Receptor transmembrane signaling Agonists An agonist is a drug that binds to a receptor and produces a biologic response based on the its concentration and the fraction of activated receptors. Agonists are classified, according to their intrinsic activity, in full, partial or inverse agonists. Classes of agonist Full agonists: If a drug binds to a receptor and produces a maximal biologic response. E.g. Phenylephrine in α1-adrenoceptors. Partial agonists: have intrinsic activities greater than zero but less than one. Even if all the receptors are occupied. e.g. aripiprazole (an atypical antipsychotic) in nigrostriatal D2 receptors. Full vs. Partial agonists Classes of agonist Inverse agonists: have an intrinsic activity less than zero, reverse the activity of receptors, and exert the opposite pharmacological effect of agonists. Antagonists Antagonists: bind to a receptor with high affinity but possess zero intrinsic activity. Antagonists are generally classified into competitive, irreversible, allosteric and functional antagonists. Classes of Antagonists Competitive antagonists: bind to agonist receptors reversibly in concentration-dependent manner. e.g. terazosin competes with NE at α1-adrenoceptors. Irreversible antagonists: bind covalently to the active site of the receptor. Competitive vs. Non competitive antagonists Classes of Antagonists Allosteric antagonists: bind to a site (“allosteric site”) other than the agonist-binding site and prevents the receptor from being activated by the agonist. E.g. an allosteric agonist is picrotoxin which binds to GABA- controlled Cl- channel. Functional antagonism (“Physiologic antagonism.”): e.g. antagonism by epinephrine to histamine-induced bronchoconstriction. Therapeutic index Is the ratio of the dose that produces toxicity in half the population (TD50) to the dose that produces a clinically desired or effective response (ED50) in half the population: TI = TD50 / ED50. The TI is a measure of a drug’s safety, because a larger value indicates a wide margin between doses that are effective and doses that are toxic. Drugs targeting on Autonomic Nervous System The nervous system is divided into the central nervous system (CNS) and the peripheral nervous system (PNS). PNS is subdivided into the efferent and afferent divisions. The efferent PNS is divided into the somatic and the ANS. Drugs targeting on Autonomic Nervous System Drugs that produce their primary therapeutic effect by mimicking or altering the functions of the ANS are called autonomic drugs. Efferent neurons include sympathetic neurons, parasympathetic neurons and enteric neurons. Drugs targeting on Autonomic Nervous System Communication between nerve cells and effector organs, occurs through the release of neurotransmitters from the nerve terminals. Types of neurotransmitters: Norepinephrine (NE), acetylcholine (ACh), dopamine (DA), serotonin (5- HT), histamine (H), glutamate, and γ-aminobutyric acid (GABA) are most commonly involved in the actions of therapeutically useful drugs. Drugs targeting on Autonomic Nervous System Drugs affecting the ANS are divided into cholinergic drugs and adrenergic drugs. Cholinergic and adrenergic drugs act by either stimulating (agonists) or blocking receptors (antagonists) of the ANS.