Intro to Clinical Pharmacology PDF

Intro to Clinical Pharmacology Alison Wix, MPA, PA-C Special thanks to Dr. Anna Carlini PAS 741 1.Identify and/or recognize the definition of the following: 1. Pharmacology 2. Pharmacotherapeutics...

Intro to Clinical Pharmacology Alison Wix, MPA, PA-C Special thanks to Dr. Anna Carlini PAS 741 1.Identify and/or recognize the definition of the following: 1. Pharmacology 2. Pharmacotherapeutics Objectiv 3. Toxicology 4. Pharmacokinetics es 5. Pharmacodynamics 2.Differentiate between the effects of an agonist, partial agonist and antagonist. 3.Identify the difference between competitive and non-competitive antagonism. 4.Identify and/or recognize the definition of each of the following processes a drug undergoes: Absorption, Distribution, Metabolism, Elimination 5.Identify the various routes of drug administration. 6.Differentiate between the concept of half-life and steady state. 7.Identify the various chemical and physiologic factors which may affect drug absorption. 8.Identify the significance of protein binding of drug distribution and action. 9.Recognize and/or apply the role of cytochrome P-450 enzymes have on drug metabolism. 10.Differentiate between active and inactive metabolites.  Pharmacology The science that deals with drugs Nature Actions Mechanism of action Pharmacokinetics Uses Preparations Administration  Selection of drugs in therapeutics Why study Understanding drug toxicity pharmacology? Identify drug interactions What is a Drug? Any chemical substance that alters body functions by interaction at the molecular level and is used in treatment, prevention, diagnosis of a disease (or pregnancy) NOTE: drugs only MODIFY existing cell function, they DO NOT create new  Routes of Drug Administration Enteral Parenteral Oral Intradermal Sublingual Subcutaneous Buccal Intramuscular (IM) Rectal Intravenous (IV) Intra-arterial (IA) Topical Intrathecal Skin, ear, eye, Intrapleual nose, vaginal, Intra-articular respiratory Inhalation Drug Nomenclature Full chemical name Nonproprietary name Active Ingredient Proprietary name Brand Name Generic name Salicylates  Half-life and Steady State The half-life of a drug is the time it takes for the amount of a drug's active substance in the body to reduce by half. You have reached 50% of the steady state by the end of ONE half-life, 75% by the end of TWO half-lives, 87.5% by the end of THREE half-lives, etc  ACHIEVE STEADY STATE AFTER 5 HALF-LIVES If you have a drug with a long half-life, you can achieve a target steady state level more quickly by using a loading dose.  Pharmacokinetics The effect of the body on the drug – what Pharmacolog happens to drugs in the body? The study of the kinetics of drugs including y ADME: Absorption Distribution Metabolism (biotransformation) Excretion Pharmacodynamics The effect of the drug on the body – what a drug “does” to the person The study of the biochemical, biophysical and physiological effect of the drugs as well as their mechanism of action. Pharmacotherapeutics Proper selection and use of drugs for the prevention and treatment of diseases Therapeutic effect Consequence of a medical treatment Toxicology Describes the adverse effects and toxicity of drugs Adverse reaction: a term used for harmful or seriously unpleasant effects of a drug occurring at doses used for therapeutic, prophylactic, or diagnostic purposes. These reactions include Side effects Overdosage toxicity Allergic reactions Drug abuse  Iatrogenic diseases Drug-induced diseases Ex: drug-induced asthma, peptic ulcers, parkinsonism Forms of Teratogenesis: Fetal abnormalities Adverse Ex: cytotoxic drugs, tetracyclines Occur when certain drugs are given early Rxn of in pregnancy Contraindications: The drug is forbidden to be prescribed Drugs because it will be harmful to patient Drug interactions: Pharmacological responses that cannot be explained by the action of one drug, but are due to multiple drugs acting concurrently Pregnan cy Drug Categori es Agonists and Antagoni sts  Agonist, Partial An agonist is a drug that binds to the Agonist, receptor, producing a similar response to the intended chemical and receptor  and stimulates a reaction after it chemically binds Antagonis Partial agonists bind to and activate a receptor but are not able to elicit the t maximum possible response that is produced by full agonists. The main difference An antagonist is a drug that binds to the between the two is that receptor either on the primary site, or on an agonist simulates the intended reaction, another site, which all together stops the where as an antagonist receptor from producing a response  binds to the receptor, *BLOCKS another chemical from and stops/ slows attaching responses  Competitiv e VS Noncompet itive Antagonist s A competitive antagonist binds to the SAME site as the agonist but does not activate it  BLOCKS the agonist's action. A non-competitive antagonist binds to an allosteric (non-agonist) site on the receptor to prevent activation of the receptor. A non-competitive A competitive antagonist binds to antagonist binds to the an allosteric (non- same site as the agonist agonist) site on the but does not activate it, receptor to prevent thus blocks the agonist's activation of the action. receptor. ADME Diagram Absorption There are four main routes of exposure: Inhalation through the respiratory system: a chemical in the form of a gas, vapor or particulate that is inhaled and can be excreted or deposited in the respiratory system. Dermal through skin or eye contact. Ingestion through the gastrointestinal system: Absorption through the digestive tract. Ingestion can occur through eating or smoking with contaminated hands or in contaminated work areas. Injection: Introducing the material directly into the bloodstream. Injection may occur through mechanical injury from “sharps.”  Factors Affecting Absorption Drug Related Body Related Lipid water solubility Area of absorptive surface Molecular size Vascularity Particle size pH Degree of ionization Physical forms Presence of other Chemical nature substances Dosage forms GI motility Formulation Functional integrity of the concentration absorptive surface Certain diseases  Distribution Four ways small molecules cross biological lipid membranes: Passive diffusion Diffusion occurs through the lipid membrane from a high to low concentration (aka concentration gradient). Filtration Diffusion occurs through aqueous pores, still from high to low concentration as a driving mechanism. Special transport Transport is aided by a carrier molecule. Can move against the concentration gradient (low to high). Endocytosis Transport takes the form of pinocytosis for liquids and phagocytosis for solids. Significance of Protein Binding for Distribution Can influence the drug's biological half-life Plasma protein binding restricts the entry of drugs that have specific affinity for certain tissues This prevents accumulation of large fraction of drugs in such tissues (and thus, subsequent toxic reactions) Plasma protein binding favors uniform distribution of drugs throughout the body by its buffer function A protein bound drug does NOT cross the BBB, the placental barrier, and the glomerulus Metabolism Drugs can be metabolized by oxidation, reduction, hydrolysis, hydration, conjugation, condensation, or isomerization Compounds begin to break down in the body by a family of enzymes in the liver called the Cytochrome P450 system. These enzymes can convert chemicals to reactive oxygen species (ROS), reactive intermediates, free radicals, and others. BIOTRANSFORMATION OF DRUGS The biotransformation is the metabolism of drugs in the body. STAGES OF BIOTRANSFORMATION Stage I (oxidation, Stage II (synthetic Drug reduction, reactions) hydrolysis) Active or most Usually often inactive inactive products products excreted from the body Biotransformation Stages Phase I: Non-synthetic reactions such as cleavage (e.g. oxidation, reduction, hydrolysis), formation or modification of a function group. Phase II: Synthetic reactions such as conjugation with an endogenous substance (e.g. sulfate, glycine, glucuronic acid).  INDUCTORS AND INHIBITORS OF MICROSOMAL OXIDATION Inductors of microsomal oxidation Drugs which increase the activity of microsomal enzymes in the liver Ex: phenobarbital, chlorpromazine Inhibitors of microsomal oxidation Drugs which decrease the activity of microsomal enzymes in the liver Ex: metronidazole INDUCTION OF MICROSOMAL OXIDATION Drug  Enzyme induction: P-450 P-450 P-450  The intensification of drugs metabolism leads to a decrease in efficacy of co- INHIBITION OF MICROSOMAL OXIDATION Drug  Enzyme inhibition: P-450 P-450 P-450  The inhibition of drugs metabolism lead to an increase in toxicity of co- administered drugs Excretion Most excretion occurs through the kidneys or liver as urine or as feces. Excretion is dependent on the process of kidney filtration at the glomerulous, and is largely based on molecular size and charge. Some molecules can be excreted through the skin as sweat and still some may be excreted through the lungs via gas exchange.