Pharmacology Lecture Notes PDF

INTRODUCTION TO PHARMACOLOGY Dr. Adam Gratton MSc ND NMT150 January 12, 2023 LECTURE COMPETENCIES Contrast an agonist and an antagonist Contrast a competitive antagonist and an allosteric antagonist Define bioavailability and describe factors that affect the bioavailability of a drug Describe factor...

INTRODUCTION TO PHARMACOLOGY Dr. Adam Gratton MSc ND NMT150 January 12, 2023 LECTURE COMPETENCIES Contrast an agonist and an antagonist Contrast a competitive antagonist and an allosteric antagonist Define bioavailability and describe factors that affect the bioavailability of a drug Describe factors that influence the distribution of a drug after administration Describe and differentiate the role of phase 1 and 2 metabolism Describe 8 different factors that affect individual drug responses LECTURE COMPETENCIES Describe the requirements that must appear on a prescription for it to be valid and write a valid prescription for a drug Describe the 8 requirements for charting a prescription an ND has given to a patient PHARMACOLOGY The study of “drugs” AND their effects on life Think of a “drug” as any exogenous chemical The goal of pharmacology is to understand the mechanisms by which drugs interact with biologic systems PHARMACOLOGY ABSORPTION Drugs need to get from the site of administration to a target tissue Most drugs are absorbed by passive diffusion Some drugs use physiological transport processes Absorption is also dependent on the route of administration EFFECT OF PH Many drugs are weak acids or bases Only non-ionized forms of drugs can easily pass through a lipid bilayer For orally administered drugs there are two significant pH compartments in the digestive tract Stomach with low pH (normally around 1) Small intestines with neutral pH (normally around 7) BIOAVAILABILITY The fraction of the administered dose of a drug that reaches the systemic circulation in an active (unchanged) form Influenced by several factors Intravenously administered drugs are 100% bioavailable by definition DISTRIBUTION In terms of tissue targets, this is influenced by: Size of the organ Blood flow Drug solubility Protein binding METABOLISM Aka biotransformation The enzyme-catalyzed conversion of drugs to their metabolites Most of this takes place in the liver, but the gut, kidneys, brain, lungs, and skin also contain drug-metabolizing enzymes METABOLISM The primary goal is to inactive or detoxify foreign substances and to prepare them for excretion Generally, the idea is to make a xenobiotic more watersoluble so that it can be readily excreted in by the kidneys METABOLISM Not every drug needs to be metabolized in order to be eliminated Not every drug is inactivated by metabolism Prodrugs are common and are activated by metabolism Metabolites may retain some degree of pharmacological activity (active metabolites) Not every xenobiotic is immediately detoxified FIRST PASS EFFECT Drugs absorbed via the gut reach the liver via the portal vein before entering the systemic circulation The degree to which the drug is inactivated by liver enzymes prior to entering the systemic circulation substantially alters the drug’s bioavailability PHASE 1 METABOLISM Primary goal is to introduce or open up a binding site for hydrophilic compounds to be added later by phase II mechanisms Oxidative reactions by far the most common Microsomal cytochrome P450 (CYP450) system PHASE 2 METABOLISM Not all drugs require phase I metabolism prior to phase II but most do These reactions essentially conjugate a water-soluble molecule to the spot opened up by phase 1 reactions In many instances, this means conjugating something to an available hydroxyl group Each phase 2 mechanism has its own enzyme that catalyzes the reactions ENTEROHEPATIC CIRCULATION Glucuronide conjugates are excreted in bile Some commensal gut bacteria have glucuronidase enzymes which can cleave the glucuronide off the metabolite resulting in the parent drug being able to be reabsorbed EXAMPLE ELIMINATION Most water-soluble drug metabolites are excreted by the kidneys Various mechanisms exist throughout the sections of the nephron Lipid-soluble drugs are excreted in the distal tubule if they’re small enough Lipid-soluble drug metabolites and glucuronide-conjugates are excreted by the liver into bile and are excreted in feces PHARMACODYNAMICS Essentially the study of a drug’s mechanism of action Drug-receptor characterization and mechanics Signal transduction mechanisms DEFINITIONS Agonist – a substance that initiates a physiological response when combined with a receptor Antagonist – a substance that interferes with or inhibits the physiological action of another substance Competitive – used to describe when two substances use the same binding site on a receptor Allosteric – used to describe when a substance binds to a receptor away from an active binding site but still alters the physiological effect MEASURES OF SAFETY Therapeutic Index (TI) LD50 – dose at which causes death in 50% of individual (animal) ED50 – dose at which causes a therapeutic response in 50% of individuals (human) LD 50 TI = ED50 PRESCRIBING STANDARDS Generic name – most suitable drug name to use as it is standard across all jurisdictions Brand name – registered trademarked name of a drug used in marketing Example: atorvastatin vs Lipitor® PRESCRIPTION REQUIREMENTS Date Name and address of patient Name, strength, quantity and form of drug or ingredient(s) Directions for use (include frequency or interval or maximum daily use) Refill authorization (number and interval between refills) Name and college ID of practitioner Signature of practitioner PRESCRIBING STANDARDS It is generally advised to write full words as much as possible and to avoid abbreviations Never abbreviate the drug name Use generic names unless you specifically want a brand name drug dispensed DRUG CHARTING Date Related subjective and objective symptoms Assessment Purpose and/or goal(s) of medication(s) Name, dose, dosage form and quantity of medication prescribed Monitoring plan Informed consent Signature