Introduction to Pharmacology and Pharmacokinetics Pharmacology 49.222 Bill Diehl-Jones RN, PhD Faculty of Nursing and Department of Zoology Agenda The instructor The course organization expectations/grading Introduction Purpose of drug therapy Principles of Pharmacokinetics The Instructor Office: 333 Helen Glass Lab: 336 Helen Glass Phone: 474-7136 Email: Bill_Diehl- Jones@umanitoba.ca Office Hours: by appointment The Course Introductory level course designed for nursing students Lecture notes are available on my website Physiological and pharmacological principles will be integrated Optional Text It is currently in the U of M bookstore Primary text: Lilly and Aucker, 2001 Core Concepts Introduction to Pharmacology General Principles Pharmacotherapeutics The Role of the Nurse Drug Issues in Society Evaluation Methods Mid Term Test - 25% Final Exam - 35% Patient Information Pamphlet - 20% Pop Quizzes (x 4) - 10% Test/exam will be multiple choice, true false and matching Why Do We Study Pharmacology? A. It’s good for you B. You will be able to use fancy terms like ’bioavailabilty’ C. My instructor likes torture D. A competent nurse must understand why his/her patient is getting a medication, and HOW IT WORKS Purpose of Drug Therapy “… to prevent, control or cure various disease states.” To achieve this, the right drug dose must be delivered to the tissues Every nurse must know… speed of onset of drug action intensity of drug effect duration of drug action A Graphical Example: Drug Concentration Lethal Dose Peak Onset Therapeutic Range Duration Sub- Therapeutic Time in Hours How Do We Study Pharmacology? General Concepts Drug Dose Administration Disintegration Pharmaceutical of Drug Pharmacokinetics Absorption/distribution metabolism/excretion Pharmacodynamics Drug/Receptor Interaction Pharmacotherapeutics Drug Effect or Response How are Drugs Administered? Routes of Drug Delivery Parenteral Inhaled (IV) Oral Transdermal Parenteral Topical (SC, IM) Rectal What Happens After Drug Administration? Drug at site of administration 1. Absorption Drug in plasma 2. Distribution Drug/metabolites 3. Metabolism in tissues 4. Elimination Drug/metabolites in urine, feces, bile Modified from Mycek et al. (1997) We are now talking about … Pharmacokinetics Factors Affecting Drug Absorption Transport ATP active vs. passive pH Physical factors ADP blood flow + Pi surface area contact time A- BH+ What Factors Affect Distribution? Blood flow Endothelial cells brain vs. fat in liver capillary Capillary permeability differences in capillary structure Binding to proteins role of albumin Endothelial cells in brain capillary Glial cell An Important Concept: BIOAVAILABIITY Def’n: Fraction of a drug that Serum Concentration reaches systemic circulation after a particular route of admin’n Injected Dose Affected by: 1st pass metabolism (eg: Lidocaine, propranolol) Solubility Instability (eg: Oral Dose Penicillin G, insulin) Time Volume of Drug Distribution Drugs may distribute into Plasma any or all of the following (4 litres) compartments: Interstitial Fluid Plasma (10 litres) Interstitial Fluid Intracellular Fluid Intracellular Fluid (28 litres) So What? Most drugs distribute into several compartments; however … Some drugs distribute into only one or two compartments Eg: Aminoglycoside antibiotics Streptomycin Gentamycin Arggh! I can’t fit through these darn fenestrations! More “So What?” It takes time for a drug to distribute in the body Drug distribution is affected by elimination Serum Concentration 1.5 Drug is not eliminated 1.0 Elimination Phase 0.5 Distribution Phase Drug is eliminated 0 0 Time Albumin Affects Distribution Albumin Drugs bind differentially to albumin 2 drug classifications: Class I: dose less than Drug X available binding sites (eg: most drugs) Class II: dose greater than binding sites (eg: sulfonamide) The problem: one drug may out- compete the other Sulfonamide Drug Metabolism (we’re still talking about Pharmacokinetics) Drug Metabolism First pass metabolism of drugs may occur as they cross the intestine or transit the liver eg: nitroglycerin Other drugs may be destroyed before absorption eg: penicillin Such reactions decrease delivery to the target tissues Drug Metabolism (cont’d) Drug Two Phases: I and II Phase I Phase I: conversion to Oxidation lipophilic cpds Reduction Phase II: conjugation Hydrolysis Phase I involves the Activation/Inactivation cytochrome P-450 system Phase II Ultimate effect is to Glucuronidation facilitate elimination Conjugation Products An Example of Phase I and II Biotransformation: CH3CON- -OC2H5 Phenacetin H PHASE I CH3CON- -OH Paracetamol H PHASE II OH CH3CON- -O- HO -OH Glucuronic Acid H Conjugate O COOH An Example of Drug Metabolism First Pass Metabolism Occurs Primarily in the Liver and Gut Drug Elimination Most important route is the kidney May also involve bile, intestine, lung, breast milk What clinical scenarios may affect drug elimination? Elimination of a drug is usually linked to renal filtration, secretion and reabsorption. Food for Thought What conditions might affect renal function (and therefore drug elimination)? What other organ systems are involved in drug clearance? Important Point The pharmacokinetic profile of a drug also depends on its mode of administration … Example: Intravenous Infusions Plasma concentration rises until elimination Plasma Concentration = input Fast Infusion Faster infusions get more drugs on board, but does not change Slow Infusion the time to achieve a steady state Time Time at which steady state is achieved Example: Intravenous Injection Peak plasma concentration of the 100 mg injected Plasma Concentration drug is achieved at time =0 There is no steady state 50 mg injected concentration. Why? Time Example: Oral Dose A single oral dose will give you a single peak Plasma Concentration plasma concentration The drug concentration then continuously declines Repeated doses result in oscillations in plasma concentration Time Are We Having Fun Yet?
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