EHS 202 Pharmacology for EMS Week 4 Lecture 1 PDF

EHS 202 Pharmacology for EMS Week 4 Lecture 1:Principles of Pharmacology (ii) At the end of this session you shall be able to: 1. Describe the general principles of pharmacokinetics; 2. Outline common variables that affect the absorption and distribution of drugs; 3. Desc...

EHS 202 Pharmacology for EMS Week 4 Lecture 1:Principles of Pharmacology (ii) At the end of this session you shall be able to: 1. Describe the general principles of pharmacokinetics; 2. Outline common variables that affect the absorption and distribution of drugs; 3. Describe the concept of drug bioavailability; and 4. Describe and compare the the various routes of drug administration and their effect on bioavailability, onset of action, peak plasma concentration and duration of action. 2 Recap: What is pharmacokinetics??? Pharmacokinetics can be defined as: ‘What the body does to the drug.’ Pharmacokinetics examines how a drug is altered during the processes of absorption, distribution, metabolism and excretion. 3  Pharmacokinetics Involves: Absorption Distribution Metabolism Excretion The taking of a drug to achieve a target concentration that correlates with a biological effect - taking individual variation into account. 4  Pharmacokinetic Process DISTRIBUTION METABOLISM Liver Extravascular Body Administration tissues Gut Wall Blood EXCRETION ABSORPTION Kidney Intravascular Administration 5 Pharmacokinetics Absorption and Distribution Metabolism and Excretion When treating a patient with any drug we must consider the pharmacokinetic effect of absorption, distribution, metabolism and excretion. 6 Pharmacokinetics Determines… Peak Concentration Onset of action Duration of action 7 Absorption 8 What is absorption? Absorption can be defined as: ‘the process by which unchanged drug proceeds from the site of administration to the blood’. Absorption is important for all routes of administration (except IV) with the drug having to cross a membrane and enter the blood stream. 9 Is the route of administration important? 10 Routes of drug administration The rate and extent to which a drug is absorbed are influenced by: The nature of the absorbing surface (no. of cells and surface area) Blood flow (circulation to site of administration - cardiac arrest?) Solubility of the drug (more soluble the drug, the faster absorbed) Ionisation (hydrophilic dissolve in H2O, lipophilic can easily cross membranes) Formulation (manipulated for slow release or prevent decomposition) 11  Oral absorption Oral absorption is the most common method for administering drugs as it has high patient compliance and few delivery complications. Some lipophilic drugs (ie. GTN) are actually absorbed from the oral cavity (buccal or sublingual) and directly enter the blood stream. The small intestine is the major site of absorption for orally ingested drugs. 12 First pass metabolism The liver is the main site of drug metabolism and often a significant amount of the absorbed drug is metabolised before entering the systemic circulation (first pass metabolism). First pass through the liver frequently reduces the bioavailability of the drug (the amount drug entering the systemic circulation. 13 But… Clinically why wouldn’t we always want a drug to be absorbed into the systemic circulation? 14 Clinically we don’t always want a drug to be absorbed into the systemic circulation: When we want a topical effect, and we have the option of administering the drug close to the desired site of action. 15 Oral absorption Not all drugs are able to be absorbed from the gastrointestinal (G.I) tract in an active form. Some must be injected as they are broken down, such as insulin. 16 Intravenous route of administration Intravenous access is invasive, time consuming and penetrates a natural defense barrier. Intravenous injection is the fastest and most certain route of drug administration. An IV bolus injection produces a very high concentration of drug initially. Large volumes of a drug can be administered in this way. 17 Intramuscular route of administration Intramuscular administration is also invasive but requires less preparation. IM produces a slower effect than that of the IV route (but faster than oral). The slower absorption results in safer plasma concentration than with IV administration. The rate of absorption depends significantly on local blood flow to the site of administration. 18 Topical route of administration Most drugs are absorbed poorly through unbroken skin. Only lipid soluble compounds are absorbed readily through the skin. Transdermal patches produce a steady state of drug delivery that can be left on for significant periods of time. 19 Distribution 20 What is distribution? Distribution can be defined as: ‘The process of reversible transfer of a drug between one location and another in the body’. Drugs are typically distributed to organs with a good blood supply initially and more slowly to organs with a poor blood supply. 21  Distribution Only free drugs can interact with receptors and once the free drug is removed from the circulation, the drug-protein complex dissociates to release more free drug into circulation. Lipid soluble drugs readily cross cell membranes and have a high affinity for adipose tissue, where they are stored. 22 Distribution and the Blood Brain Barrier (BBB) The BBB is a physiological barrier that prevents many drugs from crossing it (i.e. antibiotics) unless they have a significant lipid solubility. Alteration in the integrity of the BBB by inflammation can allow drugs such as penicillin to be used to treat bacterial meningitis. 23 Elimination – Process of Metabolism & Excretion 24 What is drug elimination? Drug elimination can be defined as: ‘the irreversible loss of drug from the body through the processes of metabolism and excretion’. Drugs are primarily metabolised by enzymes in the liver and the resultant metabolites are typically less active than the parent drug. 25 Drug elimination Drug elimination determines the rate of termination of the physiological response. The amount of drug removed will affect the time that the concentration is above the therapeutic level and the steady state concentration. 26  Rate of elimination The half-life of a drug is the time taken for the drug plasma concentration to fall by one-half. The half-life of a drug is directly influenced by the volume of distribution and clearance rate. The half life is an important consideration for the dosing frequency to avoid large fluctuations in plasma concentration. 27 Metabolism 28 What is drug metabolism? Drug metabolism can be defined as: ‘the processes of chemical modification of a drug’. Drugs are primarily metabolized by enzymes in the liver and the resultant metabolites are typically less active than the parent drug. Not all drugs undergo metabolism. Metabolism generally results in the formation of a more hydrophilic water-soluble compound or metabolite which promotes urinary excretion 29  Enzymes in the Liver The liver is the primary site of drug metabolism. The cytochrome P450 enzymes (CYP) are of the greatest significance in drug and chemical metabolism. Due to specificity, there are several CYP isoforms which differ in the drugs that they metabolize. 30 Excretion 31 What is drug excretion? Excretion can be defined as: ‘the loss of chemically unchanged drug or metabolites from the body’. Drug excretion can occur through a number of routes including urine, feces, sweat, expired air and breast milk. 32  The main routes of drug excretion Solubility of the drug (or metabolite) as well as ionization will affect accumulation and excretion by the body. 33  Renal clearance The kidneys are the major route of clearance of water-soluble drugs. Lipid-soluble drugs are poorly excreted by the kidneys. Reduced renal function can have a significant effect on the rate of excretion and elimination of drugs. 34 References 1. Nancy Caroline’s Emergency Care in the Streets, Uk Version. 7th Edition. AAOS 2.Vander’s Human Physiology’, 11th Edition. (Widmaier et al.) 3.‘Rang and Dale’s Pharmacology’, 8th Edition. (Rang et al.) 4.‘Pharmacology for Health Professionals’, 3nd Edition. (Bryant & Knights) 5.‘Fundamentals of Pharmacology’, 5th Edition. (Bullock et al.) 35