Pharmacokinetics Stage 1 PDF

Introduction to Pharmacology 21 November 20 1 24  Aims of the session Outline principles of how drugs work Explain the effects absorption, distribution, metabolism and excretion...

Introduction to Pharmacology 21 November 20 1 24  Aims of the session Outline principles of how drugs work Explain the effects absorption, distribution, metabolism and excretion has on a drug 21 November 20 2 24 Definitions Pharmacology The science that explores the composition, effects and uses of drugs. Pharmacokinetics What the body does to the drug Pharmacodynamics What the drug does to the body Pharmacokinetics- what the body does to the drug Absorption Distribution Metabolism Excretion Absorption and factors affecting absorption First pass effect Oral Destruction by enzymes Topical or transdermal Food Subcutaneous Other medications Controlled release drugs Intramuscular Enteric coated drugs Intravenous Inhalation Rectal Factors affecting absorption across the lifespan Neonate and Paediatric Older Adult Gastric absorption – acid ↓ blood flow to tissues in producing cells immature GI tract Gastric emptying – may Changes to gastric pH be decreased Variations in available Liver not fully mature - ↓ plasma proteins first pass metabolism with ↓ subcutaneous fat ↑ drug levels in the Potential ↓ in cardiac bloodstream output Distribution Drugs do not distribute evenly throughout the body: Lipid (fat) soluble drugs will concentrate in the adipose tissues Water soluble drugs will concentrate in the body water, the blood and interstitial fluid that surrounds the cells Some drugs mainly concentrate in one part of the body Drugs penetrate body tissues at different speeds depending on their ability to cross cell membranes. The blood brain barrier (BBB) is a selective semipermeable membrane that separates the brain and Factors affecting distribution across the lifespan Neonate and Paediatric Older Adult ↓ fat content ↑ body fat ↓ protein binding ↓ serum albumin capacity Blood brain barrier still developing Metabolism Metabolism comes from the Greek word that means ‘to change’. Liver is the primary site where drug metabolism occurs. Main purpose is to change to become more water soluble. Can reduce drug activity or create other active metabolites. There are two phases of metabolism Phase one: Mainly in the liver by cytochrome P450 (CYP450) enzymes Phase two: A large ionised molecule is added to the drug to increase its water solubility. Factors affecting metabolism across the lifespan Neonate and Paediatric Older Adult Infants and children - ↓ metabolism in liver Liver not fully ↓ first pass developed ↓ enzymes. metabolism Older children ↑ metabolism. Excretion Final stage of drug interaction Routes Kidney – most common route of excretion. The kidneys filter blood so majority of byproducts excreted in urine. Liver - filters blood, some drugs and their metabolites are actively transported by hepatocytes to bile. Other - Sweat, tears, reproductive fluids (such as seminal fluid), and breast milk can also contain drugs and byproducts/metabolites of drugs. Factors affecting excretion across the lifespan Neonate and Paediatric Older Adult Immature kidneys ↓ kidney function ↓ liver function Therapeutic Window Factors affecting pharmacokinetics Patient Factors age, sex, medical conditions, pregnancy Drug Factors solubility in water/lipid; size, electric charge Physiological factors first-pass effect, barriers e.g. blood brain barrier.  Task Take a minute to download the BNF app on your phone or look up a paper copy of the BNF Try and find the following medications and read the text related to that medication, try and think of the pharmacokinetics related to the medication: 1. Metformin 2. Ibuprofen 3. Penicillin (Phenoxymethylpenicillin) 21 November 15 2024