PHTH1011 001 Pharmacokinetics - Williams PDF

PHARMACOKINETICS Professor Maxine Gossell-Williams [email protected] Slides adopted from Miss Anishka Lewis objectives  On completion of this lecture, students should be able to: I. Discuss the general principles of pharmacology II. Discuss drug administration and absorption III. Discus...

PHARMACOKINETICS Professor Maxine Gossell-Williams [email protected] Slides adopted from Miss Anishka Lewis objectives  On completion of this lecture, students should be able to: I. Discuss the general principles of pharmacology II. Discuss drug administration and absorption III. Discuss drug distribution, metabolism and excretion definitions  Pharmacology: the study of drugs and their interactions with the living systems.  Drug: substances used in the diagnosis, prevention or treatment of a disease.  Pharmacokinetics: the effect of the body on the drug  Pharmacodynamics: the effects of the drugs on the body and their mechanism of action. What is Pharmacokinetics? The study of the absorption, distribution, metabolism and excretion of drugs.  Absorption – Enters the Blood  Distribution – Sent to different parts of the body  Metabolism – Broken down  Excretion – Eliminated from the body Routes of drug administration ENTERAL By the digestive tract oral (by mouth) buccal (via the cheeks), sublingual(under the tongue) rectal (via the anus) Most commonly used Effective absorption – due to the large surface area of the gastrointestinal tract. PARENTERAL Intravenous/IV Intramuscular/IM Subcutaneous/SC Intrathecal/IT Intraperitoneal/IP  All these processes involve passage of the drug across various barriers – e.g. Intestinal epithelium  Membrane is made up of two layers of phospholipids with intermingled protein molecules. Drugs are directly delivered into tissue fluids or blood. TOPICAL Transdermal Vaginal transcutaneous absorption The movement of a drug from its site of administration in the bloodstream  Occurs by processes such as passive diffusion or carrier mediated transport.  Important for all route of absorption except the IV route.  Several factors influence the rate and extent of absorption Absorption-Key terms FIRST PASS METABOLISM DRUG ENTEROHEPATIC CIRCULATION The metabolism of a drug during its passage from the site of absorption to the systemic circulation. Circulation of substances from the liver to the bile, followed by entry into the small intestine, absorption by the enterocyte and transport back to the liver.   Drugs given orally may be metabolised in the gut wall and in the liver before reaching the systemic circulation. Compensate for first pass metabolism by increasing the dose of some drugs, or changing the route for others. DRUG BIOAVAILABILITY The fraction of the drug that reaches the blood circulation following administration by any route.  IV – 100%  On IM/SC injection, drugs are almost completely absorbed while by oral route, bioavailability may be low. Absorption – bioavailability https://www.youtube.com/watch?v=adb7CcC_Ch4 distribution Dispersal of drugs from the systemic circulation to the other tissues and the site of action.  factors determine the rate and extent of distribution: PLASMA PROTEIN BINDING  most drugs bind to plasma protein{Low to High}  Acidic drugs bind mainly to albumin  Basic drugs bind to alpha-acid glycoprotein.  The free and unbound fraction of the drug is the only form available for action, metabolism and excretion.  Protein binding prolongs the duration of action of the drug.  Drugs may compete for the same binding sites Molecular weight Lipid solubility Ionisation, Blood flow Plasma proteins binding Cellular proteins Blood brain barrier Blood Brain Barrier: serves as a protective barrier for the brain.  Only lipid soluble unionised drugs can cross.  It becomes permeable to drugs during inflammation of the meninges. Placental Barrier: Lipid soluble unionised drugs readily cross the placenta while lipid insoluble drugs cross to a much lesser extent. Distribution – volume of Distribution Volume of distribution describes how extensively drugs is distributed to the rest of the body compared to plasma  May distribute in plasma, interstitial fluid, intracellular fluid.  Most drugs will distribute into more than one compartment. Interstitial: fluid between cells, lymph, spinal column, fluid in eyes, tears, synovial fluid Intracellular: fluid found inside all cells including blood cells, bone, muscles, fat Distribution – volume of Distribution Drug %Plasma Protein Binding Lipid Vd(L) solubility/Tiss ue Binding Comments Warfarin 99 Low/Low 8 Reflects a high degree of plasma protein binding. Gentamicin