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Lecture 3

HSS3106 Lecture 3: Pharmacokinetics and Pharmacodynamics

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University of Ottawa
Health Sciences
Ron Saulnier

HSS 3106 – Lecture #3 Pharmacokinetics and Pharmacodynamics • Pharmacokinetics: describes the movement of a drug from “consumption” (entry) to “elimination” (removal) - what the body does with the drug o Absorption: from site of administration to plasma o Distribution: from plasma into interstitial tissue and intracellular fluids (presented to the cells) o Metabolism: occur in the liver, kidneys or other tissues o Excretion: occurs through the urine, bile, feces or expired air • Pharmacodynamics: describes how the drug works at the target tissue – what the drug does to the body o Drug Receptor interactions: binding o Dose response: effect o Signal transduction: mechanism of action, pathways Absorption • Movement of drugs into systemic circulation • Depends on the drug’s ability to cross the cell membrane and resist presystemic metabolism • Presystemic metabolism affects drug’s bioavailability o Bioavailability: the amount of drug that reaches systemic circulation intact and its speed o It is determined by comparing plasma levels of drug after administration compared to IV injection which has a 100% bioavailability o Not all the drug is destroyed by the enzymes in the gut o In the end, only a small amount of the drug will make it through – what gets into the circulation is not necessarily what you originally swallowed • Factors affecting absorption: o Acidity of the stomach where you do not have enough acid of the stomach. Most people have a certain acidity in the stomach and the designing of the drug is based on the fact that everyone has the same acidity level o Physiochemical properties like dissolution of particles, solubility, thermodynamics, charge o Presence and type of food in stomach or intestine o Routes of administration mouth, intravenous, intramuscular, subcutaneous, transdermal, sublingual, buccal, rectal, vaginal Distribution • Passage of agent through blood or lymph to various body sites • One of the big factors for distribution is blood flow – change in blood flow to different organs will change how they will function (e.g: the kidney will have a lot) • Cartilage or connective tissue have a little amount of blood flow and therefore there will be less absorption of the drug at those areas. For instance, for diabetics, the antibiotics have a hard time getting to certain tissues since their blood tissues are poor • Factors affecting drug distribution: o Blood flow: Tissue distribution of a drug is dependent on transport in the bloodstream, high flow tissues (brain, liver & kidney) receive drugs in large volumes prior to muscle & adipose tissue o Capillary permeability: Determined by capillary structure where most capillaries will allow large molecules to pass with little impedance. Arteries are not close to the surface since they need protection and bigger blood vessels have thicker walls. Edema and inflammation will occur when there is swelling o Drug structure: The structure of the drug (hydrophobic or hydrophilic) will have an effect on distribution o Binding to plasma proteins: Things do not often circulate freely but are bound to proteins for stability but they are not in a very strong bond! When it is bound, it cannot function and therefore only free drugs are able to bind to receptors for interaction! (E.g: albumin binds drugs and comes from the liver  if you have liver disease there will be less formation of albumin and therefore not enough binding to the drug!) Metabolism • Sometimes, medications are water-soluble enough that they are able to be peed out. However, another outcome can cause accumulation or it is not water soluble enough that it cannot be excreted out • Modification of the drug can sometimes cause the drug • Most drug metabolism occurs in the liver. • First-pass effect (metabolism of drug by liver enzymes before it reaches systemic circulation) influences metabolism • Substances that are absorbed across the intestinal wall enter blood vessels and are carried directly to the liver (hepatic portal circulation) Cytochrome P450 Enzy
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