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Pharmacokinetics & Pharmacodynamics Injected Drugs

Pharmacokinetics What the body does to a drug Absorption Distribution Metabolism Excretion

Pharmacodynamics What the drug does to the body Drug effect on receptors

Two Compartmental Model Central Compartment: Intravascular fluid and any highly perfused tissues. Highly perfused tissue receive 75% of CO, but only equal 10% of total body mass. Peripheral Compartments: Not actual area but calculated.

Plasma Concentration Curves a graphic plot of the range of plasma concentrations after an injected drug is given. Plots plasma [ ] against time. Alpha Phase distribution phase This begins immediately after injection and reflects the drugs movement from the central compartment (circulation) to the peripheral (tissue) compartment. Beta Phase elimination phase Follows the Alpha phase and is a more gradual decline in plasma concentrations.

Plasma Concentration Slide...

Terms Elimination half time: The time necessary for the plasma concentration to fall 50% during the elimination phase (beta phase) Context-sensitive half time: Measures half time after an infusion is stopped. Elimination half-life: the time needed eliminate 50% of the drug from the body. Effect-site equilibrium: delay between IV administration and desired effect. Bioavailability- fraction of the administered drug available for absorption

Distribution Uptake Volume of Distribution Degree of Ionization Protein Binding

Metabolism A. First order kinetics- Constant fraction broken down in a standard time. Independent of plasma concentrations. B. Zero order kinetics- Constant amount is metabolized- constant amount each unit of time. example: alcohol

Metabolism: Pathways Hepatic microsomal enzymes Non-microsomal enzymes Oxidative Reduction Hydrolysis Conjugation

Clearance Hepatic clearance: Perfusion dependent Capacity dependent Biliary excretion: Renal clearance: Glomerular filtration Tubular secretion Tubular reabsorption

View Dose Response Curves.... (See Slide and Handout)

Dose response Curves LD 50/ED 50 ED 50 Effective Dose in 50% of the population LD 50 Lethal Dose in 50% Therapeutic Index LD 50/ED 50

Pharmacodynamics Receptors Plasma Levels

Terms Sensitivity Tolerance Tachyphalaxis Immunity Agonist/Anatagonist

Any Questions ???????????????????

Pharmacokinetics & Pharmacodynamics Inhaled Anesthetics

Pharmacokinetics Absorption Distribution Metabolism Elimination

PA=Pa=Pbr PA: Alveolar partial pressure of the gas Pa: Arterial blood partial pressure Pbr: Brain partial pressure

MAC: Minimum Alveolar Concentration The minimum alveolar concentration that will prevent movement to a surgical stimulus in the 50% of the population

Distribution:Solubility Coefficients Blood: Gas Solubility Oil: Gas Solubility Tissue: Blood Solubility

Factors that Affect MAC Increases Hyperthermia Increases in CNS catecholamines Hypernatremia Decreases Hypothermia Alpha 2 agonists Pregnancy Alcohol ingestion Lithium Decreases in CNS catecholamines Hyponatremia

No Change in MAC... Metabolism Chronic alcohol abuse Gender Length of anesthesia Hyperkalemia or hypokalemia

Meyer-Overton Theory Protein Receptor Theory GABA Suppression Theory Pharmacodynamics Meyer-Overton Theory Protein Receptor Theory GABA Suppression Theory

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