Pharmacology

• HMROBNS@aol.com

• Phone Number: (203) 467-0094

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

• ED 50

Effective Dose in 50%

of the population

• LD 50

Lethal Dose in 50%

of the population

• 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

Pharmacodynamics

Meyer-Overton Theory

Protein Receptor Theory

GABA Suppression Theory

Lecture Finished

Go home........