Pharmacology
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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: • Peripheral Compartments:
Intravascular fluid and
any highly perfused Not actual area but
tissues. Highly perfused calculated.
tissue receive 75% of
CO, but only equal 10%
of total body mass.
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 • Therapeutic Index
Effective Dose in 50%
of the population LD 50/ED 50
• LD 50
Lethal Dose in 50%
of the population
Pharmacodynamics
• Receptors
• Plasma Levels
Terms
• Sensitivity
• Tolerance
• Tachyphalaxis
• Immunity
• Agonist/Anatagonist
Any Questions
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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 Decreases
• Hyperthermia • Hypothermia
• Alpha 2 agonists
• Increases in CNS
• Pregnancy
catecholamines
• Alcohol ingestion
• Hypernatremia
• 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........