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Transcript
Pharmacology
• [email protected]
• 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
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•
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•
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
•
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•
•
•
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
•
•
•
•
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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........