Escolar Documentos
Profissional Documentos
Cultura Documentos
Reduced by:
Incomplete absorption
First-pass effect
Pulmonary uptake of drugs
DRUG DISTRIBUTION
Redistribution
Rapid entry & equally rapid egress of
lipophilic drugs from richly perfused
organs
Placental Transfer
Simple diffusion
Highly polar, water-soluble compounds
does not significantly cross the placenta
DRUG ELIMINATION
Bioavailability
Fraction of the total dose that reaches the
systemic circulation
1|Page
Drug Clearance
Elimination clearance - Theoretical volume of
blood from which drug is completely and
irreversibly removed in a given time interval
Total Drug Clearance- equal to the sum of the
clearances of all the elimination pathways
Hepatic Drug Clearance
3 biologic factors:
Hepatic blood flow
Intrinsic ability of the liver to irreversibly
eliminate the drug from the blood
Extent of drug binding to plasma
proteins or other blood constituent
Venous Equilibration Model
The unbound concentration of drug in
hepatic
venous blood is in equilibrium with the
unbound concentration in hepatocytes
Limited by deliver of drug to the liver
Elimination is a first-order process
Factors that Alter Hepatic Drug Clearance
Upright position
Exercise
Heat stress
Hypovolemia
Congestive cardiac failure
Liver diseases
Drugs that alter splanchnic
hemodynamics
Phase I Reactions
Oxidation
Reduction
Hydrolysis
Cytochrome P450 system
catalyzes most oxidative and some
reductive biotransformations
Phase II Reactions
Also known as conjugation or synthetic
reactions
Occurs only after a Phase I reaction
Produce conjugates that are polar,
water-soluble compounds
Factors Affecting Biotransformation
Polymorphism
Age
Exposure to various foreign compounds
Liver disease
Congestive heart failure
Effects of anesthesia and surgery
DRUG METABOLISM
Drug Redistribution
primary mechanism for reducing drug
concentrations in the blood
Metabolism
Biotransformation of drugs to more
polar, water soluble compounds
Facilitates the ultimate excretion of
metabolites
Biotransformation Reactions
2|Page
PHARMACOKINETIC PRINCIPLES
Pharmacokinetics is the study of what the
body does to a drug
Quantitative analysis of the relationship
between the dose of a drug and the ensuing
changes in drug concentration in the blood and
other tissues
RATE CONSTANTS AND HALF-TIMES
First-order kinetics
a constant fraction of drug is removed
during a finite period of time.
Rate constant
Half-lives
time required for the concentration to
change by a factor of 2
Volume of Distribution
Quantifies the extent of drug
distribution
Overall capacity of tissues vs capacity of
blood
Apparent volume or compartment
PHARMACODYNAMIC PRINCIPLES
Pharmacodynamics - is the study of what
a drug does to the body.
3|Page
4|Page