Pharmacokinetics (Wolff) Flashcards
What are the 4 basic pharmacokinetic processes?
ADME
Absorption, Distribution, Metabolism, Excretion
What are the factors affecting drug Absorption
rate of dissolution (eg. of tablet) surface area blood flow (to surface area) lipid solubility pH partitioning
What are the enteral routes of drug administration?
Oral
Rectal
Sublingual/buccal (in mouth but not swallowed)
What are the parenteral routes of drug administration?
Intravenous Intramuscular Subcutaneous Inhalation Topical Transdermal
What is a major transporter of drugs OUT of cells?
P-glycoprotein
What is the typical way for drugs to cross the cell membrane?
Direct penetration of the membrane
aka simple diffusion
Weak acids and bases can only cross membranes when in their _______ form
unionized
What is ka?
ka = rate constant for absorption
What is S?
S = salt factor; less than or equal to 1
drugs are often administered as their salt, but only parent compound is measured
What is F?
F = bioavailability, fraction of drug that reaches the bloodstream; less than or equal to 1
Amount of drug absorbed formula
amount absorbed = SFDose
Formula for Concentration in Plasma (Cp)
Cp = (SFDose)/Vd
Formula for Volume of distribution (Vd)
Vd = (amount of drug in body)/(Plasma concentration)
What are the factors affecting drug Distribution
Ability of drugs to enter cells
Blood flow to tissues
Ability of drugs to exit the vascular system
A drug is only bioactive if ____
free
What is the primary site of biotransformation/drug metabolism?
The liver
Drug metabolism is crucial for the renal elimination of _______ drugs?
Lipophilic drugs. They must be made more polar so they can be trapped in the renal tubular fluid
Phases of drug metabolism/biotransformation
Phase I: oxidation, reduction, hydrolysis
Phase II: conjugation
Phase I biotransformation
products are usually more polar metabolites
Oxidative processes often involve the cytochrome P450 system in the sER
Cytochrome p450 INDUCERS do what
Speeds up metabolism and leads to quicker lowering of plasma levels below minimal effective concentration
Cytochrome p450 INHIBITORS do what
slow the metabolism and can lead to toxic levels of a drug
Which enzyme does grapefruit juice inhibit
grapefruit juice is an inhibitor of CYP3A4 enzyme (the major cyt p450 enzyme)
Inhibition of this enzyme in the intestinal epithelial cells increases the bioavailability of other drugs
What is the goal of conjugation in phase II of biotransformation
Conjugation usually makes drugs more water soluble and more excretable since the molecule added is highly polar
What is the goal of acetylation and methylation in phase II of biotransformation
Typically makes drugs less water soluble
Usually inactivates the drug
