Lecture 1 Flashcards
Pharmacokinetics definition
What the body does to the drug: absorption, distribution, biotechs formation (metabolism), excretion
ADME
Pharmacodynamics
What the drug does to the body: drug action and effects
what are the 3 diff types of drug names?
INN, proprietary name, company/compound code
what might proprietary name suggest?
drug effect
what are the 2 stages of drug development?
pre clinical and clinical
what are the phases of preclinical stage?
phase 1. isolation/synthesis
phase 2. screening and determination of acute toxicity (LD50)
phase 3. pharamcological studies
phase 4. studies of subchronic (1month), chronic (6month), toxicity or teratogenic/mutagenic/cancerogenic effects
what are the phases of the clinical stage?
phase 1. human pharmacology
phase 2. therapeutic exploration
phase 3. therapeutic confirmation (random trials)
phase 4. therapeutic use (post-marketing studies)
what are the 3 ways drug can be absorbed by the body?
- passive diffusion (common; aqueous and lipid)
- carrier mediated transport (facilitated, active - primary and secondary)
- endo/exocytosis
what does fick’s law show?
passive flux of molecules down a conc. gradient
where does aqueous diffusion occur in the body?
- large aqueous compartments such as interstitial space, cytosol
- in aqueous pores of blood vessels
what kind of drug molecules do not permeate most vascular aqueous pores?
those bound to large plasma proteins (albumin etc.)
can protein bound drug be cleared? why?
no because they can’t enter the glomerulus
what is the most important limiting factor for drug permeation?
lipid diffusion
what does henderson-hasselbalch equation show?
ration of lipid soluble weak acid/base to water soluble weak acid/base
what is pKa?
pH at which durg is 50% ionised and 50% unionised
are unionised molecules lipid or water soluble?
lipid because they are not charged and thus can corss the phosolipid bilayer; it is absorbed by the body
are ionised molecules lipid or water soluble?
water because they are charged and can’t cross the membrane; goes w/the water of the body and is excreted via urine
at what pH are weak acids in the lipid soluble form?
acidic pH
at what pH are weak bases in the lipid soluble form?
alkaline pH
what form are weak acids in at a basic pH?
water soluble
what form are weak bases in at an acidic pH?
water soluble
examples of weak acids?
aspirin, penicilin, cephalosporine, loop diuretics, phenobarbitone
examples of weak bases?
local anesthetics, morphine, PCP, atropine, amphetamine
what are the 3 types of carrier molecules?
selective, saturable, inhibitable
what are the 2 types of carrier families?
ABC (ATP binding cassette)
SLC (solute carrier)
what family does transporters of facilitated diffusion belong to?
SLC
what is example of facilitated diffusion?
glucose into muscle/fat cells via GLUT 4 transporter (SLC)
what family does transporters of primary active transport belong to?
ABC; their intracellular loops have ATPase activity
what family does transporters of secondary active transport belong to?
SLC
what is bioavailability?
measure of the fraction of administered dose of a drug that reaches systemic circulation unchanged
why is bioavailability of an ingested drug lowered?
- may be not completely absorbed
- might undergo first pass metabolism in liver/intestinal wall
what is the effective barrier to orally administered drugs?
epithelial lining of the GIT
