FMS Week 4 Flashcards
Pharmacology
albumin
plasma protein binding agent for mostly neutral/acidic drugs
Significance of gefitinib and EGFR mutations
only 10% of patients respond to gefitinib due to somatic mutations around the ATP-binding pocket of the EGFR tyrosine kinase domain
DR = ([Rt][D]/(Kd + [D]))
Version of Michaelis-Menten that relates drug receptor binding to affinity, total number of receptors, and body concentration
what physiochemical properties of drugs affect distribution out of the plasma?
lipid solubility (partition coefficient) and pKa of the drug
β2AR polymorphisms and albuterol response
Homozygotes for Arg-16 in β2AR gene are 5.3x (and heterozygotes 2.3x) more likely to respond to albuterol
what is an example of a covalent bonding drug?
aspirin
what is the therapeutic window of a drug?
the range of concentrations between the minimum therapeutic concentration and the toxic concentration
what factors affect clearance of a drug?
greater volume of distribution and higher elimination constants increase clearance
TPMT
enzyme associated with thiopurine inactivation, overactive in over-metabolizers leading to decreased active (cytotoxic) products
structural changes of hydroxylation
RCH2CH3 to RCH2CH2OH
t{1/2} = 0.693(Vd)/CL
formula for the half-life of a drug based on the clearance (which is a function of the elimination constant)
what is the latency of a drug?
the time from administration to therapeutic concentration
what are spare receptor agonists?
when maximal response is achieved without using all of the receptors (intrinsic activity greater than 1)
what factors affect GI absorption?
surface area, GI pH, GI motility/gastric emptying, blood flow
how much non-interstitial, extracellular water is there in the body?
3L in a 70kg man (20% of extracellular water) in the plasma
what is the duration of a drug?
the time that blood concentrations stay in the therapeutic window
how would you calculate the desired dose of a medication?
Dose= Volume of distribution X therapeutic concentration
what form of bases can pass through lipid membranes?
unprotonated weak bases
most common phase II mechanism?
glucuronidation
what is the intrinsic activity of an antagonist?
zero
t{1/2} = 0.693/k
Formula for the half-life of a drug based on the elimination constant
define volume of distribution
the volume of fluid needed to contain the administered amount of drug at the concentration measured in blood or plasma (V=amount administered/concentration measured)
what factors decrease the rate of passive diffusion?
thickness of the membrane, concentration on “inner” side of the membrane
inhibitors of CYP
cimetidine, erythromycin, ketoconazole, chloramphenicol, acute alcohol, grapefruit juice