Chemistry Flashcards
please draw the degradation of aspirin in a basic environment
aspirin (acetylsalicylic acid) + OH- –> salicylic acid + acetate
in what conditions is aspirin degradation the fastest
basic conditions
what is total polar surface area
the total polar surface area will influence how easily a molecule will pass through lipid membranes
what is the TPSA for well absorbed molecules
usually less than 130
what its the TPSA for drugs that need to cross the BBB
usually <80
(this is because the blood brain barrier has fewer gaps tbetween the cells and tighter junctions and therefore will exclude more polar molecules, restricting access to those with a TPSA <80
if there is two enantiomers of a drug molecule, why will ne be more pharmacologically active than the other one?
for example methylphenidate and aspirin
The dopamine receptor is a protein made up of chiral amino acids, it acts like a right or left handed glove.
As the ligand is chiral, one stereoisomer will bind to the receptor with higher affinity and will stimulate it more effectively.
why do you administer drugs as the salt form
salts produce rapid dissolution profiles in the aqueous medium of the gut
generate single molecular entities rapidly that will be presented to the high surface area of the small intestine
then after that the lipophilic form in the pH 8 will be rapidly absorbed
why may a drug molecule only have a bioavailability of 30% even if the log D predicts otherwise
bioavailability takes into account the fraction absorbed from the GIT but also how much emerges after passing through the liver after direct transfer via the hepatic portal vein.
The drug must have a high first pass metabolism (liver esterases
why might different enantiomers of the same drug have different volume of distribution and different half life
metabolism is by enzymes which are chiral
they will therefore have different affinities for different stereoisomers,
therefore their metabolism rates will differ
therefore their half lives will differ
during renal excretion, filtration at the glomerulus in the Bowman’s capsule only affects free drug, not drugs bound to plasma proteins.
Plasma proteins are chiral and therefore they have different affinities for the stereoisomers
If one is more bound up by plasma proteins than the other then there will be less free drug being filtered which will lower the excretion rate and increase the half life
remember all proteins are chiral and will therefore have different affinities for the stereoisomers which means different levels of sequestration and different volumes of distrubution
what does Vd>0.7 L/kg mean and how is it caused
it indicates that the drug is extensively distrubuted
it indicates distribution wider than the aqueous compartments
it is caused by sequestration in tissues by binding to tissue proteins
all proteins are chiral and will therefore have different affinities for the stereoisomers which means different levels of sequestration and different volumes of distribution
how does protein binding influence the amount of citalopram that is filtered at the bowman’s capsule
plasma protein binding will determine how much free drug is in the glomerulus that can be filtered
bound drug cannot be removed
how does volume of distribution affect the amount of drug that is filtered at the bowman’s capsule and why
Vd determines how much is actually in the blood that can be filtered in the first place
if the drug is extensively distrubuted in the tissues (and removed from the circulation) the kidneys cannot access it to remove it even if it is in the free form in the plasma
if the Vd of a drug is >0.7 why does this mean that it will have a long half life
very extensively distrubuted
requested by the tissues and fat out of the blood stream
the organs of elimination (kidneys and liver) can only slowly access the parent drug to remove it from the system
what does aromatic oxidation by CYP450 require
removal of a hydrogen and replacement of an OH group from an electron rich phenyl ring
