drug-target pharmacodynamics part 1 Flashcards
what is a drug
molecules that interact with a biological system to produce a biological response
what is the MW of drugs
under 600
are drugs endogenous
no
examples of biologics
antibodies and proteins
what is drug safety dependent on
therapeutic index
how do you make drugs safe
keep it between the therapeutic window from efficacy vs toxicity
why are drugs administered
to achieve a biological response that alleviates the symptoms or cause of an illness
what is a biological process responsible for
producing the symptoms or causing the illness
at the molecular level what is a drug target
usually a biomacromolecule (enzyme, receptor, ion channel) that’s involved in the biological process
what are they intermolecular interactions that cause the drug to bind to the receptor
hydrogen bonding, VDW or LDF, ionic/electrostatic, pi-pi bonding and dipole interactions
what determines the types of interactions available for drug molecules
the functional groups it contains
what determines physiochemical properties such as water solubility and membrane permeability
the functional groups present
how do drugs with non polar, aliphatic side groups bind to targets
short range vdw forces
how do drugs with aromatic side groups bind to targets
short range vdw forces
how do drugs with polar uncharged side groups bind to targets
midrange H-bonds
how do drugs with positive and negatively charged side groups bind to targets
long range ionic
what does the tertiary structure allow the enzyme to do
perform its function and maintain the integrity of the active site where catalysis is performed
what do the amino acids that border the active site do
produce a particular 3D shape that maximises interactions between the enzyme and the substrate which ensure that the substrate is in the correct position
how does the movement of the active site lower the activation energy
by forcing the substrate into a transition-state confirmation which is why it is catalytic
what are the types of interactions between the amino acids that border the active site and the substrate
a mixture of H-bonds which are directional and specific for H-bonding groups on the substrate
and short range vdW interactions
what is a competitive inhibitor of cox
flurbiprofen
how does flurbiprofen work
it binds in preference to arachidonic acid and blocks prostaglandin synthesis which reduces the inflammatory response
how do competitive inhibitors compete with substrates
- must have some structural resemblance so that it can match the 3D shape of the active site
- must form stronger interactions with the active site so that it binds in preference to the substrate
- need to stay in longer than the substrate as usually the binding process is dynamic and molecules will associate and dissociate
what type of interactions happen between the enzymes that border the active site and an inhibtor/drug
the same as the interactions between the substrate and the active site
what does endogenous mean
it was produced in the body
do biologics follow basic rules of drugs
no
what do efflux pumps do
pump molecules that weren’t absorbed back out of the intestine
what is the primary site of metabolism in the body
the liver
what balance of solubility must have
a balance of water and lipid solubility
what does low logP/logD mean
low absorption
what does high logP/logD mean
high absorption
