8 pharmacodynamics I Ngu Flashcards
Define pharmacodynamics and distinguish between therapeutic and adverse drug effects.
Pharmacodynamics: the actions of the drug on the body.
Therapeutic effect: beneficial effect provided by the drug.
Adverse effect: undesired, possibly toxic effect provided by the drug.
Identify the two most important steps in receptor-mediated drug’s mechanism of action.
1- Drug + receptor interaction results in modification of the receptor.
2- Modified receptor activates an effector
Distinguish between inert binding sites and drug receptors.
Inert binding site: binding of the drug does not produce any effect. ie. drugs binding to plasma proteins
Drug receptors: binding of the drug will transduce a signal into the cell and provide some effect.
Nature of Regulatory Protein receptors
examples of autocoids, hormone and neurotrans
mediates fxn of endogenous molecules
autocoids 5HT1 rec via sumatriptan
hormones NR3C2 rec via spironolactone
neurotrans alpha 1 rec via terazosin
Nature of enzyme receptors
key in rxn pathways
ie. Achase inhib edrophonium, vit K epox red inhib warfarin, rev trans inhib zalcitibine
Nature of transport protein receptors
ion channels ie. calcium channel inhib verapamil
Nature of structural protein receptors
inhib structure formation ie. tubulun inhib colchicine
What determines the selectivity of drug-receptor binding?
stability of binding?
selectivity: drug shape, size , charge
stability: bond type
What is receptor dynamism?
receptor internalization when there is overstimulation
Apply drugs-receptor interactions to predict the selectivity of a drug for its receptors.
% receptor occupancy is proportional to the dose
ie. b/bmax = c / c+kd
drug response is proportional to the dose
ie. E= Emax x C / C +EC50
explain 4 antagonism types and 3 agonist receptor relationships
competitive antag –> competes for same binding site as agonist
noncompetitive antag –> covalent binding to receptor which may irrev. inhibit agonist binding
chemical antag –> binds and neuts agonist
physiological antag –> binds diff receptor which results in opposite effect as target receptor activity
agonist –> ligand that binds to receptor and activates it
partial agonist –> ligand that does not produce full agonist response
inverse agonist –> For a constitutively activated receptor, ligand binding will oppose receptor activity
What is the concept of spare receptors?
some receptors req. less than 100% binding to create maximal effect
thus EC50 is less than Kd
this means EC50 is unchanged in the presence of spare receptors even with noncompetitive antagonism
Identify at least 2 classes of drugs that lack receptor systems and discuss the clinical implications of therapy with such drug.
Sucralfate: coats the stomach and physically protects it from acid erosion/ulcers
osmotic diuretics works simply by causing a shifted osmotic pressure
antacids work by changing the pH of the environment (ie. stomach)
all generally fxn by changing environmental factors
