Pharmacology Exam #1

pharmacology

the science of drugs including their origin, composition, pharmacokinetics, therapeutic use, mechanisms of action and toxicology

• also the study of drug-receptor interactions

drug

a chemical, herbal or biological substance used in treatment, cure or prevention or diagnosis of disease or to enhance well-being

receptor

protein which binds or responds to stimulatory/ inhibitory molecules (hormone, neurotransmitter, antigen, antibody)

ligand

a molecule that binds to a receptor a

Agonist

molecule which stimulates the receptor

• produces a physiological effect

Antagonist

molecule which inhibits/ blocks the receptor

• prevents activation

EC50 (effective concentration)

concentration of drug that produces 50% of maximum effect

• it is the inflection (midpoint) of the S-curve

examples of cell surface receptors

• G- protein coupled receptors

• receptor tyrosine kinases

• ion channels

• transporters

example of intracellular receptors

steroid hormone receptors

2 main factors of GPCR

• 7 transmembrane domain

  • bound to hetero-trimeric G proteins

main factor of tyrosine kinase receptor

• activate via phosphorylation

potency

how much drug you need to produce a given effect

Kd

the dissociation constant which refers to the concentration at which 50% of receptors are occupied

• K2/ K1

Ka

is the affinity constant which measures the strength of binding

• K1/ K2 (opposite of Kd)

if there is tighter binding..

there is a lower Kd but higher affinity (Ka)

efficacy

the maximum effect a drug can produce, regardless of dose

full agonist

produces the maximum possible effect for the receptor system

partial agonist

produces a lower maximum effect but binds the same receptor, no matter how high the dose

what do cell surface receptors do

• cell migration

• cell proliferation

• cell shape change

• expression of new receptors

• secretion of hormones or neurotransmitters

• phagocytosis

Bmax

maximum binding which is proportional to the total receptor number

what does a concentration curve measure and how do you read it

measures the affect that the antagonist has on the effect of the agonist

• start with defined agonist responses, then measure how adding increasing amounts of antagonist reduces that response

example of irreversible bond

covalent bonde

examples of reversible bonds

• ionic

• hydrogen

orthosteric site

primary binding site for endogenous ligand (agonist)

• competitive antagonists bind here

allosteric site

a secondary site on the same receptor protein in which binding here causes a conformational change which affects against agonist binding

IC50 (inhibitory concentration)

the concentration of the antagonist which reduces a response by 50%

homologous competition

when the same ligand competes with itself

• it is used to confirm specific binding and determine the Kd

heterologous competition

when a different molecule competes with the labeled reference ligand

• used to characterize new drug candidates

Ki

true dissociation constant of antagonist

desensitization

reduction in cellular response to a given stimulus over time when that stimulus is continuously present

• same does of agonist, applied after prolonged exposure to the agonist, produces a smaller response than the initial application

ligand bias

the ability of different ligands to preferentially activate one signaling pathway over another at the same receptor

functional selectivity (ligands)

ligands are functionally selective for one signaling outcome

inverse agonist

a ligand which produces an effect LOWER than the unstimulated state of the receptor

• doesn’t block agonist activity but suppresses the spontaneous activity which exists even without an agonist

what amino acid are all catecholamines derived from

tyrosine

examples of catecholamines

epinephrine, norepinephrine, and dopamine

what are adrenergic receptors

they are GPCRs which respond to catecholamines

what are muscarinic receptors

all GPCRs

what are nicotinic receptors

they are ligand gated ion channels