Week 1: Drug Receptors

drug receptor def

place on cell/tissue where a drug binds and then begins to act

receptors are

enzymes, nucleic acids, specialized membrane bound proteins

magnitude of response is proportional to

number of drug receptor complexes

natural body substances are

already within the body and bind to sites (endogenous)

drug receptors are located

on cell surface or within the cytoplasm or nucleus (intracellular)

examples of drug receptors on cell surface

ion channels, enzymes, linked to regulatory (G) proteins/secondary messenger

ion channel drug receptors

act as an ion pore and are done through changing membrane permeability

Transmembrane channels are

gated open/closed by binding of drug on receptor site

-acts as a lock

Surface enzyme drug receptors contain proteins thast

span entire width of cell bebrane

what is the binding domain on surface enzyme receptors

extracellular receptor sites

what is the catalytic domain on surface enzyme receptors

intracellular enzymatic components

Drugs that bind to the receptor sites change the

enzyme activity and biochemical functions in the cell

When a receptor is inactive

two subunits has its own binding domain on the outer surface and catalytic domain on inner surface

-stay seperated

binding of the molecule to the binding domains causes subunits to

connect and join together and causes a change within the cell

binding of the subunits together causes

phosphorylation of tyrosine receptors on catalytic domain

tyrosine phosphorylation initiates

enzymatic activity of the catalytic units, which can cause substrate activation within the cell

drug receptors on G/regulatory proteins function

link to intermediate regulatory protein located on inner surface of cell

6 functions of g-protein couple receptors

1)drug binds to surface receptor

2)receptor changes shape

3)receptor attaches to nearby g protein

4)g protein turned on

5)alters activity of intracellular enzyme or ion channel

6)change in cell function

stimulatory g proteins

increases response of cells

when stimulatory G proteins couple with GPCR it will...

opens ion channels or turns on enzymes

inhibitory G proteins

lead to a decrease in cell activity

when inhibitory g proteins couple with GPCR it will....

inhibits channel opening or enzyme activity

after a drug has left the binding there may be

cell functions continue to be affected by G protein

what diseases can alter synthesis,function, regulation of G proteins

alcoholism, diabetes mellitus, heart failure, cancer/tumors

intracellular receptors

located in cell cytoplasm and nucleus

what are intracellular receptors specific to

certain endogenous hormones and hormone like drugs (steroids)

some intracellular receptors pass via

diffusion because they are lipid soluble

agonist

compound that binds and produces response

the biological response via agonists is the same as

endogenous responses

partial agonist

produces response but not 100% even at high doses

Efficacy

max response a drug can produce

potency

measure of dose required to produce a response

therapeutic index

measures safety, higher is safer

therapeutic window

range of plasma concentration of a drug that will elicit desired response in population of patients

antagonists

block effect of agonists or endogenous substances

-no effects

competative antagonists

make agonist look less potent by shifting curve to right

what are competing antagonists competing for

same site on receptor the agonist wants

if an agonist wins

response is produced

if antagonist wins

no response

non competitive antagonist

irreversibly bind to receptor so the agonist cannot be competed off

-only able to resolve is for receptor to die

when an agonist and non-competitive antagonist are combined...

the max response of agaonist is reduced

with a fixed concentration of noncompetative antagonists occur, increasing concentration so the agonst cannot

overcome this blockade

inverse agonists

have opposite effects from those of full agonists

affinity

attraction between drug and receptor

high affinity

binds easily to open receptors even if there isnt a high concentration

moderate/low affinity

require higher drug concentrations in body before receptors are occupied

selectiveness of drugs

only affects 1 type to produce a response

Relativity of drugs

can interact with whats its supposed to and another type thats similar

shape of dose response curve is related to

number of receptors occupied by the drug

low doses

few receptors are bound by drug, effect is small

dose increases

higher drug concentration, more binding, more response

celing effect of drugs is caused by

all available receptors are occupied

receptor desensitization

brief and transient decrease in receptor responsiveness (overstimulated)

-few minutes

receptor downregulation

decrease in number of receptors available

-few days

normal sensitivity returns once

cell replaces receptors eliminated during downregulation

receptor super sensitivity

prolonged decrease in stimulation of receptors present results in incerase in sensitivity

-brief

receptor upregulation

increase in number of receptors to increase function

-prolonged

what are nonreceptor drug mechanisms

drugs that do not bind to cellular components (antiacids, chemo)