how do drugs work Flashcards
what is the plasma mebrane
a selectively permeable barrier between the extracellular environment and the cytosol
what are the components of the plasma membrane
Na+, K+, Ca2+, Cl-, Glucose
is there a similar amount of calcium inside and outside the cell
no
is there more calcium inside or outside the cell
outside
how do drugs work
once they arrive at the proper site of action, they bind to receptors
where are receptors usually located
on the outer membrane of cells
what does the binding of drugs to receptor do
it can sometimes trigger activation of enzymes located within the cell
what type of proteins are receptors usually
integral membrane proteins at the plasma membrane, can also be found inside the cell
what do receptors do
recognise and bind to specific chemicals which invokes response
can receptor numbers change
yes they can be increased (up-regulation) or decreased (down-regulation)
why would up regulation or down-regulation occur
in response to a chronically low or high concentration of the agonist to optimise sensitivity
what two properties do agonists have
- affinity - strength of binding to receptor
- efficacy - intrinsic activity
what does efficacy do
induces a conformational change in the receptor and activation of a response
what property does an antagonist have
has affinity
what does an antagonist do
blocks the receptor
why can’t antagonists activate a response
they don’t have efficacy
examples of antagonists
anti-histamines, beta-blockers
when does down-regulation occur
in response to chronically high concentration of ligand.
what does down-regulation do
decreases the sensitivity of the cell response to frequent or intense stimulation
when does up regulation happen
in response to very low levels of a ligand
what does up regulation do
increase sensitivity
what underlies disease processes
aberrant cellular signalling
does the intercellular signal chemical (first messenger) enter the cell
no
what does binding of the SIGNAL chemical to the receptor do
initiate a series of chemical changes (activation of intracellular second messenger) in the cell
what does signal transduction enable
amplification
steps of signal transduction
- direct opening of ion channels
- direct activation of an enzyme
- indirect activation/inactivation of enzyme, indirect opening/closing of ion channel
involves a g-protein - intracellular second messengers involved include: Cyclic nucleotides (eg cAMP)
Inositol triphosphate and diacylglycerol and Ca2+
what are 3 G-protein component
- seven transmembrane receptor where the ligand binds
- G-protein (‘switch’ coupling receptor to effector enzyme)
- effector enzyme
what does GTP bound mean
the G protein is on
What does GDP bound mean
the G protein is off
how does a G protein switch itself on and off
the protein itself is an enzyme which converts GTP to GDP and thereby switches itself on and off
what is the first signal following fertilisation
calcium signalling
is Ca2+ ever produced or destroyed
no it is moved between compartments
what does the effects of Ca2+ depend on
concentration
what are the actions of calcium
- activation of specific protein kinases, ion channels
- regulation of activity of many enzymes
what can Ca2+ channel blockers be used to do
modulate muscle contractions
what do Ca2+ release channels do
release Ca2+ into the cytosol in response to an increase in intracellular IP3 or Ca2+
what is the functional effect of Ca2+ release channels
contraction, proliferation
what are targets for histamine receptors
parietal cells - decreased gastric acid secretion
what happens when opioid receptors are targeted
decreased peristalsis, increases tone of anal sphincter (partly via Ca2+ channel blockade)
example of drug that targets histamine receptors
ranitidine
examples of drugs that targets opioid receptors
loperamide
what can cause drug side effects (receptor based)
when enzymes bind to receptors found in more than one place in the body
why is there low levels of calcium intracellularly
because calcium is a trigger for many functions
what do you need to consider when designing drugs
absorption, distribution, metabolism, excretion (ADME)
how do receptors work as second messengers
chemicals enter cells and bind to the receptors which changes the confirmation of that receptor
what is the GI tract predominantly made up
smooth muscle
how are calcium ions kept low
by storing them in many different areas
what is a key factor in triggering relaxation in smooth muscle contraction
nitric oxide
