drug receptor interactions Flashcards
which form of the drug is more water soluble?
dissociated unprotonated form
which form of the drug is more lipid soluble?
undissociated protonated form
how do you calculate volume of distribution?
amount of drug in the body divided by the plasma concentration of the drug
what does Vd show?
how well a drug is distributed around the body
what does a high Vd indicate?
small concentration in the blood. more is in the tissue. drug is more lipid soluble
what does a low Vd show?
high concentration in the blood. more is in the plasma. more water soluble.
what is drug distribution?
process by which drug reversibly leaves the blood stream and enters the extra cellular fluid
what are the major body compartments?
water
fat
solid
what is the water compartment made up of?
ICF
ECF (plasma and ISF)
what proportion of the body weight does the water compartment make up?
60%
what does the fat compartment consist of?
brain
adipose tissue
cell membranes
what does the solid compartment consist of?
bone
muscle
what is albumin?
a plasma protein that drugs can bind to
how does albumin help in the transport of drugs?
drugs bind to albumin once they’re released from the GI system and they’re carried in an inert form. protects drug from body’s metabolism
in what form can drugs bind to receptor?
in the free form
not bound to proteins
what determines efficacy?
free drug concentration around target tissue
when is a drug considered active?
when its free
when is a drug considered inactive?
when it’s bound to a plasma protein
what conditions affect the level of plasma proteins?
liver disease
what is warfarin?
anticoagulant
what is phenytoin?
anti-seizure medication
what methods can a drug use to get into the intracellular fluid?
bulk flow
passive diffusion
active transport
what does the effect of a free drug depend on?
capillary structure
chemical nature of the drug
blood flow through the tissue
presence of non-active binding sites
explain how capillary structure affects the movement of free drugs?
fenestrated capillaries means there are gaps in the BM so drugs can get through
continuous capillaries - thick BM so drug cant get through
intermittent capillaries = certain amount of movement
how do hydrophobic drugs get to the blood?
across biological membranes
how do hydrophillic drugs get to the blood?
through junctions of endothelial cells in capillary eds
how do small drugs get out of a blood vessel?
free diffusion
why cant polar drugs enter the CNS?
unable to enter the endothelial cells
what happens in ion channels?
ligand binds and causes conformational change - ion channel opens. ions move down a concentration gradient
what ions move through nicotinic receptors and what effect does this have?
sodium
neuronal excitation
how does glutamate work and what does it do?
binds to calcium channels to cause neuronal excitation by causes a depolarisation
how does GABA work and what does it do?
binds to Cl- channels and causes neuronal inhibition by hyperpolarising the cell
explain how receptor tyrosine kinases work
ligand binds outside the cell causes inactive monomers to become phosphorylated dimers form the conversion of ATP to ADP activates receptor activates protein causes response
explain how nuclear receptors work
lipophillic hormone crosses the cell membrane
dimerises and crosses nuclear membrane
binds to DNA
activates transcription
mRNA transcribed and becomes protein and changes the cell function
list the receptors from fastest to slowest and state how long they take
Ligand gated - ms
GPCR - seconds
RTK - mins/hours
nuclear receptors - hours
what is tachyphylaxis?
acute and sudden decrease in response to a drug after its administration
describe the mechanism for tachyphylaxis
1 - receptor desensitisation
2 - receptor internalisation
3 - physiological adaptation - side effects decline
4 - depletion of mediators e.g. signalling molecules
5 - increased metabolic degradation
what drugs commonly cause tachyphylaxis?
drugs that affect the CNS
give an example of tachyphylaxis
salbutamol
