Drug - Receptor Interactions Flashcards
what are the major compartments for drug distribution?
what affects where a drug is distributed to?
- water (60%)
- Fat (20%; brain, adipose tissue, cell membranes)
- Solid (20% :bone, muscle)
Where a drug is distributed is affected by chemical compound properties
what is volume of distribution?
equation?
what does it show?
volume of distribution: how much or little the drug goes to plasma (fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma). relationship between amount of drug given (known) and conc in plasma (tbd)
allows you know the concentration and location of the drug in the body
VD is a know constant for each drug
work out VD of patient who has 50 mg of dose of drug A and has a plasma conc of 0.1 mg/L
what does answer tell us?
VD = 50 (mg) / 0.1 (mg/L) = 500L
(obviously way more than volume of human ~ 70L)
therefore drug A is extensively distributed to other parts of body
where do drugs with large / small VD distributed to?
Large VD: distributed to tissues (fat / bones)
Small VD: distributed to blood
why may drugs stay in the blood as opposed to going to tissues? (2)
- molecule is too large to leave
- molecule binds preferably to v (albumin) / less to tissue proteins
what influenecs the amount of drug available to bind to target?
plasma proteins
- albumin
- lots more
what is the relationship between drugs working and proteins in the blood?
- drugs are only active when unbound to proteins: unbound drugs are excreted quickly
- drug bound to protein: pharmacologically inactive. non-diffusable, non-metabolised and non excreted
what can happen to other drugs in body if you stop / start a drug that binds to proteins?
explain using warfarin (anticoagulant) and phenytoin (anti seizure) drugs
changes the level of the other protein bound drugs
e.g. warfarin (anticoagulant) and phenytoin (anti-seizure):
- both normally bind to albumin (low VD)
- for surgery: stop warfarin = more sites on albumin for phenytoin to bind
- patient may have seizure
what also can effect the distribution of drugs? (for both a) bound and b) unbound drugs)
bound:
- relationship with other drugs
unbound:
- capillary structure (blood brain barrier)
- chemical nature of drug_
- blood flow through tissues (hydrophobic drugs0
- presences of non active binding drugs
- are drugs usually aimed at being even distributed across body?
where are each normally not found / found?
a) large drugs
b) polar drugs
c) small apolar liphophilic drugs?
unusual for even distribution
- e.g. large drugs confined to cicrulation (low VD)
- polar drugs excluded by cell membranes
- small, apolar, liphophilic drugs accumulate in fat cells
what effect will plasma protein binding of a drug have on its excretion time?
excretion time will increase
how do drugs function? (basic)
what are the 4 main types of receptor of cell signals?
drugs exert chemical influence on components of the cell: must bind to a protein and alter its function
cell receptor types:
- ligand gated ion channel_
- g-protein coupled receptors
- kinase-linked receptors (like tyrosine)
- nuclear receptors
name 4 clinically important receptors for each main type of receptors
- ligand gated ion channel: GABAA receptor
- g-protein coupled receptors: B-adrenoreceptor
- kinase-linked receptors (like tyrosine): VEGF receptor
- nuclear receptors: Oestrogen receptor
how do ligand gated channels often work?
what is a membrane potential?
ligand (often NT) binds, opens up receptor for ions to pass through
membrane potential:
inside cell:
- High K+ and protein (-ve charge)
- low Ca2+, Na+
outside cell:
- High Ca2+, Na+
- low K+
when ion channels closed: membrane potential = -70mV
when ion channels open: membrane potential = - 40mV (+ charge and conc gradient causes depolarisation)
how does g-coupled protein receptor work
- dissociation of g-protein from g-protein coupled receptor
- activation of effector molecule
- effector molecule causes downstream change
how are signal pathways regulated to stop excessive activation?
- tachyphylaxis: acute tolerance from rapid and repeated admin of drugs in short intervals (the image)
- tolerance: chronic longer term admin can reduce drug effect (e.g. alchohol)
what are the mechanisms for tolerance or tachyphylaxis
- receptor desensitized or loss of receptors
- receptor internalisation (degraded in lysosome)
- increased metaboloic degradation of drug
