Help
Options
Didn't know it?
click below
click below
Knew it?
click below
click below
Don't Know
Remaining cards (0)
Know
retry
shuffle
restart
0:00
Embed Code - If you would like this activity on your web page, copy the script below and paste it into your web page.
Normal Size Small Size show me how
Normal Size Small Size show me how
WEEK 5:
Theories of Drug Action - at receptors:
| Question | Answer |
|---|---|
| receptor | proteins which respond to endogenous messenger by initiating signal |
| what can bind to a receptor (7) | metal ions, AA, lipids, protein hormones, gases, biogenic amines, peptides |
| what biogenic amines can bind to receptors | ACh + adrenaline |
| what gases can bind to receptors | nitric oxide |
| what are the main superfamilies of receptors (4) | ligand gated ion channels, g protein couple receptors, catalytic receptors, nuclear receptors |
| order the four main receptors from fastest to slowest | ligand gated ion channels (ms), g protein couples receptors (sec-min), catalytic receptors (min-hour), nuclear receptors (hr-day) |
| explain how receptors act as molecular switches | switch between inactive (R) and active (R*) states |
| what do inhibitors act on | enzymes, transporters, ion channels |
| what do agonists/antagonists act on | receptors |
| affinity | ability of a drug to bind to receptor |
| how is affinity represented | D+R (unbound) ⇌ DR (inactive) |
| efficacy | once bound, ability of drug to activate receptor by conformational change |
| how is efficacy represented | DR (inactive) ⇌ DR* (active) -> response |
| agonist | binds + activates target (has both affinity + efficacy) |
| antagonist | binds + blocks target (only has affinity) |
| drug binding obeys what law | law of mass action |
| law of mass action | rates of binding are proportional to concentration (so the more drug/ receptor you have the more likely they will bump into each other and bind) |
| forward rate equation | Kon [D][R] |
| Kon | association rate constant |
| reverse rate equation | Koff [D][R] |
| Koff | dissociation rate constant |
| Kd | equilibrium dissociation constant/ concentration of drug needed to occupy 50% receptors |
| Kd equation in terms of drug and receptor | [D][R] / [DR] |
| Kd equation in terms of receptor occupancy | [D](1-α)/ α |
| receptor occupancy represented as what | α |
| α formula | [D]/ [D] +Kd |
| what does D + R ⇌ DR represent in receptor occupancy | D + R (1-α) ⇌ DR (α) |
| receptor occupancy equation | α = [D] /[D] + Kd |
| what is the concentration of D equal to | Kd |
| SAR in words | structure activity relationships |
| SAR | the link between drug structure changes and their effect on target |
| discuss adrenoceptors in salbutamol | 1 micrometre affinity in B2, 10 micrometre affinity in B1 (has a 10 fold B2/B1 selectivity) |
| discuss adrenoceptors in formoterol | 0.01 micrometre affinity in B2, 1 micrometre affinity in B1 (has a 100 fold B2/B1 selectivity) |
| what does Kd help quantify and how can it be measured | numerical measure of affinity measured using Kd eg radioligand binding |
| compare salbutamol and formoterol | formoterol has 100 fold higher affinity for airway adrenoceptors than salbutamol, meaning it is more selective (less it needed) |
| on concentration response curve what does the Y axis represent | response |
| on concentration response curve what does the X axis represent | concentration= (Log (M) |
| Rmax | max response (effect) drug has even if you add more (efficacy) |
| Ec50 | effective concentration of drug that produces 50% maximum response (potency) |
| what do adrenaline and salmeterol look like on a concentration response curve | adrenaline higher than salmeterol (adrenaline has 100% airway, 10^-6M EC50 and salmeterol has 50% airway smooth muscle relaxation, 10^-8M EC50) |
| adrenaline Rmax | 100% |
| adrenaline EC50 | 10^-6 M |
| salmeterol Rmax | 50% |
| salmeterol EC50 | 10^-8 M |
| compare potency in salmeterol and adrenaline | salmeterol is 100 fold more potent than adrenaline |
| compare efficacy in salmeterol and adrenaline | salmeterol has a lower efficacy so is a partial agonist compared to adrenaline for airway relaxation |
| what do values (EC50 + Rmax) in concentration response curves depend on | drug receptor interaction (affinity + efficacy) + properties of functional response- amplification (how cells amplify signal) |
| receptor reserve | maximum response can be made with only a few receptors activated so not all occupied |
| many antagonists are what | competitive and reversible |
| what does it mean if antagonist is reversible | binds non covalently + can dissociate from receptor |
| describe the effect of antagonists on EC50 and Rmax | potency reduced but not Rmax |
| competitive antagonists | bind to same 3D binding site on target receptor as agonist (so share same structural similarities) |
| how does formoterol concentration response curve shift when antagonist (propranolol) is added | shifts right (changes EC50 but same Rmax) |
| where do non competitive antagonists bind | different (allosteric) site from agonist receptor |
| example of non competitive antagonists | memantine |
| how are competitive antagonists surmountable | add more agonist to overcome inhibition |
| how are non competitive anatagonists non surmountable | even if add more agonist it will not overcome inhibition |
| describe the concentration response curve for glutamate (agonist) affected by 1micrmetre of memantine (antagonist) | decrease Rmax from 100% to 50% + reduces efficacy |
| describe how memantine (non competitive antagonist) works againts glutamine (agonist) and NMDA (ligand gated ion channel) | usually glutamate binds to NMDA outside so Na+ and Ca2+ flow inside but memantine binds inside channel pore = blocks flow so even if more glutamate binds receptor no work |
| glutamate | agonist |
| memantine | antagonist |
Created by:
kablooey
Popular Medical sets