SCRIPT: pharmacodynamics Flashcards
Define.
a) agonist
b) antagonist
- competitive vs. non-competitive
- effect of increasing agonist concentrations on the efficacy of competitive vs. not competitive antagonists
c) partial vs. full agonist
d) allosteric modulator
a) Drug/chemical that binds to a receptor to increase the activity of its target
b) Drug/chemical that opposes the action of an agonist
- therefore, it only works if there is an agonist
- Beta-blockers oppose endogenous adrenaline/ NAd
- Naloxone, however, will usually only exert effect if there is exogenous opiates (as endogenous opiates are at low levels)
- Competitive = competes for same receptor (so blocks agonist from receptor site)
- Non-competitive = binds to allosteric site to alter the affinity/efficacy of agonist
- Increasing concentrations of an agonist will reduce the effects of a competitive antagonist (as they compete for the same binding sites) but will have not affect the effects of a non-competitive antagonist
c) Partial agonists bind to receptor but only have partial efficacy compared with a full agonist
d) Bind to proteins at sites other that the binding site for the principal agonist, that can either:
- Alter the affinity of the binding site for its agonists, or
- Change the efficacy of the response when the agonist binds
- The effects may be positive (to increase the potency of the agonists) or negative (to decrease the potency of an agonist)
Define, and explain the differences between affinity, efficacy and potency.
Affinity.
- how well drug binds to its receptor
- drugs bind to receptors at a rate proportional to the drug concentration
- they unbind at a rate that depends only on the chemical properties of the drug-receptor complex
Efficacy.
- how well an agonist achieves a response
- different drugs acting at the same receptor can have very different clinical responses (eg. fentanyl and morphine doses differ by factor of 100)
Potency.
- potency often described by the concentration (or dose) that is able to elicit 50% of the maximal response (i.e. the individual effective concentration, EC50 or individual effective dose, ED50*)
*Note: this is different to the LD50 - the dose that is lethal in 50% of people
Define up-regulation and down-regulation of receptors and using examples, explain how this can affect the response to drugs or alter physiological behavior.
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Explain, using key examples, how drugs can act on different types of chemically sensitive sites, including: G-protein coupled receptors, ion channels, nuclear receptors, carrier molecules, and enzymes.
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Opiate overdose.
a) Treatment
b) Why should patients not be allowed to leave hospital too soon?
a) Naloxone - opioid antagonist
b) - Naloxone has a short half life
- If they leave early, nalaxone effects will wear off and their may be a second opioid effect causing sedation and fatal overdose
Effects of repeated doses over time.
a) Desensitisation
b) Tachyphylaxis
c) Tolerance
d) Addiction
e) Withdrawal
a) Reduced receptor affinity or number after repeat doses
b) Rapid decline in the response to repeated doses of an agonist (rapid vs. tolerance)
- eg. hydralazine, dobutamine, metaraminol, adrenaline, salbutamol, nicotine
c) Increasing dose needed over time to achieve same effect
d)
e) Withdrawal of drug leads to withdrawal symptoms
Ion channels.
a) 2 basic types
b) Anaesthetic agents and antiepileptics commonly act on. what channels?
c) Antiarrhythmics - Vaughan-Williams classification
a) - Voltage-gated: K+/ Na+/ Ca2+
- Ligand-gated: eg. ACh-receptor
b) Voltage-gated sodium (Na+) channels
c) NaBKiC
- I - Na+ channels
- II - beta-blockers
- III - K+ channels
- IV - CCBs
Drug interaction with enzymes.
a) Competitive vs. non-competitive
b) Reversible vs. irreversible
a) - Competitive - binds to the binding site of substrate (enzyme cannot bind substrate)
- Non-competitive - binds to allosteric site (enzyme still able to bind to substrate)
b) - Reversible
- Irreversible - causes permanent loss of function until enzyme synthesised again
