Pharmacology Flashcards
T/F: Neostigmine is an antagonist of rocuronium
False
Neostigmine does not compete with rocuronium for the muscle end-plate receptor site.
What is the MOA of neostigmine?
Neostigmine inhibits Acetylcholinesterase, which allows acetylcholine to compete effectively with rocuronium (and other non-depolarizing NMBDs) for the receptor, leading to a recovery of muscle tone.
Therefore, it exhibits at least a partial form of indirect antagonism.
What is the MOA of Sugammadex?
Sugammadex is a selective relaxant binding agent (SRBA). It encapsulates the muscle-relaxant molecule, rendering it inactive, and the complex formed is then eliminated.
This is a form of chemical antagonism because no direct receptor action is evident.
Define MAC
the dose at which 50% of patients do not move on surgical stimulation
ED50
median effective dose: the dose at which 50% of a population responds as desired
What is the difference between competitive and noncompetitive antagonists?
Competitive antagonists: have weak affinity for the same receptor protein (i.e. atropine, esmolol); they may be displaced by an agonist.
Noncompetitive antagonists: have a strong affinity for the receptor protein (i.e. phenoxybenzamine, aspirin) usually via covalent bonds, and cannot be displaced by the agonist.A
Agonist-antagonist drugs
have receptor protein affinity and intrinsic activity, but often only a fraction of the potency of the pure agonist.
Define an “Addition” drug interaction and provide an example.
combined effect of two drugs (acting via the same mechanism) is equal to that expected by simple addition of their individual actions.
ex: midazolam plus diazepam (1 + 1 = 2)
infraadditive
the combined effect of both drugs is less than the sum of the effects of either drug alone.
ex: N2O and sevo
synergism
the combined effect of two drugs is GREATER than the algebraic sum of their individual effects
1 + 1 = 3
ex: midazolam plus propofol
potentiation
the enhancement of the action of one drug by a second drug that has no detectable action of its own
1 + 0 = 3
ex: penicillin plus probenecid
antagonism
the action of one drug opposes the action of another
1 + 1 = 0
ex: fentanyl plus naloxone
physiologic antagonism
both drugs bind to specific unrelated receptor proteins, initiate a protein conformational shift, and elicit individual tissue responses; however, the responses generate opposing forces
ex: isoproterenol-induced vasodilation and norepinephrine-induced vasoconstriction (the net effect on BP is less than it would be with either drug used alone)
chemical antagonism
a drug’s action is blocked without receptor activity
ex: sugammadex
ex: protamine (forms an ionic bond with heparin)
down-regulation
AKA desensitization
the effect that follows continued or subsequent exposure to the same drug concentration is diminished. tolerance occurs, and increasing doses are required to achieve the same effect.
up-regulation
chronic administration of an ANTAGONIST causes the number and sensitivity of the receptors to increase as a response to chronic blockade. again, tolerance occurs, and higher doses of the antagonist are required to counteract the increasing receptor number.
biosphere
the site of intervention, or the protein drug receptor, which is the primary regulator of the therapeutic response.
potency
the most potent drug of a series requires the lowest dose.
efficacy
a drug’s ability to produce the desired response expected by stimulation of a given receptor population; the maximum possible effect that can be achieved with the drug.
agonist
substance that binds to a specific receptor and triggers a response in the cell. It mimics the action of an endogenous ligand (such as a hormone or neurotransmitter) that binds to the same receptor
full agonist
in adequate concentrations of a substance, it can cause maximal activation of all receptors
antagonists have ____ but not ____
affinity; efficacy
antagonists do not activate the receptor to produce a physiologic action; by occupying the receptor, it may block an endogenous chemical response, thereby producing a physiologic consequence.
efficacy
a drug’s ability to produce the desired response expected by stimulation of a given receptor population
inverse agonist
drug/endogenous chemical that binds to a receptor, resulting in the opposite action of an agonist
tachyphylaxis
acute tolerance
the rapid appearance of a progressive disease in response to a given dose of a drug after continuous or repetitive administration
tolerance
individual variation can result in a situation in which an increasing concentration of drug is required to produce a given response
