B4.005 Prework 2 Cholinoreceptor Activating or Blocking Drugs Flashcards
what neurotransmitter do cholinoceptor activating/inhibiting drugs mimic?
ACh
called cholinomimetic agents
how are chol agonists classified pharmacologically?
by receptor action
muscarinic- G protein coupled receptrs
nicotinic- ion channels (Na and K)
how do direct acting cholinomimetic agents work?
directly bind and activate muscarinic or nicotinic receptors
what is the primary action of indirect acting cholinomimetic agents?
inhibit ACh esterase (block hydrolysis of ACh)
increase endogenous ACh concentration in synapse
excess ACh increases response
what are 3 properties of modified choline esters?
susceptibility to cholinesterase
muscarinic action
nicotinic action
describe the properties of ACh chloride
very susceptible to cholinesterase
high muscarinic and nicotinic action
describe the properties of methacholine chloride
less susceptible to cholinesterase
very his muscarinic action
no nicotinic action
describe the properties of carbachol chloride
negligible susceptibility to cholinesterase
intermediate muscarinic and nictotinic action (musc
describe the properties of bethanechol chloride
negligible susceptibility to cholinesterase
intermediate muscarinic action
no nicotinic action
what are the 3 chemical groups of cholinesterase inhibitors (indirect acting cholinomimetics)
- simple alcohols
- carbamic acid esters
- organic derivatives or phosphoric acid (organophosphates)
what drugs are in the simple alcohols group and what are the properties of each
edrophonium
-rapidly degraded, short activity
what drugs are in the carbamic acid esters group and what are the properties of each
- all are more common and last longer
1. neostigmine - quaternary ion, acts on periphery
2. physostigmine- tertiary amine, acts in CNS, prototypic drug in class
what drugs are in the organic derivatives of phosphoric acid group and what are the properties of each
- all provide long lasting covalent chelation which can only be overcome by production of new enzymes
1. soman
2. sarin
3. malathion
effects of cholinergic transmission (muscarinic agonists) on the cardiovascular system
direct effect = slows HR (rate of contraction)
no innervation of peripheral vasculature, PNS limited to effects on myocardium
effects of cholinergic transmission (muscarinic agonists) on other organ systems
contracts smooth muscle and stimulates secretions in:
- respiratory system
- GI tract
- GU tract
- secretory glands (thermoregulatory sweat glands only)
major site of action of nicotinic agonists
autonomic ganglia simultaneous SNS and PNS discharge predominant tone predicts effects (muscarinic or adrenergic) -SNS in vasculature -PNS in most other tissues
what are the two subgroups of cholinoceptor blocking drugs?
muscarinic antagonists
nictotinic antagonists
subgroups of nicotinic antagonists
ganglion blockers
neuromuscular junction blockers (paralytics) (not in this block)
subgroups of antimuscarinic drugs
tertiary compounds used for effects in eye or CNS
- atropine, scopolamine
quaternary amines selectively produce peripheral effects
-ipratropium
prototypic antimuscarinic drug
atropine
causes reversible (competitive) blockade
not selective between muscarinic receptor subtypes
causes reverse of parasympathetic activity including increased HR and blockade of secretions of peripheral organs
what are examples of nicotinic receptor antagonists?
hexamethonium
trimethaphan
mecamylamine
why are nicotinic receptor antagonists often not used?
non selectivity because located on both PNS and SNS autonomic ganglia
this produces a limiting side effect profile bc there is no ability to mount a sympathetic reflex (orthostatic hypotension)
first nicotinic antagonist
tetraethylammonium (TEA)
short duration of action
developed for management of hypertension (effective)
