Lecture 7: Cholinergic Agonists Flashcards
in neuronal nicotinic receptors, ____ (NT) is the key link to propagate the signal from the pre-ganglionic neuron to the post ganglionic neuron
Ach
the adrenal gland expresses ____ receptors that receive input from activated sympathetic nervous system pathways
NN
t/f due to widespread of nicotinic ach receptors and importance of ach as a NT, it can be challenging to specifically modulate these processes pharmacologically
true
nicotinic ach receptors in the autonomic ganglia trigger___
postganglionic neuron to transmit signal to target tissue
nicotinic ach receptors in the adrenal gland trigger ___
secretion of catecholamines into circulation
in the CNS, ach is involved in many complex processes such as : ___, ___, ___, ___ and ____ etc
sleep, wakefulness, learning, memory, neuroplasticity
one of the first discovered modulators of ach was ___
nicotine
nicotine is a ____ of the NN and NM receptors
full agonist
nicotine acts by binding to the receptor and is therefore categorized as a ____
direct acting agonist
the primary effects of nicotine happen in the ___, however nicotine in the ___can activate NM receptors and cause muscle twitches
CNS; periphery
___ is the primary active compound in tobacco products
nicotine
varenicline (champix) is a ___ of the NN receptor and competes for binding with nicotine
partial agonist
partial agonists bind to what part of the receptor?
binding site
t/f partial agonists have a smaller Emax than full agaonsts
true
which has a higher binding affinity for the nachr, nicotine or varenicline?
varenicline
directly binding nicotine agonists cause _____ effects, effects that mimic Ach when no Ach needs to be present
cholinomimetic
Ache inhibitors are called ___ because their actions increase levels of Ach (the agonist)
indirect agonists
give 2 examples of drugs used as Ache inhibitors and what condition they treat
donepezil and rivastigmine; treat Alzheimer’s disease
in patients with Alzheimer’s disease, administering a ____ improves cognitive function by allowing Ach to be present in the synapse longer, improving signalling
reversible ACHe inhibitor
what is the mechanism of action and duration of action of Donepezil?
it binds to the receptors on Ache and is metabolized the same way Ach would be; this is very easy so the time is short
what is the mechanism of action and duration of action for rivastigmine?
interacts with Ache but is not cleaved, so it dissociates slowly, have a longer effect
slowly dissociating agents, such as rivastigmine, are often called ____ because of their prolonged interaction with Ache and longer duration
pseudo irreversible
irreversible inhibition of cholinesterase’s by drugs that bind covalently to the enzymes cause ___ and ___ because the Ach is not broken down and persistently activates receptors
muscle paralysis and respiratory failure
if a patient has come in contact with an irreversible Ache inhibitor in insecticide or nerve gas, what is the treatment?
cholinergic receptor antagonists and mechanical ventilation until Ache activity can be. restored
___ is the primary receptor in the ANS and its effects are modulated by binding to ____ receptors
Ach; Ach muscarinic receptors
all muscarinic receptors belong to what class of receptors?
GPCR
M3 receptors are exposed in the ___
lungs
stimulation of M3 receptors in the lungs by Ach activates ___, which makes ___ and ____
phosolipase C; DAG and IP3
what is phospholipase C?
enzyme that cleaves membrane phospholipids
the overall downstream effect of activating the M3 receptor in the lungs in the increase in intracellular ____ (ion) which causes contraction of smooth muscle
Ca
t/f in most people, bronchoconstriction related to normal parasympathetic responses is not symptomatic, but in people with asthma, their airways are hyperresponive to cholinergic stimulation and this may result in shortness of breath
true
M2 receptors are found in the ___
heart
the primary effect of stimulating M2 receptors in the heart is an decrease in ____ production in cardiac myocytes which will decrease entry of ___ions and therefore decrease contractility
CAMP; Ca
in the activation of M2 receptors in the heart, the Gbg subunit of the Gi complex acts as positive modulator of ___ channels, resulting in hyper polarization and further inhibition
K
drugs that stimulate muscarinic receptors are called ____ or ____ because they act like Ach
parasympatomimetics or cholinomimetics
what is pilocarpine? what is its use?
non-selective muscarinic agonist used to increase saliva for treatment of xerostomia and historically used as an IOP lowering agent in treatment of glaucoma
why is pilocarpine used topically?
because the systemic effects would be extensive, given that it would activate all muscarine receptor types
in the eye, muscarinic agonists cause pupil___ and ___ in IOP
constriction, decrease
the effects of muscarinic agonists when used systemically are grouped into an acronym. What is the acronym and what does each letter stand for?
SLUDGE:
salivation, lacrimation, urination, diarrhea, Gi cramps, emesis (nausea and vomiting)
