Lecture 7: Cholinergic Agonists

Question 1

in neuronal nicotinic receptors, ____ (NT) is the key link to propagate the signal from the pre-ganglionic neuron to the post ganglionic neuron

Answer 1

Ach

Question 2

the adrenal gland expresses ____ receptors that receive input from activated sympathetic nervous system pathways

Answer 2

NN

Question 3

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

Answer 3

true

Question 4

nicotinic ach receptors in the autonomic ganglia trigger___

Answer 4

postganglionic neuron to transmit signal to target tissue

Question 5

nicotinic ach receptors in the adrenal gland trigger ___

Answer 5

secretion of catecholamines into circulation

Question 6

in the CNS, ach is involved in many complex processes such as : ___, ___, ___, ___ and ____ etc

Answer 6

sleep, wakefulness, learning, memory, neuroplasticity

Question 7

one of the first discovered modulators of ach was ___

Answer 7

nicotine

Question 8

nicotine is a ____ of the NN and NM receptors

Answer 8

full agonist

Question 9

nicotine acts by binding to the receptor and is therefore categorized as a ____

Answer 9

direct acting agonist

Question 10

the primary effects of nicotine happen in the ___, however nicotine in the ___can activate NM receptors and cause muscle twitches

Answer 10

CNS; periphery

Question 11

___ is the primary active compound in tobacco products

Answer 11

nicotine

Question 12

varenicline (champix) is a ___ of the NN receptor and competes for binding with nicotine

Answer 12

partial agonist

Question 13

partial agonists bind to what part of the receptor?

Answer 13

binding site

Question 14

t/f partial agonists have a smaller Emax than full agaonsts

Answer 14

true

Question 15

which has a higher binding affinity for the nachr, nicotine or varenicline?

Answer 15

varenicline

Question 16

directly binding nicotine agonists cause _____ effects, effects that mimic Ach when no Ach needs to be present

Answer 16

cholinomimetic

Question 17

Ache inhibitors are called ___ because their actions increase levels of Ach (the agonist)

Answer 17

indirect agonists

Question 18

give 2 examples of drugs used as Ache inhibitors and what condition they treat

Answer 18

donepezil and rivastigmine; treat Alzheimer’s disease

Question 19

in patients with Alzheimer’s disease, administering a ____ improves cognitive function by allowing Ach to be present in the synapse longer, improving signalling

Answer 19

reversible ACHe inhibitor

Question 20

what is the mechanism of action and duration of action of Donepezil?

Answer 20

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

Question 21

what is the mechanism of action and duration of action for rivastigmine?

Answer 21

interacts with Ache but is not cleaved, so it dissociates slowly, have a longer effect

Question 22

slowly dissociating agents, such as rivastigmine, are often called ____ because of their prolonged interaction with Ache and longer duration

Answer 22

pseudo irreversible

Question 23

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

Answer 23

muscle paralysis and respiratory failure

Question 24

if a patient has come in contact with an irreversible Ache inhibitor in insecticide or nerve gas, what is the treatment?

Answer 24

cholinergic receptor antagonists and mechanical ventilation until Ache activity can be. restored

Question 25

___ is the primary receptor in the ANS and its effects are modulated by binding to ____ receptors

Answer 25

Ach; Ach muscarinic receptors

Question 26

all muscarinic receptors belong to what class of receptors?

Answer 26

GPCR

Question 27

M3 receptors are exposed in the ___

Answer 27

lungs

Question 28

stimulation of M3 receptors in the lungs by Ach activates ___, which makes ___ and ____

Answer 28

phosolipase C; DAG and IP3

Question 29

what is phospholipase C?

Answer 29

enzyme that cleaves membrane phospholipids

Question 30

the overall downstream effect of activating the M3 receptor in the lungs in the increase in intracellular ____ (ion) which causes contraction of smooth muscle

Answer 30

Ca

Question 31

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

Answer 31

true

Question 32

M2 receptors are found in the ___

Answer 32

heart

Question 33

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

Answer 33

CAMP; Ca

Question 34

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

Answer 34

K

Question 35

drugs that stimulate muscarinic receptors are called ____ or ____ because they act like Ach

Answer 35

parasympatomimetics or cholinomimetics

Question 36

what is pilocarpine? what is its use?

Answer 36

non-selective muscarinic agonist used to increase saliva for treatment of xerostomia and historically used as an IOP lowering agent in treatment of glaucoma

Question 37

why is pilocarpine used topically?

Answer 37

because the systemic effects would be extensive, given that it would activate all muscarine receptor types

Question 38

in the eye, muscarinic agonists cause pupil___ and ___ in IOP

Answer 38

constriction, decrease

Question 39

the effects of muscarinic agonists when used systemically are grouped into an acronym. What is the acronym and what does each letter stand for?

Answer 39

SLUDGE:

salivation, lacrimation, urination, diarrhea, Gi cramps, emesis (nausea and vomiting)