Cholinergics

Question 1

What are the direct-acting Ach agonists?

Answer 1

• Ach (not useful as a drug)
• carbachol
• bethanechol
• nicotine
• varenicline

Question 2

What are the indirect-acting Ach agonists?

Answer 2

• neostigmine
• physostigmine
• doenpezil
• sarin (no therapeutic value)

Question 3

What chemicals and enzyme synthesize Ach in cholinergic nerve terminals?

Answer 3

choline + acetyl-CoA

choline acetyltransferase (ChAT)

Question 4

What enzyme rapidly breaks Ach down in the synaptic cleft?

Answer 4

Acetylcholinesterase

Question 5

What are the two major types of cholinergic receptors?

Answer 5

nicotinic

muscarinic

Question 6

What kind of Ach receptor are all G-protein-coupled metabotropic receptors?

Answer 6

Muscarinic

Question 7

What are the two types of muscarinic receptors and what do they do?

Answer 7

1. Evens (M2 and M4) - inhibition of cAMP production (stimulates smooth muscle) or activation of voltage-gated K+ channels (inhibits smooth muscle)
2. M1, M3, and M5 - activate IP3, diacylglycerol cascase to increase intracellular Ca2+ (stimulates smooth muscle)

Question 8

What specific muscle do the M2 and M4 cAMP inhibiting receptors act on?

Answer 8

contracts GI muscle

Question 9

What specific muscle do the M2 and M4 K+ GTP receptors act on?

Answer 9

SA node cells (hyperpolarizes and slows HR)

Question 10

What specific muscle does the M1, M3 and M5 receptors act on?

Answer 10

Ciliary muscle - increased Ca2+ contracts

Question 11

Skeletal muscle postsynaptic receptors are what type?

Answer 11

Nicotinic

Question 12

Postsynaptic autonomic ganglia and adrenal medulla receptors are what type?

Answer 12

nictonic

Question 13

Presynaptic receptors in the CNS are what type?

Answer 13

mostly nicotinic

Question 14

Postsynaptic receptors on parasympathetic end organs and sweat glands are what type?

Answer 14

muscarinic

Question 15

What type of Ach receptor is on the postsynaptic receptors of the CNS?

Answer 15

Mostly muscarinic

Question 16

What is an important effect of direct acting muscarinic agents on small blood vessels?

Answer 16

causes release of NO which dilates vessels and decreases BP

Question 17

What are the direct-acting muscarinic agonists?

Answer 17

• carbachol
• bethanechol

Question 18

what type of drug is carbachol?

Answer 18

direct-acting muscarnic agonist

*also a nicotinic agonist at high doses

Question 19

what type of drug is bethanechol?

Answer 19

direct-acting muscarinic agonist

Question 20

Which muscarnic agonists are not broken down by Achesterase?

Answer 20

carbachol and bethanechol

Question 21

What are the indications for the direct-acting muscarinic agonists?

Answer 21

• paralytic ileus (post-operative)
• urinary retention
• carbachol eyedrops in wide (open) angle glaucoma

Question 22

What are the adverse effects of the direct-acting muscarinic agonists?

Answer 22

• hypotension
• diarrhea
• vomiting
• bronchial constriction
• sweating

Question 23

Who is contraindicated from receiving direct acting muscarinic agonists?

Answer 23

• asthma
• heart conditions
• peptic ulcer
• GI or urinary obstruction
• hyperthyroidism (a fib)

Question 24

What are the effects of the muscarinic antagonists?

Answer 24

• tachycardia
• blunted reflexes
• mydriasis
• inability to sweat
• constipation
• urinary retention
• GI antispasmodic
• possible hallucinations

Question 25

What kind of drug is atropine and what does it do?

Answer 25

muscarinic antagonist * preanesthetic medication (reduce secretions, relax bronchi) * antispasmodic * antidiarrheal \*crosses the BBB

Question 26

What kind of drug is ipratropium and what does it do?

Answer 26

muscarinic antagonist * bronchodilation in COPD \*stays in lungs, limited Vd

Question 27

What kind of receptors are nicotinic?

Answer 27

excitatory ligand gated ion channels permeable to Na+ and K+ \*Nicotinic neuronal also permable to Ca2+

Question 28

What is the role of postsynaptic nicotinic receptors?

Answer 28

produce depolarization and excitation of neurons and skeletal muscle

Question 29

Where does Ach bind to nicotinic receptors?

Answer 29

The alpha subunit

Question 30

What is the function of presynaptic nicotinic receptors?

Answer 30

enhance release of many other neurotransmitters in the CNS

Question 31

vecuronium is highly specific for which receptor subtype?

Answer 31

N_M | (Muscular)

Question 32

What drug is a potent nicotinic receptor agonist?

Answer 32

nicotine \*uncharged and readily passes into the BBB

Question 33

What does nicotine do in the brain?

Answer 33

Binds to presynaptic nicotinic Ach receptors, which causes Ca2+ to enter and excitatory NTs to be released

Question 34

How does nictoine become addictive?

Answer 34

increases the release of dopamine in the midbrain reward pathway, particularly in the nucleus accumbens leads to pleasurable feeling \*same circuit as compulsive gambling

Question 35

What is the midbrain reward circuit for nicotine?

Answer 35

alpha 7 Ach presynaptic receptors on glutamate neurons--\> ventral tegmental dopaminergic neurons --\>dopmaine nucleus accumbens --\>prefrontal cortex _Note that nicotine also binds to alpha4beta2 Ach presynaptic receptors in the ventral tegmental and nucleus accumbens to enhance dopamine release_

Question 36

What are withdrawal symptoms from nicotine?

Answer 36

headache irritability inability to concentrate weight gain

Question 37

What receptors in the brain are double in amount in smokers, leading to tolerance?

Answer 37

alpha4 beta 2 nicotinic

Question 38

What are some CNS effects of nicotine in naive users?

Answer 38

nausea and emesis excitation, increased arousal increased attention

Question 39

What are some CNS effects of nicotine in experienced users?

Answer 39

excitation, increased arousal increased attention relaxation addiction craving

Question 40

What are the peripheral effects of nicotine?

Answer 40

increased BP increased HR stimulation of all autonomic ganglia and adrenal medulla GI: increased tone and activity

Question 41

What is a clinical use of nicotine?

Answer 41

smoking cessation (nicorette)

Question 42

Is vaping a good alternative to cigarette smoking?

Answer 42

Yes and No fewer carcinogens in vapor we don't know the safety of flavors/propylene glycol/glycerin in vaping products

Question 43

What are some of the smoking cessation drugs?

Answer 43

nicotine replacement buproprion (antidepressant) varenicline (chantix)

Question 44

What is the mechanism of action of varenicline?

Answer 44

partial agonist at alpha4 beta2 nicotinic receptors binds with 30-60% efficacy, competes with nicotine for access to these receptors BLACK BOX: for neuropsychiatric symptoms, including depression, suicidal ideation