7

Question 1

Cholinergic Receptors Come in Two Types:

Answer 1

Nicotinic and Muscarinic

Question 2

Nicotinic AcCHRs

Answer 2

1. Bind nicotine
2. Ligand activated ion channel (local depolarization at post synaptic membrane due to Na+ influx)
3. Receptors contain 5 subunits and bind two molecules of agonist
4. Skeletal muscle nACCh R molecular biology fairly simple.
5. CNS ACCh R molecular biology complicated.

Question 3

Muscarinic AcCHRs

Answer 3

1. Bind muscarine
2. G protein coupled receptors (really neuromodulators)
3. There are 5 different muscarinic receptors (M1 through M5). M1 through M4 are better appreciated than M5.
4. M1, M3, M5 are linked to Gaq (Activate DAG and IP3 signaling). M2 and M4 are linked to Gai (inhibit adenylate cyclase).

Question 4

Can usually figure out whether an aceylcholine receptor is of the nicotinic or muscarinic type by asking whether we want to

Answer 4

depolarize across a membrane (nicotinic) or activate a G protein coupled receptor (muscarini

Question 5

Cholinergic agonists

Direct Acting:

Answer 5

bind to muscarinic or nicotinic AcCh receptor or both

Question 6

Cholinergic agonists

Indirect acting:

Answer 6

cholinesterase inhibitor

Question 7

-zosin

Answer 7

drug is alpha 1 adrenergic receptor blocker

Question 8

-olol

Answer 8

beta adrenergic receptblocker

Question 9

-ilol, -alol

Answer 9

beta andrenergic blocker with alpha 1 activity

Question 10

Acetylcholine: hydrolyzed

Answer 10

rapidly, shortest duration of action

Question 11

Methacholine: hydrolyzed

Answer 11

slower, somewhat longer duration of action

Question 12

Carbachol*, bethanechol, cevimeline, alkaloids: not

Answer 12

hydrolyzed, longer duration of action

Question 13

Carbachol: favors ——— receptors

Answer 13

nicotinic

Question 14

Methacholine, bethanechol, muscarine, cevimeline, pilocarpine: ——- selective

Answer 14

muscarinic

Question 15

Muscarinic agonists much more

Answer 15

clinically relevant

Question 16

Neuromuscular transmission

Answer 16

1. Activation of nicotinic AcCh Receptors depolarizes post-synaptic membrane 2. Local depolarization leads to action potential
2. Post-synaptic depolarization leads to release of Ca++ from the sarcoplasmic reticulum
3. Release of Ca++ from the sarcoplasmic reticulum leads to muscle contraction

Question 17

Odd numbered muscarinic receptors activate

Answer 17

phospholipase C and promote Ca++release

Question 18

Even numbered muscarinic receptors inhibit

Answer 18

adenylcyclase

Question 19

M3 muscarinic receptors on the sphincter muscle mediate

Answer 19

pupil contraction.

Question 20

M3 receptors on ciliary muscle also mediate

Answer 20

muscle contraction. This increases drainage by the trabecular network and reduces ocular pressure.

Question 21

Cardiac muscle contains M2 receptors and parasympathetic innervation. Activation of these receptors reduce

Answer 21

cardiac output

Question 22

Most arteries and veins in the body are innervated by

Answer 22

sympathetic adrenergic nerves

Question 23

Some blood vessels are innervated by

Answer 23

parasympathetic cholinergic or sympathetic cholinergic nerves.
These nerves release acetylcholine as their neurotransmitter. Coronary arteries are a prominent example.

Question 24

vascular endothelial cells express —- receptors. Activation of these receptors produce ———–

Answer 24

M3

vasodilation

Question 25

Activation of M3 receptors increase

Answer 25

Ca++ in endothelial cells

Question 26

2. Ca++/calmodulin activates

Answer 26

NOS to produce NO.

Question 27

3. NO travels to the smooth muscle cell, enhances ----- production, leading to

Answer 27

cGMP muscle relaxation (enhances myosin light chain phosphatase activity).

Question 28

M3 muscarinic receptors on the bronchial muscle mediate

Answer 28

muscle contraction.

Question 29

Gastrointestinal Effects Mostly, --------------. However sphincter muscle

Answer 29

contractile responses M2 mediated) relaxes.

Question 30

Secretory Glands

Answer 30

(M3 receptor) | Ca++ stimulates release of glandular contents from secretory glands (including salivary glands)

Question 31

M3 muscarinic receptors mediate

Answer 31

detrusor muscle contraction. Aids in voiding the bladder

Question 32

Increased risk of adverse response to muscarinic agonists:

Answer 32

Patients with asthma (bronchoconstriction), Cardiovascular disease (vasodilation, reduced cardiac output), ulcer (lacrimation

Question 33

SLUD response:

Answer 33

Salivation, Lacrimation, Urination, Defecation

Question 34

Muscarinic agonists: | Intravenous, intramuscular routes generally

Answer 34

avoided (because of cardiopulmonary effects). Topical routes favored, if possible

Question 35

Acetylcholinesterase drugs actby

Answer 35

inhibiting acetylcholinesterase, which increases acetylcholine in synapse

Question 36

Some “reversible” anticholinesterases are slowly hydrolyzed by

Answer 36

cholinesterase

Question 37

Some anticholinesterases act in

Answer 37

a rapidly reversible manner (they are not hydrolyzed at all). Only used to kill stuff.

Question 38

1. In general anticholinesterases produce effects that are similar to the

Answer 38

direct acting cholinergic agonists. | In effect, increase the concentration of acetylcholine at effector site.

Question 39

The greater the cholinergic stimulation at the site, the

Answer 39

greater the effect. | Smooth muscle of ocular system, GI tract, urinary bladder major sites.

Question 40

. Anticholinesterases do not produce

Answer 40

muscarinic receptor mediated vasodilation (Why not). | Not much parasympathetic innervation of vascular endothelium.

Question 41

anticholinesterases Can also produce------------ through -----------. Initially prolong duration and then promote desensitization of nAcCH R (will get to this later).

Answer 41

vasodilatory effects autonomic ganglia

Question 42

Physostigmine (tertiary amine) can produce

Answer 42

vasodilatory effects through action in the CNS.

Question 43

Anticholinesterases used to terminate the

Answer 43

neuromuscular block of curare-like agents (coming soon) in general anesthesia.

Question 44

Anticholinerases that cross the blood brain barrier (donepezil, rivastigmine, galantamine) are used to improve

Answer 44

cognitive function in Alzheimer’s patients.

Question 45

In general, treatment with an anti-muscarinic drug places the target under control by the

Answer 45

sympathetic nervous system

Question 46

sweat gland , where signals from the

Answer 46

sympathetic and parasympathetic systems act upon muscarinic receptors at the target and are both blocked by the anti-msucarinic.

Question 47

Anti-muscarinics will cause

Answer 47

pupil dilation and paralysis of accommodation*. Intraocular pressure not significantly affected except in the case of narrow angle glaucoma, in which anti-muscarinics could cause a serious rise in pressure.

Question 48

Anti-muscarinics are used to produce

Answer 48

bronchodilation and diminish mucus production to treat COPD.

Question 49

Anti-muscarinics inhibit

Answer 49

Anti-muscarinics inhibit sweating and can elevate body temperature.

Question 50

Anti-muscarinics generally inhibit --------. Only inhibit gastric secretions at

Answer 50

Anti-muscarinics generally inhibit motility. Only inhibit gastric secretions at very high concentrations (not useful).

Question 51

Anti-muscarinics block

Answer 51

parasympathetic mediated secretion.

Question 52

Therapeutic Uses of Anti-muscarinics

Answer 52

1. Dilate pupils for opthalmologic procedures. 2. Treatment of COPD (quarternary amines, administered by inhalation) 3. Diminish salivary secretion before oral procedures 4. Anti-spasmodics, and anti-ulcer agents (not very useful because of side effects)*. 5. Antidote to anti-cholinesterases

Question 53

Transmission of sympathetic and parasympathetic nerve impulses mediated by

Answer 53

nicotinic AcCh receptors

Question 54

Nicotinic AcCh receptors are important mediators in the

Answer 54

Nicotinic AcCh receptors are important mediators in the CNS

Question 55

Post synaptic transmission of nerve impulse at skeletal muscle mediated by

Answer 55

nicotinic AcCh receptors

Question 56

Ganglionic AcCh blockers

Answer 56

Ganglionic blockers rarely used: too many side effects.

Question 57

Ganglionic AcCh blockers

Answer 57

Ganglionic blockers rarely used: too many side effects.

Question 58

Post synaptic transmission of nerve impulse at skeletal muscle mediated by

Answer 58

nicotinic AcCh receptors