Pharmacology - Cholinergic Drugs

Front 1

What kind of drug is Pilocarpine?

Back 1

ACh agonist (muscarinic)

Front 2

What kind of drug is Methacholine?

Back 2

ACh agonist (muscarinic)

Front 3

What kind of drug is Bethanecol?

Back 3

ACh agonist (muscarinic)

Front 4

What kind of drug is Carbachol?

Back 4

ACh agonist (muscarininc and nicotinic)

Front 5

What kid of drug is ACh?

Back 5

ACh agonist (muscarinic and nicotinic)

Front 6

What kind of drug is Nicotine?

Back 6

ACh agonist (all nicotinic receptors)

Front 7

What kind of drug is Varenicline?

Back 7

ACh agonist (partial; selective for diff subtypes w/in the CNS)

Front 8

What is the mechanism of action for Black Widow Spider Venom?

Back 8

Promotes ACh release presynaptically so there is a constant release of ACh

Front 9

What kind of drug is Phyostigmine?

Back 9

AChE inhibitor (reversible)

Front 10

What kind of drug is Rivastigmine?

Back 10

AChE inhibitor (reversible)

Front 11

What kind of drug is Neostigmine?

Back 11

AChE inhibitor (reversible)

Front 12

What kind of drug is Pyridostigmine?

Back 12

AChE inhibitor (reversible)

Front 13

What kind of drug is Erdophonium?

Back 13

AChE inhibitor (reversible)

Front 14

What kind of drug is Tacrine?

Back 14

AChE inhibitor (rev)

Front 15

What kind of drug is Donepizil?

Back 15

AChE inhib (rev)

Front 16

What kind of drug is Galantamine?

Back 16

AChE inhib (rev)

Front 17

What kind of drug is Echothiophate?

Back 17

AChE inhib (irrev)

Front 18

What kind of drug is Sarin nerve gas?

Back 18

AChE inhib (irrev)

Front 19

What kind of drugs are Malathion and Parathion?

Back 19

AChE inhibs (irrev; insecticides)

Front 20

What kind of drugs are "indirectly acting cholinomimetics"?

Back 20

These are AChE inhibitors. Cholinomimetics because they affect a cholinergic response. Indirect because they don't do so by acting at the AChR like an agonist, but instead increase ACh in the synaptic cleft by inhibiting AChE.

Front 21

What kind of drug is Atropine?

Back 21

Competitive AChR antagonist
(muscarinic)

Front 22

What kind of drug is Scopolamine?

Back 22

Competitive AChR antagonist
(muscarinic)

Front 23

What kind of drug is is Tolterodine?

Back 23

Competitive AChR antagonist
(muscarinic)

Front 24

What kind of drug is Oxybutynin?

Back 24

Competitive AChR antagonist
(muscarinic)

Front 25

What kind of drug is Tropicamide?

Back 25

Competitive AChR antagonist
(muscarinic)

Front 26

What kind of drug is Benztropine?

Back 26

Competitive AChR antagonist
(muscarinic)

Front 27

What kind of drug is Ipratropium?

Back 27

Competitive AChR antagonist
(muscarinic)

Front 28

What kind of drug is Tiotropium?

Back 28

Competitive AChR antagonist (muscarinic)

Front 29

What kind of drug is Propantheline?

Back 29

Competitive AChR antagonist (muscarinic)

Front 30

What kind of drug is d-tubocurarine?

Back 30

Competitive AChR antagonist (nicotinic)

Front 31

What kind of drug is Atracurium?

Back 31

Competitive AChR antagonist (nicotinic)

Front 32

What kind of drug is Pancuronium?

Back 32

Competitive AChR antagonist (nicotinic)

Front 33

What kind of drug is Vecuronium?

Back 33

Competitive AChR antagonist (nicotinic)

Front 34

What kind of drug is Rocuronium?

Back 34

Competitive AChR antagonist (nicotinic)

Front 35

What kind of drug is mecamylamine?

Back 35

Competitive AChR antagonit (nicotinic)

Front 36

What is the MOA for hemicholinium-3?

Back 36

Inhibits uptake of choline into presynaptic terminals (Na+ dependent Choline transporter; CHT), thereby inhibiting ACh synthesis

Front 37

What kind of drugs are:

Streptomycin, kanamucin, neomycin, gentamicin, etc.

And what is their effect on ACh release?

Back 37

They are aminoglycoside antibiotics, and they prevent ACh release by blocking Ca2+ influx into the presynaptic terminal, inhbiiting fusion of the vesicle and the presynaptic membrane

Front 38

What is the effect of high serum Mg2+ on release of ACh?

Back 38

High serum Mg2+ inhibits ACh release from the presynaptic terminal by blocking Ca2+ influx and subsequent fusion of the vesicle with the presynaptic membrane

Front 39

What is the MOA for Succinylcholine?

Back 39

Succinylcholine causes the motor endplate to depolarize, halting transmission of ACh signalling to the muscle sarcolemma resulting in muscle paralysis. (Called a "Depolarizing Blockade")

Front 40

A patient comes into your ER and is non-responsive, BP is in the tank, is sweating, and drooling. Friend says he had eaten a mushroom on a dare earlier in the day. What kind of poisoning is this patient suffering from and how would you treat it?

Back 40

Patient is suffering from muscarine poisoning and you would treat with atropine or scopolamine (competitive AChR antagonists; both tertiary amines with good CNS penetration)

Front 41

T or F: When acting on the ascending reticular core, atropine has 100x the sedating effect of scopolamine.

Back 41

F: scopolamine has 100x the sedating effect of atropine

Front 42

Scopolamine is used to treat sea-sickness. Where in the brain does it act, and how do we know this.

Back 42

First, just for review, Scopolamine is a reversible mAChR antagonist.

Second, it acts somewhere between the semi-circular canals and the emetic center in the medulla. We know this because it does not alleviate emesis caused by drugs that directly stimulate the chemotrigger receptor zone (CTZ; medullary emetic zone).

Front 43

What kind of drug is benztropine and what is it's therapeutic use?

Back 43

Benztropine is a competitive mAChR antagonist. It is used in adjunct with anti-parkinsonian drugs to alleviate symptoms of parkinson's disease (atropine used for this as well)

Front 44

What kind of drug is Pilocarpine, and what is its primary therapeutic use?

Back 44

It is a muscarinic ACh agonist. Used topically in the eye to induce miosis which opens the canal of Schlemm and other drainage routes for intraocular fluid in the anterior chamber of the eye. USED AS Tx FOR GLAUCOMA!

Front 45

What structure, under parasympathetic control ?(Cranial Nerve III), in the eye is the therapeutic target for muscarinic agonists?

What about muscarinic antagonists?

Back 45

Agonists = sphincter pupillae (responsible for pupil constriction)

Antagonists = cilliary muscles responsible for altering the shape of the lens in the eye

Front 46

Muscarine: tertiary or quaternary amine?

Back 46

Tertiary (good membrane penetration)

Front 47

Atropine: tertiary or quaternary amine?

Back 47

Tertiary (good membrane penetration)

Front 48

Scopolamine: tertiary or quaternary amine?

Back 48

Tertiary (good membrane penetration)

Front 49

Benztropine: tertiary or quaternary amine?

Back 49

Tertiary (good membrane penetration)

Front 50

Pilocarpine: tertiary or quatrenary amine?

Back 50

Tertiary

Front 51

Carbamylcholine: tertiary or quarternary amine?

Back 51

Quaternary (poor membrane abs; good for topical use)

Front 52

What is the other name for Carbamylcholine?

Back 52

Carbachol

Front 53

At what subset(s) of ACh receptors does Carbamylcholine work?

Back 53

Almost all of them (nicotinic and muscarinic)

Front 54

What two drugs are used as miotic agents in eye surgery (ex: lens replacement)?

Back 54

Carbachol and Acetylcholine (NOT Pilocarpine)

Front 55

Why is acetylcholine a suboptimal drug to administer IV in a small dose?

Back 55

Because pseudoesterases in the plasma will break it down quickly

Front 56

Is Carbachol metabolized by cholinesterases?

Back 56

NO!

Front 57

Define: Cycloplegia

Back 57

Paralysis of the ciliary muscle of the eye (responsible for accommodation reflex; induced by mAChR antagonists)

Front 58

What is the effect of ACh agonists (like pilocarpine, ACh, and carbachol) on the lens of the eye?

Back 58

They induce contraction of the ciliary muscle which causes the lens to focus closely and blurs distance vision.

Front 59

What is the effect of ACh antagonists (atropine, scopolamine) on the lens of the eye?

For what purpose is this effect beneficial?

Why do we want to avoid using atropine and scopolamine for the above purpose in patients with glaucoma?

Back 59

The induce cycloplegia (paralysis of the ciliary muscle of the eye) which puts the lens in a fixed resting position and makes focusing at close distance impossible.

This is used in setting up corrective lenses.

We don't want to give these drugs (atropine and scopolamine) to people with glaucoma (or people with shallow anterior eye chambers at risk for glaucoma) because these drugs also induce mydriasis. This blocks the canal of Schlemm (due to passive pressure of the iris) and allows intraocular fluid to build up and intraocular pressure to increase. We specifically don't want to give atropine or scopolamine for this purpose since they are long acting agents (can act for days). Instead we give a shorter acting (hours) mAChR antagonist like tropicamide to everyone.

Front 60

What kind of drug is Tropicamide, and why might we give it instead of other drugs in its class (hint: eyes)?

Back 60

Tropicamide is a mAChR antagonist, and we give it over other drugs in the class (like atropine and scopolamine) since it is very short acting and does not run the risk of exacerbating glaucoma.

Front 61

What kind of ACh receptors are found in the heart?

Back 61

M2 (which act via a Gi G-protein; beta/gamma subunit more responsible for inc in K+ efflux that results in hyperpolarization of myocytes and slowed contraction tho)

Front 62

What are the three areas in the heart to which muscarinic action is directed?

Back 62

SA node, atria, and AV node

Front 63

What are the three effects of M2 stimulation on the heart?

Back 63

Negative inotropy (dec force of contraction), chronotropy (dec HR), and dromotropy (dec rate of conduction at the AV node)

Front 64

What is the effect of increased K+ permeability due to M2 stimulation of the atrial pacemaker cells?

Hint: think about this as it relates to the three effects of M2 stimulation in the heart.

Back 64

Resting phase hyperpolarization, and decreased slope of depolarization in pacemaker cells (causes negative chronotropy since we have a greater degree of depolarization at a slower rate of depolarization to overcome before we fire an action potential; negative dromotropy for the same reasons).

Increased permeability to K+ reduces the force of contraction (neg inotropy) in atrial myocytes due to the fact that the action potential is shorter (inc K+ permeability = higher rate of repolarization) and thuse there is less Ca2+ released from the sarcoplasmic reticulum and less influx of Ca2+ for the slow response Ca2+ channel that only opens when the cardiac myocyte is depolarized (less Ca2+ release/influx = lower force of contraction).

Front 65

What kind of ACh receptor is found in the vascular bed?

Back 65

M3 (although innervation is limited!)

Front 66

What kind of G-protein do M3 receptors found in the vascular bed act via?

Back 66

Gq (IP3 and DAG second messenger system)

Front 67

What is the effect of cholinergic stimulation of M3 receptors found in the vascular bed?

Back 67

Increase in intracellular calcium (Gq stim => activates PLC => PLC cleaves PIP2 to IP3 and DAG => IP3 stimulates release of Ca2+ from intracellular stores). Increased Ca2+ stimulates Ca2+ dependent NO synthase in the endothelial cell. NO (aka EDRF) is produced from arginine and diffuses out of the cell to the smooth muscle lining the vessel causing it to relax and resulting in vasodilation/dec BP.

Front 68

What is the MOA for Vesamicol?

Back 68

Blocks the vesicle associated ACh transporter preventing ACh from being placed w/in vesicles in the presynaptic terminal.

Front 69

What is the effect of a low dose of IV ACh on the vaculature, and how does this ultimately effect the heart?

Back 69

Low dose IV ACh only effects the vasculature due to rapid metabolism by pseudocholinesterases in the plasma. The effect on the vasculature is to vasodilate (ACh acts at M3 on endothelial cells, causes inc in Ca2+ via Gq, causes inc in NO due to Ca2+-dependent NO synthase, NO diffuses to smooth muscle to cause relaxation and dilation of vessel) resulting in dec BP. Dec BP is detected by baroreceptors which respond by increasing SS tone of the heart resulting in a reflexive tachycardia (!!!!! so not the effect you want if you're trying to deliver ACh to the heart !!!!!)

Need higher doses to achieve cardiac depression.

Front 70

What are the two effects of ACh antagonists on the heart (namely atropine)?

Back 70

Pronounced tachycardia and increased AV node conduction (so positive chronotropy/dromotropy)

Front 71

What do low doses of atropine produce a paradoxical bradycardia?

Back 71

Because atropine blocks presynaptic mAChRs that are responsible for negative regulation of ACh release leading to an increase in ACh release.

Front 72

Why does atropine produce cutaneous vasodilation at toxic levels and in children?

Back 72

Atropine blocks thermal sweating, so cutaneous vasodilation is the only way to dissipate heat (dry as a bone => red as a beet). Children more susceptible to hyperthermic effect.

Front 73

Does parasympathetic stimulation directly relax the sphincters of the GI tract?

Back 73

NO! They do relax, but it is due to PS stimulation of the enteric nervous system, and enteric nervous system release of peptides onto the sphincters that cause them to dilate.

Isolated sphincters (noteably the cardiac sphincter at the base of the esophagus because IT MAKES SENSE FOR REST AND DIGEST) contract when exposed to cholinergic agonists.

Front 74

What kind of ACh receptor is found in the GI tract?

Back 74

M3 (Gq MOA; results in increased contractility and frequency of contraction)

Front 75

What kind of drug is Bethanecol?

Back 75

ACh agonist that works primarily at muscarinic receptors in the GI tract and bladder

Front 76

Is Bethanecol a tertiary or quaternary amine?

Back 76

Quaternary (poorly absorbed, but acts on GI tract so given PO or Sub-Q [not sure why Sub-Q])

Front 77

Why do we prescribe Bethanecol to someone, and when is it contraindicated?

Back 77

Used to treat GI/GU (bladder) stasis (situations: post-partum, after general anaesthesia)

Contraindicated: When there is an obstruction causing stasis as increased pressure in lumen of intestine/bladder may cause perforation.

Front 78

What is the general effect of muscarinic antagonists on the GI tract, and what can we derive from this as a possible side-effect of drugs such as atropine and scopolamine?

Back 78

It depresses GI activity and thus we can derive that CONSTIPATION might be a side effect.

Front 79

What kind of drug is Propantheline?

Back 79

mAChR antagonist

Front 80

Is Propantheline a tertiary or quaternary amine?

Back 80

Quaternary

Front 81

What is Propantheline indicated for?

Back 81

GI tract hypermotility (spasmolytic)

FYI: Quaternary amines posses ganglionic blocking action too which increases their effectiveness as spasmolytics (tertiary amines like atropine and scopolamine lack this)

Front 82

What is the effect of mAChR stimulation in the bladder?

Back 82

Increased detrusor muscle tone which increases intravesicle pressure to set off the micturition reflex.

Front 83

What are the two most selective drugs for stimulation of bladder mAChRs?

Back 83

Bethanecol (direct agonist) and Neostigmine (AChE inhibitor)

Front 84

Why are atropine-like drugs sometimes contraindicated in people with urinary tract blockages (ex: elderly men w/ prostatic hyperplasia)?

Back 84

Because atropine like drugs can have a slight effect on urinary retention (although not total; hypothesized that other chemicals [ATP, NO] released from sacral parasympathetics to increase detrusor tone at sites other than cholinoceptors), and this patient population is more sensitive to this effect than the population as a whole

Front 85

What kind of drug is oxybutynin?

Back 85

Oxybutynin is a mAChR antagonist

Front 86

Oxybutynin: tertiary or quaternary amine?

Back 86

tertiary

Front 87

What is Qxybutynin indicated for?

Back 87

Overactive bladder (ex: spasmodic bladder following radical prostatectomy)

Front 88

Where is Oxybutynin metabolised?

Back 88

In the liver (CYP3A4)

Front 89

What kind of drug is Tolterodine?

Back 89

mAChR atagonist

Front 90

What is Tolterodine indicated for?

Back 90

Urinary urgency

Front 91

Tolteridine: tertiary or quaternary amine?

Back 91

tertiary

Front 92

Where is tolteridine metabolized?

Back 92

Liver (CYP2D6)

Front 93

What kind of drugs are solifenacin, trospium, and darifenacin?

Back 93

mAChR antagonists indicated for urinary urgency

*trospium is a quaternary amine so poorer abs, but less side-effects

*darifenacin exhibits some selectivity for M3 receptors

Front 94

Which would have more side effects: a tertiary amine or quaternary amine drug?

Back 94

Tertiary amine since it is more apt to spread systemically!

Front 95

What kind of ACh receptors are found in the bronchiolar smooth muscle?

Back 95

M3 (Gq => inc in Ca2+ => CONTRACTION OF BRONCHIOLAR SMOOTH MUSCLE!)

Front 96

What kind of drug is Methacholine?

Back 96

ACh agonist (muscarinic)

Front 97

Methacholine: tertiary or quaternary amine?

Back 97

quaternary

Front 98

What is Methacholine used for?

Back 98

Used in patients with inapparent asthma to try to induce bronchiloar hyper-reactivity (ACh agonist on M3 => inc Ca2+ => contraction of bronchiolar smooth muscle)

*Caution: Use only where there is support for person going into resp. distress!

Front 99

What kind of drug is ipratropium?

Back 99

mAChR antagonist

Front 100

Ipratropium: tertiary or quaternary amine?

Back 100

quaternary

Front 101

What is ipratropium indicated for?

Back 101

Aerosol inhalation treatment of bronchospasm (inhibits M3 activity in lung)

Front 102

What kind of drug is Tiotropium?

Back 102

mAChR antagonist

Front 103

Tiotropium: tertiary or quaternary amine?

Back 103

quaternary

Front 104

What is tiotropium indicated for (and what is its advantage over ipratropium)?

Back 104

Tiotropium is indicated for treatement of bronchospasm in asthma. It has less atagonist activity at the pre-synaptic M2 receptor and thus does not block negative regulation of ACh release.

Front 105

What is the effect of Pilocarpine when it is administered orally?

Back 105

Increased salivary secretion and sweating (used to treat xerostomia in H/N cancer patients and Sjoergren's syndrome [autoimmune salivary dysfxn])

Front 106

What kind of drug is Cevimeline?

Back 106

ACh agonist used to treat xerostomia

Front 107

Where is Cevimeline metabolized?

Back 107

Liver (CYP2D6, CYP3A3/4)

Front 108

What receptors does Cevimeline exhibit some selectivity for?

Back 108

M1 and M3