Cholinergic Pharmacology

Front 1

What are the 2 classes of cholinomimetic drugs?

Back 1

Choline esters

Naturally occuring cholinergic stimulants (alkaloids)

Front 2

Name 3 choline esters

Back 2

1. Acetylcholine
2. Methylcholine
3. Carbachol

Front 3

Non-innervated ACh receptors are generally of the ______ type

Back 3

muscarinic

Front 4

What effect does parasympathetic nerve stimulation have on blood vessels?

Back 4

NONE

Front 5

What enzyme catalyzes the reaction that makes ACh?

Back 5

choline acetylase (choline acetyltransferase)

Front 6

What is the rate-limiting step in the synthesis of ACh?

Back 6

The reuptake of choline.

Front 7

What drug blocks the transport of choline and consequently will eventually cause an inhibition of cholinergic function?

Back 7

Hemicholinium

Front 8

What acts as a trigger, promoting attachment of granules containing ACh to fuse w/ the membranes of the nerve terminal?

Back 8

Sudden influx of Ca++

Front 9

What toxin prevents the release of ACh from the nerve terminal?

Back 9

Botulinum toxin (inhibits SNAREs)

Front 10

What toxin causes excessive fusing of the granules w/ the nerve membrane that leads to excessive release and eventual depletion of the transmitter?

Back 10

latrotoxin

Front 11

Why does ACh have a very short half-life?

Back 11

Cholinesterases hydrolyze the ester linkage, yielding choline and acetic acid.

Front 12

What are the 2 types of cholinesterases found in the body?

Back 12

Acetylchoninesterases

Pseudocholinesterases

Front 13

Which type of cholinesterase plays a role in the degradation of ACh that escapes from transmission sites and inactivate ACh injected intravenously?

Back 13

Pseudocholinesterases

Front 14

Where are M2 receptors found?

Back 14

Heart

Front 15

Where are M3 receptors found?

Back 15

Peripheral autonomic organs

Front 16

Where are all the other muscarinic receptors found (besides M2, M3)?

Back 16

- GI tract
- Autonomic ganglia (M1)
- CNS (M1 - M5)

Front 17

What is the effect of muscarinic stimulation on the HEART?

Back 17

- Heart rate is decreased
(atrial pacemaker cells stimulated)

Front 18

What is the effect of muscarinic stimulation of VASCULAR SMOOTH MUSCLE?

Back 18

- Vasodilation
* This effect can only be achieved by hormones--mostly exogenous
*stimulation of muscarinic receptors on endothelial cells of BV causes a release in EDRF (endothelium derived relaxing factor), which is nitric oxide. This causes relaxation of the smooth muscle.

Front 19

What is the effect of muscarinic stimulation of the EYE?

Back 19

- Miosis (pupillary constriction)
- Cyclotonia (spasm of accommodation -- see better up close)

Front 20

What is the effect of muscarinic stimulation of the GI?

Back 20

Increase tone and motility. (sphincters at beginning and end contract, while the ones in the "middle" relax)

Front 21

What is the effect of muscarinic stimulation on BRONCHIOLAR SMOOTH MUSCLE?

Back 21

Modest constriction.

Front 22

What is the effect of muscarinic stimulation on SECRETORY GLANDS?

Back 22

Causes sweating. (Remember this is from the sympathetic branch)

Front 23

Are muscarinic receptors found in the cortex and brain stem?

Back 23

YES

Front 24

Where are nicotinic receptors found? (4 places)

Back 24

1. Neuromuscular junction
2. Autonomic ganglia
3. Adrenal medulla
4. CNS (brain and spinal cord)

Front 25

What are cholinomimetic drugs?

Back 25

agents that directly enhance cholinergic function.

Basically altered versions of ACh, which aren't degraded as readily by acetylcholinesterase

Front 26

How must ACh be administered to have an effect?

Back 26

must be injected. Produces short term stimulation.

Front 27

In low doses, which receptors does ACh activate?

Back 27

Only muscarinic
(muscarinic receptors are much more sensitive to ACh than nicotinic)

Front 28

How do you administer ACh so that it will activate nicotinic receptors?

Back 28

Administer high doses

Front 29

This is a potent muscarinic stimulant, but is not effective as a drug in man as it produces so many generalized muscarinic effects.
(It is a choline ester)

Back 29

Methacoline

Front 30

Methacoline is ______ refractory to breakdown by AChase.

Back 30

partially

Front 31

This choline ester has potent nicotinic stimulating effects w/ very little muscarinic effects

Back 31

Carbachol

Front 32

Carbachol is _______ refractory to inactivation by AChase.

Back 32

Very

Front 33

This choline ester has occasionaly been used topically on the eye to produce miosis in the treatment of glaucoma

Back 33

Carbachol

Front 34

The only one of the choline esters that has a well established clinical utility.

Back 34

Bethanechol

Front 35

What is Bethanechol useful in treating?

Back 35

1. post- operative urinary retention
2. atony of the GI tract

Front 36

Bethanechol is _______ to AChase inactivation and has mostly ________ effects.

Back 36

- refractory
- muscarinic

Front 37

Name 3 naturally occurring cholinergic stimulants (alkaloids).

Back 37

1. Nicotine
2. Muscarine
3. Pilocarpine

Front 38

What would be the responses to injected nicotine?

Back 38

Activation of all autonomic ganglia (including adrenal medulla), and stimulation of the skeletal muscle endplate nicotinic receptors

Front 39

What happens when nicotine is given repeatedly or in large doses?

Back 39

It causes a blockade of nicotinic receptors due to sustained depolarization. Therefore, large doses have an inhibitory effect.

Front 40

What is the antidote for muscarine overdose?

Back 40

Atropine

Front 41

Will muscarine stimulate non-innervated muscarine receptors?

Back 41

YES.
It stimulates innervated and non-innervated muscarine receptors.

Front 42

What is pilocarpine?

Back 42

Naturally occurring cholinergic stimulant (alkaloid).

Front 43

What is methacholine?

Back 43

Choline ester

Front 44

What is carbachol?

Back 44

Choline ester

Front 45

What is bethanechol?

Back 45

Choline ester

Front 46

What is Pilocarpine used to treat?

Back 46

Glaucoma

(pilocarpine is an alkaloid)

Front 47

Which receptors do pilocarpine selectively activate?

Back 47

muscarinic

Front 48

What are anticholinesterase agents?

Back 48

Agents that indirectly enhance cholinergic function

Front 49

How do anticholinesterase agents work?

Back 49

They occupy the active sites on AChase, producing an enhancement of cholinergic function as ACh remains in the region of the synapse for a longer period

Front 50

Anticholinesterase agents only work at which receptors?

Back 50

Those that receive tonic neural input
(non-innervated musc. receptors on vascular smooth muscle will not be stimulated)

Front 51

What are the two active sites that anticholinesterase agents bind to on AChase?

Back 51

anionic site (where amine group binds)

esteratic site

Front 52

What drug is useful in the treatment of atropine poisoning?

Back 52

Physostigmine
(anti-acetylcholinesterase that penetrates CNS)

Front 53

Which compounds are effective as antidotes to curare?

Back 53

antiacetylcholinesterases

Neostigmine is best choice since it will stay in the periphery (will not cause CNS side effects)

Front 54

What is physostigmine?

Back 54

REVERSIBLE anti-AChase

Front 55

What is neostigmine?

Back 55

REVERSIBLE anti-AChase

Front 56

What are Ambenonium and Pyridostigmine

Back 56

REVERSIBLE anti-AChases

Front 57

What is edrophonium?

Back 57

REVERSIBLE anti-AChase

Front 58

What are Donepezil and Tacrine?

Back 58

REVERSIBLE anti-AChase

Front 59

Can Physostigmine readily enter the CNS?

Back 59

YES.
It has a tertiary structure, so it is not highly charged.

Front 60

What is the main use of Physostigmine?

Back 60

Topical treatment of glaucoma
(produces miosis and contraction of ciliary muscle)

Front 61

What is the most rational anti-AChase agent for the treatment of atropine poisoning?

Back 61

Physostigmine

Front 62

Should Neostigmine be used for treatment of atropine poisoning?

Back 62

No. It does not enter the CNS.

Front 63

What sites do Neostigmine stimulate?

Back 63

Nicotinic sites on skeletal muscle endplates.

Front 64

Which anti-AChase is a good choice in the treatment of myasthenia gravis?

Back 64

Neostigmine

Front 65

What are the side effects of all AChase inhibitors?

Back 65

Excessive muscarinic activation (sweating, salivation, increased GI and bladder motility..)

Front 66

What do Ambenonium and Pyridostigmine treat?

Back 66

Myasthenia gravis

(anti-AChases)

Front 67

Which anti-AChase has a short duration of action and is valuable for the diagnosis of myasthenia gravis?

Back 67

Edrophonium

Front 68

Due to its short action, _______ is beneficial in titration of the effective dose levels of longer acting anti-AChase agents.

Back 68

Edrophonium

Front 69

Which anti-AChases are used to treat cognitive dysfunction seen in patients w/ Alzheimer's disease?

Back 69

Donepezil and Tacrine

Front 70

What is Echothiophate?

Back 70

IRREVERSIBLE anti-AChase

Front 71

What are Parathion and Malathion?

Back 71

IRREVERSIBLE anti-AChases

Front 72

What are Sarin and Somen?

Back 72

IRREVERSIBLE anti-AChases

Front 73

What do irreversible anti-AChases contain?

Back 73

Phosphate groups. They can phosphorylate the esteratic site on the ACHASE enzyme

Front 74

What does recovery depend on with irreversible anti-AChase agents?

Back 74

Depends upon regeneration of the AChase enzyme (takes weeks -- months!)

Front 75

What are most irreversible anti-AChase agents used for?

Back 75

Pesticides and potent war gases

Front 76

What irreversible anti-AChase agent is sometimes used to treat glaucoma in patients refractory to other less potent miotics?

Back 76

Ecothiophate

Front 77

What must happen to Parathion for it to be activated?

Back 77

It must be converted in the liver to the active agent, paraoxon.

(parathion is an irreversible anti-AChase)

Front 78

Name two potent anti-cholinesterase war gases?

Back 78

Sarin and Soman

Front 79

Organophosphorous compounds are:

Back 79

irreversible anti-AChase agents

Front 80

Name a cholinesterase reactivator

Back 80

Pralidoxime

Front 81

What does atropine do?

Back 81

Blocks muscarinic receptors

Front 82

_______ drugs w/ CNS selectivity are used in treating Parkinson's disease.

Back 82

Antimuscarinic

Front 83

What will be some observed effects of antimuscarinic drugs?

Back 83

(sympathetic-like effects)
Examples:
- mydriasis
- cycloplegia

Front 84

Atropine produces CNS _________ (excitation or depression)

Back 84

Excitation

Front 85

Scopolamine produces CNA _________ (excitation or depression)

Back 85

Depression

Front 86

What are the effects of low doses of atropine on the heart?

Back 86

A slight paradoxical bradycardia due to CNS vagal stimulation.

Higher doses are needed to antagonize the peripheral muscarinic receptors at the heart to produce the expected tachycardia

Front 87

What type of poisoning is characterized by hot dry skin; dilated pupils, and maniacal behavior?

Back 87

Atropine poisoning.

Front 88

This alkaloid has effects almost identical to those of atropine w/ one major exception. What is it?

Back 88

Scopolamine is a CNS DEPRESSANT.

(Atropine is a CNS stimulant)

Front 89

______ is an example of a less potent and much shorter acting muscarinic antagonist.

Back 89

Tropicamide

Front 90

This drug is useful for general ophthalmological exams

Back 90

Tropicamide

Front 91

What is Scopolamine?

Back 91

muscarinic antagonist

Front 92

What is Tropicamide?

Back 92

muscarinic antagonist

Front 93

What drug is primarily used in patients w/ COPD? And why?

Back 93

Ipratropium

It produces bronchodilation w/o reduction of volume or increase of viscosity of brionchial secretions.

(muscarinic antagonists)

Front 94

What is Benztropine?

Back 94

muscarinic antagonist

Front 95

What is Oxybutynin?

Back 95

Muscarinic antagonist

Front 96

Which antimuscarinic drug is used to relieve symptoms of Parkinson's disease?

Back 96

Benztropine

Front 97

______ is an atropine-like agent that is often used to treat spasms of the bladder seen after urologic surgery and in some neurological disorders producing bladder hyperactivity.

Back 97

Oxybutynin

Front 98

What is an example of a ganglionic stimulant?

Back 98

Nicotine

Front 99

What is an example of a drug that produces a ganglionic blockade?

Back 99

Hexamethonium (C6)

Front 100

Name 2 irreversible anticholinesterase agents (really 5 total).

Back 100

Parathion and Malathion

Front 101

Name 3 reversible anticholinesterase agents

Back 101

1. Physostigmine
2. Neostigmine
3. Edrophonium

Front 102

Name 4 muscarinic blocking drugs.

Back 102

1. Atropine
2. Scopolamine
3. Tropicamide
4. Ipratropium

Front 103

Which drugs can be used to treat glaucoma?

Back 103

1. *Physostigmine
2. Carbachol (occasionally)
3. Echothiophate (if absolutely necessary)

Front 104

Which drugs can be used to treat myasthenia gravis?

Which drug can be used to diagnosis this condition?

Back 104

Neostigmine

Edrophonium to diagnose

Front 105

How exactly does ACh cause vasodilation?

Back 105

When ACh acts on the muscarinic receptors of endothelial cells, they release endothelium derived relaxing factor (EDRF), which is nitric oxide. Nitric oxide causes relaxation of smooth muscle.

Front 106

When ACh is administered, why does it produce vasodilation and not vasoconstriction?

Back 106

Muscarinic receptors are much more sensitive to ACh than nicotinic receptors. So vasodilation will predominate.

Front 107

DING!

What drug would you use for long term treatment of myasthenia gravis?

Back 107

Pyridostigmine.

It does not enter CNS, so can work at neuromuscular junction to stimulate nicotinic receptors.

Front 108

DING!

What drug is used for the diagnosis of myasthenia gravis?

Back 108

Edrophonium

(Has short duration)

Front 109

DING!

What drug should be used to reverse actions of curare-like drugs?

Back 109

Neostigmine (together w/ atropine).

Since curare works at NMJs, you want a drug that stays in the periphery, rather than diffusing into the CNS (like physostigmine)

Front 110

Why does Physostigmine cross the CNS readily?

Back 110

It is a tertiary amine, so it is uncharged and can cross membranes readily

Front 111

Why does Neostigmine NOT cross the CNS readily?

Back 111

It is a quaternary amine, so it is charged and cannot readily cross membranes.

Front 112

Which anti-AChase only binds to the anionic site on the enzyme?

Back 112

Edrophonium
(short acting)

Front 113

If you have an elderly patient whose lens has been removed (aphakic eyes) and has glaucoma. What drug would you prescribe?

Back 113

Echothiophate.

Lasts for weeks. Don't have to use every day
Danger: can cause cataract formation.

Front 114

Where do "irreversible" Anti-AChases bind on the enzyme?

Back 114

Esteratic site

Front 115

What kind of effects will you experience with antiacetylcholinesterase intoxication?

Back 115

REMEMBER: effects will only be on neuronal release of ACh. This will NOT effect ACh on muscarinic receptors on BVs.

Muscarinic effects
1. Bronchoconstriction/ secretions
2. Sweating
3. Salivation
4. Lacrimation
5. Miosis and spasm of accomodation
6. Hypermotility of bladder and GI system
8. Bradycardia

Nicotinic effects:
1. Muscle twitches (fasciculations)
2. Tachycardia and hypertension (ganglionic stimulation)

CNS effects:
1. Progressive from restlessness and tremor to convulsions and respiratory and cardiovascular depression.

Front 116

DING!
T or F.

Children are much more sensitive to atropine than adults.

Back 116

TRUE

Front 117

DING!

What's the first effect you will see when given a low dose of atropine.

Back 117

Slight paradoxical bradycadia. Even at a small dose, atropine effects the brain and excites Vagal outflow to heart, which slows down heart rate.

If bradycardia occurs, double the dose!

Front 118

With high doses of atropine, why does the skin get dry, hot, and red?

Back 118

Muscarinic receptors on sweat glands are being blocked, so skin cannot be cooled.

Front 119

If you had to choose between atropine and scopolamine as a pre-anesthetic medication, which would you use?

Back 119

Scopolamine (CNS depressant= produces sedation).

(Atropine is a CNS stimulant that produces maniacal behavior).

Front 121

Why would you not use Atropine or Scopolamine for ophthalmologic purposes?

Back 121

They are long lasting.

Front 122

DING!

What are the big differences between the effects of atropine and hexamethonium?

Back 122

Atropine enters the CNS (will produce maniacal behavior) and has no control over blood pressure (BVs have no parasympathetic tone)

Hexamethonium cannot penetrate the CNS and will have an effect on blood vessels.

Front 123

Will hexamethonium or atropine cause miosis?

Back 123

NO.

They will cause "sympathetic-like" symptoms at sites that have predominant parasympathetic tone, and "parasympathetic-like" symptoms at sites that have predominant sympathetic tone

Both of them will cause:
Mydriasis
Hypotension
Anhydrosis
Cycloplegia
Xerostomia
Tachycardia

Front 124

Which of the anti-AChases can be taken orally?

Back 124

Physostigmine

Front 125

What would be the effect of hexamethonium on arterioles?

Back 125

Vasodilation

(sympathetic tone)

Front 126

What would be the effect of hexamethonium on the heart?

Back 126

Tachycardia

(parasympathetic tone)

Front 127

What would be the effect of hexamethonium on the eye?

Back 127

Mydriasis
Cycloplegia

(parasympathetic tone)

Front 128

What would be the effect of hexamethonium on the GI tract?

Back 128

Reduced tone and mobility

(parasympathetic tone)

Front 129

What would be the effect of hexamethonium on the urinary bladder?

Back 129

Urinary retention

(parasympathetic tone)

Front 130

What would be the effect of hexamethonium on salivary glands?

Back 130

Xerostomia (reduced secretion)

(Parasympathetic tone)

Front 131

What would be the effect of hexamethonium on sweat glands?

Back 131

Anhidrosis

(Sympathetic tone)