Pharm - Lecture 9 - Cholinergic - muscarinic agonists/antagonists + acetylchoinsterase inhib.

Question 1

Which drugs are Muscarinic Receptor agonists?

Answer 1

Bethanechol

Pilocarpine

Acetylcholine (not bolded)

Muscarine (not bolded)

Question 2

Which drugs are Choline esters? (2)

Answer 2

Acetylcholine (not bolded)

Bethanechol

Question 3

What are the uses of Bethanechol?

Route of administration?

Answer 3

Used for urinary retention in the absence of obstruction
(post-op urinary retention, diabetic neuropthy, bladder disorders)

Route of administration: Oral or subcutanious

Question 4

What drugs are naturally occuring alkaloids? (2)

Answer 4

Muscarine (not bolded)

Pilocarpine

Question 5

How is Pilocarpine used?

Answer 5

1) orally to treat xerostamia (dry mouth)
2) Opthalmically: miotic agent - to treat wide angle glaucoma and emergency treatment of narrow angle glaucoma

Question 6

How are Muscarinic receptor agonists adminstered?

Why?

Answer 6

Orally or subcutaniously: can’t administer by IV because it would cause hypotension

Question 7

What does SLUDGE stand for?

Answer 7

Salivation

Lacrimation

Urination

Defecation

Gastrointestinal upset

Emesis

Question 8

What are the side effects of muscarinic receptor agonists?

Answer 8

SLUDGE (salivation, lacrimatnio, urination, defecation, gastrointestinal upset, emesis (vomiting)

also: hypotension, bradycardia, difficulty with visual accomodation (blurred vision)

Question 9

What drug blocks the toxicity of muscarinic receptor agonists?

Answer 9

atropine

Question 10

What patients should muscarinic receptor agonists be used with caution? (3)

Answer 10

Asthma and COPD

Urinary or GI obstruction

Cardiovascular disease (bradycardia, hypotension, hyperthyroidism)

Question 11

Why should you be careful about using muscarinic receptor agonists on patients with cardiovascular diseases?

Answer 11

may precipitate atrial fibrillation

Question 12

Which drugs are acetylcholinesterase inhibitors? (5)

Answer 12

anticholinesterase agents:

Edrophonium

Physostigmine

Neostigmine

Sarin (nerve gas)

Malathion (insecticide)

Question 13

How does Edrophonium bind? What is it’s onset and duration of action?

Can it penetrate CNS?

Answer 13

Truly reversible competitive enzyme inhibitor: non-covalent binding

Rapid onset and short duration of action (minutes)

Can’t penetrate CNS

Question 14

What are the uses of Edrophonium? (3)

Answer 14

1) diagnosis of myasthenia gravis
2) distinguish cholinergic crisis from myasthenic crisis
3) reversal of paralysis by competitive neuromusclar blocking drugs

Question 15

How is Physostigmine used?

Answer 15

1) wide angle glaucoma
2) toxicity by antimuscarinic drug poisoning

Question 16

How does Physostigmine treat antimuscarinic drug poisoning?

Answer 16

Because Physostigmine is lipophilic, it can travel into the brain directly to treat this toxicity

Question 17

How is Neostigmine used?

Answer 17

1) treatment of myasthenia gravis (oral)
2) prevention and treatment of post-operative atony of gut and bladder (oral)
3) reversal of paralysis by competitive neuromuscular blocking drugs (i.v.)

Has no CNS effects

Question 18

Why is malathion a relativly safe insecticide?

Answer 18

Because it is rapidly detoxified in higher organisms

Question 19

What is the cause of the side effects of acetylcholinesterase inhibitors?

Answer 19

results from activation of muscarinic and nicotinic receptors in both the periphery and CNS

Question 20

What are the side effects of REVERSIBLE acetylcholinesterase inhibitors? (4)

Answer 20

SLUDGE

hypotension, bradycardia, difficulty with visual accommodation

Question 21

What are the side effects of IRREVERSIBLE acetylcholinesterase inhibitors?

Answer 21

Same as reversible inhibitors and addisionally:

Medullary respiratory center depression

Muscle paralysis due to depolorazing neuromuscular junction blockade

Death due to respiratory failure

Question 22

What are antidotes for acetylcholinesterase inhibitor toxicity? (2)

Answer 22

1) atropine (muscarinic receptor antagonist)
2) pralidoxime (reactivates acetylcholinesterase - must treat within 2-3 hours)

Question 23

What are the effects of Muscarinic receptor antagonists? (5)

Answer 23

1) relax iris sphincter and cilary muscles (mydriasis and paralysis of accommodation)
2) relax non-vascular smooth muscle (airways, GI tract, urinary bladder)
3) inhibit exocrine gland secretion (sweat, salivary, lacrimal, intestinal, mucosal glands)
4) increase Heart Rate
5) CNS effects: low dose produces sedation

high dose produces: excitement, delirium, agitation, toxic psychosis

Question 24

What drugs are muscarinic receptor antagonists? (7)

2 alkaloids

1 semi-synthetic alkaloid

4 synthetics

Answer 24

Atropine (alkaloid)

Scopolamine (alkaloid)

Ipratropium (semi-synthetic alkaloid)

Tropicamide (synthetic)

Oxybutynin (synthetic)

Darifenacin (synthetic)

Glycopyrrolate (synthetic)

Question 25

What are the cardiac uses of Atropine? (2)

Answer 25

Used to treat bradycardia: 1) MI 2) syncope associated with hyperactive carotid sinus reflex

Question 26

What are the opthalmic uses of Atropine?

Answer 26

mydriasis (dialation and cylcoplegia (paralysis of accoomadation)

Question 27

What is the duration of action of Atropine? (opthalmically)

Answer 27

7-10 days opthalmically

Question 28

How is Atropine used in anesthesia?

Answer 28

block responses to vagal reflexes induced by surgery of visceral organs

Question 29

What types of toxicities is Atropine used for?

Answer 29

Anticholinesterase or muscarinic toxicity

Question 30

How is Scopolamine used?

Answer 30

Used as a transdermal patch to teat motion sickness and vestibular disease (greater CNS penetration and more prominent CNS effects)

Question 31

How is Ipratropium used? Via inhalation? via nasal spray? Does it penetrate CNS?

Answer 31

Inhaled: Treatement of COPD - reduces bronical secretions and constriction Nasal spray: treatment of rhinorrhae associated with common cold doesn't penetrate CNS

Question 32

How is Tropicamide used? What is the onset and duration of action?

Answer 32

Opthalmic solution to produce mydriasis and cycloplegia Onset of action: fast (20-40 minutes) duration: short (4-6 hours)

Question 33

How is Oxybutynin used?

Answer 33

Overactive bladder and incontinence

Question 34

What types of side effects is Oxybutynin known for?

Answer 34

high incidence of anti-muscarinic side effects: Mostly zerostomia but also blurred vision, constipation and drowsiness and confussion

Question 35

What receptor is Darifenacin specific for?

Answer 35

M₃

Question 36

What is Glycopyrrolate used for?

Answer 36

used to block parasympathomimetic effects during reversal of neuromusclar blockade with anticholinesterase agents

Question 37

What are the side effects of Muscaranic antagonists? (5)

Answer 37

1) hot as a hare (no sweating) 2) dry as a bone (dry mouth, dry hot skin, no sweating) 3) red as a beat (excessive heat and no sweating) 4) blind as a bat (mydriasis, cycloplegia, blurred vision) 5) drowsiness (CNS action)

Question 38

When at a toxic dose, what side effect is added for muscuranic antagonists?

Answer 38

"mad as a hatter" ataxia, restlessness, excitement, hallucinations, delirium, coma

Question 39

What is physostigmine used for?

Answer 39

Muscaranic antagonist toxicity

Question 40

What patients should you be careful with when giving muscuranic antagonists? (3)

Answer 40

1) Glaucomoa - could increase intraocular pressure 2) prostatic hypertrophy - increase difficulty voiding 3) tachycardia (ex. angina pectoris)

Question 41

What is the mechanism of substrate inhibitors of acetylcholinesterase compared to non-substrate inhibitors?

Answer 41

Substrate inhibitors: bind as a substrate for acetylcholinesterase and is metabolized way slower than acetylcholine Non-substrate inhibitor: blocks site of action for acetylcholinesterase