RCS 06 - Cholinergic Agonists & Antagonists 2

Question 1

Answer 1

D

Question 2

List the different classes and subclasses of cholinergic antagonists.

Answer 2

• Muscarinic receptor antagonist
  
  • Belladonna Alkaloids
  • Synthetics/Semisynthetics
• Nicotinic receptor antagonist
  
  • Ganglion blockers
  • NMJ blockers
• Drugs that act presynaptically

Question 3

List the muscarinic receptor antagonists we need to know.

Answer 3

• Belladonna Alkoloids - atropine and scopolamine
• Synthetics/Semisynthetics - ipratropium, tiotropium, homatropine, tropicamide, benztropine, trihexyphenidyl, glycopyrrolate, tolterodine
• Most antihistamines
• Antipsychotics
• Antidepressants

Question 4

Describe the structure and distribution profile for atropine. What type of antagonist is atropine?

Answer 4

• Tertiary amine which means it distributes easily
• Reversible competitive antagonist at muscarinic receptors

Question 5

List the effects of atropine that we need to know. Explain the MOA for the odd effects.

Answer 5

• Eye - mydriasis (pupil dilation), Cycloplegia (paralysis of ciliary muscles)
• GI - reduced gastric motility
• Urinary System - decreases bladder hypermotility
• CVS
  
  • Low doses - bradycardia, due to blockade of mostly presynaptic M2
  • Moderate/High doses - tachycardia, due to blockade of atrial M2
  • High doses or increased sensitivity causes “atropine flushing.” Mechanism unknown
• Secretions - inhibition of salivary, sweat (possible causin high body temp), and lacrimal

Question 6

What are the common uses of atropine?

Answer 6

• Antispasmodic - to relax GIT and bladder
• Antidote for cholinergic agonists
• To block respiratory tract secretions during surgery
• To overcome cardiac insufficiency due to an AV block

Question 7

What are the adverse effects of atropine? What drug is used to treat atropine poisoning and why?

Answer 7

• Adverse Effects - dry mouth, blurred vision, sandy eyes, tachycardia, constipation, urinary retention, restlessness, confusion, hallucinations, delirium which may progress to depression, and, if bad enough, collapse of the CVS and respiratory system leading to death
• Treated with physostigmine because it is the only cholinesterase inhibitor that is also a tertiary amine like atropine

Question 8

Explain the uses for scopolamine.

Answer 8

• Prevents motion sickness by blocking the M1 receptors in the vomiting center
• Blocks short-term memory
  
  • sometimes used in anasthetic procedures
  • also used by sexual predators

Question 9

List the synthetic quaternary ammonium muscarinic antagonists we need to know. What are their uses and MOA?

Answer 9

Ipratropium and Tiotropium

• Used as an inhalation drug in the treatment of COPD and Asthma by antagonizing the M3 respirators in the bronchiole smooth muscle to cause bronchodilation.

Question 10

List the synthetic tertiary amine muscarinic antagonists we need to know.

Answer 10

• Homatropine
• Tropicamide
• Benztropine
• Trihexyphenidyl

Question 11

What are the uses of homatropine and tropicamide? Why cant atropine be used for this instead?

Answer 11

Used as an eyedrop to produce mydriasis (cycloplegia is an adverse effect) for fundoscopy

Atropine’s effects last way too long

Question 12

What are the uses of benzotropine and trihexyphenidyl? Describe the MOA

Answer 12

• Used to treat Pakinson’s Disease. The basal ganglia need to receive a balanced input from cholinergic and dopaminergic neurons to maintain regular body motions. In Parkinson’s disease, the dopaminergic neurons are dying. These drugs reduce the effect of the cholinergic input so that balance is achieved again.
• Used to treat extrapyrmaidal effects (similar to parkinson’s symptoms) caused by antipsychotic drugs. Antipsychotics are potent dopamine blockers. Benzotropine/Trihexyphenidyl help to restore the cholinergic-dopaminergic balanced input to the basal ganglia

Question 13

What are the uses of glycopyrrolate and tolterodine?

Answer 13

• Glycopyrrolate - given orally to inhibit GI motility. Given intravenously to prevent anasthesia induced bradycardia during surgery
• Tolterodine - used to treat an overactive bladder

Question 14

What are the major contraindications for antimuscarinic agents?

Answer 14

• Patients with angle-closure glaucoma because mydriasis further closes the angle
• Patients with prostatic hypertrophy because they usually already have difficulty urinating
• Use with caution in the elderly because these drugs seem to cause hallucinations and psychosis in the elderly.

Question 15

What does a ganglion blocker do and how? List the ganglion blockers we need to know.

Answer 15

A ganglion blocker is a medication that inhibits transmission between preganglionic and postganglionic neurons in the ANS. They do those in one of two ways:

• By prolonged depolarization - Nicotine
• By antagonism of Nn receptors - Hexamethonium and Mecamylamine

Question 16

How can the effect of a ganglion blocker on a specific tissue be predicted?

Answer 16

You have to know what receptor/innervation has predominant control over that tissue, and what the action of that control is on the tissue. A ganglion blocker will have the opposite effect on the tissue.

Question 17

List the types of neuromuscular blockers.

Answer 17

Nondepolarizing Type - Nm competitive antagonists

Depolarizing Type - Nm agonists

Presynaptic Acting - either inhibit ACh synthesis, storage, or release

Question 18

What is the prototype drug for nondepolarizing NM blockers? What is this drug’s MOA and uses?

Answer 18

Tubocurarine is a competitive antagonist of N_m channels. It is used as an adjuvant drug with anasthesia during surgery to relax skeletal muscle

Question 19

Which durgs can be used to reverse the effects of tubocurarine?

Answer 19

Edrophonium and Neostigmine

Question 20

What is the prototype drug for depolarizing NM blockers? What is this drug’s MOA and uses?

Answer 20

Succinylcholine persistently binds to the N_m receptor and depolarizes the NMJ leading to receptor desensitization and flaccid paralysis. Primarily used during rapid endotracheal intubation and ECT (electroconvulsive therapy).

Question 21

What are the adverse effects of depolarizing NMJ blockers like succinylcholine that we need to know? How are these effects treated?

Answer 21

Malignant hyperthermia is a rapid increase in body temp accompanied by severe muscle contractions. It occurs in patients who have a mutated ryanodine receptor (releases Ca++ from SR) that opens quickly/easily and closes slowly, when they receive a combination os succinylcholine and a halogenic anesthetic.

Treated with dantrolene, which blocks Ca++ release from the SR

Question 22

Lis the drugs we need to know that inhibit ACh synthesis. What are their MOAs and uses?

Answer 22

Hemicholinium-3 is a drug that blocks CHT (choline transporter) so that choline cannot be transported into the presynaptic neuron. This drug is primarily used as a research tool

Question 23

Lis the drugs we need to know that inhibit ACh storage. What are their MOAs and uses?

Answer 23

Vesamicol is a drug that blocks VAChT (vesicular ACh transporter) so that ACh cannot be transported into vesicles. Primarily used as a research tool.

Question 24

Lis the drugs we need to know that inhibit ACh release. What are their MOAs and uses?

Answer 24

Botulinum Toxin is a drug that cleaves the SNAPs/SNAREs required for vesicle release. It is injected into muscles for treatment of several diseases involving muscles spasms. Most notably, blepharospasm, which cause the orbicularis occuli muscle to spasm. Also used to reduce wrinkles.

Question 25

Answer 25

F

Question 26

Answer 26

F

Question 27

Answer 27

B

Question 28

Answer 28

E

Question 29

Answer 29

A

Question 30

Answer 30

B

Question 31

Answer 31

A

Question 32

Answer 32

A

Question 33

Answer 33

A

Question 34

Answer 34

D

Question 35

Answer 35

B

Question 36

Answer 36

C