CIS: Cholinergic Agonists And Antagonists

Question 1

In parasympathetic innervation to a smooth muscle cell in bronchioles of lung, a muscarinic acetylcholine receptor antagonist would be expected to elicit what response?

Answer 1

Relaxation by blockade at receptor on effector cell

Question 2

If effector cell is sinoatrial node of heart, what neurotransmitter is most likely released from preganglionic neuron in sympathetic nervous system?

Answer 2

Acetylcholine

Question 3

If effector cell is a sinoatrial muscle cell in heart, what neurotransmitter is most likely released from postganglionic sympathetic cell?

Answer 3

Norepinephrine

Question 4

Compare/contrast parasympathetic vs sympathetic tone

Answer 4

Parasympathetic:
Cholinergic
Salivation, lacrimation
Pupil constriction (miosis)
Decrease in HR
Urination, defecation
Increased secretion and motility
Rest and digest
Smooth muscle contraction
Blocked by atropine

Sympathetic
Adrenergic (anticholinergic)
Cutaneous vasodilation
Pupil dilation (mydriasis)
Increase in HR
Reduction/elimination of desire to urinate
Decreased secretion and motility
Fight or flight
Smooth muscle relaxation
Reversed by acetylcholinesterase inhibitors

Question 5

29 y/o active duty male soldier presents unconscious with nonreactive, pinpointsized pupils, massive oral foaming, and muscle fasciculations. His pants are wet with urine.

1. What receptor family is most likely involved?
2. An agent from which drug class most likely ingested?
3. Which combination most likely administered as antidote?

Answer 5

1. Cholinergic
2. AChE inhibitor
3. Atropine and pralidoxime

Question 6

Describe AChE (organophosphate) inhibitor toxicity

Answer 6

SLUDGE: Salivation, lacrimation, urination, defecation, GI pain/gas, and emesis

DUMBELS: Defecation, urination, miosis, bronchorrhea/bronchospasm/bradycardia, emesis, lacrimation, salivation

Ingestion: GI symptoms first
Percutaneous absorption: localized sweating and muscle fasciculations
Lipid-soluble agents: CNS involvement follows rapidly

Question 7

Describe cholinesterase regenerators and antidote for organophosphate exposure

Answer 7

-Reactivate inactive AChE by removing phosphorous group from active site

Pralidoxime
Can restore active enzyme within minutes
Must give before aging occurs between AChE an organophosphate
Relief at nAChRs

Antidote

1. Parenteral atropine
2. Oxime (pralidoxime)
3. Benzodiazepine to alleviate convulsions

Question 8

46 y/o female presents complaining of dry eyes and dry mouth. Symptoms have been present for past 6 months and have progressively worsened. Saw ophtho 3 months ago and is using artificial tears with little relief. She often has to wake up in the night to drink water and frequently has to drink to help swallow food. She experiences feeling of grit or sand in her eyes on a daily basis.

1. Which agent is most appropriate?
2. Which drug?
3. Cevimeline (PO) is prescribed to treat her symptoms. Adverse effect?
4. If present in pt’s history, which would most likely be exacerbated by cevimeline?

Answer 8

1. mAChR agonist
2. Pilocarpine
3. Diaphoresis
4. Asthma

Question 9

2 y/o female presents to ED after accidental overdose of antihistamines. Temp 102.5F. Pupils fixed and dilated. HR 160 bpm (normal 120). Signs of delirium and noted to have marked cutaneous vasodilation upon PE.

1. Exhibiting symptoms of overactivity of which division of nervous system?
2. What additional symptom would you expect this pt to exhibit?
3. Stimulation of which receptor will most likely correct her combination of symptoms?
4. Most appropriate agent?

Answer 9

1. Sympathetic nervous system
2. Urinary retention
3. Muscarinic acetylcholine receptor (mAChR)
4. Physostigmine (uncharged AChE inhibitor)

Question 10

52 y/o female presents for routine ophthalmic exam. Visual acuity without correction was 20/40 R eye and 20/80 L eye. Intraocular pressure is elevated in both eyes. Visual field exam reveals a nerve fiber bundle defect consistent with glaucoma. No signs of cataract formation. Family history is positive for glaucoma. Currently being treated for heart failure, hypertension, and asthma.

1. What topical agents is contraindicated?

Answer 10

1. Atropine (reduces secretions)

Question 11

Describe treatment of glaucoma

Answer 11

Topical medications work either by increasing aqueous outflow (alpha agonsts, miotics, epinephrine, muscarinic antagonists, and prostaglandins) or by decreasing aqueous production (alpha agonists, beta blockers, and carbonic anhydrase inhibitors)

Iris sphincter and ciliary muscle contraction cause increased aqueous humor outflow into canal of Schlemm (drains anterior chamber)

Question 12

83 y/o female resident of nursing facility presents with 2 month history of worsening urinary incontinence. 3 years ago, presented with same symptoms, which were adequately managed with adult diapers and bladder training.

1. She is exhibiting symptoms consistent with activation of which division of nervous system?
2. Which agent will alleviate her symptoms?
3. 2 weeks after initial therapy, what adverse effect?
4. What alternative agent with fewer side effects?

Answer 12

1. Parasympathetic nervous system
2. Oxybutynin (mAChR antagonist, inhibits urinary bladder smooth muscle contraction)
3. Constipation (also dry mouth/eyes, dizziness, blurred vision)
4. Darifenacin (also solifenacin and tolterodine are selective for M3 and have longer half-lives and reduced incidence of xerostomia and constipation)

Question 13

52 y/o male smoker presents with daily cough and mild dyspnea on exertion with strenuous activity. Walking up 2 flights of steps bothers him when previously did not. Wheezing but no chest pain. PMH unremarkable. COPD.

1. Which agent appropriate?
2. Which agent prescribed?
3. Smoking cessation and #2 prescribed. Adverse effect?

Answer 13

1. MAChR antagonist
2. Tiotropium (longer bronchodilation than ipratropium)
3. Decreased mucus production (may lead to infection)