Anticholinergics/Cholinergics

Question 1

Where are nicotic receptors found?

Answer 1

Spinal cord
Skeletal muscle jxn (Na channels)
Postganglionic neurons (Ca channels)

Question 2

Where are muscarinic receptors found

Answer 2

CNS-brain
Posganglionic at end organs (heart-vagus nerve, smooth muscle -eye,GI,bladder)
Postganglionic sweat glands

Question 3

List nicotinic and muscarinic agonists and antagonists?

Answer 3

Cholinergics:
Cause ACh release:
- Aminopyridines (pesticide)
- Black widow spider venom
- alpha-2-adrenergic antagonist (mirtazapine, phentolamine)

Anticholinesterases: cause SLUDGE
- Organophosphates
- Insecticides
- Physostigmine
- Donepezil
Direct nicotinic agonist:
- Nicotine
- Succinylcholine
- Cystine
Indirect neuronal nicotinic agonist:
- Chlorpromazine
- EtOH
- ketamine
- Local anasethetics
- PCP
- Volatile anasethetics

Anticholinergics:

Direct nicotinic antagonists:
- Non-depolarizing NM blockers
- Trimethaphan

Indirect neuronal nicotinic antagonists
- Physostigmine
- Tacrine
- Galantamine

Direct muscarinic antagonists
- Antihistamines
- Atropine
- Benzatropine (cogentin)
- Clozapine
- TCA
- Cyclobenzaprine
- Disopyramine
- Orphenadrine
- Orphenadrine
- Phenothiazines
- Procainamide
- Scopolamine
- Trihexyphenidyl

Inhibit ACh release
- Botulism toxins
- Hypermagnesemia

Question 4

What plant species contain naturally occuring antichilinergic agents?

Answer 4

Jimson Weed (scopolamine)
Belladona (atropine)

Question 5

What are the features of the anticholinergic toxidrome?

Answer 5

• CNS: Altered LOC, myoclonus or choreoathetoid movements
  o Can have Sz (more common in peds)
• ENT: Mydriasis
• CVS: tachycardia
• GI/GU: Absent BS, urinary retention
  Derm: Dry MM, no sweat, flushed skin, fever à increased motor activity, impaired heat exchange

Question 6

If you have a patient with an anticholinergic toxidrome who has signs of Na channel blockade with a wide QRS, what drugs would you be thinking of?

Answer 6

• Diphenhydramine (rare)
• Other first generation antihistamines à ie chlorphenydramine (found in cough / cold preparations), can also prolong Qt
• TCA
• Carbamazepine
  Phenothiazine

Question 7

What is the main clinical difference between carbamate toxicity and organophosphate toxicity?

Answer 7

• Carbamates do not “age” / reversibly bind with acetylcholinesterase

Question 8

List 4 goals of management of acetylcholinesterase inhibitor toxicity.

Answer 8

1. Decontamination
   
   2. Supportive care
   3. Reversal of acetylcholine excess at muscarinic sites
      Reversal of toxin binding on the cholinesterase molecule

Question 9

Why is a nondepolarizing agent preferred for RSI in a cholinergic toxicity?

Answer 9

• Succinylcholine may have an extremely long duration because it is broken down by pesudocholinesterase, up to 7 hours!
• May need a higher dose of Roc to outcompete excessive ACh at NMJ

Question 10

What are the definitive therapies for organophosphate toxicity?

Answer 10

• Atropine:
  o Competitive inhibitor of ACh at muscarinic receptors
  o Reverses the clinical effects of cholinergic excess at PNS target organs and sweat glands
  o (Ryan says to use glycopyralate)
• Praladoxime (2-PAM):
  o Nucleophile that breaks the organophosphate-acetylcholineterase complex
  o Restores cholinesterase activity at muscarinic and nicotinic sites

Question 11

How is atropine dosed?

Answer 11

• 1-2 mg (0.02 – 0.05 mg/kg in peds) IV, with doubling of dose every 3 minutes
• Titrate until airway secretions become dry
• May require massive doses – 200-500mg atropine!
• Once Sx controlled, run infusion at 5-100mg/hr to maintain adequate secretion control

Question 12

What are the main types of Nerve Agents?

Answer 12

· German agents “G”
	o GA – Tabun. Ages in >40h
	o GB – Sarin. Ages in 5h
	o GD – Soman. Ages in 2 minutes. AS SUCH IT IS THE DEADLIEST!
· VX

Question 13

What is the clicical picture of chlorophenoxy herbicide toxicity (eg Agent Orange)

Answer 13

- Mild:
	o Nonspecific dermal and GI symptoms
- Severe:
	o Diffuse myotonia
	o Muscle fasciculations
	o Rhabdomyolysis
	o Hyperthermia
	o Hypermetabolism (metabolic acidosis and uncoupling of oxidative phosphorylation)

Question 14

Give examples of biprydidyl compounds

Answer 14

Paraquat, diquat

Question 15

What is the pathophysiology of bipyridyl compounds?

Answer 15

• Superoxide formation and lipid peroxidation of cellular membranes
• Concentrates in the lungs, oxygen increases paraquat induced injury à results in direct injury to alveolar capillary membrane, surfactant loss, ARDS, pulmonary fibrosis, respiratory failure
• Other organ systems damaged à liver, kidneys, heart, CNS
• Diquat is similar, with most injury concentrated on kidneys rather than lungs.

Question 16

What is in roundup and how is it managed?

Answer 16

Glyphosphate: supportive care