Anticholinergics/Cholinergics Flashcards Preview

Toxicology > Anticholinergics/Cholinergics > Flashcards

Flashcards in Anticholinergics/Cholinergics Deck (16):

Where are nicotic receptors found?

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


Where are muscarinic receptors found

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


List nicotinic and muscarinic agonists and antagonists?

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
- Volatile anasethetics

Direct nicotinic antagonists:
- Non-depolarizing NM blockers
- Trimethaphan
Indirect neuronal nicotinic antagonists
- Physostigmine
- Tacrine
- Galantamine
Direct muscarinic antagonists
- Antihistamines
- Atropine
- Benzatropine (cogentin)
- Clozapine
- Cyclobenzaprine
- Disopyramine
- Orphenadrine
- Orphenadrine
- Phenothiazines
- Procainamide
- Scopolamine
- Trihexyphenidyl
Inhibit ACh release
- Botulism toxins
- Hypermagnesemia


What plant species contain naturally occuring antichilinergic agents?

Jimson Weed (scopolamine)
Belladona (atropine)


What are the features of the anticholinergic toxidrome?

- 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


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?

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


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

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


List 4 goals of management of acetylcholinesterase inhibitor toxicity.

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


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

- 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


What are the definitive therapies for organophosphate toxicity?

- 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


How is atropine dosed?

- 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


What are the main types of Nerve Agents?

· 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


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

- 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)


Give examples of biprydidyl compounds

Paraquat, diquat


What is the pathophysiology of bipyridyl compounds?

- 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.


What is in roundup and how is it managed?

Glyphosphate: supportive care