Flashcards in Anticholinergics/Cholinergics Deck (16):
Where are nicotic receptors found?
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
Direct nicotinic agonist:
Indirect neuronal nicotinic agonist:
- Local anasethetics
- Volatile anasethetics
Direct nicotinic antagonists:
- Non-depolarizing NM blockers
Indirect neuronal nicotinic antagonists
Direct muscarinic antagonists
- Benzatropine (cogentin)
Inhibit ACh release
- Botulism toxins
What plant species contain naturally occuring antichilinergic agents?
Jimson Weed (scopolamine)
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
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.
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?
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!
What is the clicical picture of chlorophenoxy herbicide toxicity (eg Agent Orange)
o Nonspecific dermal and GI symptoms
o Diffuse myotonia
o Muscle fasciculations
o Hypermetabolism (metabolic acidosis and uncoupling of oxidative phosphorylation)
Give examples of biprydidyl compounds
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.