Term
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Definition
Black widow venom
Destroys synaptic vesicles, resulting in flooding of Ach and synaptic failure
Presentation: Localized diaphoresis, weakness, myoclonus, local paresthesias, abdominal pain, can result in CV collapse, pulmonary edema, ileus |
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Term
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Definition
Tropical snake venom
Destroys synaptic vesicles, resulting in flooding of Ach and synaptic failure
Presentation: Localized diaphoresis, weakness, myoclonus, local paresthesias, abdominal pain, can result in CV collapse, pulmonary edema, ileus |
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Term
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Definition
Botulism
Caused by ingestion of C. botulinum spores
Found in poorly canned foods, honey (infants susceptible)
Toxin inhibits vesicle release paralysis
Local tx for spastic disorders, wrinkles (Botox) |
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Term
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Definition
Increase acetylcholine release by activating K channels
Tx used for Lambert-Eaton myasthenic syndrome
RARE, first defined by Mayo Drs Lambert, Eaton in 1957
Autoantibodies to presynaptic Ca channels block Ach release (often part of paraneoplastic syndrome)
Presentation: Slowly progressive prox muscle weakness
Autonomic dysfunction often seen: Dry mouth, constipation, impotence in men
Tx includes 3,4-diaminopyridine (Side effects often mild - paresthesias) |
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Term
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Definition
Ligand-gated sodium channel
Ach Increase Na+ influx depolarization |
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Term
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Definition
G-protein coupled receptor
α (αs, αi, αq, and αo) → binds GTP, main effector |
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Term
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Definition
- Preferentially targets ganglionic nAchRs, agonist short term then antagonist chronically
- Effects mainly in CNS
- Peripheral: Mixture of sympathetic/parasymp symptoms
Effects decline with repeated dosage
CV: Tachycardia / ↑ CO, BP
↓GI motility, nausea, vomiting
Diaphoresis |
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Term
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Definition
Ganglionic Antagonists
- First effective antihypertensive
- No longer used clinically |
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Term
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Definition
Ganglionic Antagonists
- Competitive ganglionic nAchR blocker
- Short-acting (must be given IV)
- Uses : Emergent perioperative lowering of BP |
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Term
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Definition
- Poison derived from mushrooms
- Bind muscarinic receptors
- Effects: Ach-like |
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Term
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Definition
Have more targeted effects
More resistant to degradation by ACE
Acetylcholine
Bethanechol
Carbachol
Pilocarpine |
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Term
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Definition
Bowel & Bladder
- More stable than carbachol
- Selective for muscarinic receptors
- Uses: Urinary retention (eg. postop)
Neurogenic ileus |
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Term
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Definition
- Selective for muscarinic receptors
- Very stable – effects last one day
- Uses: Local for open/closed angle glaucoma
Ciliary contraction opens Schlemm’s canal for drainage of aqueous humor
- Side effects:
- Can enter CNS and cause disturbances
- Profuse sweating and salivation |
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Term
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Definition
Block muscarinic receptors (little or no effect on nicotinic “receptors” [nAchRs])
Much more clinically useful than muscarinic agonists
Inhibit muscarinic functions
- Parasympathetic
- Sympathetic innervation of sweat glands (mAchRs) |
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Term
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Definition
Muscarinic Antagonists
Competitively binds and inhibits mAchRs
Effects last up to 4 hours (days in eye)
Uses:
-Eye – mydriasis and cycloplegia for eye exams
- Antispasmodic for bladder/GI
- Cholinergic overdose (eg. Mushroom poisoning, organophosphate poisoning)
- Preop antisecretory agent for respiratory tract |
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Term
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Definition
- “Red as a beet” (cutaneous flushing)
- “Hot as a hare” (fever)
- “Mad as a hatter” (CNS disturbances)
- “Dry as a bone” (Dry mouth)
- Events in older pts with narrow angle glaucoma |
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Term
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Definition
Similar peripheral effects as atropine
Stronger CNS effects including short-term memory loss
Uses:
- Motion sickness
- Occasionally as amnesic in anesthesia
Side effects similar to atropine |
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Term
Nondepolarizing (competitive) blockers
Neuromuscular Antagonists |
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Definition
- Inhibit AchRs at the motor endplate
- Causes flaccid paralysis
- Can be overcome with anticholinesterases |
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Term
Depolarizing agents
Neuromuscular Antagonists |
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Definition
- Activate AchRs repeatedly (agonism!)
- Produces first fasciculations followed by paralysis |
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Term
| Neuromuscular Antagonists : Competitive - Curare |
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Definition
Derived as an alkaloid from S.A. plants (darts)
Causes flaccid paralysis
-Small, rapid then respiratory muscles
Derivatives used as adjuvant muscle relaxants in anesthesia (various durations – 15 min – hrs):
-Tubocurarine
-Pancuronium
-Vecuronium
-Atracurium |
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Term
| Neuromuscular Antagonists : Depolarizing - Succinylcholine |
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Definition
Binds and activates nAch (Resists degradation by ACE)
Mechanism:
- Phase I – Depolarization fasciculations
- Phase II – Channels inactivate upon chronic stimulation (minutes) paralysis
SHORT action (< 10 min) – given IV
Uses : Short procedures like endotracheal intubation during induction of anesthesia
Side effects:
- Malignant hyperthermia with halothane (Dantrolene)
- Apnea |
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Term
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Definition
Inhibit ACE activity to increase Ach signaling
Reversible
Irreversible
“SLUDGE” Drugs |
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Term
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Definition
Most common NM transmission disorder (still uncommon)
Autoantibodies to nAchR and degrade the receptor
Symptoms : Ocular (ptosis, diplopia), Bulbar (fatigable chewing), Respiratory (myasthenic crisis)
Tx – Anticholinesterases to prolong effect of Ach:
- Edrophonium – Diagnosis
- Pyridostigmine, Neostigmine – Symptom management
- Immunosuppressives, possible thymectomy |
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Term
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Definition
Anticholinesterases: Reversible
Short-acting (10-20 min)
Diagnosis of myasthenia gravis (MG)
Competes with autoantibodies to the nAchR
(Currently being phased out as a diagnostic test) |
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Term
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Definition
Medium-acting
Anticholinesterases: Reversible
(2-4 hrs) – Oral symptomatic tx of MG
– Neurogenic ileus and urinary retention postop |
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Term
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Definition
Medium-acting
Anticholinesterases: Reversible
Symptomatic tx of MG |
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Term
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Definition
Anticholinesterases: Reversible
Medium-acting
(2-4 hrs) – Topical tx of glaucoma
– Antidote to atropine poisoning |
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Term
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Definition
Anticholinesterases: Irreversible
Mechanism:
- Irreversibly binds ACE active site
- Alkyl group is released (irreversible aging)
- PRALIDOXIME rescues ACE ONLY if tx before aging occurs
Cholinergic stimulation followed by paralysis
Uses :
- Insecticides
- Nerve gas (DFP, soman : “age” in seconds – minutes)
- Echothiophate – open-angle glaucoma |
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