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Vesamicol
- Presynaptic Mechansim
- Blocks ACh uptake into storage vesicles - results in a depletion of ACh
- Not selective
-
Hemicholinium
- Presynaptic Mechansim
- Blocks choline uptake back into the presynaptic terminal - results in less ACh being produced
- Not selective
- Can't be overcome by increasing ACh (because it's an open channel block of all nicotinic receptors)
-
Black Spider Widow Toxin
- Presynaptic Mechanism
- Empties synaptic vesicles and prevents them from refilling - results in a massive release of ACh
- Trasmission across the NMJ is blocked and a paralysis of respiratory muscles results
-
4-aminopyridine (4-AP)
- Presynaptic Mechanism
- It blocks nerve fibre K+ channels and causes a prolonged action potential - results in more ACh being released
- Multiple Sclerosis: Small trials have inidcated that high doses of 4-AP has shown improvement
- Myasthenia Gravis: rarely used for this now
- Spinal Cord Injury: some promising results from small clinical trials
-
Acetylcholinesterase Inhibitors
- Presynaptic Mechansim
- Examples: pyridostigmine, neostigmine
- They inhibit the breakdown of ACh in the synaptic cleft - results in more ACh being present
- Drug of choice for myasthenia gravis
-
Botulinum Toxin A (Botox) & B (Myobloc)
- Presynaptic Mechanism
- It blocks the vesicular release of ACh by cleaving docking proteins (Toxin A/Botox cleaves SNAP 25, Toxin B/Myobloc cleaves VAMP/Synaptobrevin) - results in less ACh in the synapse
- Results in the weakening to flaccid paralysis of skeletal muscles
- Reversal takes 3-4 months
- Myobloc has a shorter action than Botox
- Cosmetic: treatment of frown lines, forhead lines, orbital lines
- Opthalmic: treatment of strabismus (lazy eye) and blepharospasm (spasmodic winking)
- Face and Neck Muscle Spasms
- Hyperhidrosis: treatment of excessive sweating
- Pain: may decrease migraine headaches and lower back pain
- Contraindications: not be used in patients with NMJ disorders (ex. myasthenia gravis, multiple sclerosis)
- Side Effects: local weakness of muscles at site of injection, ptosis (drooping eyelid), flu-like symptoms, long term use can alter muscle fiber size
-
Tubocurarine
- Non-depolarizing Postsynaptic Mechanism
- It binds to the nicotinic receptor and blocks ACh binding (blocking can be overcome by high number of ACh)
- IV Route
- Surgical Muscle Relaxation and Mechanical Ventilation (prevents respiratory effort from patient)
-
Pancuronium
- Non-depolarizing Postsynaptic Mechanism
- It binds to the nicotinic receptor and blocks ACh binding (blocking can be overcome by high number of ACh)
- IV Route
- Surgical Muscle Relaxation and Mechanical Ventilation (prevents respiratory effort from patient)
-
Atacurium
- Non-depolarizing Postsynaptic Mechanism
- It binds to the nicotinic receptor and blocks ACh binding (blocking can be overcome by high number of ACh)
- IV Route
- Surgical Muscle Relaxation and Mechanical Ventilation (prevents respiratory effort from patient)
-
α Bungarotoxin
- Cobra venom
- Non-depolarizing Postsynaptic Mechanism
- It binds to the nicotinic receptor and blocks ACh binding (blocking can be overcome by high number of ACh)
- Bite route
-
Succinylcholine
- Depolarizing PostSynaptic Mechansim
- It binds and activates the nicotinic receptor (acts like ACh) - results in muscle contraction
- The nicotinic receptor becomes desensitized over time
- IV route, rapidly broken down
- Side effects: Stimulates all nicotinic and cholinergic receptors (not selective), arrhythmias, bradycardia, emesis (vomiting), muscular pain, increased intraocular pressure
- Contraindications: People with fractures, glaucoma patients, and paraplegia patients (it could cause excessive loss of K+)
-
Dantrolene
- It reduces the release of Ca2+ which results in less muscle contraction (it does not block neuromuscular tramission)
- Taken orally
- Malignant hyperthermia: malignant hyperthermia is caused by a large release of Ca2+ which leads to an increase of body temperature. Drug of choice for this.
- Spasticity
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