L9: Drugs and the Parasympathetic Nervous System Flashcards
What is the classification of peripheral nervous system?
- somatic (skeletal muscle, voluntary)
- autonomic (smooth and cardiac muscle, exocrine glands)
i) sympathetic (Fight/Flight)
ii) parasympathetic (rest/repose)
What are the different cholinergic receptors in parasympathetic nervous system?
-
Nicotinic:
i) neuronal (brain OR ganglionic) -
Muscarinic:
i) M 1, 3, 5 (Gq/11);
ii) M 2, 4 (Gi/Go)
What is the reaction of Acetylcholine synthesis?
Acetyl CoA + Choline –> Acetylcholine + CoA
By choline acetyltransferase
In which pathology is choline acetyltransferase implicated?
Alzheimer’s disease
What does hemicholinium do in regard to acetylcholine synthesis?
Hemicholinium blocks the transport of choline into the nerve terminal. (no therapeutic use, but pharmacological tool)
What does vesamicol do in regard to acetylcholine storage?
Vesamicol inhibits transport of acetylcholine into vesicles
What does tetrodotoxin do in regard to acetylcholine release?
Tetrodotoxin is the toxin found in the Puffer fish, blocks voltage gated Na+ channels, stopping an AP from being generated in a nerve and thus blocking AP-dependent release of neurotransmitter from nerve terminals
How does botulinum toxin affect synaptic vesicles?
It prevents fusion of synaptic vesicles with membrane of the presynaptic terminal
What are the therapeutic uses of botulinum toxin?
Treatment of:
- persistent and disabling eyelid spasm
- excessive extensor muscle tone (hypertonia, muscle stiff and hard to move)
- bladder over activity
- squint (injection into extra ocular muscles)
- excessive salivary secretion or sweating
What are neuromuscular blockers? What are they classified as? What are they used for usually?
Clinically useful drugs that act to block the interaction of acetylcholine with the nicotinic receptor. Used for general anaesthesia. Classified as:
- non-depolarizing
- depolarizing antagonists.
What are non-depolarizing blockers?
They compete with acetylcholine for the agonist binding site on the nAChRs, they competitive receptor antagonists (block neurotransmission)
How can the action of non-depolarizing blockers be overcome?
It can be overcome by the administration of an anti-cholinesterase drug.
Increasing [agonist] in the synaptic cleft increases the probability that an agonist molecule will occupy the binding site on the receptor-channel rather than an antagonist molecule.
When are neuromuscular blockers often used?
Commonly they are used as adjuncts to general anaesthesia.
What’s the action of atracurium in terms of non-depolarizing blockers? (onset; duration; side effects, usage)
- onset: intermediate
- duration: <30min
- side effects: transient hypo
- usage: +++
What’s the action of Pancuronium in terms of non-depolarizing blockers? (onset; duration; side effects, usage)
- onset: intermediate
- duration: long
- side effects: sI tachycardia
- usage: +++
What are depolarizing blockers? Give an example (chemical nature, mechanism of action, duration of action; side effects)
- Depolarizing blockers activate the nicotinic receptor.
- Suxamethonium - only depolarizing blocker used clinically.
- Chemical nature: two acetylcholine molecules linked by their acetyl groups.
- Mechanism of Action: It produces a small amount of sustained depolarisation at the endplate, that ultimately cause the nicotinic receptors to inactivate - i.e. the pore does not open in response to the binding of agonist.
- Duration of action: It’s broken down by cholinesterase, so short duration of action. Used for brief procedures.
- Side effects: bradycardia, potassium release, raise intraocular pressure; prolonged paralysis in individuals with low plasma cholinesterase levels or in those receiving anti-cholinesterase drugs.
What’s the mechanism of action of Suxamethonium in terms of depolarizing blockers?
Mechanism of Action: It produces a small amount of sustained depolarisation at the endplate, that ultimately cause the nicotinic receptors to inactivate - i.e. the pore does not open in response to the binding of agonist.
What’s the duration of action of Suxamethonium in terms of depolarizing blockers? Why is it like that?
Duration of action: It’s broken down by cholinesterase, so short duration of action. Used for brief procedures.
What are the side effects of Suxamethonium in terms of depolarizing blockers?
Side effects:
- bradycardia,
- potassium release,
- raised intraocular pressure;
- prolonged paralysis in individuals with low plasma cholinesterase levels or in those receiving anti-cholinesterase drugs.
How can the action of depolarizing blockers be overcome?
The block produced by a depolarizing blocker is NOT relieved by an anti-cholinesterase.
What are parasympathomimetic or cholinomimetic drugs?
Drugs that mimic the effects of parasympathetic nerve stimulation, particularly by activation of responses mediated by muscarinic cholinergic receptors.
What are the effectors of muscarinic receptor activation?
Mucarinic receptors can:
- activate phospholipase C to cause production of IP3 and diacyl glycerol (second messengers)
- inhibit adenylate cyclase causing a decrease in the levels of cAMP
- activate K+ channels and inhibit Ca2+ channels (hyperpolarisation)
What are the main subtypes of muscarinic receptor? What are their functions?
- M1 receptors - neural (slow EPSP in ganglia)
- M2 receptors - cardiac (decrease rate and force of contraction; heart)
- M3 receptors - secretion, contraction of visceral smooth muscle, vascular relaxation
- M4 and M5 receptors - found in CNS
What is the classification of direct acting agonists? What are their examples?
- choline esters (acetylcholine, methacoline, carbachol, bethanecol)
- natural plant compounds (pilocarpine, muscarine)
