Lecture 13: Nerves II - Cholinergic neurotransmission Flashcards
*Outline the different classes of cholinergic agonists
DIRECT ACTING
INDIRECT ACTING => REVERSIBLE & IRREVERSIBLE
*Describe, with examples, the mode of action of the direct acting cholinergic agonists
ACETYLCHOLINE = agonist at both MUSCARINIC and CHOLINERGIC receptors. It has few therapeutic actions because of its multiplicity of actions. Miochol-E is used to obtain complete miosis of the iris in seconds after placement of the intraocular lens (IOL) in cataract surgery and in penetrating keratoplasty, iridectomy and other anterior segment surgery where rapid miosis may be required.
BETHANECHOL = agonist at only MUSCARINIC receptors. directly stimulates receptor => increased intestinal
motility and tone. + stimulates detrusor muscles of the bladder whilst the trigone and sphincter are relaxed
causing expulsion of urine. stimulate the atonic bladder,
particularly in postpartum or postoperative, non-obstructive urinary obstruction.
*Describe, with examples, the mode of action of the indirect acting cholinergic agonists (REVERSIBLE)
ACETYLCHOLINESTERASE enzyme cleaves acetylcholine to choline and acetate thus removing the neurotransmitter from the synapse and attenuating its
response. Anticholinesterase inhibitors prolong the presence of acetylcholine in the synapse. These drugs can provoke a response in all cholinoceptors in the ANS as well as at neuromuscular junctions and in the brain.
NEOSTIGMINE is used in the symptomatic treatment of
myasthenia gravis, an autoimmune disease
caused by antibodies against the nicotinic receptor
at neuromuscular junctions. This causes their degradation and makes fewer receptors available for available for interaction with the neurotransmitter. It has a duration of action of 0.5-2 hours.
TACRINE, DONEZEPIL (Aracept), RIVASTIGMINE (exelon) &;
GALANTAMINE (Reminyl) = Tx mild/moderately severe dementia of the Alzheimer type. Tacrine was first used but
was quickly replaced due to its hepatotoxicity.
These drugs can delay the progression of the
disease but cant stop progression.
*Describe, with examples, the differences between the 3 major groups of cholinergic antagonists
- The ANTIMUSCARINIC agents selectively block the
muscarinic receptors at the muscarinic synapses of the
parasympathetic system. The effects of parasympathetic
innervation are disrupted but the actions of sympathetic
stimulation are left unopposed. - The GANGLIONIC BLOCKERS show a preference for the
nicotinic receptors of the sympathetic and parasympathetic
ganglia. - The NEUROMUSCULAR BLOCKERS bind to acetylcholine receptors postsynaptically (nicotinic receptor) and inhibits action of acytlcholine = paralysis of muscle
*Describe in detail the systemic effects, therapeutic uses and adverse events of ATROPINE.
SYSTEMIC EFFECTS
Eye = (causes mydriasis = pupil dilation, unresponsiveness to light, cycloplegia – inability to focus)
GI Tract = (antispasmodic)
Urinary system = (reducing hypermotility states of the urinary bladder, enuresis in children)
CV system = (decrease in cardiac output)
Secretory system = (blocks the salivary glands causing dry mouth, effects on sweat and lacrimal glands)
THERAPEUTIC USES
Eye = (used for its mydriatic and cytoplegic effects allowing eye examination and measurement)
GI tract and urinary system = (used as an antispasmodic to relax the gut and bladder)
Secretory system = (used as an antisecretory agent to block secretions in the upper and lower respiratory tracts prior to surgery)
Antidote for cholinergic agonists = Tx overdose with cholinesterase inhibitor pesticides and to block the effects of excess acetylcholine resulting with treatment with inhibitors such as physostigmine)
ADVERSE EVENTS
Low levels = mild effects i.e. dry mouth
High doses = death can occur.
*Describe in detail the systemic effects, therapeutic uses and adverse events of SCOPOLAMINE.
SYSTEMIC EFFECTS
greater action on the CNS and a longer duration of action in comparison to atropine
THERAPEUTIC USES
Anti-motion sickness drug
blocking short term memory.
ADVERSE EVENTS
Similar to atropine although it can have
sedative effects.
*Describe, with examples, how ganglionic blockers exert their effects
specifically act on the NICOTINIC receptors of BOTH sympathetic and parasympathetic autonomic ganglia.
no selectivity = not effective as neuromuscular antagonists.
These drugs are rarely used therapeutically.
E.G. NICOTINE
TRIMETHAPHAN and MECAMYLAMINE can be used as
emergency treatments for severe hypertension.
*Compare and contrast the mechanisms of action of depolarising and non-depolarising neuromuscular blockers
- NON-DEPOLARISING blocking agents (the majority) which act by blocking acetylcholine receptors or ion channels. Examples = TUBOCURARINE, PANCURONIUM
- DEPOLARIZING blocking agents which are agonists at acetlycholine receptors.
Examples = SUCCINYLCHOLINE, DECAMETHONIUM
*Describe in detail the systemic effects, therapeutic uses and adverse events of TUBOCURARINE
Neuromuscular blockers
SYSTEMIC EFFECTS
THERAPEUTIC USES
originally used as a muscle relaxant in conjunction with anaethetics during surgical operations.
ADVERSE EVENTS
At low doses, tubocurarine antagonises the effects of acetylcholine in end plate smooth muscle, inhibiting muscle contraction. At high doses, tubocurarine also blocks the ion channel at the end plate, further weakening the neuromuscular transmission.
*Describe in detail the systemic effects, therapeutic uses and adverse events of SUCCINYLCHOLINE
Neuromuscular blockers
SYSTEMIC EFFECTS
THERAPEUTIC USES
Because of its rapid onset and short duration, succinylcholine is used in aiding endotracheal intubation during the introduction of surgical anaesthesia. It is also used during ECT.
ADVERSE EVENTS
Hyperthermia, apnea
