Pharmacology of Neuromuscular and Ganglionic Blockers Flashcards
Nicotinic receptor antagonists are also known as
ganglionic blockers
Reflexes blocked by nicotinic receptor antagonists/ganglionic blockers
baroreceptor reflex and pupillary reflex
Two important ganglionic blocker drugs
Trimethaphan and mecamycalamine
Trimethaphan
hypotension for surgery
Mecamylamine
Tourette’s, smoking cessation, and severe hypertension
In general which is stronger, the PANS tone or the SANS tone
the PANS tone, except for regulating the smooth muscles of the vascular system
ganglionic blockade will result in
vasodilation and tachycardia
What do neuromuscular blockers do?
locally antagonize nicotinic receptors on skeletal muscle in the somatic nervous system
How do neuromuscular blockers block acetylcholine transmission pre-synaptically
decrease Ach formation/release, or increase metabolism
How do neuromuscular blockers block acetylcholine transmission post-synaptically
block cholinergic receptors (Nm)
Therapeutic use for neuromuscular blockers is primarily
to relax skeletal muscle: in surgery, orthopedic procedures, bronchoscopy and for artificial respiration/intubation
How do you monitor neuromuscular blockade with TOF impulses
procedures are usually performed when the patient responds with 1-2 twitches, as long as 1 twitch responses is observed the blockade can be quickly reversed, no additional dose of blocker should be given if no twitches are observable
Sequence of muscle paralysis by curare/neuromuscular blocker OD
muscles of the eye and those controlling speech are first to relax; fingers, toes then limbs become heavy; intercostals and diaphragm muscles are last; blockade of diaphragm muscles will lead to respiratory depression and eventual death
depolarizing neuromuscular blockers
agonist nicotinic acetylcholine receptors; persistent depolarization makes the muscle fiber resistant to further stimulation by ACh
Succinylcholine
depolarizing nicotinic acetylcholine receptor agonist - neuromuscular blocker
When is succinylcholine used
used in trauma care for intubation; also used for electro-convulsant therapy
What patients should you NOT give succinylcholine to?
patients with hyperkalemia as the additional release of potassium by the depolarizing agonist can cuase cardiac arrest
How does succinylcholine (suxamethonium) work?
agonist of the NAchR, causing a persistent opening of the channel, thereby preventing repolarization and thus preventing further action potentials from occuring
Non-depolarizing (curare-like) neuromuscular blockers
Pancuronium (Pavulon)
Vecuronium (Norcuron)
Atracurium (Tacrium)
Trimethaphan
How does the endogenous neurotransmitter acetylcholine bind
as an agonist to nicotine acetylcholinergic receptors; thereby opening the channels are causing an influx of sodium ions
Rocuronium
non depolarizing muscle relaxant and antagonist of the NAchR blocking acetylcholine induced activation and blocking nerve transmission
how can you reverse the actions of rocuronium
using an Ache inhibitor like neostigmine, which will increase the levels of acetylcholine that can compete with rocuronium or using sugammedex which directly binds and sequesters/scavenges rocuronium
Types of cholinesterases
Acetylcholinesterase (AChE) and Plasmacholinesterase (BuChE)
Where is AChE and BuchE located?
AchE is located in synapses
BuchE is located in the plasma
Classes of AchE inhibitors
carbamates, organophosphates, quarternary ammonium alcohols
Describe carbamates
quaternary or teritary amine groups, temporary covalent modification to AChE, reversible and rapid
Three important carbamate class AchE inhibitors
physostigmine, neostigmine, and pyridostigmine
Describe physostigmine
tertiary amine and can enter the CNS
What is physostigmine used for?
used for atropine OD, glaucoma and Alzheimer’s disease
What are neostigmine and pyridostygmine used to treat?
myasthenia graviis, reversal of neuromuscular blockers and post-operative ileus
Why is pyridostygmine better than neostigmine?
pyridostygmine is orally available and has a longer duration of action and fewer side effects compared to neostigmine
How do organophosphates bind
covalently but irreversibly to AchE
How has the irreversible nature of organophosphates been exploited?
in their use as insecticides and as nerve gas (ex. sarin gas)
How can insecticides cause problems in mammals?
although they are rapidly inactivated in mammals, high concentrations will still lead to paraysympathomimetic symptoms
Primary antidote for organophosphate poisoning?
parlidoximine (2-PAM) in combination with atropine
Explain why you have to use 2-PAM within a couple of hours after exposure to an organophosphate?
after an organophosphate has covalently bonding with AchE it will be further hydrolysed, once this has occured the bond is permanent and cannot be rescued anymore by 2-PAM, this hydrolysis process is known as aging
Signs of AchE inhibitor overdose or poisoning
DUMBBELSS
diarrhea, urination, miosis, branchospasms, bradycardia, excitation of skeletal muscle and CNS, lacrimation, sweating, salivation
Describe edrophonium
AchE inhibitor
How is edrophonium used?
used for the diagnosis of myasthenia gravis
Myasthenia gravis
autoimmune disease in which antibodies attack nicotinic acetylcholine receptors at the postsynaptic neuromuscular junction
Lambert Eaton induced myasthenia gravis
antibodies against vg calcium channels
What happens when you exercise with myasthenia gravis?
exercise worsens muscle strength
What happens when you exercise with Lambert Eaton induced myasthenia gravis?
exercise improves muscle strength
What happens when you give a mysasthenia gravis patient edrophonium?
edrophonium improves muscle strength
What happens when you give a lambert eaton MG patient edrophonium?
edrophonium has no effect/small increase in muscle strength
What happens when you give edrophonium in a patient experiencing a cholinergic crisis?
edrophonium has no effect/small decrease in muscle strength
What is a cholinergic crisis?
ex) overdose of Ache inhibitor
overstimulation -> paralysis -> weak muscles
Contraindications to the use of parasympathomimetic drugs?
asthma/COPD; coronary deficiency; peptic ulcer; obstruction of the urinary or GI tract; epilepsy
Cholinergic (Ach) centers in the CNS
nucleus basalis of meynert; medial septal nuclei; mesopontine tegmentum (brainstem)
Adrenergic (NE) centers in the CNS
locus ceruleus (pons-brainstem)
Degernation of the cholinergic cells in the nucleus basalis occurs in what?
dementia and PD (identified by Lewy bodies)
Alzheimer’s disease
most common cause of dementia after age 50; atrophy of the brain, widening of sulci and thinning of gyri; senile plaques, neurofibrillary tangles
Reversible AchE inhibitors that are used in managing symptoms of Alzheimer’s
donepezil, rivastigmine, galanthamine
Rivastigmine
reversible carbamate AChE inhibitor, enhances cognitive ability in AD by increasing cholinergic function
Galanthamine
reversible competitive AChE inhibitor; extract from daffodil bulbs; loses effectiveness as AD progresses
