Cholinergic & Anticholinergics Flashcards
A direct anticholinergic drug used for the treatment of chronic obstructive pulmonary disease (COPD) and sometimes as an adjunct in the treatment of asthma.
Ipratropium bromide: a muscarinic antagonist
In certain genetically susceptible patients, succinylcholine can cause…
Apnea
A drug was given to cause surgical paralysis. After surgery, the paralysis was reversed with neostigmine. The drug could have been…
Pancuronium or any other non-depolarizing neuromuscular blocking agent (NMBA).
These drugs are direct competitive antagonists at the neuromuscular nicotinic receptors. Increasing the availability of ACh with an AChE inhibitor, such as neostigmine, competes with the antagonism.
After initial transient activation that can cause fasciculations, succinylcholine causes flaccid paralysis. What is the reason for the flaccid paralysis?
Secondary non-depolarising block due to desensitization of nicotinic receptors.
For depolarizing NMBAs, this is referred to as Phase II of the block to avoid confusion with non-depolarizing NMBAs (e.g., pancuronium).
Nicotine depolarizes cells opening and inactivating Na+ channels, preventing the firing of action potentials. What is this called?
Depolarizing block
List at least THREE non-cosmetic clinical uses for botulinum toxin.
Treatment of:
Cervical dystonia
Blepharospasm (excessive blinking)
Strabismus (squints)
Migraine and other headache disorders
Upper limb spasticity
Name at least TWO examples of drugs that increase acetylcholine availability at neuromuscular junctions?
Neostigmine, physostigmine, pyridostigmine, donepezil or any other acetylcholine esterase (AChE) inhibitors.
Explain the mechanism of action of botulinum toxin.
When injected into skeletal muscle, botulinum toxin acts as an indirect anticholinergic by inhibiting the vesicular exocytosis of acetylcholine (ACh) at synaptic terminals.
It works by cleaving the SNARE proteins required for the capture/docking of synaptic vesicles at the presynaptic membrane.
Can surgical paralysis with succinylcholine be reversed by the administration of an acetylcholine esterase (AChE) inhibitor?
No. Succinylcholine is a depolarizing NMBA. It is a potent agonist at neuromuscular junction nicotinic receptors causing depolarising block and receptor desensitization. The addition of an AChE inhibitor will increase the availability of the endogenous agonist acetylcholine and so will not reverse succinylcholine-induced surgical paralysis.
Succinylcholine is an indirect anticholinergic agent clinically used for…
Surgical paralysis
To which class of cholinergic or anticholinergic drugs does botulinum toxin injected into skeletal muscle belong?
Botulinum toxin is an indirect anticholinergic drug. It works by inhibiting vesicular exocytosis of acetylcholine.
Why does pancuronium sometimes cause increases in heart rate as an adverse effect?
Muscarinic receptor antagonism
Why does pancuronium sometimes cause flushing, oedema and hypotension at high doses?
Histamine release
List TWO important characteristics/properties of drugs selected to be nondepolarising neuromuscular blocking agents.
Low lipid solubility: do not penetrate BBB.
Small volume of distribution (Vd):
By what route are MOST non-depolarizing neuromuscular blocking agents (NMBAs) excreted?
Non-depolarizing NMBAs, such as pancuronium, are primarily excreted unchanged in the urine.
Exceptions are rocuronium and vecuronium and their metabolites which are found mainly in bile.
By what route are non-depolarizing neuromuscular blocking agents (NMBAs) administered?
IV
Pancuronium is an example of an intermediate-acting non-depolarizing neuromuscular blocking agents (NMBA). How fast a duration of action is considered intermediate for a non-depolarizing NMBA?
Approximately 2-5 min. All NMBAs have short durations of action due to a small volume of distribution and rapid excretion. This is essential to allow titration of the level of paralysis during surgery.
What is the clinical use of non-depolarising neuromuscular blocking agents (NMBAs)?
To paralyse skeletal muscle for surgical paralysis.
List at least TWO non-depolarising neuromuscular blocking agents (NMBAs) ranked from longest-acting to shortest-acting
Non-depolarizing NMBAs from longest-acting to shortest-acting: Tubocurarine (2-13 min) > Pancuronium/Atracurium (2-5 min) > Rocuronium (0.5-3 min).
Note that tubocurarine is now rarely used for surgical paralysis as its duration action is too long to allow fine titration of the depth of paralysis. However, it is still sometimes used to provide temporary muscle paralysis to allow stabilisation of the injured neck or joints.
What are the blanks in the following sentence? “Parasympathetic activation of ___ stimulates secretions in most tissues but gastric acid secretion is due to ___.”
M3 receptors
M1 receptors
Parasympathetic activation of _M3 receptors__ stimulates secretions in most tissues but gastric acid secretion is due to _M1 receptors__
What are the blanks in the following sentence? “Patients with organophosphate poisoning present with bradycardia due to
________ of cardiac ____ receptors.”
Activation
M2
Patients with organophosphate poisoning present with bradycardia due to _activation__ of cardiac _M2__ receptors.
In organophosphate poisoning, which occurs last (a) twitching/fasciculations of skeletal muscle, (b) rigid paralysis of skeletal muscle, or (b) flaccid paralysis of skeletal muscle?
Flaccid paralysis of skeletal muscle.
Organophosphate poisoning inhibits acetylcholine esterase resulting in increased availability of acetylcholine at the neuromuscular junctions. This first causes increased activity of muscle resulting in twitching and sometimes transiently rigid paralysis. However, continued excess of acetylcholine progresses to causing depolarizing and desensitizing block resulting in flaccid paralysis.
List at least FOUR parasympathomimetic symptoms of organophosphate poisoning.
Lacrimation
Blurred distant vision
Miosis resulting in darkening of vision
Salivation
Fluid in airways
Bronchoconstriction resulting in wheezing
Diarrhoea due to increased GIT motility and secretions
Urination
What are the blanks in the following sentence? “Pralidoxime is effective in treatment of malathion poisoning because it has a higher affinity for _____ than _____.”
Phosphate
AChE
Pralidoxime is effective in treatment of malathion poisoning because it has a higher affinity for _phosphate__ than _AChE__
Pralidoxime is a/an
Cholinesterase regenerator used as an antidote to poisoning with organophosphate pesticides and chemicals
Why are organophosphates are described as suicide inhibitors of AChE?
Because they donate their phosphate to AChE and so are destroyed in the process of inhibiting AChE
Why are organophosphates are described as suicide inhibitors of AChE?
Because they donate their phosphate to AChE and so are destroyed in the process of inhibiting AChE
List at least TWO anticholinesterases ranked from longer-acting to shorter-acting
AChE inhibitors ranked from longer-acting to shorter-acting: Sarin > Malathion ~ Pyridostigmine > Neostigmine > Physostigmine > Edrophonium
The major clinical use of edrophonium is…
Diagnosis of myasthenia gravis
Edrophonium is used for diagnosis not treatment of myasthenia gravis because it…
Has a very short half-life
Name an example of an organophosphate insecticide
Malathion, parathion
Name an example of an indirect anticholinergic ganglionic blocker
High dose nicotine
