Cholinergic Drugs and Neuromuscular Blockers Flashcards
What do cholinergic drugs act on?
Acetylcholine (ACh) receptors
Which nervous systems have acetylcholine receptors?
Parasympathetic, Sympathetic, and Somatic Nervous Systems
Where does ACh synthesis occur?
In the presynaptic cell
Which enzyme synthesizes ACh?
Choline acetyltransferase
What are the precursors for ACh synthesis?
Acetyl coenzyme A and choline
Where is ACh stored before release?
In synaptic vesicles in the presynaptic cell
Why is ACh stored in synaptic vesicles?
To protect it from degradation and keep it ready for release
What triggers ACh release?
An action potential when the snyaptic vesicle fuses to the snyaptic memrbane
How many vesicles fuse to release ACh in one signaling event?
100 or more
Where does ACh bind after being released?
To receptors on the postsynaptic cell
What are the two types of acetylcholine receptors?
Nicotinic ACh receptors (nAChR) and muscarinic ACh receptors (mAChR)
How is ACh degraded?
By the enzyme acetylcholinesterase (ACE)
What happens to ACh after its metabolized?
It is broken down into choline and acetate
How fast does acetylcholinesterase break down ACh?
Within 150 microseconds of release
What happens to choline after ACh is broken down?
It is scavenged by transporters on the presynaptic cell and recycled for ACh synthesis
How is bethanechol administered?
Orally, intramuscularly (i.m.), or intravenously (i.v.)
What is the effect of a muscarinic ACh receptor (mAChR) agonist?
Activates the receptor, mimicking parasympathetic nervous system activation (parasympathomimetic)
Why do some muscarinic agonists have prolonged effects?
They are completely resistant to acetylcholinesterase (ACE), preventing breakdown
What is the main therapeutic use of bethanechol?
Treats loss of bladder smooth muscle tone (e.g., post-surgery or post-labor)
How does bethanechol help with xerostomia?
Stimulates salivation from parotid, submandibular, and sublingual glands
How does bethanechol restore bladder function and what dose it activate?
Activates muscarinic receptors in the bladder, causing smooth muscle contraction and urination
What is an off-label use of bethanechol?
Treatment of xerostomia (dry mouth)
How is carbachol administered?
As eye drops
What receptors does carbachol activate?
Primarily muscarinic ACh receptors, but also nicotinic ACh receptors
What is carbachol used to treat?
Wide-angle glaucoma
How does carbachol reduce intraocular pressure?
Causes contraction of smooth muscle around canals of Schlemm, opening them to drain excess aqueous humor
How is pilocarpine administered?
As eye drops (topically) or orally
What happens if intraocular pressure is too high?
It compresses retinal arteries, leading to retinal death
What is pilocarpine used for?
Reduces intraocular pressure in wide-angle glaucoma
What is an additional use of pilocarpine?
Treatment of xerostomia (oral form, Salagen)
What does a muscarinic ACh receptor (mAChR) antagonist do?
Competes with ACh for receptor binding, preventing activation
What are the effects of muscarinic ACh receptor antagonists?
Opposite of parasympathetic activation (antimuscarinic effects)
What are common antimuscarinic side effects?
Drowsiness, dry mouth, urinary retention
Which drug classes can block mAChRs?
Antihistamines, antipsychotics, antidepressants
What common medications contain antihistamines?
Many cold medications and over-the-counter sleep aids
Why is it illegal to drive after taking antihistamines in Virginia (VA)?
They cause drowsiness, impairing driving ability
How do antihistamines interact with alcohol?
They enhance CNS depression caused by alcohol
How is atropine administered?
Intravenously (i.v.) or orally
How does atropine work?
Competes with ACh for receptor binding, preventing signaling
What are the therapeutic uses of atropine?
Preanesthetic: decreases respiratory secretions (antisialogogue)
Dilates bronchial passages
Reverses life-threatening bradycardia (slow heart rate)
Does atropine affect the CNS at clinical doses?
No
How is scopolamine administered?
Subcutaneously (s.c.), intravenously (i.v.), or transdermally
How does scopolamine work?
Competes with ACh for receptor binding, relaxing smooth muscle
How does scopolamine differ from atropine?
It also has CNS effects in addition to atropine’s effects
What are the therapeutic uses of scopolamine?
Preanesthetic: decreases the amount of anesthesia needed
Motion sickness treatment (Transderm-Scop patch behind the ear)
How does scopolamine prevent motion sickness?
Blocks vestibular input (inner ear to brain)
Inhibits brainstem chemoreceptor trigger zone
Prevents the vomit reflex
What precautions should be taken with scopolamine?
Wash hands after applying
Leave patch on for 4 hours after event
Strongly enhances depressant effects of alcohol
How do Acetylcholinesterase (ACE) inhibitors work?
Prevent ACh degradation, causing ACh accumulation in the synapse
What is the effect of ACE inhibitors on ACh receptors?
Tonic activation of ACh receptors
How is neostigmine administered?
Orally, subcutaneously (s.c.), intramuscularly (i.m.), or as eye drops
How does neostigmine enhance ACh signaling?
Prevents ACh breakdown, amplifying the signal
What conditions is neostigmine used to treat?
Postoperative urinary retention
Wide-angle glaucoma
What is Myasthenia Gravis?
An autoimmune neuromuscular disease where the body makes antibodies against nicotinic ACh receptors at the neuromuscular junction
How does neostigmine help Myasthenia Gravis patients?
Increases ACh levels in the synapse, compensating for fewer ACh receptors and enhancing muscle stimulation
What are the reversible and irreversible anticholinesterase drugs?
Reversible:
- neostigmine
Irreversible:
- organophosphates
What is the main danger of irreversible ACE inhibitors?
Causes paralysis, including diaphragm paralysis, leading to respiratory failure
What are organophosphates primarily used for?
Pesticides (e.g., Acephate, Chlorpyrifos, Malathion, Trichlorfon)
How are organophosphates used in warfare?
As nerve agents (e.g., Sarin, Tabun, Soman, VX)
Which nervous systems do neuromuscular blockers affect?
Parasympathetic, sympathetic, and central nervous systems
How much nerve agent is lethal?
As little as 200 μg
Which drug is used as an antidote for organophosphate poisoning?
Atropine
How does atropine counteract organophosphate poisoning?
Blocks muscarinic receptor effects, reducing toxic overstimulation
How do nicotinic receptor antagonists work?
Block ACh binding at nicotinic receptors, preventing muscle contraction
How does d-tubocurarine work?
Competitively binds to ACh sites but does not cause depolarization
Does d-tubocurarine affect consciousness?
No, it does not cross the blood-brain barrier (BBB)
What effect does d-tubocurarine have on muscles?
Causes complete skeletal paralysis
What is d-tubocurarine used for?
Adjunct to anesthesia to reduce anesthetic requirements
Decreases respiratory and cardiac depressive side effects of anesthesia
How does succinylcholine work?
Mimics ACh, causing initial depolarization followed by receptor desensitization
What effect does succinylcholine have on muscles?
Complete skeletal paralysis
How is succinylcholine metabolized?
By acetylcholinesterase (ACE), leading to a brief duration of action, which is fast
What is succinylcholine used for?
Intubation
Electroshock therapy
What is the phase I of succinylcholine’s effect?
Prolonged ACh receptor stimulation → disorganized contractions (fasciculations)
What is the phase II of succinylcholine’s effect?
ACh receptor desensitization, preventing new action potentials (main anesthetic effect)
