Cholinergic Pharmacology Flashcards
What are the two major parts of the autonomic nervous system?
Sympathetic and parasympathetic systems.
Name 2 KEY neurotransmitters in the autonomic nervous system?
Acetylcholine and noradrenaline.
Which neurons are cholinergic in the autonomic nervous system?
Preganglionic neurons and postganglionic parasympathetic neurons.
What inhibits the rate-limiting step of choline uptake into the nerve terminal?
Hemicholinium.
How is ACh transported into its vesicles for storage?
By the vesicular acetylcholine transporter (VAChT).
What is the major mechanism for the termination of ACh’s action?
Inactivation via acetylcholinesterase (AChE).
How do reversible AChE inhibitors work?
They prevent the breakdown of ACh, enhancing its action.
Name two families of cholinoceptors.
Muscarinic receptors and nicotinic receptors.
What are the effects of muscarinic agonists on the cardiovascular system?
Decrease in cardiac output via M2 receptors
How do muscarinic agonists affect the eye?
Contraction of the ciliary muscle and constrictor pupillae, reducing intraocular pressure via M3 receptors.
What are the side effects of the non-selective muscarinic agonist bethanechol?
Blurred vision, increased salivation, bronchial constriction, hypotension, abdominal cramping, diarrhea, urinary urgency.
What are the main effects of muscarinic antagonists like atropine?
Reduced secretions, urinary retention, mydriasis, relaxation of the gut
What is the primary action of pralidoxime?
To reactivate cholinesterase inactivated by organophosphates.
What distinguishes muscarinic from nicotinic receptors?
Muscarinic receptors are G-protein-coupled, while nicotinic receptors are ligand-gated ion channels.
What is the role of nicotine in ganglion stimulation?
It stimulates both sympathetic and parasympathetic ganglia.
What is the mechanism of action for nondepolarizing neuromuscular blockers?
They act as competitive antagonists at ACh receptors, without depolarizing the motor end plate preventing muscle contraction.
How does succinylcholine work as a depolarizing blocker?
It binds to nicotinic receptors, causing persistent depolarization and eventual transmission block.
What is the primary cause of myasthenia gravis?
Autoimmune production of antibodies that destroy/block nicotinic acetylcholine receptors.
How are cholinesterase inhibitors used in the treatment of myasthenia gravis?
They enhance communication between nerves and muscles by preventing ACh degradation (increase ACh levels).
What is the clinical application of edrophonium?
Diagnosis of myasthenia gravis. (It is a short acting acetylcholinesterase inhibitor)
Describe the therapeutic use of neostigmine.
Treatment of myasthenia gravis and reversal of neuromuscular block. (It is an intermediate acting acetylcholinesterase inhibitor)
What are the adverse effects of organophosphates like parathion?
Parasympathetic effects, muscle paralysis, and coma.
What is the action of sarin?
Like parathion, but more rapid and lethal, used as a nerve gas.
What differentiates direct-acting from indirect-acting cholinergic drugs?
Direct-acting drugs act on receptors, while indirect-acting drugs inhibit cholinesterase to prolong ACh action.
Why are antimuscarinic drugs like atropine used in cholinergic poisoning?
As an antidote for cholinesterase inhibitor toxicity and to relieve symptoms of organophosphate poisoning.
How do neuromuscular blocking drugs aid in surgery?
They facilitate muscle relaxation and tracheal intubation
What is the main pharmacological action of muscarinic agonists on smooth muscle?
Contraction of smooth muscles.
How does botulinum toxin affect acetylcholine release?
It prevents the release of ACh, used in treating dystonia and cosmetic applications.
What is the role of cholinesterase inhibitors in cholinergic function?
Enhance cholinergic function by preventing ACh degradation, affecting muscarinic and nicotinic receptors.
What is the primary use of pilocarpine (non selective M agonist)?
Treatment of acute angle glaucoma
How does atropine affect heart rate?
Causes modest tachycardia by blocking M2 receptors.
What are the effects of muscarinic antagonists on gastrointestinal motility?
Inhibit gastrointestinal motility at larger doses
Describe the action of depolarizing blockers like succinylcholine on muscle fibers.
They cause persistent depolarization, leading to flaccid paralysis.
How do nondepolarizing blockers work?
They block Nic receptors competitively without depolarizing the motor endplate, inhibiting muscular contraction.
How does mydriasis affect intraocular pressure?
IO pressure may rise due to relaxation of the ciliary muscle.
What are the primary signal transduction pathways for muscarinic receptors?
Phosphatidylinositol pathway (M1, M3) and cAMP pathway (M2).
What is the significance of acetylcholinesterase inhibitors in the treatment of Alzheimer’s disease?
They enhance cholinergic neurotransmission by preventing ACh breakdown.
What distinguishes muscarinic agonists from antagonists in their effects on the eye?
Agonists induce miosis (pupil constriction) and may decrease intraocular pressure, while antagonists cause mydriasis (pupil dilation) and may increase intraocular pressure.
How does the presence of choline acetyltransferase (ChAT) affect acetylcholine synthesis?
ChAT catalyzes the synthesis of ACh from choline and acetyl-CoA.
How do competitive (non-depolarizing) neuromuscular blockers achieve muscle relaxation, and what can potentially reverse their effects?
Block ACh receptors without depolarization; reversed by cholinesterase inhibitors.
Analyze the clinical significance of reversible AChE inhibitors in the management of Myasthenia Gravis.
Increase ACh concentration, improving muscle strength by enhancing neuromuscular transmission.
How does botulinum toxin’s mechanism of action in preventing ACh release contribute to its cosmetic and therapeutic uses?
Reduces muscle contraction and wrinkles by inhibiting ACh release at neuromuscular junctions.
Evaluate the use of muscarinic antagonists in asthma management considering their mechanism of action.
They relax bronchial muscles by blocking M3 receptors, reducing constriction.
Considering the side effects, discuss the practicality of using cholinergic drugs for specific gastrointestinal disorders.
Effective in stimulating GI motility but can cause cramping and diarrhea.
Discuss the rationale behind the use of cholinergic drugs in treating dry mouth conditions.
Stimulate saliva production by activating M3 receptors in salivary glands.
How do cholinergic agonists’ effects on the cardiovascular system illustrate the principle of selective action?
They decrease heart rate and blood pressure by selectively activating M2 receptors in the heart.
Evaluate the therapeutic approach of using cholinergic drugs for bladder dysfunction.
Improve urination by stimulating bladder muscle contraction but may cause abdominal discomfort.
How does the action of cholinergic drugs on the gastrointestinal system support their use in specific disorders?
Increase GI motility and secretion, beneficial in conditions like gastroparesis.
Why are cholinergic drugs like atropine used in ophthalmic exams avoided in patients with glaucoma?
Atropine causes pupil dilation and paralysis of accommodation, aiding in diagnostics and treatment, but is used cautiously in glaucoma due to potential intraocular pressure increase.
Evaluate the impact of cholinergic drugs on salivary and sweat glands in treating disorders.
Increase secretion, useful in dry mouth or eye conditions but can cause excessive sweating.
How does the differentiation between M1, M2, and M3 receptors influence the design of cholinergic drugs?
Allows for targeted drug development to minimize side effects by selective receptor activation/inhibition.
