ANS Pharmacology: Cholinergic Drugs

Podcast Beta

Play an AI-generated podcast conversation about this lesson

Questions and Answers

Which type of fibers uses acetylcholine as a neurotransmitter?

Preganglionic fibers terminating in the adrenal medulla

Postganglionic fibers of the sympathetic division

Somatic motor neurons

All of the above (correct)

What is the function of choline acetyltransferase?

Transport of choline into the cytoplasm

Storage of acetylcholine in vesicles

Degradation of acetylcholine

Catalysis of the reaction to form acetylcholine (correct)

What is the role of voltage-sensitive calcium channels in the release of acetylcholine?

To increase the concentration of intracellular calcium (correct)

To open the voltage-sensitive sodium channels

To synthesize acetylcholine

To decrease the concentration of intracellular calcium

What is the primary neurotransmitter stored in synaptic vesicles?

Acetylcholine Signup and view all the answers

What is the function of hemicholinium?

To inhibit the transport of choline into the cytoplasm Signup and view all the answers

What is the sequence of events in neurotransmission at cholinergic neurons?

Synthesis, storage, release, binding, degradation, recycling Signup and view all the answers

What is the cotransmitter stored in synaptic vesicles along with acetylcholine?

Proteoglycan Signup and view all the answers

What is the function of voltage-sensitive sodium channels?

To propagate an action potential at the nerve ending Signup and view all the answers

What is the purpose of recycling choline and acetate?

To conserve choline and acetate for future use Signup and view all the answers

Which division of the autonomic nervous system uses acetylcholine as a neurotransmitter?

Both the parasympathetic and sympathetic divisions Signup and view all the answers

What is the effect of botulinum toxin on the release of acetylcholine from synaptic vesicles?

It blocks the release of acetylcholine into the synaptic space Signup and view all the answers

Which receptors are G protein–coupled receptors?

Muscarinic receptors Signup and view all the answers

What is the effect of acetylcholinesterase on acetylcholine in the synaptic cleft?

It breaks down acetylcholine into choline and acetate Signup and view all the answers

Which subtype of muscarinic receptors is found on gastric parietal cells?

M1 receptors Signup and view all the answers

What is the effect of nicotine on nicotinic receptors at high concentrations?

It blocks the receptor Signup and view all the answers

Where are nicotinic receptors found in the nervous system?

In the CNS, adrenal medulla, autonomic ganglia, and neuromuscular junction Signup and view all the answers

What is the effect of direct-acting cholinergic agonists?

They mimic the effects of acetylcholine by binding directly to cholinoceptors Signup and view all the answers

Which subtype of muscarinic receptors is found on cardiac cells and smooth muscle?

M2 receptors Signup and view all the answers

What is the effect of activation of M1 or M3 receptors?

It leads to the production of inositol-1,4,5-trisphosphate and diacylglycerol Signup and view all the answers

What is the effect of nicotinic receptors on the effector cell?

It depolarizes the effector cell Signup and view all the answers

What is the reason why acetylcholine has no therapeutic importance?

It has multiple actions and is rapidly inactivated by cholinesterases Signup and view all the answers

What is the mechanism of action of acetylcholine in decreasing blood pressure?

It activates M3 receptors on endothelial cells, leading to the production of nitric oxide Signup and view all the answers

What is the action of bethanechol on the detrusor muscle of the bladder?

It increases the tone of the detrusor muscle, causing urination Signup and view all the answers

What is the therapeutic use of bethanechol?

To stimulate the atonic bladder, particularly in postpartum or postoperative, nonobstructive urinary retention Signup and view all the answers

What is the effect of pilocarpine on the eye?

It produces rapid miosis and contraction of the ciliary muscle Signup and view all the answers

What is the mechanism of action of pilocarpine in glaucoma?

It opens the trabecular meshwork around the Schlemm canal, causing an immediate drop in intraocular pressure Signup and view all the answers

What is the adverse effect of pilocarpine?

It causes profuse sweating and salivation Signup and view all the answers

What is the action of anticholinesterase agents?

They inhibit the activity of AChE, leading to an accumulation of ACh in the synaptic space Signup and view all the answers

What is the effect of atropine on the muscarinic receptors?

It blocks the muscarinic receptors Signup and view all the answers

What is the common use of atropine?

To treat the toxicity of pilocarpine and bethanechol Signup and view all the answers

What is the primary difference between edrophonium and physostigmine in terms of their duration of action?

Edrophonium has a shorter duration of action than physostigmine. Signup and view all the answers

What is the primary use of neostigmine in the management of myasthenia gravis?

To manage symptoms of myasthenia gravis. Signup and view all the answers

What is the primary adverse effect of tacrine, donepezil, rivastigmine, and galantamine?

GI distress. Signup and view all the answers

What is the mechanism of action of echothiophate?

Irreversible inhibition of AChE. Signup and view all the answers

What is the therapeutic use of a topical ophthalmic solution of echothiophate?

Treatment of open-angle glaucoma. Signup and view all the answers

What is the primary difference between reversible and irreversible AChE inhibitors?

Reversible inhibitors bind non-covalently to AChE. Signup and view all the answers

What is the antidote for edrophonium-induced cholinergic crisis?

Atropine. Signup and view all the answers

What is the primary use of pyridostigmine?

Chronic management of myasthenia gravis. Signup and view all the answers

What is the primary source of toxicity for irreversible AChE inhibitors?

All of the above. Signup and view all the answers

What is the primary difference between edrophonium and neostigmine in terms of their therapeutic uses?

Edrophonium is used to diagnose myasthenia gravis, while neostigmine is used to stimulate the bladder and GI tract. Signup and view all the answers

What is the primary mechanism of action of botulinum toxin?

Inhibition of acetylcholine release from synaptic vesicles Signup and view all the answers

What is the function of phospholipase C in muscarinic receptor signaling?

Production of diacylglycerol Signup and view all the answers

What is the primary difference between muscarinic and nicotinic receptors?

Muscarinic receptors are G-protein coupled, while nicotinic receptors are ligand-gated ion channels Signup and view all the answers

What is the effect of butyrylcholinesterase on acetylcholine?

It is involved in the synthesis of ACh Signup and view all the answers

What is the primary mechanism of action of M2 receptors?

Inhibition of adenylyl cyclase Signup and view all the answers

What is the effect of choline uptake on synaptic transmission?

It recycles choline back into the neuron Signup and view all the answers

What is the primary difference between M1 and M3 receptors?

M1 receptors are found on gastric parietal cells, while M3 receptors are found on cardiac cells Signup and view all the answers

What is the effect of nicotine on nicotinic receptors?

It stimulates the receptor at low concentrations and blocks it at high concentrations Signup and view all the answers

What is the primary mechanism of action of direct-acting cholinergic agonists?

They bind directly to muscarinic or nicotinic receptors Signup and view all the answers

What is the effect of acetylcholinesterase on acetylcholine?

It terminates the action of ACh by breaking it down into choline and acetate Signup and view all the answers

Which anticholinesterase agent is used for the diagnosis of myasthenia gravis?

Edrophonium Signup and view all the answers

What is the primary difference between edrophonium and physostigmine?

Duration of action Signup and view all the answers

What is the antidote for edrophonium-induced cholinergic crisis?

Atropine Signup and view all the answers

Which anticholinesterase agent is used in the treatment of overdoses of anticholinergic drugs?

Physostigmine Signup and view all the answers

What is the primary use of neostigmine?

All of the above Signup and view all the answers

What is the primary adverse effect of tacrine, donepezil, rivastigmine, and galantamine?

GI distress Signup and view all the answers

What is the mechanism of action of echothiophate?

Irreversible inhibition of AChE Signup and view all the answers

What is the therapeutic use of a topical ophthalmic solution of echothiophate?

Treatment of open-angle glaucoma Signup and view all the answers

What is the primary source of toxicity for irreversible AChE inhibitors?

All of the above Signup and view all the answers

What is the primary use of pyridostigmine?

Treatment of myasthenia gravis Signup and view all the answers

What is the primary mechanism of ACh degradation?

Hydrolysis by acetylcholinesterase Signup and view all the answers

Which of the following is NOT a component of the mature synaptic vesicle?

Norepinephrine Signup and view all the answers

What is the role of sodium in the uptake of choline by the cholinergic neuron?

Sodium is cotransported with choline into the neuron Signup and view all the answers

Which of the following receptors is NOT stimulated by norepinephrine or epinephrine?

Muscarinic receptor Signup and view all the answers

What is the effect of inhibiting choline uptake on the synthesis of acetylcholine?

Decreased synthesis of acetylcholine Signup and view all the answers

What is the primary mechanism by which acetylcholine decreases blood pressure?

Indirect stimulation of nitric oxide production Signup and view all the answers

Which of the following steps is NOT part of the neurotransmission process at cholinergic neurons?

Exocytosis of acetylcholine into the bloodstream Signup and view all the answers

Which of the following has a strong muscarinic activity and no nicotinic action?

Bethanechol Signup and view all the answers

What is the primary function of voltage-sensitive calcium channels in the release of acetylcholine?

To increase the concentration of intracellular calcium Signup and view all the answers

What is the primary therapeutic use of pilocarpine?

Treatment of glaucoma Signup and view all the answers

What is the primary mechanism of action of hemicholinium?

Inhibition of choline uptake Signup and view all the answers

What is the effect of indirect-acting cholinergic agonists on acetylcholine?

They inhibit the degradation of acetylcholine Signup and view all the answers

Which of the following is a postganglionic fiber that uses acetylcholine as a neurotransmitter?

Parasympathetic postganglionic fibers Signup and view all the answers

What is the primary function of the cholinergic neuron in the autonomic nervous system?

To modulate the activity of the parasympathetic nervous system Signup and view all the answers

What is the adverse effect of bethanechol that can be treated with atropine sulfate?

Overdose Signup and view all the answers

What is the mechanism of action of pilocarpine in the eye?

Stimulation of the muscarinic receptors Signup and view all the answers

What is the duration of action of bethanechol?

1 hour Signup and view all the answers

What is the therapeutic use of bethanechol in the gastrointestinal tract?

Stimulation of intestinal secretions and motility Signup and view all the answers

What is the effect of acetylcholine on the heart rate?

Decrease in heart rate Signup and view all the answers

What is the therapeutic use of atropine in relation to pilocarpine?

Treatment of pilocarpine toxicity Signup and view all the answers

Study Notes

Cholinergic Neurons

Cholinergic neurons use acetylcholine (ACh) as a neurotransmitter
Found in:
- Preganglionic fibers terminating in the adrenal medulla
- Autonomic ganglia (both parasympathetic and sympathetic)
- Postganglionic fibers of the parasympathetic division
- Postganglionic sympathetic division of sweat glands
- Muscles of the somatic system

Neurotransmission in Cholinergic Neurons

6 sequential steps:
1. Synthesis
2. Storage
3. Release
4. Binding of ACh to a receptor
5. Degradation of the neurotransmitter
6. Recycling of choline and acetate

Synthesis of Acetylcholine

Choline is transported into the cytoplasm of the cholinergic neuron by cotransport with sodium
Choline acetyltransferase catalyzes the reaction of choline with acetyl-CoA to form ACh

Storage of Acetylcholine

ACh is stored in presynaptic vesicles by an active transport process
Mature vesicles contain ACh, ATP, and proteoglycan

Release of Acetylcholine

When an action potential reaches the nerve ending, voltage-sensitive calcium channels open, causing an increase in intracellular calcium
Elevated calcium levels promote the fusion of synaptic vesicles with the cell membrane and the release of their contents into the synaptic space

Binding to the Receptor

ACh released from the synaptic vesicles diffuses across the synaptic space and binds to postsynaptic receptors on the target cell
Postsynaptic cholinergic receptors are divided into two classes: muscarinic and nicotinic
Binding to a receptor leads to a biologic response mediated by second messenger molecules

Degradation of Acetylcholine

ACh is rapidly terminated by acetylcholinesterase (AChE) that cleaves ACh to choline and acetate in the synaptic cleft
Butyrylcholinesterase (pseudocholinesterase) is found in the plasma but does not terminate the effect of ACh in the synapse

Recycling of Choline

Choline may be recaptured by a sodium-coupled transporter that transports the molecule back into the neuron

Cholinergic Receptors

Two families of cholinoceptors: muscarinic and nicotinic receptors

Muscarinic Receptors

G protein–coupled receptors (metabotropic receptors)
Bind ACh and muscarine, but show only a weak affinity for nicotine
Five subclasses of muscarinic receptors: M1, M2, M3, M4, and M5
Mechanisms of acetylcholine signal transduction:
- M1 and M3 receptors: activation leads to production of second messengers (IP3 and DAG)
- M2 receptors: activation leads to inhibition of adenylyl cyclase and increase in K+ conductance

Nicotinic Receptors

Ligand-gated ion channels
Bind ACh and nicotine, but show only a weak affinity for muscarine
Found in:
- CNS
- Adrenal medulla
- Autonomic ganglia
- Neuromuscular junction (NMJ) in skeletal muscles

Direct-Acting Cholinergic Agonists

Mimic the effects of ACh by binding directly to cholinoceptors (muscarinic or nicotinic)
Examples:
- Acetylcholine
- Bethanechol
- Pilocarpine

Indirect-Acting Cholinergic Agonists (Anticholinesterase Agents)

Inhibit AChE, allowing ACh to accumulate in the synaptic space
Examples:
- Edrophonium
- Physostigmine
- Neostigmine
- Pyridostigmine
- Tacrine, donepezil, rivastigmine, and galantamine
- Echothiophate (irreversible AChE inhibitor)