Cholinergic agonist

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Questions and Answers

What is the primary mechanism by which botulinum toxin blocks the release of acetylcholine?

By blocking voltage-sensitive calcium channels

By inhibiting the activity of acetylcholinesterase

By preventing the fusion of synaptic vesicles with the cell membrane (correct)

By blocking voltage-sensitive sodium channels

What is the effect of the toxin in black widow spider venom on synaptic vesicles?

It prevents the release of acetylcholine from synaptic vesicles

It inhibits the recycling of choline back into the neuron

It causes the release of all acetylcholine stored in synaptic vesicles into the synaptic cleft (correct)

It increases the synthesis of acetylcholine in synaptic vesicles

What is the primary function of acetylcholinesterase in the synaptic cleft?

To release acetylcholine from synaptic vesicles

To synthesize acetylcholine

To cleave acetylcholine into choline and acetate (correct)

To bind to postsynaptic receptors

What is the role of butyrylcholinesterase in the synaptic cleft?

It is found in the plasma and does not terminate the effect of acetylcholine in the synapse Signup and view all the answers

What is the mechanism by which choline is recaptured by the neuron?

Through a sodium-coupled transporter Signup and view all the answers

What is the characteristic of muscarinic receptors?

They are G protein-coupled receptors Signup and view all the answers

What is the effect of muscarine on muscarinic receptors?

It binds to the receptor with a high affinity Signup and view all the answers

How many subclasses of muscarinic receptors are there?

Five Signup and view all the answers

Which of the following receptors is not primarily involved in smooth muscle function?

M1 receptors Signup and view all the answers

What is the effect of IP3 on intracellular Ca2+ levels?

IP3 increases Ca2+ levels Signup and view all the answers

Which G protein is activated when M1 or M3 receptors are stimulated?

Gq Signup and view all the answers

What is the primary effect of diacylglycerol (DAG) in acetylcholine signal transduction?

DAG activates protein kinase C Signup and view all the answers

What is the primary effect of M2 receptor stimulation on cardiac muscle?

M2 receptor stimulation decreases heart rate Signup and view all the answers

What is the primary mechanism of nicotine's effect at high concentrations?

Nicotine blocks nicotinic receptors at high concentrations Signup and view all the answers

What is the primary location of nicotinic receptors in the nervous system?

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

What is the primary function of nicotinic receptors in the NMJ?

To depolarize the effector cell Signup and view all the answers

What is the primary action of bethanechol on the bladder?

Stimulation of the detrusor muscle Signup and view all the answers

What is the therapeutic use of bethanechol in postpartum or postoperative cases?

Stimulation of the atonic bladder Signup and view all the answers

What is the effect of pilocarpine on the eye?

Rapid miosis and contraction of the ciliary muscle Signup and view all the answers

What is the duration of action of pilocarpine in lowering intraocular pressure?

4 to 8 hours Signup and view all the answers

Which receptor is responsible for the vasodilation caused by acetylcholine?

M3 receptor Signup and view all the answers

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

Overdose Signup and view all the answers

What is the effect of acetylcholine on the heart rate?

Decrease in heart rate and cardiac output Signup and view all the answers

What is the primary action of pilocarpine on salivation?

Increased salivation Signup and view all the answers

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

Indirectly stimulating nitric oxide production Signup and view all the answers

What is the effect of atropine on acetylcholine?

Blocks the action of acetylcholine Signup and view all the answers

In what condition is pilocarpine used to treat xerostomia?

Sjögren syndrome Signup and view all the answers

What is the unique property of pilocarpine that allows it to penetrate the CNS?

Stability to hydrolysis by AChE Signup and view all the answers

What is the unique property of bethanechol?

It has strong muscarinic activity and is not hydrolyzed by AChE Signup and view all the answers

What is the effect of acetylcholine on the gastrointestinal tract?

Increases salivary secretion and intestinal motility Signup and view all the answers

What is the effect of acetylcholine on the genitourinary tract?

Increases the tone of the detrusor muscle Signup and view all the answers

What is the effect of acetylcholine on the eye?

Stimulates the ciliary muscle and constricts the pupil Signup and view all the answers

What is the duration of action of neostigmine?

30 minutes to 2 hours Signup and view all the answers

What is one of the therapeutic uses of neostigmine?

Stimulation of the bladder and GI tract Signup and view all the answers

What is a common adverse effect of neostigmine?

Decreased blood pressure Signup and view all the answers

What is the duration of action of pyridostigmine?

3 to 6 hours Signup and view all the answers

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

Management of Alzheimer's disease Signup and view all the answers

What is a common adverse effect of tacrine, donepezil, rivastigmine, and galantamine?

GI distress Signup and view all the answers

What is the mechanism of action of echothiophate?

Covalent binding to the active site of AChE Signup and view all the answers

What can reactivate the enzyme inactivated by echothiophate?

Pralidoxime Signup and view all the answers

Study Notes

Acetylcholine Release and Binding

Acetylcholine (ACh) release from the synaptic vesicles is triggered by an action potential, which opens voltage-sensitive calcium channels, increasing intracellular calcium levels.
Elevated calcium levels promote the fusion of synaptic vesicles with the cell membrane, releasing ACh into the synaptic space.
Botulinum toxin can block ACh release from the synaptic vesicles.

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 receptors.
Binding to a receptor leads to a biological response, which is mediated by second messenger molecules.

Degradation of Acetylcholine

The signal is rapidly terminated by acetylcholinesterase (AChE), which cleaves ACh into choline and acetate in the synaptic cleft.
Butyrylcholinesterase (also known as pseudocholinesterase) is found in the plasma but does not terminate the effect of ACh in the synapse.

Recycling of Choline

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

Cholinergic Receptors (Cholinoceptors)

There are two families of cholinoceptors: muscarinic and nicotinic receptors.
Muscarinic receptors are G protein-coupled receptors (metabotropic receptors) that bind ACh and muscarine.
Nicotinic receptors are ligand-gated ion channels that bind ACh and nicotine.

Muscarinic Receptors

Muscarinic receptors have five subclasses: M1, M2, M3, M4, and M5.
Only M1, M2, and M3 receptors are the most important receptors.
M1 receptors are found on gastric parietal cells, M2 receptors on cardiac cells and smooth muscle, and M3 receptors on the bladder, exocrine glands, and smooth muscle.
Activation of M1 or M3 receptors leads to the production of second messengers, including inositol-1,4,5-trisphosphate (IP3) and diacylglycerol (DAG).

Nicotinic Receptors

Nicotinic receptors are found in the CNS, adrenal medulla, autonomic ganglia, and the neuromuscular junction (NMJ) in skeletal muscles.
Nicotinic receptors can be stimulated by nicotine at low concentrations, but blocked by nicotine at high concentrations.
Nicotinic receptors of autonomic ganglia differ from those of the NMJ.

Direct-Acting Cholinergic Agonists

Direct-acting cholinergic agonists mimic the effects of ACh by binding directly to cholinoceptors (muscarinic or nicotinic).
Examples of direct-acting cholinergic agonists include acetylcholine, bethanechol, and pilocarpine.

Acetylcholine

Acetylcholine has no therapeutic importance due to its multiple actions and rapid inactivation by cholinesterases.
Acetylcholine has both muscarinic and nicotinic activity.

Bethanechol

Bethanechol is a direct-acting cholinergic agonist that is not hydrolyzed by AChE.
It has strong muscarinic activity and no nicotinic action.
Bethanechol is used to stimulate the atonic bladder and treat neurogenic atony.

Pilocarpine

Pilocarpine is a direct-acting cholinergic agonist that is stable to hydrolysis by AChE.
It has muscarinic activity and can penetrate the CNS at therapeutic doses.
Pilocarpine is used to treat glaucoma and is the drug of choice for emergency lowering of intraocular pressure.

Neostigmine

Neostigmine is a direct-acting cholinergic agonist that has an intermediate duration of action.
It is used to stimulate the bladder and GI tract and also as an antidote for competitive neuromuscular-blocking agents.
Neostigmine is also used to manage symptoms of myasthenia gravis.

Pyridostigmine

Pyridostigmine is a direct-acting cholinergic agonist that has an intermediate duration of action.
It is used in the chronic management of myasthenia gravis.

Anticholinesterase Agents (Reversible)

Anticholinesterase agents, such as tacrine, donepezil, rivastigmine, and galantamine, are used to treat loss of cognitive function in Alzheimer's disease.
These agents delay the progression of Alzheimer's disease but cannot stop it.

Anticholinesterase Agents (Irreversible)

Some organophosphate compounds, such as echothiophate, can bind covalently to AChE, leading to a long-lasting increase in ACh.
These compounds are extremely toxic and were developed by the military as nerve agents.
Related compounds, such as parathion and malathion, are used as insecticides.

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Description

Learn how action potentials trigger the release of neurotransmitters such as acetylcholine into the synaptic space. Understand the role of calcium channels and synaptic vesicles in this process.