MPP block 2 lecture 2

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Questions and Answers

What is the primary goal of using eteplirsen in the treatment of DMD?

To slow or prevent the progression of DMD (correct)

To completely replace damaged muscle cells

To eliminate dystrophin production entirely

To enhance the production of normal dystrophin

How do indirect-acting cholinergic agonists primarily exert their effects?

By inhibiting enzymes that break down acetylcholine (correct)

By blocking the reuptake of acetylcholine

By mimicking the action of acetylcholine in the synaptic space

By directly stimulating acetylcholine receptors

What characterizes the mechanism of action of edrophonium?

It provides a slow and prolonged cholinergic effect

It permanently inhibits acetylcholinesterase

It acts as a direct agonist on cholinergic receptors

It binds reversibly to the active site of acetylcholinesterase (correct)

Which of the following is a potential adverse effect associated with physostigmine?

Generalized cholinergic stimulation Signup and view all the answers

What is one of the specific therapeutic uses of edrophonium?

Acute diagnosis of myasthenia gravis Signup and view all the answers

What is the duration of action for edrophonium compared to physostigmine?

Physostigmine acts for a longer duration than edrophonium Signup and view all the answers

In myasthenia gravis (MG), which physiological mechanism leads to muscle weakness?

Autoimmune attack on acetylcholine receptors Signup and view all the answers

Which statement accurately describes the role of acetylcholinesterase in neuromuscular transmission?

It prevents the accumulation of acetylcholine in the synapse Signup and view all the answers

Why is cholinergic stimulation contraindicated in cases of intestinal or urinary bladder obstruction?

It enhances motility, which can worsen obstruction Signup and view all the answers

What is the primary mechanism of action of neuromuscular-blocking agents?

Blockage of nicotinic receptors at the NMJ Signup and view all the answers

Which of the following best describes the action of neostigmine?

Reversible inhibition of AChE Signup and view all the answers

Which of the following neuromuscular-blocking agents is classified as non-depolarizing?

Both B and C Signup and view all the answers

What distinguishes depolarizing neuromuscular-blocking agents from non-depolarizing agents?

They cause persistent depolarization of the muscle fibers. Signup and view all the answers

Which phase of succinylcholine action leads to flaccid paralysis?

Phase II due to gradual repolarization Signup and view all the answers

What is a common adverse effect of generalized cholinergic stimulation?

Diarrhea Signup and view all the answers

Which characteristic of neostigmine affects its absorption and central nervous system penetration?

It is poorly absorbed and does not enter the CNS. Signup and view all the answers

In which clinical situation is neostigmine primarily useful?

Managing symptoms of myasthenia gravis Signup and view all the answers

Which side effect is most likely associated with the depolarizing agent succinylcholine?

Flaccid paralysis followed by muscle twitching Signup and view all the answers

What effect does non-depolarizing neuromuscular-blocking agents have on action potentials at the NMJ?

Inhibition of muscle fiber depolarization Signup and view all the answers

Study Notes

Antisense Therapy for DMD

Eteplirsen is an antisense therapy designed for Duchenne Muscular Dystrophy (DMD).
Utilizes antisense oligonucleotides targeting mRNA to modify splicing mechanisms.
Mechanism of Action: Binds to dystrophin pre-mRNA, promoting increased production of dystrophin.
Aims to boost levels of a functional but abnormal dystrophin to slow disease progression.

Cholinergic Agonists vs. Cholinergic Antagonists

Acetylcholinesterase (AChE) cleaves acetylcholine (ACh) into acetate and choline, halting its action.
AChE inhibitors prevent degradation of ACh, resulting in increased synaptic ACh accumulation.
Cholinergic agonists stimulate receptors to enhance cholinergic effects, while antagonists prevent ACh action.

Clinical Manifestation of Myasthenia Gravis (MG)

MG leads to muscle weakness due to impaired communication at the neuromuscular junction (NMJ).
Autoimmune destruction of nicotinic ACh receptors results in decreased muscle activation.

Mechanisms of Action of MG Drugs

Edrophonium:
- Short-acting AChE inhibitor; effects last 10-20 minutes due to rapid renal clearance.
- Clinically used for diagnosing MG; a rapid increase in muscle strength follows IV administration.
Physostigmine:
- Intermediate-acting AChE inhibitor; duration of action spans 30 minutes to 2 hours.
- Increases cholinergic activity, enhancing intestinal and bladder motility, treating MG symptoms.
- Can cause generalized cholinergic stimulation; contraindicated in cases of obstruction.
Neostigmine:
- Reversibly inhibits AChE; similar to Physostigmine with an intermediate duration of action.
- More polar and poorly absorbed from the GI tract; does not penetrate the CNS.
- Greater effect on skeletal muscle contractility; used for stimulating GI and bladder function in MG treatment.

Mechanism of Action of Neuromuscular Blocking Agents (NMBAs)

Cholinergic antagonists inhibit cholinoceptors, blocking ACh and cholinergic agonist effects.
NMBAs interfere with ACh transmission at the NMJ, functioning as antagonists (non-depolarizing) or agonists (depolarizing).
Non-depolarizing Agents: Competitive blockers at nicotinic receptors
- Pancuronium: Long-acting; caution in renal failure.
- Vecuronium: Few side effects; not affected by renal function.
- Rocuronium: Short-acting; caution in liver failure.
Depolarizing Agents: Mimic ACh by continuously activating nicotinic receptors.
- Succinylcholine: Rapid onset yet shorter duration; works in two phases.
  - Phase I: Initial depolarization and muscle twitching occur.
  - Phase II: Gradual repolarization leads to flaccid paralysis due to sustained receptor occupancy.

Changes in Action Potential with NMBAs

NMBAs block ACh action at the NMJ, leading to inhibition of muscle contraction.
Non-depolarizing agents prevent ACh from binding, while depolarizing agents lead to initial muscle activation followed by paralysis.

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Description

This quiz explores the mechanisms of antisense therapy, specifically Eteplirsen, used in treating Duchenne Muscular Dystrophy (DMD). It also provides a comparative analysis of cholinergic agonists and antagonists, focusing on their functions and effects. Engage with the content to better understand these crucial biomedical concepts.