Duchenne Muscular Dystrophy and Treatment Strategies

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Questions and Answers

What is the underlying genetic cause of Duchenne muscular dystrophy (DMD)?

Mutation in the actin gene

Mutation in the myosin gene

Mutation in the troponin gene

Mutation in the dystrophin gene (correct)

How does antisense therapy like Eteplirsen work to treat DMD?

By binding to dystrophin protein directly

By binding to pre-mRNA to alter splicing (correct)

By neutralizing the effect of dystrophin mutations

By enhancing the function of dystrophin protein

Which physiological consequence results from the loss of dystrophin function in muscle fibers?

Inhibition of muscle fibers necrosis

Enhanced muscle regeneration capabilities

Attachment failure of the cytoskeleton to the sarcolemma (correct)

Increased muscle contractility

What is the ultimate consequence of muscle degeneration in DMD patients?

Respiratory muscle failure Signup and view all the answers

What type of drug is Eteplirsen considered in the context of DMD treatment?

Antisense oligonucleotide Signup and view all the answers

How do cholinergic agonists differ from cholinergic antagonists?

Agonists mimic the action of neurotransmitters, whereas antagonists block their effect. Signup and view all the answers

What happens to the action potential in muscle fibers when neuromuscular blocking agents (NMBAs) are used?

Action potential transmission is decreased. Signup and view all the answers

In the context of myasthenia gravis (MG), which statement correctly relates clinical manifestation to muscle physiology?

MG results from an autoimmune attack on acetylcholine receptors, leading to weakness. Signup and view all the answers

What is the main therapeutic goal of Eteplirsen in the treatment of Duchenne muscular dystrophy?

Slow or prevent the progression of DMD Signup and view all the answers

Which of the following is NOT a reversible acetylcholinesterase inhibitor?

Donepezil Signup and view all the answers

What adverse effect is commonly associated with the use of physostigmine?

Salivation and flushing Signup and view all the answers

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

Non-depolarizing agents act as competitive blockers Signup and view all the answers

How does edrophonium contribute to the diagnosis of Myasthenia Gravis?

It leads to a decrease in muscle weakness Signup and view all the answers

What is the primary mechanism of action for acetylcholinesterase inhibitors?

Prevent the degradation of acetylcholine Signup and view all the answers

Which of the following statements about neostigmine is correct?

Its main effects are on skeletal muscle. Signup and view all the answers

Which type of drug binds to cholinoceptors and prevents the effects of acetylcholine?

Cholinergic antagonists Signup and view all the answers

What is the clinical significance of succinylcholine?

Rapid onset but shorter-acting compared to non-depolarizing agents Signup and view all the answers

Which acetylcholinesterase inhibitor has the shortest duration of action?

Edrophonium Signup and view all the answers

What condition may lead to generalized cholinergic stimulation when using acetylcholinesterase inhibitors?

Intestinal blockage Signup and view all the answers

Which of the following is a feature of non-depolarizing neuromuscular blocking agents?

They require continuous infusion for effect. Signup and view all the answers

What happens during Phase II of succinylcholine action?

The muscle fibers are resistant to depolarization. Signup and view all the answers

Study Notes

Duchenne Muscular Dystrophy (DMD)

DMD is caused by a mutation in the dystrophin gene (recessive and x-linked)
Dystrophin connects the cytoskeleton to the sarcolemma
Loss of dystrophin leads to muscle fiber necrosis and wasting
Respiratory muscle failure is a leading cause of death in DMD patients

Eteplirsen for DMD Treatment

Antisense therapy targets pre-mRNA of dystrophin to rearrange splicing and produce more dystrophin
This results in more functional dystrophin being present
Goal is to slow or prevent the progression of DMD

Cholinergic Agonists and Antagonists

Indirect-acting cholinergic agonists (anticholinesterase agents) inhibit acetylcholinesterase (AChE)
AChE degrades acetylcholine (ACh), so inhibiting it leads to ACh accumulation and increased signaling
Reversible AChE inhibitors can be categorized as short-, intermediate-, or long-acting
Edrophonium: short-acting, rapid absorption, short duration of action, used to diagnose myasthenia gravis (MG)
Physostigmine: intermediate-acting, forms a stable intermediate with AChE, used to manage symptoms of MG
Neostigmine: reversibly inhibits AChE, long-acting, has a similar duration of action to physostigmine, used to manage symptoms of MG

Myasthenia Gravis (MG)

Autoimmune condition affecting the neuromuscular junction (NMJ)
Antibodies against nicotinic acetylcholine receptors interfere with signaling
Symptoms include varying muscle weakness
Treatment includes anticholinesterase inhibitors

Cholinergic Antagonists

Block the effects of acetylcholine (ACh) at muscarinic or nicotinic receptors
Used to treat various conditions
Include antimuscarinic agents, ganglionic blockers, and neuromuscular-blocking agents (NMBAs)

Neuromuscular Blocking Agents (NMBAs)

Block cholinergic transmission between motor nerve endings and the nicotinic receptors on skeletal muscle
NMJ blockers are useful during surgery
Non-depolarizing agents (e.g., pancuronium, vecuronium, rocuronium) act as competitive antagonists at the nicotinic receptor
Depolarizing agents (e.g., succinylcholine) act as agonists at the nicotinic receptor, causing initial depolarization and subsequent resistance to further stimulation

Non-Depolarizing NMBAs

Pancuronium: long-acting
Vecuronium: short-acting
Rocuronium: shortest-acting

Depolarizing NMBAs

Succinylcholine: rapid onset, short-acting, resistant to AChE
Overall, the lecture covers the pharmacology of skeletal muscle, specifically focusing on drugs that target the NMJ. It explores the mechanisms of action of various medications used to treat DMD, MG, and muscle paralysis during procedures.*

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Description

Explore the causes and treatment options for Duchenne Muscular Dystrophy (DMD) with a focus on innovative therapies like Eteplirsen. Understand the role of dystrophin and the impact of cholinergic agonists and antagonists in muscle function. This quiz covers essential concepts in neuromuscular disorders.