Lecture 22 - Ganglionic and Neuromuscular Blockers

A comprehensive set of flashcards designed to review key concepts, historical discoveries, and pharmaceutical advancements in the field of ganglionic and neuromuscular blockers.

What is the primary concept introduced in the lecture on ganglionic and neuromuscular blockers?

The concept of ganglionic and neuromuscular blocking agents.

What is tubocurarine known for?

It was the first nicotinic antagonist discovered.

What are the two types of neuromuscular junction blockers?

Nondepolarizing agents (competitive antagonists) and depolarizing agents.

What role does pharmacogenomics play in relation to butyrylcholinesterase?

It affects the duration of neuromuscular blocking effects.

What are nicotinic ligands used for outside of medicine?

They are used as pesticides and insecticides.

What type of receptor are Nicotinic Acetylcholinergic (nAChR) channels?

Ligand-gated ion channels.

What is the subunit composition example of nAChR mentioned?

(α4)3(β2)2.

Where are nAChRs found in the body?

In ganglia, neuromuscular junctions, and parts of the brain.

What neurotransmitter is present at both SNS and PSNS ganglia?

Acetylcholine.

Which blocking agents possess the necessary affinity to nicotinic receptors but lack intrinsic activity?

Non-depolarizing competitive ganglionic blocking agents.

What is the function of Trimethaphan (Arfonad®)?

It is used as a ganglionic blocker in hypertension and anesthesia.

Why were ganglionic blocking agents discontinued for hypertension treatment?

Due to numerous undesirable side effects.

What drug class is Mecamylamine (Inversine®; Vecamyl®) associated with?

Non-depolarizing noncompetitive ganglionic blocking agents.

What is the effect of ganglionic blockade on arterioles?

Causes vasodilation and increased peripheral blood flow.

What is the effect of ganglionic blockade on the heart?

It may lead to tachycardia.

What is curariform or curarimimetic activity associated with?

Neuromuscular blocking agents' ability to cause muscle relaxation in surgery.

What are the characteristics of nondepolarizing blocking agents?

They are competitive antagonists that prevent depolarization of muscle end-plates.

What happens to muscles when mixed with depolarizing blocking agents?

They become insensitive due to desensitization.

What distinguishes competitive (nondepolarizing) blockers from depolarizing ones?

Competitive blockers are bulky and rigid; depolarizing blockers are smaller and more flexible.

What historical discovery is linked to the development of neuromuscular blocking agents?

The use of curare by South American natives.

What critical milestone occurred in 1956 in relation to ganglionic blockers?

Mecamylamine was the first orally available antihypertensive agent.

When was pure tubocurarine first isolated?

In 1943 by Wintersteiner and Dutcher.

Which neuromuscular agent is indicated for skeletal muscle relaxation during anesthesia?

Atracurium besylate (Tacrium®).

What is unique about Cisatracurium compared to Atracurium?

It is 3-5 times more potent and has a shorter half-life.

What type of mechanism does Cisatracurium metabolism involve?

Ester hydrolysis and Hoffman elimination.

What is Mivacurium chloride known for?

A neuromuscular blocker with a shorter duration of action due to rapid ester hydrolysis.

What kind of neuromuscular blocking agent is Succinylcholine chloride?

A depolarizing neuromuscular blocker used during intubation.

What is a common consequence of prolonged effects from succinylcholine?

It occurs in patients with BChE mutations.

What innovative drug acts to reverse neuromuscular blockade induced by rocuronium?

Sugammadex (Bridion®).

What is the major characteristic of Imidacloprid as a pest control agent?

It binds more effectively to insect nAChRs than to mammalian receptors.

What are conopeptides?

Small peptides from cone snails that can paralyze their prey.

How does Ziconotide function in pain management?

As an N-type calcium channel antagonist.

What class of insecticides are derived from the exploration of nicotinic receptors?

Neonicotinoids.

What impact did the discovery of Imidacloprid have on pesticide development?

It led to extensive research on neonicotinoids.

What phenomenon occurs when muscle end-plate response diminishes with depolarizing agents?

Desensitization or tachyphylaxis.

What structural characteristics do competitive neuromuscular blockers have?

Large, bulky, and relatively rigid molecules.

In terms of structure, how do depolarizing agents differ from non-depolarizing agents?

They are smaller and more flexible.

Why is it critical to understand the pharmacogenomics of butyrylcholinesterase?

It helps predict patient response to succinylcholine.

How does the structure of pancuronium influence its function?

It possesses two bulky, positively charged centers separated by a steroid framework.

What adverse effect can occasionally occur with Rocuronium?

Allergic reactions in some patients.

What is the common indication for Vecuronium?

Adjunct in general anesthesia.

What is the significance of hexamethonium and decamethonium?

They illustrate the structure-activity relationship in neuromuscular blockers.

What biological effects does curare produce when used as an arrow poison?

Paralysis of skeletal muscles.

What is the primary function of neuromuscular blockers in surgical settings?

Facilitate muscle relaxation.

What is the potential benefit of sugammadex over succinylcholine?

It can allow greater flexibility in surgical timing and patient safety.

Why were certain neuromuscular blocking agents discontinued?

Due to safety and efficacy issues.

What role does acetylcholine play in the autonomic nervous system?

It acts as a neurotransmitter at ganglia in both SNS and PSNS.

Which condition is treated by nondepolarizing ganglionic blocking agents?

Hypertension.

What is the therapeutic use of Atracurium?

Adjunctive use in anesthesia for muscle relaxation.

How does the structure of neuromuscular blockers affect their action?

Molecule size and rigidity influence their receptor affinity and action.

What kind of muscle response is typically induced by succinylcholine during medical procedures?

Rapid muscle relaxation.

What is a critical consideration when using agents at neuromuscular junctions?

Balancing efficacy with potential side-effects.

What concept does the term 'pachycurares' refer to?

Historically used term for large, rigid neuromuscular blockers.

What is the significance of drug interactions with neuromuscular blockers?

They can alter drug effectiveness and patient outcomes.

Name a neuromuscular blocking agent with a very rapid onset.

Succinylcholine.

What is a characterized use of conotoxins in laboratory settings?

Research into neuromuscular pathways.

Mention a side effect often associated with ganglionic blocking agents.

Hypotension.

How can the action of nondepolarizing blockers be reversed?

By administering acetylcholinesterase inhibitors.

What factors can alter the effects of neuromuscular blockers in patients?

Genetic variations in butyrylcholinesterase.

What aspect of pharmacology is critical in drug development for neuromuscular agents?

Understanding the structure-activity relationship.

Which agent is now primarily used in the clinical setting as a ganglionic blocker?

Mecamylamine.

What critical aspect should be assessed before administering succinylcholine?

The patient's butyrylcholinesterase phenotype.

Why might tubocurarine be deemed unsafe for contemporary use?

It has excessive side effects compared to newer alternatives.

What does re-challenge with depolarizing blockers lead to?

Insensitivity of the muscle to further stimulation.

How long can succinylcholine effects last?

Typically between four to six minutes.

What receptor activity is directly affected by Imidacloprid?

Nicotinic acetylcholine receptors.

Describe the relationship between hexamethonium and tubocurarine.

Hexamethonium is a shorter-acting analogue of tubocurarine.

What innovative research method has been linked to understanding insecticide action?

Study of nicotinic receptors in insects.

Identify a significant drawback of traditional ganglionic blocking agents.

They have many undesirable side effects.

What physiological impact do neuromuscular blockers have during surgical procedures?

They induce relaxation of skeletal muscles.

What necessitated the development of sugammadex?

To provide a rapid way to reverse the effects of neuromuscular blockers.

What condition does Mivacurium treat?

It is a neuromuscular blocker used for muscle relaxation.

What is necessary to reverse the action of neuromuscular blockers?

The administration of acetylcholinesterase inhibitors.

What distinguishes succinylcholine from other neuromuscular blockers?

Its rapid onset and short duration of action.

Why was metocurine discontinued?

Due to its safety profile compared to other agents.

What is the mechanism of action for nondepolarizing neuromuscular blocking agents?

They compete with ACh for binding to nAChR.

What historical context should pharmacologists consider regarding neuromuscular blocking agents?

Their origins stem from hunting poisons like curare.

What is the primary predictor of response to succinylcholine?

Butyrylcholinesterase activity.

What is the structural requirement for competitive neuromuscular blockers?

They need to be bulky to prevent ACh binding.

Which neurotransmitter is responsible for parasympathetic responses?

Acetylcholine.

How do nondepolarizing blockers affect nerve impulses?

By reducing effective receptor activation, they prevent action potentials.

What are the typical side effects associated with neuromuscular blockers?

They may include cardiovascular effects and prolonged paralysis.

What therapeutic advantage does cisatracurium offer?

Less histamine release compared to atracurium.

What is the relevance of studying nicotinic antagonists derived from venoms?

To develop novel therapeutics against pain and neuromuscular disorders.

What muscle-related condition can succinylcholine be critical in managing?

Muscle paralysis for rapid intubation.

What links both succinylcholine and conotoxins?

Their ability to induce paralysis via nicotinic receptors.

Why do neuromuscular blockers represent a vital component of anesthesia?

To promote muscle relaxation and immobility during surgery.

What characteristic is essential for drug efficacy in neuromuscular blockers?

Binding affinity to nicotinic acetylcholine receptors.

How does suxamethonium act differently than traditional neuromuscular blockers?

It causes depolarization followed by desensitization.

Name an effective reversal agent for neuromuscular blockade.

Sugammadex.

What legislative changes are impacting the practice of administering neuromuscular blockers?

Regulations on anesthetic practices and neuromuscular monitoring.

Which producer was pivotal in the formulation of synthetic neuromuscular blockers?

Pharmaceutical companies focusing on anesthetics.

What enzyme is crucial in modulating the action of succinylcholine?

Butyrylcholinesterase.

What structural aspect is common in neuromuscular blockers?

Positively charged centers to bind to the receptor.

Describe the activity of muscarinic receptors as it relates to cholinergic drugs.

They mediate effects in target organs of the autonomic nervous system.

What are the challenges with using neuromuscular blocking agents in pediatrics?

The variations in enzyme activity compared to adults.

How does acetylcholine influence muscle contractions?

By binding to nAChRs and inducing muscle action potentials.

Identify the primary concern with long-acting neuromuscular blockers.

Risk of prolonged paralysis and recovery issues.

What therapeutic areas might benefit from advances in neuromuscular drug design?

Surgery, pain management, and emergency medicine.

What common structure is found in many neuromuscular blocking agents?

A quaternary ammonium salt structure.