Pharmacology - Ganglionic and Neuromuscular Blocking Agents

What happens when drugs block nicotinic cholinergic receptors?

Preventing muscle contractions and peripheral arterial constriction

Where are nicotinic ACh receptors found?

On the postganglionic neurons and the motor end plates at the neuromuscular junction and the peripheral autonomic ganglion

What is teh finction of nicotinic receptors (nAChR)?

Opening to allow diffusion of cations (Na, K, and Ca) upon binding by ACh

How are muscle type nicotinic receptos different from neuronal type?

Composition of subunits and location in the body

What are analogs of nicotine used for?

Insecticide

How does nicotine induce vomiting?

By stimulating the chemoreceptor trigger zone

Why is nicotine of considerable medical significance?

Because of its toxicity, presence in tobacco, and propensity for conferring dependence on its users

What does nicotine do?

It can both stimulate and desensitize the receptors making pharmacological effects hard to predict

What is varenicline?

Chantix, a partial agonist at neuronal alpha₄beta₂ nicotinic receptor and thus prevents nicotine stimulation of a mesolimbic dopamine system associated with nicotine addiction

What are the pharmacokinetics and adverse effects of varenicline?

Half life 24h, excreted unchanged from kidneys, headache, insomnia, abnormal dreams, suicidal ideation, depression, irritability, nausea, vomiting

What is an example of a depolarizing muscle relaxant?

Succinylcholine

What is an example of a short acting non-depolarizing muscle relaxant?

Mivacurium

What are examples of intermediate acting non-depolarizing muscle relaxants?

Atracurium, cisatracurium, vecuronium, rocuronium

What are examples of long acting non-depolarizing muscle relaxants?

Doxacurium, pancuronium, pipecuronium

What are characteristics of succinylcholine?

Rapid, ultra-short acting, structurally similar to ACh, adjunct to general anesthesia, facilitates rapid intubation, muscle relaxation during surgery, prevention of injury during electroconvulsive therapy

What is phase I of depolarization by succinylcholine?

Binding to nicotinic receptor causing the prolonged opening of the sodium channels and leading to depolarization at the neuromuscular junction, giving rise to muscle tremors and fasciculations when the drug is first administered

What is phase II of depolarization by succinylcholine?

The muscle cell partially or completely repolarizes but remains unresponsive to ACh because the drug has transiently modified/desensitized the nicotinic receptor leading to muscle relaxation

What are adverse effects of succinylcholine?

Hyperkalemia, malignant hyperthermia, histamine release, transient sinus bradycardia accompanied by hypotension, cardiac arrhythmias, and possible cardiac arrest due ot increased vagal stimulation

What is the structure of non-depolarizing blocking agents?

Positively charged quaternary amines

Waht are non-depolarizing blocking agents?

Competitive antagonists of ACh at the nicotinic receptors at the neuromuscular junction and at the autonomic ganglia, causing flaccid paralysis

Which non-depolarizing neuromuscular blocking agents block muscarinic receptors?

Pancuronium, vecuronium, pipecuronium, rocuronium, rapacuronium

Which non-depolarizing neuromuscular blocking agents do not cause tachycardia?

Amino-steroidal compounds - Vecuronium, rocuronium

Which non-depolarizing neuromuscular blocking agents have less vagolytic activity and cause histamine release?

BZIQ analogs - d-Tubocurare, doxacurium, atracurium, mivacurium, cisracurium

What are contraindications of neuromuscular blocking agents?

Asthma, neonates, old age, obesity, hepatic disease, renal disease