Pharmacology of Neuromuscular and Ganglionic Blockers Flashcards
Why are nicotinic receptor blockers not commonly used?
Nn receptors are in the ganglia, thus blocking the entire ANS.
What are nicotinic receptor blockers also called?
Ganglionic blockers
Examples of reflexes blocked by ganglionic blockers?
Baroreceptors
Pupillary
Name the two important ganglionic blockers used.
Mecamylamine and Trimethaphan
Mecamylamine is a treatment for….
Tourette’s
Smoking Cessation
Severe hypertension
At rest, which system (SANS or PANS) has the largest role in vascular smooth muscle tone?
SANS
The endogenous tone is mild vasoconstriction
An autonomic blockade of the vascular smooth muscle will cause…
vasodilation
At rest, which system (SANS or PANS) has the largest role in non-vascular functions.
PANS
The endogenous tone is mild bradycardia
An autonomic blockade of the heart will trigger…
Tachycardia
Neuromuscular blockers work by (general)….
blocking local nicotinic receptors on skeletal muscle in the somatic nervous system
More specifically, how does acetylcholine blockage happen pre- and post-synaptically?
Pre – Decreased Ach formation/release or increased metab.
Post – Block cholinergic receptors (Nm->Clinical Use)
What is unique about the structure of nicotinic receptor blockers used for skeletal muscle?
Drugs have a quaternary amonium
This restricts them peripherally
When would you used a neuromuscular blocker?
Surgery
Orthopedic Procedures
Bronchoscopy
Intubation
The first clinically used nicotinic receptor neuromuscular blocker?
Curare
How does one monitor a neuromuscular blockade?
Train of Four electrical stimulation test
What is a train of Four electrical stimulation test?
Electrode on wrist and nerves in the hand
Without blockade, you see 4 twitches with stimulation
Look for 75% block (patient responds to 1-2)
Problem with knocking a person down to having no twitches?
No way to monitor anymore
Sequence of muscle paralysis in a neuromuscular block?
Eye Muscles, Speech Control First
Intercostals and Diaphragm last
The order of muscle loss folowing curare/neuromoscular blocker od looks a lot like what disease?
Guillain Barre Syndrome
Two types of neuromuscular blockers?
Depolarizing and Non-depolarizing
The depolarizing agonist you need to know?
Succinylcholine
What is so great about succinylcholine (Sux)?
Short Acting
Rapidly metabolised by BeChE
When would you use Succinylcholine?
Trauma care
Reduce muscle stress from anti-convulsant therapy
Who should you never use a depolarizing agent on?
Patients with hyperkalemia
Extra potassium release from the agent can cause cardiac arrest
Molecular activity of succinylcholine?
Agonist to nicotine acetylcholinergic receptors
Influx of Sodium Ions, Stuck Open
Prevents repolarization and thus preventing more action potentials.
Why does acetylcholine have a short duration?
Quick degradation by acetylcholinesterase
First use of Sux will do what?
Muscle Twitch
Non-depolarizing neuromuscular blockers are frequently used why?
Easily Reversible with a Long Duration of Action
Non-depolarizing neuromuscular blockers are antagonists of ____ receptors
Nm
What it trimethaphan?
A ganglionic blocker used as short acting non-depolarizing neuromuscular blocker
What is Pancuronium?
An antagonist nicotinic acetylcholine with a long duration
Endogenous acetylcholine binds to _______
An agonist to nicotine acetylcholinergic receptors
Allows a sodium influx
Rocuronium is what kind of drug?
A non-depolarizing muscle relaxant and antagonist of NAchR (blocking acetylcholine induced activation and nerve transmission)
How do you reverse Rocuronium?
AchE inhibitor (neostigmine) Sugammedex (binds and sequesters rocuronium)
Two types of cholinesterases?
Acetylcholinesterase in synapses, high affinity
Butyrylcholinesterase in plasma
Acetylcholinesterase of Butrylcholinesterase – who breaks down Sux and other anesthetics?
BuchE
Three classes of AchE inhibitors
Carbamates
Organophosphates
Quaternary ammonium alcohols
How to carbamates interact with AchE? What is important to remember about this interaction?
Temporarily create a covalent modification to AChE
Rapid and Reversible
Three important types of carbamate AchE inhibitors?
Physostigmine
Neostigmine
Pyridostigmine
Physostigmine is an _______ amine.
Tertiary
Physostigmine can act where in the body?
Can get into CNS
Indications for use of Physostigmine?
Atropine Overdose
Glaucoma, Alzheimer’s Disease
Neostigmine and Pyridostigmine are _____ amines
Quaternary
Neostigmine and Pyridostigmine can act where in the body?
Only peripherally
Indications for use of Neostigmine and Pyridostigmine?
Myasthenia gravis
Reversal of NM blockers
Post Operative Ileus
Neostigmine and Pyridostigmine. Which one has fewer side effects and a longer duration?
Pyrido
How to organophosphate acetylcholinesterase inhibitors work?
They bind covalently, irreversibly to AchE
Makes for a very long duration of action (over a week)
Why care about organophosphate acetylcholinesterases?
Historically used in glaucoma treatment, but not anymore.
They show up now in the context of nerve gas or insecticide poisoning.
Especially famous organophosphate nerve gases
Sarin and Soman
Poisoning with organophosphates can be reversed if….
Antidote (Pralidoxime Chloride-2PAM) must be given within a few hours of exposure
Symptomatic treatment for organophosphate poisoning?
Atropine (a competitive agonist of muscarinic)
Why can’t you just use 2-pam to reverse organophosphate poisoning whenever?
After the organophosphate and AchE covalently bind, the AchE will be further hydrolyzed, forming a permanent bond that can’t be rescued.
Symptoms of Acetylcholinesterase Inhibitor Poisoning
Diarrhea Urination Miosis Branchospasms Bradycardia Excitation of skeletal muscle and CNS (perm in diaphragm = fatal) Lacrimation Sweating Salivation
Who is most likely to get acetylcholinesterase inhibitor poisoning?
Farmers
Describe the chemical structure of Edrophonium
Quaterenary Ammonium Alcohol
What is Edrophonium used for?
Diagnosis of Myasthenia Gravis
Two things Edrophonium can be used to distinguish?
MG from Lambert Eaton induced MG
Myasthenic Crisis from a Cholinergic Crosis
What is Lambert Eaton MG?
Antibodies against vg Calcium Channels
Edrophonium influence on a patient in cholinergic crisis?
None, maybe a small decrease in muscle strength
Edrophonium influence on MG
Improves overall muscle strength
Contraindications for the use of PS drugs
Asthma and COPD Coronary deficiency Peptic ulcer Obstruction of urinary or GI tract Epilepsy
CNS Norepinephrine is produced by…
locus ceruleus
Ach is produced where in the CNS
Brain Stem and Nucelus Basalis of Meynert
Degeneration of cholinergic cells in the nucleus basalis occurs in what disease processes? How are these diseases identified?
Dementia and PD
Lewy Bodies
Reversible AchE inhibitors that are used to manage symptoms of Alz. Disease
Donepezil, Rivastigmine, and Glanthamine
Locus ceruleus plays a role in….
Stress, panic, and emotional pain
Important details for Donepezil (Aricept)
Bind to anionic site and block ACh binding
Reversible
Enhances cognitive ability
Important details for Rivastigmine?
Reversible AChE inhibitor
Increased cholinergic function –> increased cognitive ability
Nausea, Vomiting, Weight-loss
Important details for Galanthamine?
Reversible AChE inhibitor
use with inhibitors of p450 to increase half life/bioavailability
