Lecture 5 Flashcards by T I

What precursors are used to synthesise ACh?

choline - acetyl coenzyme A

How well did you know this?

Not at all

Perfectly

What enzyme synthesise ACh?

Choline acetyltransferase (ChAT)

How well did you know this?

Not at all

Perfectly

What have amyloid proteins been implicated with?

Inhibiting ChAT in patients with Alzheimer’s disease

How well did you know this?

Not at all

Perfectly

What is choline uptake blocked by?

Hemicholinium 3 (HC-3)

How well did you know this?

Not at all

Perfectly

Is hemicholinum 3 competitive or non-competitive

Competitive

How well did you know this?

Not at all

Perfectly

What is uptake and storage blocked up?

Vesamicol

How well did you know this?

Not at all

Perfectly

How does tetrodotoxin work?

blocks voltage gated Na+ channels - inhibits action potentials - no ACh release

How well did you know this?

Not at all

Perfectly

How do conatoxins work?

blocks P/Q and N type voltage gated Na+ channels - inhibits Ca2+ influx - no ACh release

How well did you know this?

Not at all

Perfectly

How do dendrotoxins work?

block voltage-gated K+ channels - prolongs Ca2+ influx - increased ACh release

How well did you know this?

Not at all

Perfectly

How does ziconotide work?

selective N-type voltage-gated Ca2+ channel blocker - given via intrathecal route to manage severe pain

How well did you know this?

Not at all

Perfectly

Mechanisms of botulinum toxin action

-blocks vesicular release of ACh causing flaccid paralysis - binds to exposed synaptotagmin (Ca2+ sensor) - light chain (a protease) cleaves from heavy chain and attacks SNARE proteins (SNAP-25, syntaxin or synaptobrevin) at a neuromuscular junction - preventing vesicles from anchoring to the membrane to release ACh

How well did you know this?

Not at all

Perfectly

What are the effects of botulinum toxin?

treats dystonias= muscular spasms e.g. belpharospasm (eye muscules) - treats muscle spasticity, tremor - treats sialorrhea (drroling), hyperhidrosis (sweating - cosmetic uses

How well did you know this?

Not at all

Perfectly

what do miniature end-plate potentials (MEPP) represent?

The release of a single quanta of vesicular content at the NMJ

How well did you know this?

Not at all

Perfectly

What does 𝛼-latrotoxin do?

initial excess ACh release= muscle spasms - afterwards distends nerve terminals - depletion of vesicle pool, desensitisation and inhibition of endocytosis= paralysis

How well did you know this?

Not at all

Perfectly

Is the release between synaptic vesicles and quantum of chemical transmitter equivalent or not?

Equivalent

How well did you know this?

Not at all

Perfectly

How does 𝛼-latrotoxin work?

dimers= promotes and enhances Ca2+ release - tetramers= embeds itself into channel and is Ca2+ permeable

How well did you know this?

Not at all

Perfectly

what do miniature end-plate potentials (MEPP) become?

End plate potential (EPP)

How well did you know this?

Not at all

Perfectly

What happens if an (EPP) is large enough?

Initiate an action potential causing muscular contraction

How well did you know this?

Not at all

Perfectly

What enzyme terminates ACh at the NMJ?

Acetylcholinesterases (AChE)

How well did you know this?

Not at all

Perfectly

What are anticholinesterases?

Drugs that inhibit AChE

What do anticholinesterases do?

increase concentration and effects of ACh - can cause muscle spasms

What is an example of a competitive non-depolarising blocker?

Tubocurarine

What happens when you use a competitive blocker with an anticholinesterase?

anticholinesterase increases the concentration of agonists - regular muscle response returns

Is this the action of a competitive or irreversible blocker?

Competitive non-depolarising blocker

What is an example of an irreversible non-depolarising blocker?

𝛼-bungarotoxin

What happens when you use a irreversible blocker with an anticholinesterase?

- no effect - even increasing the agonist concentration cannot outcompete the irreversible blocker

Is this the action of a competitive or irreversible blocker?

Irreversible non-depolarising blocker

Names examples of competitive non-depolarising blockers

- tubocurarine - vecuronium - rocuronium

What are the side effects of tubocurarine?

- decreased BP due to ganglion block - resultant vasodilation - respiratory paralysis

Why would you use vecuronium and rocuronium over tubocurarine?

- fewer side effects - rocuronium is rapid in onset

What are competitive blockers reversed by?

Anticholinesterases e.g. neostigmine

What are the two stages that occur from depolarising blockers ?

- Phase I block - Phase II block

What happens in Phase I block?

- persistent activation of endplate nAChRs - prolonged desensitisation of endplate - inactivation of voltage-gated Na+ channels

What happens in Phase II block?

- desensitisation of endplate nAChRs - repolarisation of endplate - receptor desesnitisation maintains blockade

What is an example of a depolarising blocker?

Suxamethonium

Why would you use suxamethonium clinically?

- rapid onset of paralysis - short duration (broken down by plasmacholinesterases) - tracheal intubation - electroconvulsive therapy

What are the side effects of suxamethonium?

- bradycardia= M2 mAChR activation - K+ release in trauma (e.g. burns)= cardiac dysrythmias and arrest - prolonged paralysis (1:3500 people)

What are the subtypes of ganglionic nicotinic receptors?

- 𝛼 (primarily 𝛼3) - β (primarily β4)

What are the effects of ganglionic blockers?

Reduced actions of both the sympathetic and parasympthetic nervous systems

What are examples of irreversible ganglionic antagonists?

- 𝜅-bungarotoxin - hexamethonium - tubocurarine

What are examples of competitive ganglionic antagonists?

Trimethaphan

Why would you use trimethaphan?

Occasionally used in surgery for controlled hypotension and hypertensive crises

How does hexamthonium and tubocurarine work at the ganglion?

Drug sits in channel like plug in a bottle

What would you use hexamthonium for?

Hypertension

What are the side effects of hexamethonium?

- dry mouth and skin - blurred vision - constipation - urinary retention - postural hypotension

What are examples of ganglionic agonists?

- nicotine - lobeline

How do nicotine and lobeline work at the ganglion?

- repeatedly stimulate receptors - inactivate voltage-gated Na+ channels - desensitise nAChRs

Would suxamethonium generate an effect at ganglionic nAChR?