Wk4 Neuromuscular Function And Dysfunction Flashcards

1
Q

On injecting suxamethonium what symptom/sign would you observe in the patient which would distinguish its action from that of d-tubocurarine or pancuronium? What is the reason for this effect?

A

Suxamethonium is a depolarising blocker that acts as agonist (does something e.g. twitches so cant be antagonist) to nAChR. That causes initial small muscle contractions. If it isn’t broken down it leads to prolonged EPP which leads to overactivity of the Na+ channels, leading to their inactivation and therefore paralysis.
Pancuronium and D-Tubocurarine is a non-depolarising blocker and hence a competitive antagonist and nAChRs. This causes a proportion of channels to be covered so EPP is smaller, this causes a smaller chance of AP generation and so paralysis caused. Unlike suxamethonium, there is no initial muscle twitch.

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2
Q

In the British National Formulary (BNF) it states “suxamethonium is contraindicated in severe burns”. Why?

A

Its use is contraindicated due to the risk of hyperkalaemia leading to cardiac arrest, thought to be due to release of potassium from extrajunctional ACh receptors

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3
Q

What does contraindicated mean?

A

An indicator of when a particular drug shouldn’t be used e.g. in this instance suxamethonium shouldn’t be used in severe burns

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4
Q

What happens to ion fluxes in the presence of suxamethonium?

A

The ion flux of Na+ is maintained as the ion channels are continually opened, so the membrane is continually depolarisation as na+ keeps moving in

As a result, the constant flow of Na+ causes the continual release of Ca2+ ions from the sarcoplasmic reticulum into the sarcoplasm of the muscle

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5
Q

What might extensive burns do to extracellular ion levels?

A

Extensive burns lead to an increased water retention which results in more sodium retention. Also there is an increased potassium urinary loss

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6
Q

What does high K+ concentration do?

A

Gradient decreases as increase in K+

Becomes less negative

Can cause cardiac cells to fire off more APs - disturbs cardiac rhythm

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7
Q

It is also particularly important to avoid its use in patients with a damaged eyeball. Why?

A

Due to your ion imbalance, the osmotic balance is also disrupted, therefore water moves into the vitreous humour of the eye, increasing pressure – causes extrusion of the eye, which can lead to sight loss.

Can cause glaucoma (pressure and fluid affect optic nerve)

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8
Q

Suxamethonium normally produces rapid, complete and predictable paralysis for approximately 5 minutes and recovery is spontaneous. In some patients however prolonged muscle paralysis may occur when this drug is used. Why?

A

Suxamethonium broken down by plasma cholinersterase (normally terminates it) - normally takes 2-6 mins to break down but there are genetic variants so may take longer to hydrolyse

Variation in people - due to weight and height

Hydrolysis by enzyme may be slower due to a genetic variation - enzyme has different shape

(In rare cases the enzyme may be absent + therefore the drug is not broken down so paralysis lasts for many hours

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9
Q

Repeated doses of suxamethonium may also produce prolonged paralysis. Why?

A

Repeated doses cause a phase 2 block as prolonged stimulation results in desensitisation. nAChRs are degraded and expression is lost on cell membrane therefore leading to paralysis. Time is therefore needed to synthesise new nAChRs.

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10
Q

If too much of this drug is given could the effect be antagonised? If so, how?

A

Depolarising drug – enzyme required to break it down. Inject the patient with more acetylcholine to outcompete the drug.

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11
Q

How does the toxic agent produce the effects described?

A

Affects motor neurones by inhibiting the release of ACh

Paralyses the nerves so that the muscles cannot contract - this occurs as the toxin blocks the release of ACh

Paralyses the nerves so that the muscles cannot contract, this occurs as the toxin blocks the release of ACh from the presynaptic motor neurones at the neuromuscular junction.

The toxin does this via the cleavage of components of the exocytosis machinery - prevents them from being released into the synaptic cleft

The toxin acts at 4 different sites of the body, the NMJ, autonomic ganglia, post ganglionic parasympathetic nerve endings and postganglionic sympathetic nerve endings.

The lack of ACh passing across the NMJ will cause a lack of a subsequent muscle contraction

The toxin is only able to act at synaptic junctions that actively recycle vehicles as this is the method they use to enter the neurone

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12
Q

Why is diplopia one of the first symptoms to appear?

A

Diplopia = double vision. The toxin attacks the cranial nerves. As you’re ingesting close to the eyes, the cranial nerves are a primary target of the toxin

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13
Q

Whilst the hospital is waiting for the results of some tests, they are given a treatment to try and stop them deteriorating further. What is this likely to be?

A

An anti-toxin is required. This prevents more damage being done, but is unable to reverse the damage already caused. Antibodies bind to the toxin in the blood so the toxin is unable to affect the release of acetylcholine as it has been neutralised.

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14
Q

Why was it important to start treating them before the diagnosis was confirmed?

A

To prevent any more damage occurring – increases chances of survival. No harm is done by treating it prior to damage occurring.

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15
Q

What is it used for cosmetically and how does it bring about its desired action?

A

Botox – reversible paralysis of local muscles.

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16
Q

What is it used for therapeutically and how does it bring about its desired action?

A

Chronic pain – decreases pain response by stopping pain receptors working at full function. Also used for bladder spasms and uncontrolled blinking by reducing muscle contraction.