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Year 2 - LCRS - Pharmacology > Neuromuscular Blocking Drugs > Flashcards

Neuromuscular Blocking Drugs Flashcards

1
Q

What part of the nervous system do NM blocking drugs affect?

A
  • the somatic NS
  • alpha motor neurones innervating skeletal muscle
  • NMJ with ACh receptors
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2
Q

What happens at the NMJ?

A
  1. Acetyl Coa + Choline -> acetylcholine via CAT and ACh is packaged into vesicles
  2. AP at presynaptic cell
  3. Ca2+ influx
  4. vesicles move towards the nerve terminal -> exocytosis of ACh
  5. ACh binds to AChR (alpha subunits) on postsynaptic cell
  6. Na+ influx and depolarisation (end plate potential)
  7. ACh is broken down to Acetic Acid and Choline vie Ash-Esterase
  8. Choline is taken up by the presynaptic cell (pump?)
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3
Q

CAT

A

Cholineacetyl Transferase

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4
Q

What are the subunits of the AChR?

A

2 alpha (ACh binds here)
1 beta
1 gamma
1 delta

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5
Q

How many molecules of ACh have to bind to the receptor to cause a response?

A

2

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6
Q

What are the 5 steps in the neuromuscular pathway?

A
  1. Central porcesses
  2. Conduction of nerve AP in Motor neurone
  3. ACh release
  4. Depolarisation of motor end-plate -> AP initiation
  5. propagation of AP along muscle fibre and muscle contraction
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7
Q

What drugs can affect central processes in the NM pathway?

A
  • spasmolytics
  • e.g. diazepam, baclofen (-> GABAergic drugs)
    reduce NM transition in spinal cord
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8
Q

What drugs can affect conduction of AP in motor neurone in the NM pathway?

A
  • local anaesthetics
  • blocks Na+ channels -> stops/limits APs to the brain
  • can cause skeletal muscle weakness
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9
Q

What drugs can affect ACh release in the NM pathway?

A
  • HEMICHOLINIUM
  • Ca2+ ENTRY BLOCKERS
  • NEUROTOXINS (e.g. botulinum toxin)
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10
Q

Botulinum toxin

A
  • disrupts release of ACh
  • Botox paralyses skeletal msucles of forehead and causes the skin to look smoother -> also same muscles that are responsinbel for facial expression -> flat looking faces.
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11
Q

What drugs affect the depolarisation of motor end-plate -> AP initiation in the NM pathway?

A
  • tubocurarine

- suxamethonium

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12
Q

What drugs affect the propagation of AP along muscle fibre and muscle contraction in the NM pathway?

A
  • spasmolytics
  • e.g. dantrolene
  • redeces Ca2+ release
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13
Q

What is some general info about NM blocking drugs?

A
  • POSTsynaptic action
  • relax skeletal muscles
  • 2 types: depolarising and non-depolarising
  • they do not affect consciousness
  • they do not affect pain sensation
  • they are used in surgery
  • ALWAYS assist respiration until the drug is inactive or antagonised
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14
Q

Non-Depolarising NM blocking drugs

A

= competitive antagnosists

- e.g. tubocurarine, atracurium

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15
Q

Depolarising NM blocking drugs

A
  • agonists

- e.g. suxamethonium (=succinylcholine)

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16
Q

Molecular structures of NM blocking drugs?

A
  • Tubocurarine: can bind to AChR but has no efficacy; quaternary ammonium groups -> similarity to ACh
  • Suxamethonium: essentially 2 ACh molecules -> agonist
  • in general antagonists have a rigid, bulky structure with relatively little free rotation -> bind and block receptor
  • agonists e.g. suxamethonium: much more rotation around free bonds -> have better efficacy
17
Q

MoA of suxamethonium

A
  • extended end-plate depolarisation -> depolarisation block
  • fasciculations -> flaccid paralysis
  • depolarises the end-plate
  • does not dissociate rapidly from receptors -> prolonged receptor activation
  • this causes a brief train of muscle APs and muscle fibre twitches
  • NM block occurs because:
    a) voltage sensitive Na+ channels are inactivated in the surrounding muscle fibre membrane -> APs are no longer generated.
    b) activated receptors are transformed into a desensitised state and are unresponsive to ACh
18
Q

Pharmacokinetics

A
  • rapid onset
  • RoA: i.v. (highly charged)
  • duration of action ~5 minutes (2-6 minutes)
  • usually hydrolysed rapidly by (plasma) pseudocholinesterase -> in liver or plasma
19
Q

Why do some people react differently to Suxamethonium?

A
  • about 1 in 3000 people inherit an atypical pseudocholinesterase
  • in those individuals the NM block can last for hours
20
Q

What are the clinical uses of suxamethonium?

A
  • endotracheal intubation

- muscle relaxant for ECT (electrocompulsive therapy - last resort treatment in depression)

21
Q

Why is suxamethonium used in ECT?

A
  • prevents movements

- this decreases the likelihood that there will be damage to the brain as the patient does not move.

22
Q

What are unwanted effects of suxamethonium?

A
  • post op muscle pains -> due to fasciculations which cause damage
  • Bradycardia: direct muscarinic action on the heart (atropine can block this effect)
  • Hyperkalaemia: deinnervation supersensitivity post soft tissue injury such as burns -> more nicotinic receptors added to the end plate region; Such patients there would be a massively enhanced response: big Na+ influx and K+ efflux which can lead to hyperkalaemia. This may lead to ventricular arrhythmia or cardiac arrest
  • increased intra-ocular pressure
23
Q

In what patients would you avoid the use of suxamethonium?

A
  • burn injury patients
  • patients with soft tissue damage

=> due to deinnervation supersensitivity: ascending innervation reduced after injury but more nicotinic receptors added onto the end-plate region there. In those patients there would be a more profound effect due to the increased number of channels with more Na+ influx and K+ efflux which could cause ventricular arrhythmia or even cardiac arrest due to HYPERKALAEMIA.

  • also Glaucoma and eye-injury patients as suxamethonium increases intra-ocular pressure
  • in those patient groups use a non-depolarising blocker
24
Q

Tubocurarine general information

A
  • non-depolarising NM blocking drug
  • Naturally occurring 4° AMMONIUM COMPOUND (ALKALOID) FOUND IN S. AMERICAN PLANT (ARROW POISON)
  • RANGE OF SYNTHETIC DRUGS NOW AVAILABLE
25
Q

What is the mode of action of tubocurarine?

A
  • competitive nAChR antagonist

- 70 - 80% block necessary to achieve flaccid paralysis

26
Q

What are the effects of tubocurarine?

A
  • flaccid paralysis
  1. extrinsic eye muscles (double vision if the patient is concious)
  2. small muscles of face, limbs and pharynx (difficulty swallowing)
  3. respiratory muscles

Recovery: 3 -> 2 -> 1

27
Q

What are the clinical uses of tubocurarine?

A
  • relaxation of skeletal muscle during surgical operations -> you need less general anaesthetic which makes the patient come around from the surgery quicker
  • to permit artificial ventilation -> the patient is not working against the ventilator.
28
Q

How can actions of non-depolarising NM blockers be reversed?

A
  • by anticholinesterases

- e.g. neostigmine (+atropine)

29
Q

Pharmacokinetics of tubocurarine

A
  • RoA: i.v. (highly charged)
  • does not cross BBB or placenta
  • duration of paralysis: 1-2 h(-> long)
  • NOT metabolised
  • Excretion: 70% urine, 30% bile -> care if renal or hepatic function is impaired.
30
Q

Atracurium

A
  • 15 min duration

- chemically unstable - breaks down spontaneously in 15 minutes

31
Q

What are unwanted effects of tubocurarine?

A

Ganglion block + histamine release

  • Hypotension (ganglion blockade causes reduction in TPR, so does histamine (=vasodilator) release from mast cells)
  • Tachycardia: Reflex to hypotension, may give rise to arrhythmias; blockade of vagal ganglia.
  • Bronchospasm
  • excessive secretions (bronchial and salivary)
  • these 2 are due to histamine release
  • apnoea (ALWAYS assist reparation)
32
Q

SBA 1: The clinical use of neuromuscular blocking drugs will most likely involve interference with which of following physiological processes?

A: Kidney function
B: Consciousness
C: Body temperature regulation
D: Pain sensation
E: Respiration
A

E

33
Q

SBA 2: Which of the following effects would be observed with a non-depolarising neuromuscular block?

A: Initial muscle fasciculations
B: Irreversible nAChR blockade
C: The block would be enhanced by anti-cholinesterase drugs
D: A flaccid paralysis
E: Increased arterial pressure
A

D

Year 2 - LCRS - Pharmacology (34 decks)

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