Use of myorelaxant drugs
- During surgical anaesthesia to obtain skeletal muscle relaxation
- Assist in intubation
- Corneal/retinal surgery
- Therapy of spastic disorders
Competitive neuromuscular blocking agents: Function
Selectively antagonise nicotinic receptors by preventing endogenous ACh binding & subsequent muscle cell depolarisation
Give the classes of neuromuscular blocking agent
- Competitive (non-depolarising)
- Depolarising
Competetive neuromuscular blocking agents:
To produce a complete block…% of receptors must be blocked
90%
Competitive neuromuscular blocking agents: properties
- Ionised and water-soluble
- Onset is slow & short duration
Competitive neuromuscular blocking agents: Metabolism & excretion
- Metabolised in liver
- Excreted by kidenys
Competitive neuromuscular blocking agents are antagonised by…
Cholinesterase inhibitors (Neostigmine)
Competitive neuromuscular blocking agents: Effect
- Motor weakness →
- Flaccid paralysis of skeletal muscles
- ↓ Blood pressure
- ↓ Coagulability of blood because of heparin release from mast cells
Competitive neuromuscular blocking agents: Examples
- Curare (Histamine release)
- Gallamine (Tachycardia; long-acting)
- Atracurium (Safe in liver & kidney disease; most used; intermediate action)
- Cisatracurium (intermediate-acting)
- Rocuronium (intermediate-acting)
- Vecuronium (intermediate-acting)
Central muscle relaxants
Relative specific depressant action in CNS
- Causing ↓ motor activity/paralysis of voluntary muscles without LOC
- Do not inhibit other CNS functions
- Can potentiate the effect of anaesthetics and combinations
Central muscle relaxants: Examples
- Guaiphenesin
- Baclophen
- Carisoprodol
- Methocarbamol
Guaiphenesin
- Spinal interneuronal blocking agent
- Used to adjunct anaesthesia
- Blocks polysynaptic and not monosynaptic reflexes
- Effective against:
- Convulsions
- Tetanus
Baclophen
- GABAB receptor agonist in CNS
- Causes hyperpolarisation of neurons due to ↑ K+ ion conductance
- Large therapeutic index
Carisoprodol
Useful for pain - Due to analgesic-sparing effect on opioid analgesics
Methocarbamol
- Acts on internuncial neurones of the spinal cord
- ↓ Skeletal muscle hyperactivity
Depolarising neuromuscular blocking agents: Function
- Stimulates opening of nicotinic ACh receptor channel
- Produces depolarisation of cell membrane
- Succinylcholine persists at neuroeffector junction, activating nicotinic receptor channels continuously
- Inactivation of voltage-gated Na+ channels → Cannot support further APs
Depolarising neuromuscular blocking agents: Properties
Rapid onset; short duration
Neuromuscular blocking drugs do not produce…
Analgesia
Metabolism of depolarising neuromuscular blocking agents
Metabolised by plasma pseudocholinesterase & liver
Depolarising neuromuscular blocking agents: Example
Succinylcholine
Succinylcholine
- Dog, cattle, sheep are sensitive
- Weakness & paralysis of skeletal muscles
- ↑ Blood pressure
Succinylcholine: Side effects
- Bradycardia
- Hyperkalaemia
- ↑ intraoccular & intragastric pressure
- Anaphylaxis
Succinylcholine: Phase I block
- Depolarising block of motor end-plate
Succinylcholine: Phase II block
- Competetive block of motor end-plate/partially susceptible to reversal by cholinesterase inhibitors
“Muscle relaxants” refers to which 2 therapeutic groups?
- Neuromuscular blockers
- Spasmolytics
Spasmolytics: Use
Alleviate musculoskeletal pain and spasms
- Specifically depress the CNS → ↓ Motor activity/ paralysis
- No LOC
- May cause drowsiness/sedation
Neuromuscular blocking drugs: Aims
- Relax skeletal muscles for surgery
- Reduction of dislocations and fractures
Neuromuscular blocking drugs: Function
Interferes with transmission at NMJ → Relaxation/paralysis
Spasmolytics-smooth muscle relaxants
Parasympatholytics, Sympathomimetics, direct acting substances
Spasmolytics-smooth muscle relaxants: Examples
- Papaverine
- Drotaverine
Papaverine: Effect
- Reduces spasm of visceral smooth muscle
- Vasodilation
- Bronchodilation
- ↓ Heart excitability
Papaverine: Indications
- Excessive smooth muscle contraction
- Urethral spasm
- Colic spasm
- Bronchial spasm
- Relax uterus (drotaverine)