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Muscle relaxation is part of a ''balanced anaesthetic technique''. Most anaesthetic agents produce a mild-moderate amount of muscle relaxation and often this is not sufficient. Increased muscle relaxation can be produced by increasing anaesthetic depth, the use of local anaesthetic techniques, or the use of centrally or peripherally acting muscle relaxants.  

Muscle relaxation is part of a ''balanced anaesthetic technique''. Most anaesthetic agents produce a mild-moderate amount of muscle relaxation and often this is not sufficient. Increased muscle relaxation can be produced by increasing anaesthetic depth, the use of local anaesthetic techniques, or the use of centrally or peripherally acting muscle relaxants. However, it is important to realise that muscle relaxants have no anaesthetic or analgesic effect themselves and so should never be used alone.  

'''Neuromuscular blocking agents'''(NMBA) are peripherally acting muscle relaxants. They can be classified as '''depolarising''' or '''non-depolarising''' depending on whether they are competitive or not.  

'''Neuromuscular blocking agents'''(NMBA) are peripherally acting muscle relaxants. They can be classified as '''depolarising''' or '''non-depolarising''' depending on whether they are competitive or not.  

==Neuromuscular Transmission==

==Neuromuscular Transmission==

To understand tranmission of an action potential at the neuromuscular junction it is important to understand the anatomy of the junction. At the nerve terminal, there are a huge number of vesicles containing ''acetylcholine'' (ACh), a neurotransmitter. On the muscle membrane there are a number of nicotinic ACh recpetors. As an action potential reaches the nerve terminal, the ACh contain vesicles fuse with the prejunctional membrane releasing it into the junctional cleft. They diffuse across the cleft and bind to the post-junctional receptors. After binding of two ACh molecules to the two binding sites on the repector the activation of ion channel opening leading to an end-plate potential. If enough channels open, the muscle membrane depolarises and an action potential is generated. This causes release of calcuim ions from the sarcoplasmic reticulum leading to muscle contraction. Binding of ACh is extremely short before it is released and hydrolysed, causing the end of the action potential and muscle contraction. If only one of the two sites is occupied, then ion channel opening does not occur and no action potential is produced.  

To understand tranmission of an action potential at the neuromuscular junction it is important to understand the anatomy of the junction. At the nerve terminal, there are a huge number of vesicles containing ''acetylcholine'' (ACh), a neurotransmitter. On the muscle membrane there are a number of nicotinic ACh recpetors. As an action potential reaches the nerve terminal, the ACh contain vesicles fuse with the prejunctional membrane releasing it into the junctional cleft. They diffuse across the cleft and bind to the post-junctional receptors. After binding of two ACh molecules to the two binding sites on the repector the activation of ion channel opening leading to an end-plate potential. If enough channels open, the muscle membrane depolarises and an action potential is generated. This causes release of calcuim ions from the sarcoplasmic reticulum leading to muscle contraction. Binding of ACh is extremely short before it is released and hydrolysed, causing the end of the action potential and muscle contraction. If only one of the two sites is occupied, then ion channel opening does not occur and no action potential is produced.  

==Where do they Act?==

==Monitoring after NMBA Administration==

NMBAs act on all skeletal muscles  

NMBAs act on all skeletal muscles, which includes respiratory muscles. This means that it is essential to have facilities to provide controlled ventilation. Muscles have different sensitivities for NMBAs, with the diaphragm being particularly resistant making it the last to be paralysed and the first to recover. However, laryngeal tissues appear to be relatively sensitive, meaning it may take longer for these tissues to recover after administation. This makes patients at risk of ''upper airway obstruction'' after the endotracheal tube has been removed.

 

 

 

 

==Mechanism of Action==

==Indications for Use==

[[Depolarising|Depolarising NMBAs]] are ''non-competive'' agents, with the only clinically available product being suxamethonium (succinylcholine) comprising of 2 ACh molecules bound together. Binding to post synaptic receptors, suxamethonium generating an action potential. However, it is not broken down by acetylcholinesterases and so remains bound to the receptor. It is this binding that prevents normal transmission at the site. Therefore, it produces an initial muscle contraction followed by a prolonged period of muscle relaxation. It relies on a fall in concentration of the agent in the blood before it unbinds to travel down the concentration gradient back into the circulation. It is here that is broken down by ''pseudocholinesterase'' enzyme.  

*Replacement of dislocations and fractures.

*Intraocular procedures.

[[Non-depolarising|Non-depolarising NMBAs]] are ''competitive'' agents. They act by binding to the post synaptic ACh receptors, but unlike the depolarising agents, do not cause ion channel opening and therefore there is no action potential. However, by binding to the receptors they prevent binding by ACh thereby blocking normal transmission. This means that there is no stimulation before relaxation is seen upon administration. It also only requires binding at one of the two sites on the receptor to have its blocking effect.

*[[Non-Depolarising|Non-Depolarising Agents]]