2 Succinylcholine

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Succinylcholine = Suxamethonium chloride 

Succinylcholine acts as a Depolarizing neuromuscular blocker (=DMR - Depolarising muscle relaxant)

Mnemonic : SSSS

• FasSiculations
• FaSt dissociation at receptors (Therefore Short acting )

Mnemonic : DND

• Not reversed by Neostigmine
• No fade or Post tetanic stimulation. 

Potentiated by

1. Isoflurane
2. Respiratory Alkalosis
3. Hypothermia
4. Mg

Antagonised by : Acidosis and NDMR

Repeated use  - causes Phase II block (similar to NDMR) -- (MCQ)

Other points about Sch :

• Onset within 30 sec --- lasts 10-12 mins.
• Bradycardia in children (especially after 2nd dose) (MCQ)
• All presures are increased ( BP , ICP , IOP , Intra gastric )
• Enzyme metabolism - by PseudoCholinestrase (= plasma = Butyrylcholinesterase) (read below in short about Cholinestrases )

Dibucaine Number :

• The Dibucaine Number is a measure of the qualitative activity of Pseudocholinesterase and is the percentage of inhibition of the enzyme by the local anesthetic Dibucaine.
Normally 75 - 85 % inhibition , But if homozygous defficiency - then 30%

• It is used to differentiate individuals who have substitution mutations of the Butrylcholinesterase enzyme.

Side effects :

• Increase K+ (especially after Burns , spinal cord injury , stroke , cerebral palsy )

Therefore Sch is Avoided 48hrs - 9months after acute injury. 

• Post Op muscular pain which can be decreased by :

                                  1. Self Taming (Pretreatment with small (10 mg) doses of succinylcholine)

                                  2. Precurarization (NDMR + Sch)

                                  3. Lignocaine

• Malignant Hyperthermia

Note: 

1. Sch is the MC drug which causes Malignant Hyperthermia.
2. All Fluranated inhalational anaesthetics & Lignocaine are other drugs which can cause Malignant Hyperthermia.

• Allergy - releases histamine.

• Contraindicated in Myotonic Dystrophy : as it causes severe muscle rigidity , preventing respiration and intubation.

• Can cause Masseter spasm in children.

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NeuroMuscular monitoring (Adductor Pollicis , Ulnar Nerve)  (No use in Sch block)

1. TOF (Train of 4)
2. PTC ( Post tetanic count )
3. DBS ( Dual burst stimulation )
4. Tetanus

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Cholinesterases :

1. True :  RBC and Grey Matter.
2. Pseudo/False :  Liver and Plasma.

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2 Neuromuscular-blocking drugs

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Neuromuscular-blocking drugs

These drugs fall into two groups:

• Non-depolarizing blocking agents: These agents constitute the majority of the clinically relevant neuromuscular blockers. They act by competitively blocking the binding of ACh to its receptors, and in some cases, they also directly block the ionotropic activity of the ACh receptors.
• Depolarizing blocking agents: These agents act by depolarizing the plasma membrane of the skeletal muscle fiber. This persistent depolarization makes the muscle fiber resistant to further stimulation by ACh.

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0 Neuromuscular junction (NMJ)

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Neuromuscular junction (NMJ):
The neuromuscular junction connects the nervous system to the muscular system via synapses between efferent nerve fibers and muscle fibers, also known as muscle cells.

Neuromuscular junction 

1. presynaptic terminal
2. sarcolemma
3. synaptic vesicles
4. Acetylcholine receptors
5. mitchondrion

Points to remember : ( Mnemonic - MU CaR )

Acetylcholine Uploading into vesicles -- Magnesium (Mg)

Acetylcholine Release from vesicles -- Calcium (Ca)

Excitation-contraction coupling of vertebrate skeletal muscle :

1. Upon the arrival of an action potential at the presynaptic neuron terminal, voltage-dependent calcium channels open and Ca2+ ions flow from the extracellular fluid into the presynaptic neuron's cytosol.
2. This influx of Ca2+ causes neurotransmitter-containing vesicles to dock and fuse to the presynaptic neuron's cell membrane through SNARE proteins.
3. Fusion of the vesicular membrane with the presynaptic cell membrane results in the emptying of the vesicle's contents (acetylcholine) into the synaptic cleft, a process known as exocytosis.
4. Acetylcholine diffuses into the synaptic cleft and can bind to the nicotinic acetylcholine receptors on the motor end plate.
5. These receptors are ligand-gated ion channels, and when they bind acetylcholine, they open, allowing sodium ions to flow in and potassium ions to flow out of the muscle cell.
6. Because of the differences in electrochemical gradients across the plasma membrane, more sodium moves in than potassium out, producing a local depolarization of the motor end plate known as an end-plate potential (EPP).
7. This depolarization spreads across the surface of the muscle fiber and continues the excitation-contraction coupling to contract the muscle.
8. The action of acetylcholine is terminated when ACh diffuses away from the synapse or the enzyme acetylcholinesterase degrades part of ACh (producing choline and an acetate group).
9. The choline produced by the action of acetylcholinesterase is recycled — it is transported, through reuptake, back into the presynaptic terminal where it is used to synthesize new acetylcholine molecules.

ref: 
http://en.wikipedia.org/wiki/Neuromuscular_junction

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0 Xenon

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Xenon :

• Weak anaesthetic , more like N2O

• Most closest to ideal anaesthetic agent.

• Used radioactively to study cerebral blood flow.

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