MUSCLE RELAXANTS

Muscle relaxants are drugs that interrupt transmission of neural impulses at the neuromuscular junction

History

Involved research using Banded Krait (bungarotoxins) and cobra as well as curare from South American plants

Banded Krait from Taiwan

Most potent source of curare

Clinical uses

1. Provide skeletal muscle relaxation to facilitate intubation of the trachea

2. Provide optimal surgical working conditions

3. In the intensive care setting to facilitate mechanical ventilation of the lungs

Note

MR lack anesthetic or analgesic effects and must not be used to render an inadequately anesthetized patient immobile

The choice of MR is influenced by:

1. Its speed of onset

2. Duration of action

3. Rout of elimination

4. Associated side effects

Neuromuscular junction

Consist of a prejuctional motor nerve ending separated from the highly folded postjunctional membrane by synaptic cleft

Neuromuscular transmission is initiated by arrival of an impulse at the motor nerve terminal with an associated influx of calcium and a resultant release of neurotransmitter acetylcholine

Ach binds to nicotinic cholinergic receptors on postjunctional membrane, causing a change in membrane permeability to ions, principally K & Na ions

Ach is rapidly hydrolyzed by enz. Acetylcholine esterase (true cholinesterase)

Nicotinic cholinergic receptors

1.Prejunctional

2.Postjunctional

3.extrajunctional

Neuromuscular Junction

ACh ACh (8-10,000 (8-10,000 molecules)molecules)~100mM~100mM

Acetate and Acetate and cholinecholine

50% recaptured 50% recaptured by nerve terminalby nerve terminal

Voltage-dependentVoltage-dependentCaCa2+ 2+ channelschannels

High affinity High affinity choline carriercholine carrier

Empty Empty

vesiclevesicle

CATCATAcCoAAcCoA

CoACoA

cholinecholine

AChACh

active transportactive transport

AChEAChE

cholinecholine

NaNa++

CaCa2+2+

CaCa2+2+

CaCa2+2+

AChACh

AChACh

AChACh

NaNa++

KK++nAChRnAChR

NaNa++

Muscle fibreMuscle fibre

Muscle relaxants

Depolarizing noncompetitive

Nondepolarizingcompetitive

Depolarizing (succinylcholine or Suxamethonium)

Clinical use: - - - - - -

Averse effects

1. Cardiac dysrthymia: Bradycardia, arrest

2. Myalgia

3. Myoglobinuria

4. Increased Intraocular pressure

5. Increased Intragastric pressure

6. Increased Intracranial pressure

7. Trismus

8. Allergic reactions

9. Trigger for malignant hyperthermia

10. Hyperkalemia

• Denervation injury (spinal cord transection)

• Unhealed skeletal muscle injury as produced by 3rd degree burn

• Upper motor neuron injury

• Multiple trauma

Causes of delayed recovery from succinylcholine1. Sever liver disease

2. Potent anticholine esterase (insecticides)

3. Chemotherapy (cyclophosphamide)

4. A typical pseudo cholinesterase

Nondepolarizingcompetitive

Long acting>)30 min(

PancuroniumD-tubocurarine

Gallamine

Intermediate acting)15-25 min(

VecuroniumCis (atracurium)

rocuronuim

Short acting<)15 min(

Mivacurium

Nondepolarizingcompetitive

Factors enhance effects of NDMR

1. Volatile anesthetics2. Aminoglycosides Antibiotics3. Mg4. Local analgesics5. Calcium channel blockers (verapamil)6. Cardiac antiarrythmias (quinidine) 7. Hypothermia8. Acidosis9. Hypokalemia

Drug-assisted antagonism of Nondepolarizing muscle relaxants

Anti-cholineesterase

Neostigmine edrophonium pyridostigmine

Anticholinesterase

Drug accelerates the already established pattern of spontaneous recovery at the neuromuscular junction by inhibiting the activity of acetylcholinesterase leading to accumulation of ach. At nicotinic (neuromuscular junction) and muscarinic sites

The competition between ach and a Nondepolarizing MR in favor of the neurotransmitter (Ach) and restores neuromuscular transmission

• Anticholinesterase does not cross blood brain barrier

• Peripheral muscarinic effects block by anticholinergic drugs like Atropine

Thank you