1. MUSCLE RELAXANTS
Muscle relaxants are drugs that interrupt transmission of neural impulses at the neuromuscular junction

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

3. Banded Krait from Taiwan

5. Most potent source of curare

6. Clinical uses

7. Provide skeletal muscle relaxation to facilitate intubation of the trachea
Provide optimal surgical working conditions
In the intensive care setting to facilitate mechanical ventilation of the lungs

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

9. The choice of MR is influenced by:
Its speed of onset
Duration of action
Rout of elimination
Associated side effects

10. 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

11. 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

12. Neuromuscular Junction

13. CAT Ca2+ AChE Ca2+ Ca2+ nAChR ACh ACh Acetate and choline ACh ACh Na+
High affinity
choline carrier
choline
Na+
CAT
AcCoA
CoA
choline
ACh
active transport
50% recaptured
by nerve terminal
ACh
Empty
vesicle
ACh
Acetate and choline
ACh
Ca2+
AChE
ACh
(8-10,000
molecules)
~100mM
Na+
Ca2+
Voltage-dependent
Ca2+ channels
Na+
Ca2+
nAChR K+
Muscle fibre

15. Depolarizing (succinylcholine or Suxamethonium)
Clinical use:

16. Averse effects Cardiac dysrthymia: Bradycardia, arrest Myalgia
Myoglobinuria
Increased Intraocular pressure
Increased Intragastric pressure
Increased Intracranial pressure
Trismus
Allergic reactions
Trigger for malignant hyperthermia

17. 10. Hyperkalemia
Denervation injury (spinal cord transection)
Unhealed skeletal muscle injury as produced by 3rd degree burn
Upper motor neuron injury
Multiple trauma

18. Causes of delayed recovery from succinylcholine
Sever liver disease
Potent anticholine esterase (insecticides)
Chemotherapy (cyclophosphamide)
A typical pseudo cholinesterase

19. Nondepolarizing competitive

20. Factors enhance effects of NDMR
Volatile anesthetics
Aminoglycosides Antibiotics Mg
Local analgesics
Calcium channel blockers (verapamil)
Cardiac antiarrythmias (quinidine)
Hypothermia
Acidosis
Hypokalemia

21. Drug-assisted antagonism of Nondepolarizing muscle relaxants

22. 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

23. 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

24. Thank you