This PPT cover Drugs acting on skeletal muscle as a relaxants. They are also known as Neuromuscular blocking agents. Drugs like d-tubocurarine and Succinylcholine which are Non depolarizing and Depolarizing blockers respectively

1. SKELETAL MUSCLE
RELAXANTS
PREPARED BY: JEGAN. S. NADAR

2. • Skeletal muscle relaxants are drugs that act peripherally at
neuromuscular junction/muscle fibre to reduce muscle tone
and/or cause paralysis
• The neuromuscular blocking agents are used primarily in
conjunction with general anaesthetics to provide muscle
relaxation for surgery,
• While centrally acting muscle relaxants are used mainly for
painful muscle spasms and spastic neurological conditions.
Jegan

3. PERIPHERALLY ACTING MUSCLE RELAXANTS
Jegan

4. CENTRALLY ACTING MUSCLE RELAXANTS
Jegan

5. • Curare is the generic name for certain plant extracts used by
south American tribals as arrow poison for game hunting.
• The animals got paralysed even if not killed by the arrow.
• Natural sources of curare are Strychnos toxifera,
Chondrodendron tomentosum and related plants.
• Muscle paralysing active principles of these are tubocurarine,
toxiferins, etc
NEUROMUSCULAR BLOCKING AGENTS
Jegan

6. • The site of action of both competitive and depolarizing blockers is the
end plate of skeletal muscle fibres
• The competitive blockers have affinity for the nicotinic (NM)
cholinergic receptors at the muscle end plate, but have no intrinsic
activity
• It is a protein with 5 subunits (α2 β ε or γ and δ) which are arranged
like a rosette surrounding the Na+ channel
MECHANISM OF ACTION
(Competitive Blockers)
Jegan

7. • The two α subunits carry two ACh binding sites; these have negatively
charged groups which combine with the cationic head of ACh →
opening of Na+ channel.
• Most of the competitive blockers have two or more quaternary N+
atoms which attracts to the same site
• The bulk of the antagonist molecule does not allow opening the channel.
• ACh released from motor nerve endings is not able to combine with its
receptors to generate end plate potential (EPP).
• d-TC thus reduces the frequency of channel opening
• Muscle relaxes.
Jegan

8. Jegan

9. • They are always given i.v., or i.m.
• All neuromuscular blockers are polar quaternary compounds—
 Not absorbed orally,
 Do not cross cell membranes,
 Have low volumes of distribution
 Do not penetrate placental or bloodbrain barrier.
PHARMACOKINETICS
Jegan

10. • Respiratory paralysis and prolonged apnoea is the most
important problem.
• Flushing is common with d-TC (due to histamine release)
• Fall in BP and cardiovascular collapse can occur
• Precipitation of asthma by histamine releasing neuromuscular
blockers.
SIDE EFFECTS
Jegan

11. • Depolarizing blocking agents work by depolarizing the plasma
membrane of the muscle fiber, similar to the action of ACh.
• However,these agents are more resistant to degradation by
acetylcholinesterase (AChE) and can thus more persistently
depolarize the muscle fibers.
• Succinylcholine is the only depolarizing muscle relaxant in use
today.
MECHANISM OF ACTION
(Non-competitive Blockers)
Jegan

12. • Succinylcholine attaches to the nicotinic receptor and acts like ACh
to depolarize the junction
• Unlike ACh, succinylcholine is not instantly destroyed by AChE.
• The depolarizing agent persists at high concentrations in the synaptic
cleft, remaining attached to the receptor for a longer time and
providing constant stimulation of the receptor.
• The depolarizer act by 2 phases
Jegan

13. Phase I
• The depolarizing agent first causes the opening of the sodium
channel associated with the nicotinic receptors, which results in
depolarization of the receptor.
• This leads to a transient twitching of the muscle
(fasciculations).
.
Jegan

14. Phase II
• Continued binding of the depolarizing agent renders the
receptor incapable of transmitting further impulses.
• With time, continuous depolarization gives way to gradual
repolarization as the sodium channel closes or is blocked.
• This causes a resistance to depolarization and flaccid paralysis.
Jegan

15. Jegan

16. PHARMACOKINETICS
• Succinylcholine is injected intravenously.
• It has brief duration of action
• Metabolism-Rapid hydrolysis by plasma pseudocholinesterase.
• Drug effects rapidly disappear upon discontinuation.
Jegan

17. SIDE EFFECTS
• Apnea: due to paralysis of the diaphragm.
• Hyperkalemia: Succinylcholine increases potassium release
from intracellular stores
Jegan