This document summarizes skeletal muscle relaxants and spasmolytics, dividing them into peripherally and centrally acting drugs. Peripherally acting drugs include neuromuscular junction blockers like non-depolarizing blockers (isoquinoline and steroid derivatives) and depolarizing blockers (succinylcholine). Centrally acting spasmolytics include benzodiazepines, GABA analogues, alpha-2 agonists, baclofen, and tizanidine. The document discusses the mechanism of action, pharmacokinetics, uses, and adverse effects of various muscle relaxants and spasmolytics.

1. SKELETAL MUSCLE RELAXANTS
&
SPASMOLYTICS
By
Dr. Abdul Azeem

2. I) PERIPHERALLY ACTING
1) NEUROMUSCULAR JUNCTION BLOCKERS
a) NON DEPOLARIZING NEUROMUSCULAR BLOCKERS
 ISOQUINOLINE DERIVATIVES
D- TUBOCURARINE
GALLAMINE
ATRACURIUM
CIS ATRACURIUM
ALCURIUM
DOXACURIUM
MIVACURIUM

3. • STEROID DERIVATIVES
PANCURONIUM
VECURONIUM
RAPACURONIUM
PIPECURONIUM
ROCURONIUM
b) DEPOLARIZING NEUROMUSCULAR BLOCKERS
SUXAMETHONIUM (SUCCINYLCHOLINE)
DECAMETHONIUM
2) DIRECTLY ACTING
DANTROLENE

4. II) CENTRALLY ACTING MUSCLE RELAXANTS
(SPASMOLYTICS)
• BENZODIAZEPINES
DIAZEPAM
CHLORDIAZEPOXIDE
CLONAZEPAM
NITRAZEPAM
• GABA ANALOGUES
BACLOFEN
PROGABIDE
oALPHA 2 AGONIST
TIZANIDINE

5. OTHERS
GLYCINE
MEPROBAMATE
MEPHENESEN
IDROCILAMIDE
RILUZOLE
BOTULINUM TOXIN

6.  NEUROMUSCULAR JUNCTION BLOCKERS
 Classification according to duration of action
› Short acting
 Succinylcholine <8 min
 Mivacurium 10-20 min
› Intermediate acting
 Atracurium 25-35 min
 Cisatracurium 25-40 min
 Rocuronium 25-35 min
 Vecuronium 25-35 min

7.  Long acting
 Doxacurium more than 35 min
 Tubocurarine more than 35 min
 Pancuronium more than 35 min
 Pipecuronium more than 35 min

8. Nicotinic Transmission At NMJ

9. NEUROMUSCULAR JUNCTION

11. NICOTINIC ACETYLCHOLINE RECEPTOR

12. History
Strychnos toxifera

13. Chemistry

14. • Pharmakokinetics

15. MOA
Non Depolarizing / Competitive N.M Blockers- Tubocurarine etc.

16. Mechanism of Action:
Non Depolarizing / Competitive N.M Blockers i.e . Tubocurarine etc.
Competitive antagonist to Ach at Nicotinic (Nm) Receptor at MEP
N.M Transmission is interrupted leading to N.M. Blockade.
At Larger doses, some drugs also enter pore of ion channel of Nm ,
further decrease in N.M. Transmission.

17. Blockade is:
Antagonised by:
Anticholinesterases (Neostingmine, Edrophonium,
Pyridostigmine )

18. Potentiated by:-
• GA.(Ether, Enflurane, Halothane)
• Amino glycoside Antibiotics. (Streptomycin, Gentamicyn)
• Acidosis
• L.A (Procaine)
• Hypokalemia
• Myasthenia gravis
• Dehydration
• Advanced age-Prolonged Effect

19. D-TUBOCURARINE (PROTOTYPE)
Non depolarizing N.M. Blocker.
Source:
Chief alkaloid of curare Obtained from
Chondrodendron & Strychnos
Chemistry:
Mono quaternary Ammonium Compound.

20. Pharmacokinetics:
Not Abs. from GIT. Given I/V
It is redistributed. Not metabolised.
Excreted unchanged by kidney 40 % / Bile 60 %
Crosses Placenta but not harmful.
It does not cross BBB.
Mechanism of action:
O.O.A : 4 min.
D.OA: more than 35 min

21. Pharmacological effects
No central effects
Skeletal muscle relaxation. First weakness &
then paralysis.
Sequence of Paralysis of Skeletal Muscles:
Eye, Jaw, Facial muscles .
Muscles of Neck, Limbs , Trunk.
Interocostal muscles
Diaphragm
Recovery in reverse order.
Ganglionic blockade: Mild in high doses

22. CVS:
Hypotension due to
Release of Histamine.Vasodilatation, decreased PR , decreased
BP.
Bronchoconstriction due to Histamine release
Ganglionic Blockade (Vasodilatation) in larger doses.
 PANCURONIUM
› Steroidal quaternary ammounioum compund
› 6 times more potent than Tubocurarine
› Quick onset of action
› No effect on ganglia
› Vagolytic effect
› Moderate increase in Blood Pressure
› No effect on CNS
› No effect on foetus
› No Histamine release
›
›

23. • ATRACURIUM
• Isoquinoline
• Intermediate acting
• Metabolism – Hepatic
• Hofmann Elimination
• Laudanosine
Seizures
• Cis-Atracurium
• Mivacurium: Shortest duration of action. Metabolised
by pseudocholine esterase

24. Depolarizing Skeletal Muscle Relaxant (Succinylcholine)
• Pharmakokinetics

25. M.O A of Depolarizing drugs (Succinylcholine)
The Blockade occurs in 2 Phases
 Phase I (depolarizing)
Phase I block: is augmented by anticholinestrase & not
reversed

26. Phase I (depolarizing)
1. Succinylcholine reacts with nicotinic receptors
2. Ion channels are opened → depolarization of motor end
plate.
3. Depolarization spreads to adjacent membrane
4. Result in disorgansed / generalized contraction of motor
unit.
5. Not hydrolyzed in synapse → persistent depolarization
→ flaccid paralysis

27. Phase II Block (Desensitizing Block)
With continued exposure—Initial end plate depolarization decreases
and membrane is re polarized but unresponsive/ desensitized to Ach.
due to:
Blockade of channel.
Development of in excitable area in muscle membrane immediately
surrounding the M.E.P which prevent the spread of impulses or
desensitization of membrane occurs .

28. MOA OF SUCCINYLCHOLINE

29.  SUCCINYLCHOLINE
› Hydolysed by plasma & liver Pseudochlone & butyryl
cholinesterases
› Duration of action is very short (8 min)
 DIBUCAINE NUMBER TEST

30. Adverse Effects
• Non Depolarising Drugs
• Histamine Release
• Vagolytic Effect
• Depolarising Drugs (Succinyl choline)
• Malignant Hyperthermia
• Apnea
• Hyperkalamia
• Increased intra gastric pressure
• Increased IOP
• Muscular Aches & Pain
•

31. Drug Interactions

32. • Uses of NMJ Blockers
• Surgical operations
• Endotracheal intubation ,laryngoscopy
• Orthopedic manipulation
• Convulsive disorders
• Electroconvulsive therapy (ECT)
• For assisted ventilation

33. SUGAMMADEX
 When given post operatively there is rapid recovery from
even profound degree of Neuro muscular blockade.
 It rapidly inactivate the steroidal neuro muscular blocking
drugs by forming an in active complex which is excreted in
urine

34. DANTROLENE
MOA: It reduces the release of activator calcium from the
sarcoplasmic reticulum

35. DANTROLENE
MOA
PHARMACOKINETICS
ADVERSE EFFECTS
THERAPEUTICS USES
Spasmolytic
Malignant hyperthermia
DOSE

36. PHARMACOKINETICS
1/3 of oral dose is absorbed
t ½ is 8 hrs.
ADVERSE EFFECTS
•Muscle Weakness
•Sedation
•Occasionally hepatitis
THERAPEUTICS USES
Spasmolytic
Malignant hyperthermia
DOSE:
As Spasmolytic
Initially 25mg / day gradually increase over 7
weeks to a maximum of 100 mg 4 times a day
For Malignant Hyperthemia

37. Botulinum Toxin
MOA

38. Uses
Strabismus
Blepharospasm
Hemifacial spasm
Spasm associated with lower esophageal sphincter and
anal fissure

39. Dystonias e.g. cervical dystonia,
Oromandibular dystonia
Generalized spastic disorders( cerebral palsy)
Hyperhidrosis of palms and axillae

40. Cosmetic procedure for wrinkles of the face

41. Central Spasmolytics
• Spasticity is increased muscle tone.
• increase in tonic stretch reflexes and flexor muscle spasm with
muscle weakness
• Often observed in
– Cerebral palsy
– Multiple sclerosis
– Stroke
– ALS (Amyotrophic lateral sclerosis)
• Aim
• Reduction of excessive skeletal muscle tone without reduction of muscle
strength.

42. DIAZEPAM
MOA: It facilitates the action of GABA in CNS.

43. USES: Muscle Spasm
(local truma to tetanus)
DOSE: Oral dose initially 5 mg / day and
gradually increase to
maximum of 60 mg / day.
ADVERSE EFFECTS
Sedation

44. BACLOFEN
MOA: GABA B Agonist
ADVERSE EFFECTS
• Drowsiness
• Increase in seizure activity in epileptic patients
• Excessive somnolence
• Respiratory depression
• Coma
THERAPEUTICS USES
– Relieves muscles spasm. Most useful agent for
symptomatic treatment of spasticity
– Prevention of migraine
– Reduces craving in recovering alcoholics

45. TIZANIDINE
MOA: Centrally acting Alpha 2 agonist
Inhibits release of excitatory amino acids in the
spinal interneurons
It re-inforces both pre-synaptic & post- synaptic
inhibition in the cord
ADVERSE EFFECTS
Drowsiness
Hypotension
Dry mouth
Asthenia

47. GABAPENTIN
Antiepileptic drug is a good spasmolytic agent in patient
with multiple sclerosis
PRE GABALIN
Newer analogue of gabapentin usefull in muscle spasm
PROGABIDE
Gaba A and Gaba B agonist and has active metabolites
including GABA itself

48. Riluzole
• Pharmacokinetics
– Absorption orally
– Highly protein bound
– Half life 12 hours
– Metabolism --- in liver by both cyotchrome P450-mediated hydroxylation and
glucurnidation
MOA
– it inhibits glutamate release
– It also blocks postsynaptic NMDA- and kainite-type glutamate receptors and
inhibits voltage-dependent sodium channels

49. Uses
• ALS
Dose
• 50 mg every 12 hours
Adverse effect
• Nausea
• Diarrhea
• Hepatic injury

50. GLYCINE
inhibitory neurotransmitter. When Given crosses
BBB
IDROCILAMIDE
Newer drugs for treatment of ALS
MOA
Inhibit glutamatergic transmission in CNS

51. • Seditive, Hypnotic and Anti anxiety drug
Carisoprodal
• Its active metabolite is meprobamate.
Cyclobenzaprine

52. DIAZEPAM
MOA
USES
DOSE
ADVERSE EFFECTS

53. BACLOFEN
MOA
ADVERSE EFFECTS
THERAPEUTICS USES
– Relieves muscles spasm. Most useful agent for
symptomatic treatment of spasticity
– Prevention of migraine
– Reduces craving in alcoholics

54. TIZANIDINE
MOA
It re-inforces both pre-synaptic & post- synaptic
inhibition in the cord
ADVERSE EFFECTS
Drowsiness
Hypotension
Dry mouth
Asthenia

55. Meprobamate
• Saditive, Hypnotic and Anti anxiety drug
Carisoprodal
• Its active metabolite is meprobamate.
Glycine