THE NEUROMUSCULAR BLOCKING DRUGS HERE ARE PRESENTED WITH DEPOLARIZING AND NON DEPOLARIZING ALSO KNOWN AS COMETATIVE AND NON COMPETATIVE, WITH ITS DETAIL ACCOUNT ARE DISCUSSED HERE.

1. NEUROMUSCULAR BLOCKING
DRUGS
CURARE ALKALOIDS

2. Neuromuscular Blocking Agent
These are the drugs that prevent interaction
of Ach at nicotinic receptor at neuromuscular
junction
Uses:
Intubation of trachea and other endoscopic
procedures
Induce muscle relaxation
Make orthopaedic surgery easy and bone
setting
Reduce dose of anasthesia

3. Types of Neuromuscular
Blocking Drugs
Nondepolarizing drugs (competative)
Depolarizing durgs (non-competative)
Centrally acting drugs

4. Nondepolarizing (competative)
blocking agents
 Long acting: d-Tubocurarine
Pancuronium
Doxacurium
Pipercurium
 Intermediate acting: Atracurium
cis atracurium
Vecuronium
Rocuronium
 Short acting: Mivacurium

5. Depolarizing agents (non-
competative)
Suxamethonium
Decamethonium
Centrally acting
Beclofenac
Chlozoxazone
Diazepam
cariosoprodol

6. Competative (non depolarizing)
blocking agent
 Most of the competative blockers have
two or more quarternary N+ atoms which
provide the necessary attraction to the
same site at N receptor
 And have long , flexible bulky molecules
and were termed Pachycurare by Bovet
(1951)
 The bulk group of drug molecules does
not allow conformational changes in the
subunits needed for the channel

7. Mechanism of Action of
Nondepolarizing/ competative
Neuromuscular Blocking Drugs
 Ach released from motor nerve ending
is not able to combine with its N-
receptors to generate endplate
potential(EPP)
 Intravenous injection of competative
blockers rapidally produces skeletal
muscle weakness followed by flaccid
paralysis

8. Depolarizing drugs (non-
competative)
 Depolarizing agents aiso have two
quarternery N+ atoms but their molecules
is long slender and flexible they
Leptocurare by Bovet (1951)
 Succinylcholine differ from Ach only in
duration of action , that is longer duration
of action and more stable depolarization

9. Depolazation agents (Non
competative)
 They depolarize muscle endplate by
oprapening Na+channels (just as Ach
does) and initially produces twitching and
fascilations
 These drugs do not dissociate rapidally
from the receptor , induce prolonged
partial depolarization of the region around
muscle endplate and inactivation of Na+
channels

10. Introduction:
 Curare alkaloids are the neuromuscular blocking agent
 Agents that block the transmission of Ach at the motor end plate
 The therapeutic use of these compound is primarily as adjuvant in
surgical anaesthesia to obtain relaxation of skeletal muscles
 Obtained from bark and steam of strychnos castelnoci and
strychnos toxifera, chondodendron tomentosum
 South American Indians used curare as a very potent arrow
poison
 Early preparations:
• Calabash (gourd)
• Tube (bamboo)
• Pot curare (clay pot)

11. General Structure

13.  Tubocurarine:
• By extraction
• Quaternary compound
• Contains bis-benzylisoquinoline structure
• Block the nicotinic receptor at neuromuscular junction
• Produce paralyzing effect on voluntary muscle
• Used as a diagnosis agent for myasthenia gravis
• Toxic action blood vessels

14.  Tubocurarine chloride, USP:
• Prepare from crude curare
• by process of purification & crystallization
• Non-depolarizing blocking agent
• Block the nicotinic receptor at neuromuscular junction
• Physical property-
a. White or yellowish white to greyish white
b. Odourless
c. Crystalline powder
d. Soluble in water

15. Quaternary ammonium
Tertiary amine
In acidosis
+ charge increase potency
•SAR- Bis- quaternary ammonium compound having two quaternary
ammonium salts separated by 10-12 carbon atoms was required for
neuromuscular blocking activity
•1o-12 carbon bridge between 2 nitrogen max.
Neuromuscular blockade

16. • Use-
i. as a diagnosis agent for myasthenia gravis
ii. Skeletal muscle relaxant
iii. adjuvant in surgical anaesthesia to obtain relaxation of skeletal
muscles
iv. Control convulsions of strychnine poisoning & of tetanus
• Side effect- hypotension, bronchoconstriction
• Drawback –
Incidence of bone & spine fractures & dislocations from
convulsions because of shock

17.  Metocurine Iodide, USP:
 (+)-O,O-dimethylchondrocurarine diiodide
• Prepared from natural crude curare
• By extracting the curare with methanolic pot. Hydroxide
• MOA same as a d-tubocurarine
• More potent than d-tubocurarine

18. • Excess of methyl iodide give metocurine iodide
• 2 phenolic hydroxyl group are methylated

19. Synthetic compounds with curariform activity
 Atracurium Besylate:
 2-(2-carboxyethyl)-1,2,3,4-tetrahydro-6,7-dimethoxy-2-methyl-1-
veratryl isoquinolinium benzenesulfonate pentamethylene ester
(Tracrium)
• Intermediate acting Non-depolarizing neuromuscular blocking
agent
• 2-5 time potent than d-tubocurarine
• Duration of action (30-40 min.) shorter than d-tubocurarine
• Metabolized rapidly
• Safe in hepatic & renal impairment

20.  Doxacurium chloride:
 1,2,3,4-tetrahydro-2-(3-hydroxypropyl)-6,7,8-trimethoxy2-
methyl-1-(3,4,5-trimethoxybenzyl) isoquinolinium chloride
succinate (Nuromax)
• Long acting non-depolarizing blocking agent
• Use- skeletal muscle relaxant

21.  Gallamine Triethiodide, USP:
 [v-phenenyl-tris(oxyethylene)]tris[triethylammonium]
triiodide(Flaxedil)
• MOA same as a d-tubocurarine
• Less potent than d-tubocurarine
• Shorter onset (2-3min) & longer duration (>2hr.) than d-
tubocurarine
• It also has muscarinic antagonistic activity
• Stronger vagolytic effect
• Side effect- tachycardia
• Contraindicated in myasthenia gravis & renal failure
• Antidote for gallamine triethiodide is neostigmine

22.  Mivacurium chloride:
 1,2,3,4-tetrahydro-2-(3-hydroxypropyl)-6,7-dimethoxy-2-methyl-
1-(3,4,5-trimethoxybenzyl)isoquinolinium chloride, (E)-4-
octandioate (Mivacron)
• Short acting non depolarizing drug
• Used as an adjunct to anaesthesia to relax skeletal muscle
• Side effect – transient hypotension

23.  Pancuronium bromide:
 2,16-dipiperidino-5-androstane-3,17-diol diacetate
dimethobromide (Pavulon)
• Synthetic product
• Non depolarizing blocker
• Act on nicotinic receptor & in the ion channel, inhibiting normal
ion fluxes
• 6 time potent than d-tubocurarine
• Slow onset of action (4-6 min.)
• Longer duration of action (2-3 hr.)
• First steroid based compound
• Use- adjunct to anaesthesia to induce relaxation of skeletal
muscles
• Side effect- tachycardia
2Br-

24. SAR:

25.  Pipecurium bromide:
 4,4-(3,17-dihydroxy-5-androstan-2,16-ylene)bis(1,1-dimeth-
ylpiperazinium)dibromide diacetate (Arduan),
• Non-depolarizing muscle relaxant
• Long acting
 Vecuronium bromide:
 1-(3,17-dihydroxy-2-piperidino-5-androstan-16-yl)-1-
methylpiperidinium bromide diacetate (Norcuron)
• Intermediate onset of action (2-4 min.)
• Intermediate duration of action (30-40 min.)
• 6 time potent than d-tubocurarine
• Produce skeletal muscle relaxation during surgery
• Controlled respiration after general anaesthesia has been induced
• Side effect- fewer
2Br-

26. 2Br-
Vecuronium bromide
SAR:

27.  Succinylcholine chloride, USP:
• Very short duration of action
• Unstable in alkaline solution & stable in acidic solution
• Quick recovery because its rapid hydrolysis after injection
• Suitable for continues iv drip administration

28. Thank you......!