mastrate of pharmacy

1. NEUROMUSCULAR BLOCKING
DRUGS
CURARE ALKALOIDS
Presented by –
Vishakha N. Giradkar

2. 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
adjuvants in surgical anesthesia 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 preprations:
• Calabash (gourd)
• Tube (bamboo)
• Pot curare (clay pot)

3. Classification:

5.  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

6.  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 grayish white
b. Odourless
c. Crystalline powder
d. Soluble in water

7. Quaternary ammonium
Tertiary amine
In acidisis
+ 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

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

9.  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

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

11. 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

12.  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

13.  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

14.  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 anesthesia to relax skeletal muscle
• Side effect – transient hypotension

15.  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 anesthesia to induce relaxation of skeletal
muscles
• Side effect- tachycardia

16. SAR:
2Br-

17.  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-

18. 2Br-
Vecuronium bromide
SAR:

19.  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

20. Thank you......!