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by : Amaal Nabil sadek

Neuromuscular blockers

:Drugs may act


.Pre-synaptically (pre-junctional)

:Or post-synaptically
non-depolarizing (competitive)- 1
depolarizing (non-competitive)- 2

by : Amaal Nabil sadek


Pre-synaptically
(pre-junctional) acting drugs
are those that interfere with
synthesis and or release of
Ach.

by : Amaal Nabil sadek


Non-depolarizing
(competitive)
Tubocurarine (prototype )
Metcurine.
Pancuronium. (long acting )
Gallamine.
Vecuronium.
Atricurium.
Doxacurium.
Rocuronium ( the most rapid onset )
by : Amaal Nabil sadek
Depolarizing (non-competitive)

Succinylcholine.
Decamethonium.

Succinylcholine is the member


commonly used clinically

by : Amaal Nabil sadek


:Mechanism of action
Non-depolarizing (competitive):
* Reversible.
*Compete with Ach at nicotinic receptors.
* This action can be overcome by increasing
ACH concentration ( by cholinesterase
inhibitors)
*at higher doses they also block Na channels &
this further weakens Neuromuscular
transmission.
*SO this reduces the ability of cholinesterase
inhibitors to reverse their action.
by : Amaal Nabil sadek
:Effects are antagonized by

Neostigmine (choline esterase inhibitors):

at the end of operation but preceded by

ATROPINE to block muscarinic

receptors and so avoid bradycardia &

cardiac arrest )
by : Amaal Nabil sadek
Depolarizing (non-competitive):
succinylcholine (partial agonist )
Its action involves 2 phases:
phase 1 (depolarization):

Interact with nicotinic receptors on post-


synaptic membrane, causing depolarization.
This causes disorganized contraction (initial
twitching or fasciculation).

by : Amaal Nabil sadek


Unlike Ach (Ach destroyed rapidly ), it persist
attaching to receptors for relatively longer
time.
Continued binding of it renders the receptor
incapable of binding to Ach.

Phase 2 : receptor desensitized to Ach


& causes flaccid paralysis.
Phase2 = block or desensitization phase.
Usually happen with repeated or prolonged
administration of succinylcholine
by : Amaal Nabil sadek
by : Amaal Nabil sadek
:Actions
Non depolarizing:
Not all muscles are equally sensitive to
blockage.

Small rapidly contracting muscle of face and


eye paralyzed first.

Then fingers, limbs, neck and trunk.


Intercostal muscles.
Lastly diaphragm.
Recovery occurs in the reverse order
(diaphragm
by : Amaal Nabil sadek first)
Therapeutic uses
(non-depolarizing)
Adjuvant drugs to anesthesia during surgery

(facilitate incision & intubation, decrease the dose

of anesthesia, decrease cough & laryngospasm )

To assess mechanical ventilation( paralyses resp.

muscles to not interfere with mechanical

ventilation) .
by : Amaal Nabil sadek
Pharmacokinetics
(non-depolarizing)
All NM blockers are injected IV.
( as all of them highly polar
compounds & so poor lipid soluble
(limit entry to CNS),,, inactive orally)
MANY OF THEM ARE NOT
METABOLIZED, & then excreted
unchanged in urine like
tubocurarine or bile like vecuronium
by : Amaal Nabil sadek
Atracurium is degraded spontaneously in
plasma by esterase enzyme (Hofmann
elimination) , in addition to liver
metabolism, so it is relatively safe in hepatic
or renal patients. .

(but it releases histamine and its liver


metabolite can cause seizures in high doses ).

Cisatracurium as atracurium but less side


effects so it replace it clinically)

by : Amaal Nabil sadek


Adverse effects
(of Tubocurarine
mainly)
Tubocurarine has no CNS effects, but causes hypotension ,

flushing, bronchoconstriction, allergy due to histamine release.

Ganglionic blockade ( nicotinic receptors) ( hypotension).

Generally theses agents are safe.

Contraindicated in renal disease (renal excreted).

by : Amaal Nabil sadek


Drug interactions
Cholinesterase inhibitors like : neostigmine,
(decrease its effect).
Calcium channel blockers (increase NM
Blocking).
Halogenated hydrocarbon anesthesia like
halothane enhance NMB action by stabilizing
NM junction & increase its sensitivity to NMB.
Aminoglycosides.
Like gentamicin enhancing NMB activity.
By competing with Calcium ions SO inhibit ACH
release
by : Amaal Nabil sadek
by : Amaal Nabil sadek
Actions
(depolarizing)
Sequence of paralysis slightly different.

But as it as respiratory muscles are


paralyzed last..

by : Amaal Nabil sadek


Therapeutic uses of
:depolarizing NMBs
Due to rapid onset (1 minute) and short
duration of action (5-10 minutes)

Rapid endotracheal intubation. (to avoid


aspiration).

Electroconvulsive shock treatment


(decrease pain ).
by : Amaal Nabil sadek
Pharmacokinetics
:depolarizing NMBs
Iv injection.
Destroyed by

pseudocholinesterase.
Usually given by continuous
infusion.
by : Amaal Nabil sadek
Adverse effects of
:depolarizing NMBs
Malignant hyperthermia.
Hyperkalemia.
Apnea.
Post-operative muscle pain.
Increase intraocular & gastric
pressure.
by : Amaal Nabil sadek
Malignant hyperthermia:
When taken with halothane.
Sk. Muscles fail to sequester Ca in sarcoplasmic
reticulum
Muscular rigidity & hyperthermia.
In genetically susceptible.
Treatment:
1- Rapidly cooling.

2-Dantrolene= Spasmolytic ( block Ca release from


sarcoplasmic reticulum) decreasing rigidity.

by : Amaal Nabil sadek


Apnea:
In patient genetically deficient or has

atypical form of plasma cholinesterase


(due to liver disease) .

prolonged respiratory muscle


paralysis or even the diaphragm.

Treatment : blood transfusion ( to


supply the enzyme )

by : Amaal Nabil sadek


Hyperkalemia:

Increase K release from stores.

More dangerous in patients with burn or

massive tissue damage in which k rapidly

lost from cells

by : Amaal Nabil sadek

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