S

Skeletal muscle relaxants

They are groups of drugs which affects skeletal muscle

function and decreases the muscular tone. Thus, cause the

muscle to relax.

Skeletal muscle relaxants

Muscle Relaxants Agents

Neuromuscular Blockers

Non Depolarizing

Blockers

Depolarizing Blockers

Spasmolytic

Neuromuscular blocking agents

S Drugs can block neuromuscular transmission either by

acting presynaptically to inhibit ACh synthesis or release,

or by acting postsynaptically, the latter being the site of

action of all the clinically important drugs (except for

botulinum toxin

Neuromuscular blocking agents

S Clinically, neuromuscular block is used only as an adjunct

to anaesthesia, when artificial ventilation is available; it is

not a therapeutic intervention.

S The drugs that are used all work postsynaptically, either

(a) by blocking ACh receptors (or in some cases the ion

channel) or (b) by activating ACh receptors and thus

causing persistent depolarization of the motor endplate.

They fall into two categories: 1.non-depolarising blocking

agent agents 2.depolarising blocking agents

Non Depolarizing neuromuscular blockers

How do muscles contract?

Mechanism of action:

Action

S It starts with the smaller muscles in the eyes and face and then

moves to the larger muscle groups in the tongue, neck and

shoulder, and finally to the respiratory muscles: the intercostal, the

larynx and diaphragm.

S Recovery from neuromuscular blocking drugs occurs in the reverse

order.

Pharmacokinetics:

S Neuromuscular-blocking agents are used mainly in anaesthesiato produce muscle

relaxation

S They are given intravenously but differ in their rates of onset and recovery

S Most of the non-depolarising blocking agents are metabolised by the liver or

excreted unchanged in the urine, exceptions being atracurium, which hydrolyses

spontaneously in plasma, and mivacurium, which, like suxamethonium), is

hydrolysed by plasma cholinesterase.

S Atracurium was designed to be chemically unstable at physiological pH (splitting

into two inactive fragments by cleavage at one of the quaternary nitrogen atoms),

although indefinitely stable when stored at an acid pH. It has a short duration of

action, which is unaffected by renal or hepatic function

Examples of competitive neuromuscular

blockers

S Tubocurarine (curare):

S It is a plant alkaloid that has slow onset of action (> 5 min) and longer

duration(1-2 h). It also affect autonomic ganglia.

S The main side effects is Bronchoconstriction and hypotension. In

addition to other side effects related to its ganglion blocking activity

( blurred vision , urine retention , constipation and male impotence)

S Gallamine (Flaxedil):

S It is synthetic compound has less potent NM blocking activity than

curare ( 1/5 potency)

S It has shorter onset (2-3 min) and longer duration ( > 2h) than d-

tubocurarine.

S It is execrated unchanged mainly by kidney. It is contraindicated in

renal failure

S Main side effect is “tachycardia” due to an atropine-like action and

stimulation of NA release from adrenergic nerve endings.

S Mivacurium:

S It is new drug that is chemically-related to Atracurium. It has Fast

onset (∼2 min) and short duration (∼15 min).

S It is metabolized by plasma pseudocholinesterases (Longer duration

in patient with liver disease or genetic cholinesterase deficiency).

S Transient hypotension is the main side effect.

S Pancuronium:

S It is the first steroid-based compound that is more potent than curare ( 6 times ). It has Intermediate onset (2-3 min) and slight long duration (>2h)

S Excreted mainly by the kidney ( 80 % ).

S Tachycardia is the main side effect (due to an atropine-like action and stimulation of NA release from adrenergic nerve endings).

S Vecuronium:

S It is more potent NMBs than curare (6times) with Intermediate

onset (2-3 min) and Intermediate duration (30-40 min)

S It is metabolized mainly by liver. It has few side effects (no

histamine release, no ganglion block and no antimuscarinic action).

Occasionally causes prolonged paralysis, probably owing to active

metabolite

S It is widely used.

Depolarizing neuromuscular blockers

S Depolarization at the endplate region of the muscle fiber

Fasciculation (twitching) because the developing endplate

depolarization initially causes a discharge of action potentials in

the muscle fiber Paralysis because re-polarization doesn’t

occur.

Mechanism of action:

Examples:

S Decamethonium :

Was used clinically but has the disadvantage of too long a duration of action.

S Suxamethonium :

The only depolarising blocking drug currently used.

Closely related in structure to both decamethonium and ACh (consisting of two

ACh molecules linked by their acetyl groups).

Its action is brief, because it is quickly hydrolysed by plasma cholinesterase.

When given intravenously, however, its depolarising action lasts for long

enough to cause the endplate region of the muscle fibres to become inexcitable.

Unwanted effects and dangers of

suxamethonium:

S Bradycardia

S Increased intraocular pressure

S Prolonged paralysis

S Malignant hyperthermia

Comparison of non-depolarising and

depolarising blocking drugs:

S Anticholinesterase drugs are very effective in overcoming

the blocking action of competitive agents (non

depolarizing).

S The fasciculations seen with suxamethonium as a prelude to

paralysis do not occur with competitive drugs (non-

depolarizing).

S Tetanic fade is increased by non-depolarising blocking

drugs, compared with normal muscle.

Thank You!

S Lama Al Jlayl.

S Alaa Assiri

S Esraa Sebieh

S Sarah Abu El Asrar