mivacurium

MIVACURIUMVerdah SabihHouse officerAnesthesiology dept. HFH

ROAD MAP INTRODUCTION STRUCTURE MODE OF ACTION PHARMACOKINETICS DOSAGE INDICATIONS SIDE EFFECTS INTERACTIONS WITH OTHER DRUGS

INTRODUCTION: non-depolarizing/competitive neuro

muscular-blocking drug or skeletal muscle relaxant.

Fast onset & short duration(10-20 mins). no sedative or analgesic effects. not considered to trigger malignant

hyperthermia. not associated with vagolytic activity or

ganglionic blockade.

STRUCTURE Belong to

benzylisoquinolinium group non-depolarizing skeletal muscle relaxants.

Symmetrical molecule.

PHARMACOKINETICS Onset time : 2-4 mins Duration :12-18 mins Elimination by plasma cholinesterase. Hepatic impairment reduce dose in severe

impairment Renal impairment clinical effect prolonged in

renal failure—reduce dose according to response ED95 of mivacurium is 0.08 mg/kg. mean elimination half-life : 1.7 to 2.6 min Poor lipid solubility does not enter CNS Highly polar,inactive when given by mouth

only intravenous route avaliable.

MODE OF ACTION

1.resting:

2.active:Na Ca

K

ACh

ACh

Normal transmission Non depolarizing neuromuscular blockade

Low doses: •competitive antagonist of Ach•Action reversed by Ach esterase inhibitors

Large doses:•Ion channel is blocked•More weakness of neuromuscular transmission•Action could not be reversed by Ach esterase inhibitors

Other actions:Can block pre-junctional sodium channels and interfere with mobilization of Ach at nerve endings

MODE OF REVERSAL cholinesterase

inhibitors as neostigmine and pyridostigmine by:

1- increasing the availability of acetylcholine at the motor end plate

2- to a lesser extent, neostigmine and pyridostigmine increase release of transmitter from the motor nerve terminal

The deeper the level of neuromuscular block at reversal, the longer the time required for recovery of neuromuscular function and the greater the dose of anticholinesterase agent required. Because spontaneous recovery after mivacurium is rapid, routine reversal may not always result in a clinical. benefit

DOSAGE AND ADMINISTRATION By intravenous injection:

ADULT 70–250 mg/kg; maintenance 100 mg/kg every 15 min;

CHILD 2–6 months initially 150 mg/kg, 7 months–12 years initially 200 mg/kg; maintenance (CHILD 2 months–12 years) 100 mg/kg every 6–9 minutes

By intravenous infusion ADULTafter initial bolus intravenous dose, maintenance

of block, 8–10 mg/kg/min, adjusted if necessary every 3 min by 1 mg/kg/minto usual dose of 6–7 mg/kg/min;

CHILD 2 months–12 years, usual dose 11–14 mg/kg/min Resistance can develop in patients with burns, who

may require increased doses; low plasma cholinesterase activity in these patients requires dose titration for mivacurium.

INDICATIONS Skeletal muscle relaxation during

surgery Mechanical Ventilation Endotracheal Intubation

CONTRAINDICATIONSNo documented contraindications except in

such conditions; Allergy Myasthenia Gravis Asthma

CLINICAL SIDE EFFECTS histamine release, which can cause skin

flushing, hypotension, tachycardia, bronchospasm,

anaphylactoid reactions (rare). Acute myopathy

INTERACTIONS WITH OTHER DRUGS Inhaled anesthetics: augment the

neuromuscular blockade produced by nondepolarizing muscle relaxants because

1) CNS depression 2) peripheral vasodilatation larger

fraction of the injected muscle relaxant to reach the neuromuscular junction

3) decreased sensitivity of the postjunctional membrane to depolarization.

Aminoglycosides: augment the neuromuscular blockade produced by nondepolarizing muscle relaxants by decreasing release of Ach

Local Anesthetics enhance the neuromuscular block produced by both nondepolarizing and depolarizing.

Calcium Channel Blockers synergistic effect.

Interactions between Nondepolarizing Blocking Drugs synergistic/additive.

Depolarizing relaxants antagonistic.