18.MUSCLE RELAXANTS & CHOLINESTRASE INHIBITORS                                                                                 
                                              NEOSTIGMINE  

General information :

 

Drug code                   Preparation                                         Strength

      119                                    Inj. Neostigmine                                               0.5 mg/ml.

 

Description of the Drug

Neostigmine is a synthetic quartenary ammonium compound, which is a reversible anti cholinesterase agent.

 

Mode of Action

It binds to cholinesterase the enzyme, which degrades acetlycholine in the synapse, therapy increasing acetylcholine and its effects. it also has a direct cholinomimetic action at the acetylcholine receptors.

 

Pharmacokinetics:

Following parenteral (IM) administration, it is rapidly absorbed with peak level at 30 minutes and plasma half-life 1.5 hours. It does not cross the blood barrier. It is metabolized by in hepatic microsomal enzyme system and excreted in the urine as both unchanged drug (50%) and as metabolites.

 

Clinical Information

 

Indications

·    Reversal of muscular relaxation produced by competitive (non-depolarizing) muscular relaxants
such as d-tubocurarine and gallamine.

·    In the treatment of myasthenia gravis (when oral therapy is not feasible).

·    For the treatment of postoperative urinary retention and distension, after obstruction is ruled out.

 

Dosage

·    For myasthenia : 0.5 mg S.C. repeated every 4 hours as necessary depending on clinical response.

·    For postoperative urinary retention or distension: 0.25 mg 6 the hourly for 2 –3 days after the surgery.

·    For reversal of non-depolarizing block: 0.5 –2 mg, slow IV (over 1 minute) for children 0.025 – 0.08 mg/kg/dose.

 

Route of Administrations

 

Contraindications

·    Patients with mechanical obstruction in intestinal or  urinary tract.

·    Known hypersensitivity.

 

Precaution / Practice points

·    Dose to be individualized for each patient in the treatment of myasthenia gravels.

·    To be used with extreme caution inpatients with recent intestinal or bladder surgery.

·    To be used with caution inpatients with CVS disorders including, arrhythmias, bradycardia,
recent myocardial infarction and hypertension.

·    Use with caution in patients with epilepsy, parkinsonism, hyperthyroidism, bronchial asthma, or peptic ulcer, pregnancy and lactation.

·    Atropine to be coadminstered when neostigmine is used for reversal of non-depolarizing block to
prevent its musarinic size effects.

·    Use with caution in renal impairment and reduce dose (see appendix).

·    Administration instructions:

·    When giving I.V. very slowly.

·    When atropine is given simultaneously, use a separate syringe.

 

 

Drug Interactions

Non fatal

·    Amino glycosides, antimalarials like chloroquine may antogonise effects of neostigmine by enhancing nondepolarising neuromuscular blockade.

·    Lithium and procainmide also antogonise effects of neostigmine.

 

Adverse Effects

            Adverse effect is due to its cholinergic activity.

Common effects :

            Increased salivation, abdominal cramps, nausea, vomiting and diarrhoea.

Rare effects :

·    Fasciculation, miosis and visual changes, increased pharyngeal and bronchial secretions and sweating.

·    CVS – bradycardia.

·    Hypersensitivity or allergic reactions like skin rashes, urticaria etc.,

 

Drug Toxicity

Over dosage leads to :cholinergic crisis: characterized by excessive sweating, increased peristalsis  leading to involuntary defecation and urination, increased bronchial secretions, increasing muscle weakness, mitosis, nystagmus, bradycardia, hypotension, AV blocks, respiratory paralysis and death may occur.

 

Treatment of Toxicity

·    Prompt withdrawal of the drug.

·    Atropine can be used for the control of muscarinic effects.

·    Maintenance of airway ventilatory support.

 

Storage

            Store in a cool, dry, dark place.

 

Shelf life         3 years.

 

 

PANCURONIUM BROMIDE

 

General Information

 

Drug code                   Preparation                                         Strength

      122                        Inj. Pancuronium bromide         2 mg/ml..

 

Description of the Drug

Pancuronium is a non-depolarizing, curare like neuromuscular blocking agent belonging to the administered group. It is five times more potent than d-tubocurarine.

 

Mode of Action

It is a competitive antagonist of the acetylcholine receptor acting at the motor end plate. Therefore
it prevents action of acetylcholine at its receptors and hence caused paralysis of skeletal muscle. It does not cause histamine release, but has antimuscarinic and some sympathomimetic effects.

 

Pharmacokinetics :

It is rapidly distributed into the body tissues. Duration of action is 2 – 3 hours and onset of action is 4 –6 minutes. It is excreted in the urine after metabolism in the liver.

 

Clinical Information

 

Indications

·    To produce skeletal muscle relaxation during surgery after induction of general anesthesia.

·    To increase pulmonary compliance during mechanical ventilation.

 

Dosage:

Adult:

0.04 – 0.1 mg/kg/body weight I.V.  With supplementary doses of 10 –20 microgram/kg as required.

Children:

- 30–40 microgram/kg body weight with supplementary doses of 10 –20 microgram/kg.

 

Routes of Administration      I.M., I.V.

 

Contraindications

            Hypersensitivity.

 

Precaution / Practice points

·    Order of paralysis – jaw muscles, followed by muscles of limb and trunk lastly diaphragm and muscles of respiration.

·    It causes tachycardia and mild increase in cardiac output unlike other muscle relaxant.

·    Elderly patients and myasthenia gravis patients have prolonged duration of action. Hence does must be adjusted in these patients.

·    Use with caution in hepatic or renal or pulmonary dysfunction. Reduce dose in renal impairment (see appendix).

·    Administration Instructions:

-  Inject slowly when giving I.V.

-  always monitor heart rate, blood pressure and vital signs when administering

-  Patients should always receive ventilatory support while on pancuronium.

 

Drug Interactions

Potentially fatal:

Amino glycosides lincomycin, clindamycin, colistin, nifedipine, verapamil have an additive effect and can prolong neuromuscular blockade.

 

Non fatal

·    Succinylcholine given before pancuronium increase its effect and duration of action.

·    Inhaled anesthetic like isoflurane, enflurane, halothane potentiate the effects of pancuronium.

·    Azathioprine, aminophylline, theophyline, carbamazepine and phenytoin antogonise the effects of pancuronium (increased doses required or accelerated recovery).

 

Adverse Effects

Common effects:

·    Hypertension and tachycardia.

Rare effects

·    Hypersensitivity reactions like wheezing, bronchospasm, skin reactions etc.,

 

Drug Toxicity

Prolonged aponea due to respiratory depression and paralysis of intercostals muscles and diaphragm.

 

Treatment of Toxicity

·    Assisted respiration and airway maintenance.

·    Maintain fluid and electrolyte balance.

·    Neostigmine methyl sulphate 2-3 mg I.V. along with atropine 0.6-1.2 mg (to block muscaranic effects) can be used for reversal, since it is a competitive blocker of acetyl choline receptors and an excess of acetycholine may reverse it actions.

 

Storage

            Store at 2 –8 oC. Do not allow to freeze.

 

Shelf life         2 years.

 

SUCCINYLCHOLINE

 

General Information

 

Drug code                   Preparation                                         Strength

       198                       Inj.Succinylcholine                                50 mg/ml.

 

Description of the Drug

It is a depolarizing neuromuscular blocker used to produce skeletal muscle relaxation. It is also called as suxamethonium.

 

Mode of Action

Succinylcholine, by virtue of its similarity to acetylcholine is an agonist at the acetylcholine receptors in the motor endplate and causes depolarization. Since it is not degraded in the neuromuscular junction, the depolarized membrance remains depolarized and unresponsive to any other impulse, causing muscle paralysis. It stimulates autonomic cholinoreceptors and muscarinic receptors in the heart causing bradycardia.

 

Pharmacokinetics

After injection it is rapidly hydrolyzed by pseudocholinesterase in the plasma. Only a small proportion of the ingested drug reaches the target site. Duration of action is only 5 –10 minutes, after which succinylcholine diffuses away from the motor endplate into the extra cellular fluid.

 

Clinical Information

 

Indications

·    Prior to intubations, endoscopies and other procedures in which a rapid onset and brief duration of muscle relaxation is needed.

·    Prior to electro convulsive therapy to minise trauma during the procedure.

 

Dosage:

Adult L for endotracheal intubations: 0.6 – 1 mg/kg upto a maximum of 5— mg/hour.

Children – 1-2 mg/kg body weight.

 

Routes of Administration     I.V, I.M.

Contraindications

·    Patients with family history of malignant hyperthermia.   

·    In patients with muscular dystrophies.

·    Patients with abnormal or deficient pseudocholinesterase enzyme.

·    Penetrating eye injures and acute glacucoma.

·    Hyperkalemia.

·    Hypersensitivity.

 

Precaution / Practice points

·    Pattern of onset of paralysis – facial, glottis and laryngeal muscles are first affected followed by arm, leg, and trunk muscles. Finally respiratory muscles and diaphragm are affected.

·    Succinylcholine increases intragastric (hence increase emesis), interlobular and intracranial pressure and hence cannot be used for ocular surgeries.

·    Some patients have abnormal or absent cholinesterase. They can be identified by their dibucaine number (A test for ability to metablize succinylcholine). In such persons prolonged apnoea may result due to deficient or absent peseudo cholinesterase.

·    Tachyphylaxis may occur with repeated usage.

·    Succinylcholine should be given after anesthetic induction to reduce muscle fasciculation and damage.

·    Use with caution in patients with renal failure, major burns and multiple trauma – risk of hyperkalemia is greated in these patient of groups.

·    Administration instructions:

-  Succinylcholine is acidic and should not mixed with alkaline solution (like barbiturates) and intravenous infusion should have made up in 5 % dextrose or normal saline to a concentration of 1-2 mg/ml.

-  Use with caution in  patients with cardiac and respiratory disease.

 

Drug Interactions

Potentially fatal:

·    Digoxin may enhance cardiovascular depression of succlnylcholine, bradyarrhythmias may occur.

·    Anticholinesterases (neostgmine,  physostigmine), lignocaine, quinine, procainamide can enhance toxicity and cause cardio respiratory depression.

Non fatal

Neuromuscular blocking action is enhanced by general anesthetics, local anesthetics like lidocaine, procaine, beta-blockers, metaclopramide, lithium carbonate, and terbutaline.

 

Adverse Effects

Common effects:

·    Initial depolarization by succinylcholine is manifested as generalized muscle fasciculation. This
may cause acute rhabdomyolyais, myoglobinuria and hyperkalemia, postoperative muscle pain may be
severe.

·    Bradycardia and hypotension due to cardiac cholinoreceptor activation.

Rare effects

·    Hypersensitivity reactions – histamine release by succinylcholine may cause flush in, bronchospasm etc.,

·    Maliganant hyperthermia can occur in susceptible patients when administered with volatile
anesthetics.

 

Drug Toxicity

·    Prolonged apnoea, neuromuscular paralysis and cardiac arrest may occur.

 

Treatment of Toxicity

·    Assisted ventilation, transfusion of fresh whole blood or frozen plasma to provide pseudo cholinesterase enzymes.

·    Atropine can be used to treat bradyarrhythmias.

 

 

Storage

            Do not allow to freeze. Store at in 2 – 8 oC.

 

Shelf life          2  years.

 

METHACARBAMOL

General Information

 

Drug code                   Preparation                                         Strength

      473                        Inj.Methacarbaml                                 100 ml/ml.;

                                                                                                10 ml amp.

Description of the Drug

             Methacarbamol is a centrally acting muscle relaxant.

 

Mode of Action

It acts by causing generalized CNS depression and inhibition of impulse conduction from spinal cord to skeletal a muscle.

            It has no direct action on the motor end plate.

 

Pharmacokinetics

Following intravenous administration, methacarbomol is rapidly metabolized. It causes the blood brain barrier for effective CNS effects. It is 25 % bound to plasma.

 

Clinical Information

 

Indications

·    It is used in the treatment of muscle spasm associated with the symptomatic treatment of acute painful musculoskeletal conditions.

·    Management of  tetanic spasms.

 

Dosage

Adult:

·    1gm  = 10 ml for moderate conditions, divided between both buttocks (5 ml + 5 ml) 8 hourly.

·    For management of  tetanus : intravenous infusion upto 30 ml/day.

Children: (only used for control of tentanus).

-  15 mg/kg/dose, repeated every 6 hours if needed.

 

Routes of Administration                  IV, IM.

 

Contraindications

·    Renal failure.

·    Pregnancy.

·    Preexisting CNS depression – coma.

·    Epilepsy.

·    Myasthenia gravis.

 

Precaution / Practice points

·    It may cause drowsiness. Hence instruct patients not to not derive or operate machinery.

·    Instruct patients to abstain from alcohol.

·    Avoid in children.

·    With caution in hepatic and renal impairment.

·    Administration instructions:

-  Avoid extravasations carefully; rate of injection should not be more than 3 ml/minute.

 

Drug Interactions

CNS effects of methacarbamol may be potentiated by alcohol or other CNS depressant like narcotics, sedative hypnotics etc.,

 

Adverse Effects

Common effects:

·    Lightheadedness, dizziness, drowsiness, vertigo, headache, metallic taste.

Rare effects :

·    Gastro – intestinal disturbances like nausea and committing.

·    Local thromobophlebitis or irritation and pain.

·    Hypersensitivity reactions – flushing of face, allergic dermatitis etc.,

 

Drug Toxicity

Cardiac arrhythmias, hypotension nausea, vomiting, drowsiness and coma may occur.

 

Treatment of Toxicity

·    Supportive measures – control hypotension with I.V. fluids and Trendelenburg’s position.

·    Dialysis and osmotic diuresis can be done to hasten drug excretion.

Storage

            Do not allow freezing.

 

Shelf life          3  years.