Dantrolene Centrally Acting Muscle Relaxant Drug

INTRODUCTION

Dantrolene sodium is a postsynaptic muscle relaxant that lessens excitation-contraction coupling in muscle cells. It achieves this by inhibiting Ca2+ ions release from sarcoplasmic reticulum stores by antagonizing ryanodine receptors.[1] It is the primary drug used for the treatment and prevention of malignant hyperthermia, a rare, life-threatening disorder triggered by general anesthesia. It is also used in the management of neuroleptic malignant syndrome, muscle spasticity (e.g. after strokes, in paraplegia, cerebral palsy, or patients with multiple sclerosis), and 2,4-dinitrophenol poisoning.

THERAPEUTIC USES:

This medication is used to treat muscle tightness and cramping (spasms) caused by certain nerve disorders such as spinal cord injury, stroke, cerebral palsy, and multiple sclerosis. It works by relaxing the muscles. Dantrolene helps reduce muscle pain and stiffness, improves your ability to move around, and lets you do more of your daily activities.

Dantrolene is also used with other treatments to prevent or treat special cases of high fever (malignant hyperthermia) related to anesthesia and surgery.

OTHER USES: This section contains uses of this drug that are not listed in the approved professional labeling for the drug but that may be prescribed by your health care professional. Use this drug for a condition that is listed in this section only if it has been so prescribed by your health care professional.

This drug may also be used to treat a certain uncommon condition (neuroleptic malignant syndrome) involving muscle stiffness, fever, and fast heartbeat caused by psychiatric medications.

SIDE EFFECT:

• Central nervous system side effects are quite frequently noted and encompass speech and visual disturbances, mental depression and confusion, hallucinations, headache, insomnia and exacerbation or precipitation of seizures, and increased nervousness. Infrequent cases of respiratory depression or a feeling of suffocation have been observed. Dantrolene often causes sedation severe enough to incapacitate the patient to drive or operate machinery.

• Gastrointestinal effects include bad taste, decreased appetite, nausea, vomiting, abdominal cramps, and diarrhea.

• Liver side effects may be seen either as asymptomatic elevation of liver enzymes and/or bilirubin or, most severe, as fatal and nonfatal liver inflammation. The risk of liver inflammation is associated with the duration of treatment and the daily dose. In patients treated for hyperthermia, no liver toxicity has been observed so far.

• Pleural effusion with inflammation of the fibrous sac around the heart (oral treatment only), rare cases of bone marrow damage, diffuse muscle pains, backache, dermatologic reactions, transient cardiovascular reactions, and crystals in the urine have additionally been seen. Muscle weakness may persist for several days following treatment.

• muscle weakness

• drowsiness,dizziness,diarrhea,fatigue,difficulty swallowing

PRECAUTIONS:

Before taking dantrolene, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver problems (such as hepatitis, cirrhosis), breathing problems (such as chronic obstructive pulmonary disease-COPD), heart problems.

This drug may make you dizzy or drowsy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Limit alcoholic beverages.

CONTRAINDICATIONS:

Oral dantrolene cannot be used by

• people with a pre-existing liver disease

• people with compromised lung function

• people with severe cardiovascular impairment

• people with a known hypersensitivity to dantrolene

• pediatric patients under five years of age

• people who need good muscular balance or strength to maintain an upright position, motoric function, or proper neuromuscular balance

MECHANISM OF ACTION

Dantrolene depresses excitation-contraction coupling in skeletal muscle by binding to the ryanodine receptor, and decreasing free intracellular calcium concentration. Neurotransmitters or MAP are not affected. Intracellular release is needed for excitation and contractions.

PHARMACOKINETICS

Dantrolene is slowly but adequately absorbed from g.i.t. It penetrates brain and produces some sedation, but has no selective effect on polysynaptic reflexes responsible for spasticity.

It is metabolized in liver and execrated by kidney with a half life of 8-12 hours.

DRUG-DRUG INTERACTION:

• Verapamil  Intravenous treatment +dantrolene =severe cardiovascular collapse, abnormal heart rhythms, myocardial depressions, and high blood potassium

• Diltiazem +dantrolene =severe cardiovascular collapse, abnormal heart rhythms, myocardial depressions, and high blood potassium

• Vecuronium bromide+ dantrolene= Neuromuscular blockade is potentiated.

• Benzodiazepines + dantrolene= cause additive muscle weakness.

• Estrogens+ dantrolene=   enhance liver toxicity of dantrolene, particularly in women over 35 years of age. Similarly in contraceptives.

REFERENCE: Tripathi K.D; "Essentials of medical pharmacology"; Page no-356,359,374