#dantrolene

Common Brand Names: Dantrium

Therapeutic Class: Skeletal Muscle Relaxant

Common Injectable Dosage Forms:

Powder for Reconstitution: 20 mg in vials

Dosage Ranges:

For the treatment of spasticity associated with spinal cord injury, stroke, cerebral palsy, or multiple sclerosis: Normal dosage is 2.5-5 mg/kg approximately 1.25 hours prior to anesthesia and infused over 1 hour. May repeat dose up to accumulated dose of 10 mg/kg.

Administration and Stability: Reconstitute with 50 mL Sterile Water for Injection and use within 6 hours. Avoid use of glass bottles. Emergency or therapeutic dose may be given over rapid continuous IV push. Follow up doses given over 2-3 minutes.

Pharmacology/Pharmacokinetics: Dantrolene acts directly on skeletal muscle by interfering with release of calcium ions from the sarcoplasmic reticulum. It prevents or reduces the increase in mycoplasma calcium ion catabolic processes. Elimination half-life is 8.7 hours. Excretion is via feces (45-50%) and urine (25% as unchanged drug and metabolites).

Drug and Lab Interactions: Dantrolene is a major substrate of CYP3A4. Estrogens, CNS depressants, MAOIs, phenothiazines, verapamil, warfarin, azole antifungals, isoniazid, protease inhibitors, carbamazepine, phenobarbital, phenytoin, valerian root, St. John’s Wort, Kava Kava.

Contraindications/Precautions: Contraindicated in patients with active hepatic disease and where spasticity is used to maintain posture or balance. Use with caution in those with impaired cardiac function or impaired pulmonary function. Black box warning for hepatotoxicity. Pregnancy Category C.

Monitoring Parameters: Motor performance, nausea and vomiting, LFTs, cardiac monitoring, and blood pressure.

Adverse Effects: Possible adverse effects include drowsiness, dizziness, rash, diarrhea, vomiting, muscle weakness, blurred vision, and respiratory depression.

May 23 2018

The combination of therapy session, anxiety medication and anti-depressants have helped cope with recent traumatizing events. Today I spoke with my PCP and informed me that she spoke to her colleague about switching a person off of Baclofen (a muscle relaxer) who has taken this medication for more than five years and at the highest dosage. She informed me that I would have to wing off slowly for the two first weeks. Then I will merge towards taking Dantrolene, I think that was what it’s called.

The risky part of all of this lowering the Baclofen can have some negative effects. The one I already knew is the constant state of muscle contracting will increase meaning more pain but I can handle that. The one we are worrying about is that it can induce seizures which is something we do not want. I am choosing to do this change as of right now as in the next couple of months I will be winging off of Keppra (seizure medication) to another anti-seizure medication and doing so can also increase the chances of seizures too.

Taking Dantrolene I was informed I would be monitored and do bloodwork as it works on muscles and does not go directly to the whole central nervous system.

Get help

Stop trigger (volatile/suxamethonium)

Dantrolene (2.5mg/kg)

Dantrolene

Dantrolene

NB - Malignant hyperthermia (MH) is, by definition, a disease of the ryanodine receptor. Abnormal ryanodine receptors allow uncontrolled calcium release from the sacroplasmic reticulum causing all the clinical problems you see with MH. The only diseases actually associated with MH are:

Central Core Disease

Minicore Disease

Evans Myopathy

King Denborough Syndrome

Nemaline Rod Myopathy

Similar clinical syndromes are seen with Anaesthesia Induced Rhabdomyolysis (AIR) and Propofol Infusion Syndrome, the major difference being that dantrolene may not help in the treatment.

Dantrolene is the priority in MH, however there are many other things that need to be done, so enlisting a team to help is essential. Many hospitals will have an MH trolly with all the equipment and medications needed, plus MH job cards that describe the tasks for each team member.

If you think about what the uncontrolled release of calcium would do, this   will help you remember what needs to be done to manage the patient.

Muscle contraction causing increased metabolic demand, production of heat, and release of potassium -> Deliver 100% oxygen, cool, and treat hyperkalaemia 

Inflammation and heat causing vasodilation -> pressor support

Stimulation of the clotting clotting cascade -> Treat disseminated intravascular coagulation

Increased cardiac activity causing arrhythmias -> Antiarrhythmic treatment