Tizanidine - An Effective Treatment for Multiple Sclerosis

Overview

Tizanidine is used widely in the treatment of muscular spasms. It belongs to the group of alpha-two adrenergic agonists. Neuromuscular disorders like multiple sclerosis can be managed by the drug Tizanidine. The medicine helps to treat muscle spasticity, which is sometimes quite painful. Tizanidine helps to relax the affected muscles, thereby alleviating pain. Tizanidine was approved by the FDA (Food and Drug Administration) in 1996 to manage muscle spasms. The article further sheds light on the mechanism of action, pharmacological considerations, and effectiveness of Tizanidine in specific populations.

What Are the Uses of Tizanidine?

• Used in the reduction of muscle spasms due to neuromuscular disorders like multiple sclerosis.

• Used in reducing pain due to muscle spasticity.

• It does not completely cure the condition but helps increase the effectiveness of physiotherapy in patients with muscle spasms.

• It helps to reduce muscle tightness and relaxes the muscles in patients with different injuries like spine injury or acquired brain injury.

• In cases of stroke and TBI (traumatic brain injury).

Doses-

The drug Tizanidine is available in two forms:

• Oral Capsules: It is available in a dose of 2 mg (milligrams), 4mg, and 6 mg.

• Oral Tablets: It is available in a dosage of 2 mg, 4mg, and 6 mg.

Warnings-

• Risk of Blurred Vision: Tizanidine may cause drowsiness, unsteadiness, and vision disturbances, so it is advised to avoid any heavy machinery usage and driving when under the drug Tizanidine.

• Risk of Liver Disease: Tizanidine carries a risk of liver disease. Inform the doctor immediately in case of any symptoms like abdominal pain, pale stools, or yellowing of the skin or eyes after starting the drug.

• Risk of Anaphylactic Reactions: The drug Tizanidine carries a risk of severe anaphylactic or hypersensitive reactions which can be life-threatening. Inform the doctor in case of any signs of allergy develop after starting the medication.

• Risk of Dry Oral Mucosa: The drug Tizanidine may result in dry mouth. Inform the doctor in case of a dry sensation in the oral mucosa. The doctor may provide some sugar-free chewing gums or candies for managing the dry mouth condition.

For Patients

What Is Multiple Sclerosis?

Multiple sclerosis is a neuromuscular disease characterized by improper functioning of the nerve accompanied by loss of muscular coordination, muscular weakness, speech problems, bladder control issues, and vision problems.

How Does the Drug Tizanidine Work for Multiple Sclerosis?

The drug Tizanidine is an alpha-two receptor agonist and acts by inhibiting the motor neurons at presynaptic endings. It is a centrally acting drug that inhibits the excitatory amino acids like aspartate and glutamate that causes muscle spasm.

When and Why to Take Tizanidine?

The drug Tizanidine should be consumed in the exact doses and scheduled as prescribed by the doctor. It is usually prescribed by the doctor for the management of muscle spasticity and reduces muscle spasms after a thorough clinical examination and diagnosis of the underlying causes of muscle stiffness. It is usually suggested by the doctor in cases of muscle spasms due to neuromuscular disorders like multiple sclerosis, acquired brain injuries, stroke, or spinal cord injuries.

Things to Inform The Doctor Before They Prescribe Tizanidine Medication-

• In case of any allergy to any drug or its composition.

• In case of any underlying medical history like diabetes, hypertension, liver disease, etc.

• Inform the doctor if any medications (prescribed or non-prescribed) like Ciprofloxacin, vitamin supplements, antihistamines, or CNS (central nervous system) depressants are ongoing. As these drugs may result in drug interactions which may lead to the worsening of symptoms. The doctor usually stops these drugs or might replace them with an alternate drug regimen before starting with Tizanidine.

• Inform the doctor if undergone any surgeries in the past.

• Inform in case of pregnancy or planning for pregnancy.

• Breastfeeding mothers should inform their doctors regarding their health status.

How To Take Tizanidine?

• Tizanidine tablets or capsules should be taken orally with water, with or without food, in the accurate doses and schedule as the doctor suggests based on the clinical condition and diagnosis. The drug is usually suggested by the doctor three times daily.

• The tablet or capsule should be taken as a whole; it is advised not to crush or chew the tablets and not to open the capsules while consuming the medication.

• It is advised not to stop taking the drug suddenly without the doctor's consent.

Things to Do After One Starts Taking Tizanidine:

• Look for any adverse events if present and report them to the doctor immediately.

• Check for symptom improvement and update the doctor on the follow-up visit.

• In case of worsening symptoms, inform the doctor about it.

What Are the Side Effects of Tizanidine?

Common Side Effects:

• Blurred vision.

• Drowsiness.

• Lethargy.

• Hallucination.

• Dry mouth.

• Dizziness.

• Constipation.

• Rhinitis (swelling of the mucous membranes of the nose).

• Asthenia (weakness).

• Abdominal pain.

• Nausea and vomiting.

• Back pain.

• Tingling sensation in the feet and hands.

Serious Side Effects:

• Liver failure.

• Anaphylactic reaction.

• Dermatitis (swelling of the skin).

• Hypotension.

• Severe bradycardia.

• Hypokalemia (low potassium).

• Loss of appetite.

• Yellowish discoloration of skin or eyes.

• Unusual bleeding.

Withdrawal Symptoms:

• Tachycardia (increased heart rate).

• Rebound hypertension.

• Muscle spasticity.

• Other withdrawal symptoms might occur due to the abrupt stopping of drugs.

In case any of the above side effects are noticed, it is advised to inform the doctor immediately.

Dietary Alterations: No dietary alterations are needed when on the Tizanidine drug. It is advised to avoid alcohol when under Tizanidine as the drug can react with alcohol and can result in hallucinations and increased drowsiness.

What Should Be Done if the Dose Is Missed?

Take the missed dose as soon as remember. Avoid taking a double dose of the drug to compensate for the missed dose. If it is time for the next dose, skip the missed dose and continue with the regular dose of the drug.

What Should Be Done in Case of Overdose?

In case of an overdose of the drug Tizanidine, try calling the poison control helpline immediately. Overdose of the drug Tizanidine can result in different symptoms like:

• Lethargy.

• Confusion.

• Shallow breathing.

• Feeling unconscious.

• Reduce heart rate.

Avoid Self-Prescription: The drug is not available over the counter. It should be started only under the doctor's supervision after a thorough clinical examination of the health condition by the doctor.

For Doctors:

Indications:

• Used in the reduction of muscle spasms.

• Muscle spasticity due to stroke and TBI (traumatic brain injury).

• Management of muscle pain due to spine injury or acquired brain injury.

• Management of headaches and back pain.

Contraindications:

• Hypersensitivity Reactions: Patients allergic to the drug or its composition.

• Patients With Liver Disease: In patients with liver diseases, the drug Tizanidine should be used very cautiously or should be avoided as multiple research has proved that the drug Tizanidine can result in liver failure and death.

• Patients With Kidney Diseases: In patients with kidney disorders, drug-dose adjustment is needed. Tizanidine should be used cautiously in patients with kidney diseases as the renal clearance of the drug is quite low (less than 25 milliliters per minute), which may result in renal toxicity.

Pharmacology:

1. Mechanism of Action: The drug Tizanidine is an alpha-two receptor agonist and acts by inhibiting motor neurons at the presynaptic terminal which results in a reduction in the release of glutamate and aspartate (excitatory amino acids). The reduction in the release of these amino acids can result in a reduction of the muscle spasm and manage the muscle spasticity due to inhibition of motor neurons.

2. Pharmacodynamics: Tizanidine helps manage muscle spasticity by acting as an agonist on the alpha-two-adrenergic receptor sites.

3. Chemical Taxonomy:

• Kingdom - Organic compound.

• Superclass - Organoheterocyclic compounds.

• Class - Benzothiadiazole.

• Direct Parent - Benzothiadiazole.

Ingredients:

A. Active Ingredients: The only active ingredient is Tizanidine HCL.

B. Inactive Ingredients:

• Silicon dioxide.

• Stearic acid.

• Microcrystalline cellulose.

• Lactose monohydrate.

• Anhydrous lactose.

4. Pharmacokinetics:

• Absorption: The oral bioavailability of the drug Tizanidine is around 40 percent. According to the research, the food shows an increase in the absorption of Tizanidine.

• The Volume of Distribution: The drug Tizanidine has an average steady-state volume of distribution of 2.4 Liter per kilogram.

• Protein Binding: Tizanidine is bound to almost 30 percent of the plasma proteins.

• Metabolism: Tizanidine is metabolized almost 95 percent after consumption by the enzyme CYP1A2 (Cytochrome P450).

• Elimination: The route of elimination of the drug Tizanidine is mainly through the kidneys.

• Half-Life: The average half-life of the drug is approximately two and a half hours.

• Doses and Forms: Tizanidine is available in the form of oral capsules and tablets in the dose of 2 mg, 4mg, and 6mg. The dose of both the capsule and tablet start with 2 mg orally. There should be a minimum 6 hours gap between the two doses. The doctor usually increases the dose gradually from 2 mg to 4 mg based on the symptoms presented by the patient. The maximum dose should not exceed more than 36 mg per day. The doctors usually taper the drug from high to low doses before completely stopping the drug to minimize the withdrawal symptoms.

• Storage: The drug Tizanidine should be stored in an airtight container at room temperature. Keep the drug away from moisture and heat. Keep the medicine away from the reach of children and pets. Dispose the expired medicines carefully.

Administration of the Drug: The drug Tizanidine is prescribed to the patient to consume orally in doses of 2 mg, 4 mg, or 6 mg based on the patient's conditions. The doctor usually tapers the drug before stopping the drug.

Toxicity: The recommended dose of the drug Tizanidine is a maximum of 36 mg per day. Crossing the average maximum dose may be lethal and can result in various toxic symptoms like:

• Coma.

• Low heart rate.

• Agitation.

• Weakness.

• Hypotension (low blood pressure).

• Altered mental status.

Management of Tizanidine Toxicity: There is no known antidote yet known to manage Tizanidine toxicity. However, a few measures can be taken to manage the toxicity:

• Continuous airway monitoring in patients with Tizanidine overdose.

• Administration of intravenous fluids and vasopressor as needed.

• The drug Naloxone when administered intravenously in the dose of 10 mg, has proven to be effective in managing Tizanidine toxicity to a certain extent based on the research however, hemodynamic (blood circulation) parameters cannot be reversed by the drug Naloxone.

Drug Interactions:

• The drug Tizanidine increases the severity of the adverse events if combined with Benzodiazepines and Acetazolamide.

• The drug serum concentration increases when combined with Abemetapir.

• The drug Tizanidine when combined with Abatacept results in increased metabolism of the drug.

• The efficacy of the drug Tizanidine reduces when combined with Acebutolol.

• The drug Tizanidine can result in increased sedation and cardiac toxicity when combined with alcohol.

• The drug Tizanidine when given along with Ciprofloxacin can result in an increased risk of psychomotor impairment.

Use In Specific Populations:

• Tizanidine in Pregnant and Lactating Women: The use of the drug Tizanidine in pregnancy can be done only if indicated by the healthcare professionals based on careful evaluation of the risk and benefits matrix for the patients. It can be used for managing spinal injuries in pregnant females if indicated. The safety and efficacy of the use of the drug in breastfeeding mothers are yet not established so it should be avoided in lactating women.

• Tizanidine in Patients with Liver Disease: According to numerous research, Tizanidine can result in liver failure and death due to its excessive metabolism in the liver, so it should be avoided or used very cautiously in patients with underlying liver disorders.

• Tizanidine in Patients with Kidney Disease: According to the research, the drug Tizanidine has a very low renal clearance rate of around 25 mL per minute. So, it is advised to use the drug very safely in patients with underlying kidney diseases. Drug-dose adjustment is needed in such patients.