Tizanidine Hydrochloride is the hydrochloride salt form of tizanidine, an imidazoline derivative structurally similar to clonidine and an adrenergic agonist with muscle relaxant property. Tizanidine is a short-acting drug for the management of spasticity. Tizanidine is an agonist at a2-adrenergic receptor sites and presumably reduces spasticity by increasing presynaptic inhibition of motor neurons. In animal models, tizanidine has no direct effect on skeletal muscle fibers or the neuromuscular junction, and no major effect on monosynaptic spinal reflexes. Tizanidinestimulates alpha-2 adrenergic receptors in the central nervous system, thereby inhibiting presynaptic release of norepinephrine.
Mechanism of Action of Tizanidine
Tizanidine reduces spasticity by increasing presynaptic inhibition of motor neurons through agonist action at a2-adrenergic receptor sites. Tizanidine is a central-acting alpha2-adrenergic agonist which acts at presynaptic receptors. It is structurally and pharmacologically related to clonidine but has only 2—10% of clonidine’s antihypertensive potency. The antispasmodic activity of tizanidine results from agonism at central pre-synaptic alpha2-receptors. The response to agonism at these receptors is a decrease in the release of excitatory amino acids which in turn leads to inhibition of spinal motor neurons. In animal models, tizanidine has no direct effect on skeletal muscle fibers or the neuromuscular junction, and no major effect on monosynaptic spinal reflexes. The effects of tizanidine are greatest on polysynaptic pathways. The overall effect of these actions is thought to reduce the facilitation of spinal motor neurons.
Indications of Tizanidine
- Treatment of increased muscle tone associated with spasticity
- Muscle spasm
- Cluster headaches
- Acute low back pain
- Muscle spasticity
- Acute myofascial low back pain.
- Spondylosis
- Spondylarthrosis
- Cervical and lumbar syndromes
- Arthrosis of the large joints
- Obliterating atherosclerosis of the extremity vessels
- Diabetic angiopathy
- Low back pain syndrome6
- Painful reflex muscle spasm
- Post-cerebral stroke spasticity
- For the management of increased muscle tone associated with spasticity
Contra-Indications of Tizanidine
- Mental Disorder with Loss of Normal Personality & Reality
- Slow Heartbeat
- abnormally low blood pressure
- severe liver disease
- kidney disease with a reduction in kidney function
- Allergies to Alpha 2 Adrenergic Agonist
Dosage of Tizanidine
Strengths: 2mg; 4 mg; 6 mg
Muscle Spasm
- Initial dose: 2 mg orally every 6 to 8 hours as needed
- Peak effects occur in approximately 1 to 2 hours and last for 3 to 6 hours; treatment can be repeated as needed to a maximum of 3 doses in 24 hours; gradually increase dose by 2 to 4 mg at intervals of 1 to 4 days until the satisfactory reduction of muscle tone is achieved.
- Maximum single dose: 16 mg
- Maximum daily dose: 36 mg in 24 hours
Side Effects of Tizanidine
The most common
- Chest pain or discomfort
- Dry mouth
- headache
- joint painPain
- dizziness
- nausea and vomiting
- Severe stomach ache
- epigastric pain,
- diarrhoea,
- anorexia,
- flatulence,
- headache,
- dizziness,
- fainting, fast or pounding heartbeats.
More common
- Fast or irregular heartbeat
- appetite loss
- changes in nails
- constipation
- fatigue
- fever
- Back pain
- dizziness
- headache
- increased cough
- Acid or sour stomach
- decreased appetite
- Agitation
- chest congestion
- chest pain
- cold sweats
- confusion
- decreased sexual ability or desire
- stomach or abdominal cramps, gas, or pain
- trouble sleeping
Less common
- bleeding gums
- blood in the urine or stools
- chest pain
- diarrhea
- Burning, crawling, itching, numbness, prickling, “pins and needles“, or tingling feelings
- difficulty in moving
- muscle stiffness
- redness of the face, neck, arms and occasionally, upper chest
- lack or loss of strength
- muscle spasm
- difficult or labored breathing
- dry mouth
- headache
- irritability
- lack or loss of strength
- loose stools
- loss of interest or pleasure
- muscle stiffness
- night sweats
- passing gas
- stomach discomfort, upset, or pain
- swollen joints
- trouble concentrating
- increased blood pressure
Drug Interactions of Tizanidine
Tizanidine may interact with following drugs ,supplements & may change the efficacy of drug
- “azole” antifungal medications (e.g., fluconazole, itraconazole, ketoconazole)
- beta-blockers (e.g., atenolol, propranolol, metoprolol)
- barbiturates (e.g., butalbital, pentobarbital, phenobarbital)
- benzodiazepines (e.g., chlordiazepoxide, clonazepam, diazepam, lorazepam)
- calcium channel blockers (e.g., nifedipine, diltiazem, verapamil, amlodipine, felodipine)
- carbamazepine
- mirtazapine
- montelukast
- norfloxacin
- ondansetron
- carbamazepine
- peginterferon alfa-2b
- phenytoin
- other selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, fluoxetine,sertraline)
- 5-HT3 antagonists (e.g., granisetron, ondansetron)
- tamsulosin
- thiazide diuretics (e.g., hydrochlorothiazide, indapamide)
- tricyclic antidepressants (e.g., nortriptyline, amitriptyline, imipramine,
Pregnancy & Lactation
FDA Pregnancy Category C
Pregnancy
Tizanidine has not been studied for use by pregnant women. In some animal studies, tizanidine caused birth defects and other pregnancy problems. This medication should not be used during pregnancy unless the benefits outweigh the risks. If you become pregnant while taking this medication, contact your doctor immediately.
Lactation
It is not known if tizanidine passes into breast milk. If you are a breastfeeding mother and are taking this medication, it may affect your baby. Talk to your doctor about whether you should continue breastfeeding. The safety and effectiveness of using tizanidine have not been established for children less than 18 years of age.
References
