WRITE ABOUT THE ROLE OF MUSCLE RELAXANTS IN THE MANAGEMENT OF SPASTICITY ?
B ) MENTION THE MECHANISM OF ACTION , INDICATIONS , CONTRAINDICATIONS AND PRECAUTIONS FOR SUCH TWO DRUGS ?
A 13 INTRODUCTION
1 Skeletal muscle relaxants are a heterogeneous group of medications commonly used to treat two different types of underlying conditions -
A ) spasticity from upper motor neuron syndromes -
1 Spasticity from the upper motor neuron syndrome (a complex of signs and symptoms that can be associated with exaggerated reflexes, autonomic hyperreflexia, dystonia, contractures, paresis, lack of dexterity, and fatigability, in addition to spasticity) can result from a variety of conditions affecting the cortex or spinal cord.
2 Some of the more common conditions associated with spasticity include -
A ) multiple sclerosis
B ) spinal cord injury
C ) traumatic brain injury
D ) cerebral palsy and
E ) post-stroke syndrome
3 In many patients with these conditions, spasticity can be disabling and painful, with a marked effect on functional ability and quality of life
B ) muscular pain or spasms from peripheral musculoskeletal conditions.
4 Only baclofen, dantrolene, and tizanidine are approved for the treatment of spasticity.
B ) MECHANISM OF ACTION , INDICATIONS AND CONTRAINDICATIONS OF 2 DRUGS
1 BACLOFEN
A ) Chemically it is a derivative of the neurotransmitter γ-aminobutyric acid (GABA).
B ) MECHANISM OF ACTION
1 Baclofen produces its effects by activating the GABAB receptor.
2 Baclofen is postulated to block mono-and-polysynaptic reflexes by acting as an inhibitory neurotransmitter, blocking the release of excitatory transmitters.
3 However, baclofen does not have significant affinity for the GHB receptor, and has no known abuse potential.
4 The modulation of the GABAB receptor is what produces baclofen’s range of therapeutic properties.
5 is believed that the drug works mainly at the level of the spinal cord to block polysynaptic afferent pathways and, to a lesser extent, monosynaptic afferent pathways
INDICATIONS
1 Spasticity
A ) Baclofen is primarily used for the treatment of spastic movement disorders, especially in instances of spinal cord injury, cerebral palsy, and multiple sclerosis.
B ) Its use in people with stroke or Parkinson’s disease is not recommended.
2 Alcoholism
3 Other
1 It is being studied along with naltrexone and sorbitolfor Charcot-Marie-Tooth disease (CMT), a hereditary disease that causes peripheral neuropathy.
2 It is also being studied for cocaine addiction.
CONTRAINDICATIONS AND PRECAUTIONS
1 Baclofen should not be used in patients who require spasticity to maintain upright posture and balance.
2 oral baclofen is not recommended in patients with trauma-induced cerebral lesions, intracranial bleeding, parkinsonism, or a prior cerebrovascular accident (stroke ) vv imp
3 In geriatric patients with cerebral palsy as it can increase toxicity
4 Patients with pre-existing psychiatric disorders (e.g., bipolar disorder, depression, psychosis, schizophrenia) are at increased risk for baclofen-induced psychiatric adverse reactions vv imp
5 Hyperglycemia is associated with oral and intrathecal baclofen use. Use with appropriate caution in patients with diabetes mellitus. **
6 Baclofen has caused deterioration in the control of seizures and EEG changes in patients with epilepsy. Baclofen should be prescribed cautiously to patients with a history of a seizure disorder or a history of seizures.
7 Cases of baclofen toxicity (manifesting as encephalopathy, abdominal pain, and in some cases, seizures and respiratory depression) have been reported in patients with severe renal impairment (e.g., serum creatinine > 2 mg/dl) and renal failure who received oral baclofen.
8 Patients should be warned that baclofen may impair the ability to perform certain tasks that require mental alertness or physical coordination such as driving or operating machinery.
9 Patients should also be cautioned that the central nervous system (CNS) depressant effects of baclofen may be additive to those of ethanol ingestion and coadministration with other CNS depressants.
10 patients with dental disease may be at increased risk for the development of caries, periodontal disease, or oral candidiasis due to decreased salivary flow.
11 At therapeutic oral doses, baclofen is excreted in human milk; caution is recommended when using the drug during breast-feeding
12 Phenylketonuria
Baclofen orally disintegrating tablets (Kemstro) may contain aspartame, a source of phenylalanine. Use such formulations with caution in patients with phenylketonuria.
13 Ovarian cyst
A dose-related increase in the incidence of ovarian cyst and a less marked increase in enlarged and/or hemorrhagic adrenal glands was observed in female rats treated chronically with baclofen.
2 TIZANIDINE
MECHANISM OF ACTION
1 Tizanidine is a central-acting alpha2-adrenergic agonist which acts at presynaptic receptors.
2 It is structurally and pharmacologically related to clonidine, but has only 2—10% of clonidine’s antihypertensive potency.
3 The antispasmodic activity of tizanidine results from agonism at central pre-synaptic alpha2-receptors.
4 vv imp 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.
5 The effects of tizanidine are greatest on polysynaptic pathways.
6 vv imp The overall effect of these actions is thought to reduce facilitation of spinal motor neurons.
INDICATIONS
For the acute and intermittent management of increased muscle tone associated with spasticity (including spasticity related to multiple sclerosis or spinal cord injury).
DOSAGES
2 mg PO every 6 - 8 hrs ** - increase and decrease the dose slowly to minimise risk of rebound hypertension , tachycardia , hypertonia
Max dose - 36 mg PO
CONTRAINDICATIONS AND PRECAUTIONS
1 Tizanidine can be very strong even at the 2 mg dose and may cause hypotension, so caution is advised when it is used in patients who have a history of orthostatic hypotension, or when switching from gel cap to tablet form and vice versa.
2 Tizanidine can occasionally cause acute liver failure. Clinical trials show that up to 5% of patients treated with tizanidine had elevated liver function test values, though symptoms disappeared upon withdrawal of the drug. Care should be used when first beginning treatment with tizanidine with regular liver tests for the first six months of treatment.
3 Fluoroquinolone antibiotics such as moxifloxacin, levofloxacin, and ciprofloxacin should also be avoided due to an increased serum concentration of tizanidine when administered concomitantly.
4 Concomitant use of tizanidine and moderate or potent CYP1A2 inhibitors (such as zileuton, certain antiarrhythmics (amiodarone, mexiletine, propafenone, verapamil , cimetidine, famotidine, aciclovir, ticlopidine and oral contraceptives) is contraindicated. Concomitant use ( v imp )
5 Tizanidine use has been associated with hallucinations; tizanidine should be used with caution in patients with psychosis.
6 Tizanidine can cause drowsiness and sedation. Patients receiving tizanidine should be advised to avoid driving or operating machinery until the effects of the drug are known.
7 Use tizanidine with caution in patients with cardiac disease or other conditions that may increase the risk of QT prolongation including cardiac arrhythmias, congenital long QT syndrome, heart failure, bradycardia, myocardial infarction, hypertension, coronary artery disease, hypomagnesemia, hypokalemia, hypocalcemia