Carbidopa/L-Dopa (Sinemet)
This is a combination of an enzyme inhibitor (carbidopa) and levodopa. The enzyme inhibitor protects the levodopa in the peripheral circulation and allows more of it to reach the brain where it can be converted to dopamine.
Mechanism of Action: Levodopa, the metabolic precursor of dopamine, crosses the blood-brain barrier, and is converted to dopamine in the brain. This replaces the dopamine that has been lost in Parkinson s disease.
Therapeutic Use: All types of Parkinsonism. Is being investigated for use with post-anoxic (oxygen deprivation to the brain) intention myoclonus.
Absorption: Variable absorption depending on gastric pH, rate of gastric emptying and presence of food in the G.I. Tract. Peak plasma concentration of levodopa is reached in 2 hours.
Metabolism: Levodopa is decarboxylated to dopamine. Carbidopa reduces the amount of levodopa required to produce a given effect by about 75%.
Half-life: 1-2 Hours for levodopa.
Average Daily Dose (adult): 200-1200 mg of levodopa.
Adverse Effects: Dyskinesias (impairment of normal movement). Nausea, confusion and dizziness.
Drug Interaction: Symptomatic postural hypotension has occurred when Sinemet is added to the treatment of a patient receiving antihypertensive drugs. Phenothiazines and butyrophenones may reduce the therapeutic effects of levodopa.
Contraindication: MAO inhibitors. Contraindicated in patients with a known hypersensitivity to any component of this drug.
References:
- Kraus, M. & Maki, P. (1997). The combined use of amantadine and l-dopa/carbidopa in the treatment of chronic brain injury. Brain Injury. 11(6), 455-460.
- Ockey, R.R., Mowry, D., & Varghese, G. (1995). Sinemet recommended for consideration in management of locked-in syndrome. Brain Injury Update. 10(10), 76.
- Wolf, A.P. & Gleckman, A.D. (1995). Sinemet and brain injury: Functional versus statistical change and suggestions for future research designs.Brain Injury. 9(5), 487.
- Haig, A.J. & Ruess, J.M. (1990). Recovery from vegetative state of six months' duration associated with Sinemet (Levodopa/Carbidopa). Archives of Physical Medicine & Rehabilitation. 71, 1081-1083, Dec.
- Eames, P. (1989). The use of Sinemet and bromocriptine.Brain Injury. 3(3), 319-320.
- Rao, N. & Costa, J.L. (1989). Recovery in non-vascular locked-in syndrome during treatment with Sinemet.Brain Injury. 3(2), 207-211.
- Lal, S., Merbtiz, C.P. & Grip, J.C. (1988). Modification of function in head-injured patients with Sinemet.Brain Injury. 2(3), 225-233.
Levodopa (L-Dopa)
Mechanism of Action: Converted to dopamine which replaces that which has been lost in Parkinson s disease.
Therapeutic Use: Treatment of Parkinsonism Pharmacokinetics.
Absorption: Variable absorption depending on gastric pH, rate of gastric emptying and presence of food in the G.I. Tract. Peak plasma concentration of levodopa is reached in 2 hours.
Metabolism: Converted into dopamine by decarboxylation in the periphery as well as in the CNS.
Half-life: 1-3 Hours.
Average Daily Dose (adult): 3-6 g
Adverse Effects: Choreiform and/or dystonic movements, cardiac arrhythmias, hypotensive episodes, bradycardia, psychotic episodes and depression.
Drug Interaction: May enhance the action of antidepressants leading to hypertension and increase the action of drugs that stimulate the sympathetic nervous system.
Contraindication: MAO inhibitors and Levodopa should not be given concomitantly. Contraindicated in patients with known hypersensitivity to the drug and in narrow angle glaucoma.
Bromocriptine (Parlodel)
Mechanism of Action: Parlodel is a dopamine receptor agonist, which activates post-synaptic dopamine receptors. A nonhormonal agent that inhibits the release of the hormone prolactin by the pituitary gland.
Therapeutic Use: Treatment of Parkinson s disease, hyperprolactinemia and acromegaly (excessive bone growth).
Absorption: Poorly absorbed from the G.I. tract.
Time for peak effect: 1-3 hours .
Metabolism: Completely metabolized in the liver prior to excretion and metabolites are excreted in the bile.
Half-life: 7 Hours.
Average Daily Dose (adult): 3.75-40 mg
Adverse Effects: Nausea, headache, dizziness, fatigue, lightheadedness, vomiting, abdominal cramps, nasal congestion, constipation, diarrhea and drowsiness.
Drug Interaction: Alcohol may potentiate effects and dopamine receptor antagonists such as chlorpromazine or haloperidol will block action of bromocriptine.
Contraindication: Uncontrolled hypertension and sensitivity to any ergot alkaloids.
References:
- Passler, J. and Riggs, R. (2001). Positive outcomes in traumatic brain injury - vegetative state: patients treated with bromocriptine. Archives of Physical Medicine and Rehabilitation. 82(3), 311-315.
- Powell, J., Al-Adawi, S., Morgan, J., & Greenwood, R. (1996). Motivational deficits after brain injury: effects of bromocriptine in 11 patients. Neurology, Neurosurgery & Psychiatry. 60(4), 416-421.
- Powell, J., Al-Adawi, S., Morgan, J., & Greenwood, R. (1996). Motivational deficits after brain injury: effects of bromocriptine in 11 patients. Neurology, Neurosurgery & Psychiatry. 60(4), 416-421.
- Gupta, S.R. & Mlcoch, A.G. (1992). Bromocriptine treatment of nonfluent aphasia. Archives of Physical Medicine & Rehabilitation. 73, 373-376, Apr.
- Eames, P. (1989). The use of Sinemet and bromocriptine.Brain Injury. 3(3), 319-320.
- Stewart, J.T. (1989). Akathisia following traumatic brain injury: Treatment with bromocriptine. Journal of Neurology, Neurosurgery, & Psychiatry. 52, 1200-1201.
Baclofen (Lioresal)
Mechanism of Action: GABAB receptor agonist. Activation of these receptors reduces the release of excitatory neurotransmitters.
Therapeutic Use: Reduce muscle spasms such as that occurring in multiple sclerosis and diseases of the spinal cord.
Absorption: Well absorbed. Peak effect 2-3 hours.
Metabolism: 35% of the drug is excreted unchanged in the urine and feces.
Half-life: 3-4 Hours.
Average Daily Dose (adult): 100-150 mg/day in four divided doses.
Adverse Effects: Drowsiness, slight nausea, occasional mental disturbances such as confusion, euphoria and depression. Hypotension has been noted following overdose.
Drug Interaction: Increased sedation with other CNS depressants such as benzodiazepines.
Contraindication: In patients with hypersensitivity to Baclofen.
References:
- Gornley, M. (1999). Management of spasticity in children: part 2: oral medications and intrathecal baclofen. Journal of Head Trauma Rehabilitation. 14(2), 207-209.
- Meythaler, J. (1997). Intrathecal baclofen for spastic hypertonia in brain injury. Journal of Head Trauma Rehabilitation, 12(1), 87.
- Craig, C.R. and Stitzel, R.E. (1997) In: Modern Pharmacology with Clinical Applications Fifth Edition. Little Brown Publishers, Boston, 361-362.
- Penn, R.D., Gianino, J.M. et al. (1995). Intrathecal baclofen for motor disorders. Movement Disorders. 10(5), 675-677, Sept.
Dantrolene (Dantrium)
Mechanism of Action: It acts by decreasing the release of calcium from the sarcoplasmic reticulum thereby interfering with muscle contraction.
Therapeutic Use: Muscle spasticity associated with chronic disorders, such as MS, CP, spinal cord injury, TBI and stroke. It is also used for the treatment of malignant hyperthermia.
Absorption: Slow and incomplete after oral administration.
Peak effect: 4-6 hours
Metabolism: Probably metabolized by hepatic microsomal enzymes. and eliminated in the urine and bile.
Half-life: 8.7 hours.
Average Daily Dose (adult): 4-8 mg/kg/day oral, 2.5 mg/kg intravenous.
Adverse Effects: The most prominent adverse effect is dose dependent muscle weakness. Other side effects include: drowsiness, dizziness, malaise, fatigue and diarrhea. Transient elevation of liver enzymes may also occur. Symptoms of hepatitis have been reported in 0.5% of the patients receiving the drug.
Drug Interaction: Muscle relaxants. Should not be used together with calcium channel blockers such as verapamil.
Contraindication: Respiratory muscle weakness or liver disease.
Teng, C., Bhalerao, S., Lee, Z., Farber, J., Morris, H., Foran, T. & Tucker, W. (2001). The use of buproprion in the treatment of restlessnes after a traumatic brain injury. Brain Injury, 15(5), 463-?.
Shiller, A., Burke, D., Kim, H., Calvanio, R., Deckman, K. & Santini, C. (1999). Treatment with amantadine potentiated motor learning in a patient with traumatic brain injury of 15 years duration. Brain Injury, 13(8), 715-722.
Meythaler, J., Guin-Renfroe, S., Crabb, P., & Hadley, M. (1999). Long-term continuously infused intrathecal baclofen for spastic-dystonia hypertonia. Archives of Physical Medicine and Rehabilitation. 80(1), 13-19.
Gormley, M. (1999). Management of spasticity in children: part 1: chemical denervation. Journal of Head Trauma Rehabilitation. 14(1), 97-99.
Ellis, K., & Speed, J. (1998). Pharmacologic management of movement disorder after midbrain haemorrhage. Brain Injury, 12(7), 623-628.
Wilson, D., Childers, M., Cooke, D., & Smith, B. (1997). Kinematic changes following botulinum toxin injection after traumatic brain injury. Brain Injury, 11(3), 157-168.
Hammond, F., Francisco, G., & Bontke, C. (1996). Should we use etidronate disodium as prophylaxis in patients with brain injury at risk for hetertopic ossification? Journal of Head Trauma Rehabilitation. 11(6), 80-88.
Burbaud, P., Wiart, L., Dubos, J.L., Gaujard, E. et al. (1996). A randomised, double blind, placebo controlled trial of botulinum toxin in the treatment of spastic foot in hemiparetic patients. Journal of Neurology, Neurosurgery, & Psychiatry. 61(3), 265.
Dall, J.T., Harmon, R.L., & Quinn, C.M. (1996). Use of clonidine for treatment of spasticity arising from various forms of brain injury: A case series.Brain Injury. 10(6), 453.
Tighilet, B. & Lacour, M. (1995). Pharmacological activity of the Ginkgo Biloba Extract (EGb 761) on equilibrium function recovery in the unilateral vestibular. Journal of Vestibular Research. 5(3), 187.
Borg-Stein, J. & Stein, J. (1993). Pharmacology of botulinum toxin and implications for use in disorders of muscle tone.Journal of Head Trauma Rehabilitation. 8(3), 103-106.
Glenn, M.B. (1993). Etidronate disodium: Effects on heterotopic ossification and osteoporosis.Journal of Head Trauma Rehabilitation. 8(3), 99-102.
Spielman, G., Gennarelli, T.A. & Rogers, C.R. (1983). Disodium etidronate: Its role in preventing heterotopic ossification in severe head injury. Archives of Physical Medicine & Rehabilitation. 64, 539-542, Nov.
Motor System
