Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026838 (spasticity)
 6,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adjuvant analgesics are drugs that are not primarily used as analgesics but can produce analgesia in certain types of pain. Adjuvant analgesics can be administered together with non-opioid and opioid analgesics on each step of the WHO analgesic ladder. They should be given when an additional or specific indication exists, but should not be used as a substitute for a thorough treatment with opioids and nonopioids. Adjuvant analgesics can be classified into groups according to the type of pain to be treated: continuous neuropathic pain or lancinating neuropathic pain, sympathetically maintained pain, bone pain and those for multipurpose use. Adjuvant drugs used for continuous neuropathic pain include local anaesthetics, clonidine, capsaicin, and antidepressants. Tricyclic antidepressants are the group that have been best investigated, and are therefore the drugs of choice. An analgesic effect is probably produced via enhancement of transmitter concentrations in pain-modulating pathways. This occurs at lower doses than those necessary to treat depression. Anticholinergic actions, acute glaucoma, constipation, orthostatic hypotension and cardiac arrhythmias are adverse effects that are seen predominantly with teritiary amine drugs and less often with secondary amine compounds. Initial doses should be small to avoid these adverse effects. Local anaesthetics are used less often, because of the high incidence of side effects (especially with tocainide, flecainide). An analgesic effect has been described in neuropathic pain, however, probably due to membrane stabilization and reduction of aberrant signal conduction. Mexiletine is considered to be the safest local anaesthetic, and should be used initially in small doses (100-150 mg/d). If side effects do not occur, doses can be increased step-wise up to 900 mg/d. Local anaesthetics are indicated for the treatment of severe neuropathic pain; this treatment is contraindicated in patients with cardiac arrhythmias. Systemic or intrathecal clonidine can be tried in neuropathic pain refractory to opioid therapy. The same stands for the topical application of capsaicin in certain types of pain. Lancinating neuropathic pain is an indication for anticonvulsant drugs. Carbamazepine, clonazepam, valproate and phenytoin seem to reduce aberrant signal conduction in damaged nerves in a manner similar to the supression of epileptiform activities in the brain. Common side effects include sedation, dizziness and nausea. Of greater concern are the more severe side effects, such as bone marrow depression (carbamazepine) and hepatotoxicity (phenytoin, valproate). Low initial doses and stepwise increases in dosage, repeated blood counts, and monitoring of plasma levels are helpful in recognizing and avoiding these adverse effects. Baclofen, a GABA agonist primarily used for spasticity, is effective in the treatment of trigeminal neuralgia and is often used in the management of lancinating pain of unspecific origin. The initial dosage is 10-15 mg/d, increasing to 30-90 mg/d, or higher. If neural blockade fails to reduce sympathetically maintained pain sufficiently specific adjuvants can be used. Sympatholytic drugs, e.g. phenoxybenzamine (60-120 mg/d) or prazosin, can be administered to patients without major cardiovascular dysfunction. There is experimental evidence of the involvement of calcium channels in nociception, and a beneficial clinical effect of nifidepine in reflex sympathetic dystrophy (RDS) has been demonstrated. Bone pain is common in tumor patients and can often be treated effectively with non-steroidal anti-inflammatory drugs. Biphosphonates (etidronate, clodronate, pamidronate derivates) also produce analgesic effects in patients with bone metastases. However, differences among the various compounds have not been clearly evaluated yet. Potent and specific radioisotopes are still under development and the use of calcitonin in bone pain is considered controversial.
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PMID:[Pharmacotherapy of cancer pain. 3. Adjuvant drugs.]. 1841 35

Spasticity is often observed in patients with brain or spinal cord injuries. Patients with severe spasticity experience considerable difficulty in performing the activities of daily living (ADLs). Baclofen is an agonisit at gamma-aminobutyric acid (GABA) receptors, and is, therefore, a neuroinhibitor, and decreases spasticity. However, because of blood-brain-barrier (BBB) sufficient concentrations of baclofen do not reach the spinal cord. Intrathecal administration of baclofen enables its direct infiltration into the spinal cord, and drastically reduce spasticity. In Japan, the government approved intrathecal baclofen (ITB) treatment in April, 2006. Thus far we have 40 patients administered ITB treatment. Further, we have implanted a pump that delivers baclofen in 22 patients who nevertheless require baclofen administration. All patients implanted with the pump are satisfied with the reduction in spasticity which has improved the performance of activities among wheelchair users and facilitates locomotion. In 2 patients, the implants were removed; in 1, the reason for the removal infection, and in the other was disruption of catheter. Re-implantation surgery was performed on both patients and baclofen treatment was continued.
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PMID:[Intrathecal baclofen for severe spasticity]. 1911 Jul 52

Autonomic dysreflexia may occur following spinal cord injury above mid-thoracic level, commonly developing in the early posttraumatic period. Cardiovascular dysregulation is the most prominent feature, characterized by paroxysmal high blood pressure attacks, which are precipitated by distension of urinary bladder or bowels, skin wounds, or increased spastic muscle tone. Severe drops in blood pressure may occur in orthostatic conditions. Baclofen is effective for treating spasticity. While orally administered baclofen often fails to alleviate severe spasticity adequately, intrathecal baclofen (ITB) is more effective and thus is being used increasingly. A 61-year-old male sustained a cervical spinal cord injury, subsequently developing severe spastic tetraparesis, predominantly in the legs. Some 30 years later he experienced marked spasms of the muscles of the abdominal wall, leading to extreme fluctuations of blood pressure. After positive evaluation with ITB the patient underwent implantation of a pump-catheter-system for continuous ITB application. Abdominal wall spasms ceased entirely with a daily dose of 190 microg ITB, accompanied by a sustained normotensive blood pressure profile. However, spasms reoccurred after inadvertent reduction of ITB flow when increasing the pump's ITB concentration but subsided again when the optimal antispastic dose was reestablished. Baclofen per se has the potential of lowering blood pressure. In this patient, however, ITB treatment enabled permanent stabilization of insidious blood pressure fluctuations. It would appear that suppression of abdominal spasms prevented the triggering of dysautonomic crises. This case demonstrates that ITB administration may help to stabilize autonomic dysreflexia and orthostatic hypotension in patients with spinal cord lesions.
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PMID:Intrathecal baclofen for autonomic instability due to spinal cord injury. 1915 92

We report a case of catheter obstruction due to complete narrowing of the lumen of a connecting pin, and catheter disconnection in a patient undergoing intrathecal Baclofen pump exchange. The patient underwent intrathecal baclofen pump implantation for treatment of lower extremity spasticity and hypertonia secondary to congenital tetraplegia. Intrathecal baclofen dose escalation occurred over the course of treatment (73 mo) from 80 to 708 mcg/d representing a 189% increase in dose. The pump had neared the manufacturer's recommended exchange interval; therefore, a pump exchange was scheduled to surgically replace the device. One week before surgery, the patient noted a distinct increase in his symptomatology and began enteral baclofen therapy. During the surgery, the pump catheter was noted to be disconnected from the pump. Upon further examination, the lumen of the connection pin positioned between the pump catheter and intrathecal catheter was completely obstructed. Postsurgically, the patient's intrathecal baclofen dose was substantially reduced from 708 to 527 mcg/d (25.6% reduction) to control hypotonicity and to reestablish an Ashworth score of 2. We discuss intrathecal baclofen therapy and a unique complication associated with a catheter connecting pin.
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PMID:Obstructed catheter connection pin discovered during intrathecal baclofen pump exchange. 1933 78

Baclofen is a racemic GABA(B) receptor agonist that has a number of significant pharmacokinetic limitations, including a narrow window of absorption in the upper small intestine and rapid clearance from the blood. Arbaclofen placarbil is a novel transported prodrug of the pharmacologically active R-isomer of baclofen designed to be absorbed throughout the intestine by both passive and active mechanisms via the monocarboxylate type 1 transporter. Arbaclofen placarbil is rapidly converted to R-baclofen in human and animal tissues in vitro. This conversion seems to be primarily catalyzed in human tissues by human carboxylesterase-2, a major carboxylesterase expressed at high levels in various tissues including human intestinal cells. Arbaclofen placarbil was efficiently absorbed and rapidly converted to R-baclofen after oral dosing in rats, dogs, and monkeys. Exposure to R-baclofen was proportional to arbaclofen placarbil dose, whereas exposure to intact prodrug was low. Arbaclofen placarbil demonstrated enhanced colonic absorption, i.e., 5-fold higher R-baclofen exposure in rats and 12-fold higher in monkeys compared with intracolonic administration of R-baclofen. Sustained release formulations of arbaclofen placarbil demonstrated sustained R-baclofen exposure in dogs with bioavailability up to 68%. In clinical use, arbaclofen placarbil may improve the treatment of patients with gastroesophageal reflux disease, spasticity, and numerous other conditions by prolonging exposure and decreasing the fluctuations in plasma levels of R-baclofen.
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PMID:Arbaclofen placarbil, a novel R-baclofen prodrug: improved absorption, distribution, metabolism, and elimination properties compared with R-baclofen. 1950 31

Baclofen, a gamma-aminobutyric acid receptor(B) agonist, is used to reduce symptoms of spasticity (hyperreflexia, increases in muscle tone, involuntary muscle activity), but the long-term effects of sustained baclofen use on skeletal muscle properties are unclear. The aim of our study was to evaluate whether baclofen use and paralysis due to cervical spinal cord injury change the contractile properties of human thenar motor units more than paralysis alone. Evoked electromyographic activity and force were recorded in response to intraneural stimulation of single motor axons to thenar motor units. Data from three groups of motor units were compared: 23 paralysed units from spinal cord injured subjects who take baclofen and have done so for a median of 7 years, 25 paralysed units from spinal cord injured subjects who do not take baclofen (median: 10 years) and 45 units from uninjured control subjects. Paralysed motor unit properties were independent of injury duration and level. With paralysis and baclofen, the median motor unit tetanic forces were significantly weaker, twitch half-relaxation times longer and half maximal forces reached at lower frequencies than for units from uninjured subjects. The median values for these same parameters after paralysis alone were comparable to control data. Axon conduction velocities differed across groups and were slowest for paralysed units from subjects who were not taking baclofen and fastest for units from the uninjured. Greater motor unit weakness with long-term baclofen use and paralysis will make the whole muscle weaker and more fatigable. Significantly more paralysed motor units need to be excited during patterned electrical stimulation to produce any given force over time. The short-term benefits of baclofen on spasticity (e.g. management of muscle spasms that may otherwise hinder movement or social interactions) therefore have to be considered in relation to its possible long-term effects on muscle rehabilitation. Restoring the strength and speed of paralysed muscles to pre-injury levels may require more extensive therapy when baclofen is used chronically.
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PMID:Effects of baclofen on motor units paralysed by chronic cervical spinal cord injury. 1990 33

Baclofen is widely used to control spasticity in children with cerebral palsy. Several publications described clinical adverse effects of baclofen oral treatment, but the effect of baclofen on seizure potentiation is still controversial. We describe a 10-year-old female patient with cerebral palsy, epilepsy, and mental retardation who developed clinical adverse effects (confusion, agitated state, insomnia, diffuse hypotonia, and hyporeflexia) and electroencephalographic (EEG) changes (quasiperiodic, generalized burst of sharp waves that take up >50% of standard EEG) during long-term oral baclofen treatment, after gradually increasing the dosage but still within the therapeutic dose. Our case showed clearly that the EEG changes in our patient, with a history of epilepsy in good control, have been induced by the baclofen increase, and we describe the possible mechanisms that could explain proconvulsive effect of baclofen.
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PMID:Long-term oral baclofen treatment in a child with cerebral palsy: electroencephalographic changes and clinical adverse effects. 2013

Baclofen is a skeletal muscle relaxant, used to control spasticity in both adults and children with neuromuscular disorders. Several cases of baclofen overdose have been reported, but only a small number have involved children. We report a 3-year-old girl with accidental ingestion of baclofen, who presented with coma, bradycardia and hypotension. She recovered within 24 hours with supportive treatment. The case emphasizes the importance of warning parents about the potential toxicity of baclofen when the drug is prescribed to a family member.
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PMID:Baclofen intoxication after accidental ingestion in a 3-year-old child. 2033 25

Baclofen is a gamma amino butyric acid (GABA) derivative that is a specific agonist at GABA-B receptors. Initially used in the treatment of spasticity, it is now being used in the treatment of alcohol dependence. Although it has several known adverse effects, incidence of rashes developing due to baclofen is very rare, and morbiliform rashes due to baclofen, an exceedingly rare adverse effect, has been reported only once before. We report a case series of 4 patients who developed morbiliform rashes after initiation of baclofen.
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PMID:Baclofen-induced morbiliform rashes: a case series. 2111 92

Baclofen withdrawal syndrome is a rare and potentially life-threatening condition manifesting with autonomic dysreflexia, high fevers, spasticity, seizures, and multiorgan failure. Reversible cardiomyopathy due to this condition is extremely rare. A high level of suspicion is needed to recognize this condition and start an early intervention to improve patient outcome. Electrocardiographic ST-segment elevation in lead aVR was previously described in association with left main, left anterior descending, and triple-vessel coronary artery disease as well as Takotsubo cardiomyopathy. In this article we present a rare case of reversible cardiomyopathy due to baclofen withdrawal syndrome associated with diffuse ST-segment depressions and ST-segment elevation in lead aVR.
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PMID:Reversible electrocardiogram changes and cardiomyopathy secondary to baclofen withdrawal syndrome. 2119 52


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