To describe nurse practitioner (NP) roles in medical rehabilitation settings.
lioresal drug information
To describe a case of chronic use of oral baclofen in a patient with spinal cord injury limiting lower extremity movements.
Accumulating evidence shows the efficacy of the gamma-aminobutyric acid (GABA(B)) receptor agonist baclofen in reducing alcohol intake in rats, but no studies have been performed in alcoholics. In the present preliminary study we investigated the effect of short-term baclofen administration on craving for alcohol, ethanol intake, and abstinence from alcohol in alcoholic individuals.
A 12-year-old girl suffering from spastic diplegia was implanted with a Medtronic SynchroMed II pump (Medtronic Inc., Minneapolis, Minn., USA). During a refill at 3 months 19 ml of baclofen were still in the pump. It was assumed that there was a lumbar catheter obstruction and a revision was performed. At 11 months she was receiving 180 microg/day. When she presented for refill, there were again 19 ml of baclofen in the reservoir. The pump was refilled, stopped and restarted at a lower dose. Ten minutes after restart the patient was complaining that she could not move her legs. Within the next 50 min she lapsed into coma, from a presumed baclofen overdose. She was intubated and ventilated. The reservoir was emptied of baclofen and the pump stopped. Seventeen hours after the baclofen overdose, the patient woke up gradually with no new neurological deficits. The pump was removed a week later. Medtronic laboratories examined the pump and reported no technical fault.
lioresal 40 mg
Six patients with long-lasting spasticity resistant to different drug therapies including oral baclofen received a bolus injection of lumbar intrathecal baclofen. Electromyographic (EMG) reactions of leg muscles (soleus, tibialis anterior, quadriceps, and hamstrings) to standard stimuli and during attempts at voluntary activation were recorded before the drug injection and up to 3 h after the injection. Responses to joint movements, H-reflexes, ankle clonus, and defensive reactions were noticeably suppressed within 30-45 min after the injection and had practically disappeared after 2 h. Ankle clonus was seen only in patients with H-reflexes, and clonus disappeared when the reflex responses to the n. tibialis stimuli were absent. A decrease in clonus EMG burst amplitudes was accompanied by a decrease in the clonus frequency. These observations favor the autooscillation hypothesis of clonus. Baclofen injection led to improvement in selective voluntary activation of leg muscles in patients with residual motor control. These results suggest that execution of voluntary motor commands in the patients suffered from functionally abnormal spinal circuitry rather than from changes in the descending motor commands. Intrathecal baclofen appears to be an effective way of eliminating increased muscle tone and spasms which can allow for voluntary motor function when it is present.
Up to 50% of patients with gastroesophageal reflux disease (GERD) still suffer from GERD symptoms despite proton pump inhibitor (PPI) therapy, indicating a need for new treatments. The lower esophageal sphincter (LES) plays a crucial role in maintaining the mechanical barrier necessary for prevention of gastric reflux. Transient LES relaxation (TLESR) is an important factor behind the occurrence of reflux, and preclinical studies have identified a number of targets for pharmacologic modification of TLESR. However, only gamma-aminobutyric acid (GABA) type B receptor (GABA(B)) agonists and metabotropic glutamate receptor 5 (mGluR5) modulators have shown positive proof of concept in the clinical setting. The mGluR5 negative allosteric modulator ADX10059 improved symptoms in GERD patients, but was associated with central side effects such as dizziness. Baclofen, a GABA(B) receptor agonist, reduces the incidence of TLESR and improves GERD symptoms in both adult and pediatric GERD patients. However, the utility of baclofen is similarly limited by poor tolerability and recent research has focused on the development of GABA(B) receptor agonists with improved tolerability. XP19986, a prodrug of R-baclofen, reduced the number of reflux episodes in a dose-ranging study and was similarly tolerated to placebo. AZD3355 and AZD9343 are GABA(B) receptor agonists with limited central nervous system activity that have been shown in preclinical studies to reduce the incidence of TLESR and decrease esophageal acid exposure; data from clinical studies of these agents in GERD patients are awaited with interest. Agents that target TLESR activity may therefore offer a promising new add-on treatment for patients who suffer from GERD symptoms despite PPI therapy.
lioresal maximum dose
The properties of GABA-activated current in Xenopus oocytes and its underlying mechanism were studied using the two-electrode voltage-clamp technique. External application of GABA (10(-10) - 10(-3)mol/L) induced a concentration-dependent outward current in a proportion of oocytes (35.5%, 55/155). Selective GABA(A) receptor antagonist bicuculline (10(-5) mol/L) did not block the GABA-activated current (n=6). However, 2-hydroxysaclofen (10(-4) mol/L), a GABA(B) receptor antagonist, reversed the GABA-activated outward current to an inward current (n=9), which was abolished completely by application of I4AA (10(-5) mol/L), a GABA(C) receptor selective antagonist (n=6). In 20% (12/60) of oocytes, application of baclofen (10(-10) - 10(-4) mol/L), a GABA(B) receptor agonist, also induced a concentration-dependent outward current 2-Hydroxysaclofen at the concentrations of 3 x 10(-6), 3 x 10(-5) and 3 x 10(-4) mol/L blocked the baclofen(10(-5) mol/L)-activated outward current by (6.3+/-3.2) %, (44.1+/-2.2) %, and (86.0+/-1.6) %, respectively (n=6). The reversal potential for baclofen-activated current was around 96.8+/-7.2 mV (n=6), and the baclofen-activated current could be blocked by TEA (n=5) and Ba(2+) (n=5). These results suggest that there exist endogenous GABA receptors, GABA(B) receptors mediating a slow and sustained outward current and GABA(C) receptors mediating an inward current in follicular Xenopus oocytes.
lioresal drug class
A fatal suicidal intoxication with unusual drugs is reported. A 56-year-old man was found dead in his house; near by the corpse several empty drugs boxes were found. An autopsy was performed and the biological fluids were submitted to a full toxicological work-up. The analytical results supported the hypothesis of a death due to the acute baclofen (4-amino-3-(p-chlorophenyl)butyric acid) and dipyrone (sodium [N-(1,5-dimethyl-3-oxo-2-phenylpyrazolin-4-yl)-N-methylamino] methanesulfonate) intoxication.
lioresal baclofen alcohol
The Modified Ashworth Scale (MAS) and Spasms Frequency Score (SFS) have been used as a primary outcome measure. The Disability Rating Scale (DRS) and Level of Cognitive Functioning (LCF) scores have been computed in order to verify possible interferences of baclofen therapy at an early stage on a global outcome. An intrathecal bolus test was not performed. Drug tolerability was tested by oral administration of baclofen 100 mg.
lioresal alcohol dependence
We have been able to observe in our series 3 (12%) patients with hypotonia, 2 with impairment on erection (8%) and 1 (4%) with constipation; 5 (20%) patients showed also tolerance but only 1 (4%) needed a ''drug holiday''. In the literature the side effects range from 4% to 16%. Moreover the tolerance is reported from 3% to 15%. The overdose has been reported from 0% to 14%, while the syndrome of withdrawal is reported in 16 patients with 6 fatalities. In our series these two last complications were not observed.
lioresal dosage forms
We searched the Cochrane Stroke Group Trials Register (May 2016), the Cochrane Central Register of Controlled Trials (CENTRAL, 2016, Issue 5), MEDLINE (1946 to May 2016), Embase (2008 to May 2016), CINAHL (1982 to May 2016), AMED (1985 to May 2016), and eight further databases and trial registers. In an effort to identify further studies, we undertook handsearches of reference lists and contacted study authors and commercial companies.
We report a case of acute transient encephalopathy with confusion, drowsiness, myoclonic jerks, periodic triphasic sharp wave EEG patterns induced by low doses of baclofen. We discuss the pathogenesis and the differential diagnosis from the subacute spongiform encephalopathy of sudden onset.
Of 38 patients identified, 32 had adequate data available for inclusion in the study (16 with cerebral palsy, 7 with dystonic cerebral palsy, 4 with head injury, and 5 with other diagnoses). The mean age at pump insertion was 10.6 years and the mean follow-up period was 31 months (range 1-118 months). The mean annual Cobb angle progression was 19 degrees (range 0-68 degrees, median 12 degrees).
The behavioural sensitization has been recognized as the increased behavioural response and the undesirable long-lasting changes in brain functions after repeated administration of abuse drugs. We examined whether behavioural sensitization to hyperlocomotion induced by intermittent morphine treatment could result from any changes in dopamine and GABA(B) receptor functions to activate G-proteins in the brain rewarding system in mice. Intermittent morphine treatment results in the upregulation of dopamine receptor-regulated G-protein activation in the mouse limbic forebrain, whereas this treatment causes the downregulation of GABA(B) receptor function to activate G-protein in the mouse lower midbrain. In behavioural experiments, intermittent administration of morphine in combination with either a dopamine receptor antagonist haloperidol or a GABA(B) receptor agonist baclofen abolished the development of sensitization to morphine-induced hyperlocomotion. The present data provide evidence that these G-protein activation changes may lead to behavioural sensitization to morphine-induced hyperlocomotion in mice.
Eight 1,3-cyclohexanediones with an aminoalkyl side chain in the 5-position were synthesized as rigid enolic analogues of GABA (gamma-aminobutyric acid). Biochemical investigations about their abilities to displace [3H]GABA and [3H]baclofen [beta-(p-chlorophenyl)-gamma-aminobutyric acid] in binding studies or to inhibit the high-affinity sodium-dependent GABA uptake showed that these compounds were generally devoid of affinity for the two GABA receptors and for the GABA carrier. Only compound 1 exhibited a weak affinity in the GABA-A binding experiments (IC50 = 6.5 X 10(-5) M). Graphic computer modeling was applied in an attempt to explain this activity in comparison to some reference GABA agonists. Electrophysiological studies on dorsal root ganglia (DRG) also excluded agonistic or antagonistic properties on GABA-A or GABA-B receptor models but pointed out an atypical prolongation of Ca2+-dependent action potential for compound 1.
In the South African clawed toad Xenopus laevis, background adaptation is regulated by alpha MSH, a POMC-derived peptide. After transfer of the animal from a black to a white background, secretion of alpha MSH from the intermediate pituitary lobe is inhibited by the hypothalamic neurotransmitter neuropeptide Y (NPY). The neurointermediate lobe in vitro is also subject to inhibitory regulation by dopamine and gamma-aminobutyric acid (GABA). In the nerve terminals contacting the intermediate lobe of the pituitary, GABA is contained in electron-lucent vesicles, whereas dopamine and NPY coexist in electron-dense vesicles. To study the role of these secreto-inhibitors in the regulation of POMC biosynthesis, the rate of incorporation of radioactive amino acids into POMC protein was determined after in vitro treatment of the neurointermediate pituitary with NPY, apomorphine (dopamine D2 receptor agonist), isoguvacine (GABAA receptor agonist) and baclofen (GABAB receptor agonist). After 24 h of treatment, inhibition of POMC biosynthesis by NPY and apomorphine was 77% and 74%, respectively. Isoguvacine treatment resulted in an inhibition of 59%, whereas no significant effect of baclofen was observed. When neurointermediate lobes were treated for 3 days, inhibition of POMC biosynthesis by NPY was maintained, and inhibition by apomorphine was even stronger, whereas isoguvacine gave an inhibition of 52%, and baclofen produced 34% inhibition. Superfusion experiments on alpha MSH secretion showed that prolonged treatment with the GABA receptor agonists results in a desensitization of GABA receptor-mediated signal transduction mechanisms, whereas the NPY receptor does not show desensitization. The observations indicate differential actions of the secreto-inhibitors NPY, apomorphine, and GABA agonists on POMC biosynthesis in the Xenopus intermediate pituitary, suggesting a major role for dopamine and NPY, whereas GABA, acting via two receptor types, does not seem to have a major function in long term control of POMC biosynthesis.
lioresal drug interactions
The use of baclofen in neonates has been minimally reported. We report on two term neonates who were treated successfully for hypertonia with baclofen.
Pharmacies in the United States advertising compounded intrathecal baclofen preparation.
lioresal intrathecal dose
In all cases the infection was eradicated and the integrity of the pump maintained. None of the patients required a procedure under general anesthesia.
lioresal 30 mg
The oesophago-gastric junction functions as an anti-reflux barrier preventing increased exposure of the oesophageal mucosa to gastric contents. Failure of this anti-reflux barrier results in gastro-oesophageal reflux disease, and may lead to complications such as oesophagitis, Barrett's oesophagus and eventually oesophageal carcinoma. Recent studies have suggested that transient lower oesophageal sphincter relaxation is the main mechanism underlying gastro-oesophageal reflux. It involves a prolonged relaxation of the lower oesophageal sphincter, mediated by a vago-vagal neural pathway, synapsing in the brainstem. Several drugs, such as atropine, baclofen and loxiglumide, have been shown to reduce the rate of transient lower oesophageal sphincter relaxations and concomitantly the number of reflux episodes. These findings illustrate that transient lower oesophageal sphincter relaxations may represent a potential new target for the pharmacological treatment of gastro-oesophageal reflux disease. It is possible that the reduction in the number of transient lower oesophageal sphincter relaxations may also contribute to the beneficial effect of fundoplication and new endoscopic anti-reflux procedures. It should be emphasized, however, that other factors, such as low lower oesophageal sphincter pressure, the presence of a hiatal hernia and impaired oesophageal peristalsis, are also of great importance. Therefore, whether the targeting of transient lower oesophageal sphincter relaxations is the 'golden bullet' in anti-reflux therapy remains to be proven, as evidence of an effective control of gastro-oesophageal reflux in reflux patients is still lacking.
lioresal tablets 10mg
Dipyrone administered intravenously (iv) or intracerebroventricularly (icv) delays gastric emptying (GE) in rats. Gamma-aminobutyric acid (GABA) is the most potent inhibitory neurotransmitter of the central nervous system. The objective of the present study was to determine the effect of icv baclofen, a GABAB receptor agonist, on delayed GE induced by dipyrone. Adult male Wistar rats received a saline test meal containing phenol red as a marker. GE was indirectly evaluated by determining the percent of gastric retention (%GR) of the meal 10 min after orogastric administration. In the first experiment, the animals were injected iv with vehicle (Civ) or 80 mg/kg (240 micromol/kg) dipyrone (Dpiv), followed by icv injection of 10 microl vehicle (bac0), or 0.5 (bac0.5), 1 (bac1) or 2 microg (bac2) baclofen. In the second experiment, the animals were injected icv with 5 microl vehicle (Cicv) or an equal volume of a solution containing 4 micromol (1333.2 microg) dipyrone (Dpicv), followed by 5 microl vehicle (bac0) or 1 microg baclofen (bac1). GE was determined 10 min after icv injection. There was no significant difference between control animals from one experiment to another concerning GR values. Baclofen at the doses of 1 and 2 microg significantly reduced mean %GR induced by iv dipyrone (Dpivbac1 = 35.9% and Dpivbac2 = 26.9% vs Dpivbac0 = 51.8%). Similarly, baclofen significantly reduced the effect of dipyrone injected icv (mean %GR: Dpicvbac1 = 30.4% vs Dpicvbac0 = 54.2%). The present results suggest that dipyrone induces delayed GE through a route in the central nervous system that is blocked by the activation of GABAB receptors.