-
British Medical Journal (Clinical... Aug 1985
Topics: Adrenergic beta-Antagonists; Antihypertensive Agents; Female; Humans; Hypertension; Methyldopa; Pregnancy; Pregnancy Complications, Cardiovascular
PubMed: 2861881
DOI: 10.1136/bmj.291.6492.365 -
British Medical Journal May 1972
Topics: Animals; Barbiturates; Bile; Drug Interactions; Female; Injections, Intraperitoneal; Methyldopa; Phenobarbital; Rats
PubMed: 5031674
DOI: 10.1136/bmj.2.5811.468-a -
Brain and Behavior Dec 2021Levodopa-carbidopa-intestinal-gel (LCIG) infusion is an effective treatment for advanced PD with motor fluctuations. Polyneuropathy occurs as a complication in 10-15% of...
OBJECTIVES
Levodopa-carbidopa-intestinal-gel (LCIG) infusion is an effective treatment for advanced PD with motor fluctuations. Polyneuropathy occurs as a complication in 10-15% of patients. We wanted to assess the frequency of polyneuropathy in Finnish advanced Parkinson's disease (PD) patients with continuous LCIG infusion, and the value of different clinical monitoring parameters during follow-up.
MATERIALS AND METHODS
Patient records of PD patients started on LCIG infusion at Helsinki University Hospital who received nerve conduction studies at baseline and 6 months after treatment initiation were reviewed for epidemiological information, mini mental state examination, baseline and 6 months' UPRDS-III, weight, body mass index, levodopa dose (LD), plasma homocysteine levels, folate, vitamin B6 and B12.
RESULTS
Out of 19 patients (n = 6 on B-vitamin substitution), two (10.5%) developed new-onset polyneuropathy after initiation of LCIG therapy (n = 0 with vitamin substitution). Neuropathy was associated with significant weight loss (BMI reduction > 1.5), but not with other monitoring parameters. Homocysteine rose significantly in patients not substituted with B-vitamin complex, but not in patients with B-vitamin substitution. Homocysteine changes correlated with LD changes in the absence of vitamin B substitution. After oral B-vitamin substitution, both patients' polyneuropathy remained electrophysiologically and clinically stable.
CONCLUSIONS
Rates of polyneuropathy in Finnish PD patients with LCIG treatment are comparable to previous studies. Patients' weight should be included in regular follow up monitoring and can be used for patient self-monitoring. Vitamin B substitution appears to reduce coupling between levodopa dose and homocysteine and may be useful to prevent polyneuropathy related to LCIG.
Topics: Antiparkinson Agents; Carbidopa; Gels; Humans; Levodopa; Parkinson Disease; Polyneuropathies
PubMed: 34758207
DOI: 10.1002/brb3.2408 -
British Journal of Pharmacology Feb 19741 The absorption, tissue distribution, and metabolism of [(14)C]-O-methyldopa were compared with those of [(14)C]-L-DOPA after oral administration to rats.2 Total...
1 The absorption, tissue distribution, and metabolism of [(14)C]-O-methyldopa were compared with those of [(14)C]-L-DOPA after oral administration to rats.2 Total radioactivity in the plasma and brain of rats treated with [(14)C]-O-methyldopa was significantly higher (2 fold and 30-50 fold, respectively) than that of rats treated with [(14)C]-L-DOPA.3 Total radioactivity in the gut washings and intestinal tissue 2 h after oral administration was significantly higher in rats treated with [(14)C]-L-DOPA than in rats treated with [(14)C]-O-methyldopa. The reverse was observed in the stomach tissues.4 Peripheral metabolism of [(14)C]-O-methyldopa was much lower than that of [(14)C]-L-DOPA; the major metabolite of [(14)C]-O-methyldopa in the plasma is L-DOPA, whereas L-DOPA is mainly metabolized to phenylcarboxylic acids.
Topics: Administration, Oral; Animals; Brain Chemistry; Carbon Radioisotopes; Dihydroxyphenylalanine; Intestines; Male; Methyldopa; Phenylacetates; Rats; Stomach
PubMed: 4425764
DOI: 10.1111/j.1476-5381.1974.tb08570.x -
British Medical Journal Aug 1974Twenty patients are described in whom liver damage appeared to be directly related to the administration of methyldopa. Sixteen had hepatitic syndromes from which they...
Twenty patients are described in whom liver damage appeared to be directly related to the administration of methyldopa. Sixteen had hepatitic syndromes from which they recovered on stopping methyldopa; four of these patients had recurrences of jaundice after a second course of the drug. Features suggestive of active chronic hepatitis were found in two patients. There were two deaths attributed to methyldopa, one of these being in a patient with pre-existing undiagnosed macronodular cirrhosis.
Topics: Adult; Aged; Alanine Transaminase; Alkaline Phosphatase; Aspartate Aminotransferases; Autopsy; Bilirubin; Chemical and Drug Induced Liver Injury; Eosinophils; Female; Humans; Hypertension; Jaundice; Liver; Liver Diseases; Male; Methyldopa; Middle Aged; Necrosis; Organ Size; Recurrence
PubMed: 4414663
DOI: 10.1136/bmj.3.5930.545 -
British Journal of Clinical Pharmacology Jun 19821 The anti-hypertensive effects of labetalol have been compared and contrasted with other groups of anti-hypertensive drugs in this review of the published literature. 2... (Comparative Study)
Comparative Study Review
1 The anti-hypertensive effects of labetalol have been compared and contrasted with other groups of anti-hypertensive drugs in this review of the published literature. 2 The data show that the pharmacological and haemodynamic profile of labetalol in man is distinctly different from that of other specific anti-hypertensive agents; namely the properties of competitive alpha-and beta-adrenoceptor blockade leading to haemodynamic effects of reduced blood pressure and peripheral vascular resistance with little accompanying changes in resting heart rate or cardiac output. 3 The anti-hypertensive effects of labetalol are dose related. In fixed dose comparative studies equivalent anti-hypertensive effects to those of labetalol have been shown for individual drugs of the beta-adrenoceptor-blocking and diuretic groups. In dose titration studies, equivalent anti-hypertensive effects at given doses of labetalol have been demonstrated for drugs of the following types: beta-adrenoceptor blockers, beta-blockers plus diuretics, methyldopa, adrenergic neurone blockers and the combination of beta-blockers plus a peripheral vasodilator. 4 Comparing side-effect liabilities, it is clear that quantitatively labetalol produces no greater burden of side-effects than drugs of the beta-adrenoceptor-blocking group. Qualitative differences, however, do exist; in particular, symptomatic postural hypotension is dose related and is more likely to occur when excessive doses (greater than 2 g daily) are used.
Topics: Adrenergic beta-Antagonists; Antihypertensive Agents; Diuretics; Drug Therapy, Combination; Ethanolamines; Hemodynamics; Humans; Hydralazine; Hypertension; Labetalol; Methyldopa
PubMed: 6124265
DOI: 10.1111/j.1365-2125.1982.tb01888.x -
Molecules (Basel, Switzerland) May 2023Levodopa (L-DOPA) treatment, combined with the administration of dopa-decarboxylase inhibitors (DDCIs), is still the most effective symptomatic treatment of Parkinson's...
Development and Validation of a New LC-MS/MS Bioanalytical Method for the Simultaneous Determination of Levodopa, Levodopa Methyl Ester, and Carbidopa in Human Plasma Samples.
Levodopa (L-DOPA) treatment, combined with the administration of dopa-decarboxylase inhibitors (DDCIs), is still the most effective symptomatic treatment of Parkinson's disease (PD). Although its efficacy in the early stage of the disease has been confirmed, its complex pharmacokinetics (PK) increases the variability of the intra-individual motor response, thus amplifying the risk of motor/non-motor fluctuations and dyskinesia. Moreover, it has been demonstrated that L-DOPA PK is strongly influenced by several clinical, therapeutic, and lifestyle variables (e.g., dietary proteins). L-DOPA therapeutic monitoring is therefore crucial to provide personalized therapy, hence improving drug efficacy and safety. To this aim, we have developed and validated an ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method to quantify L-DOPA, levodopa methyl ester (LDME), and the DDCI carbidopa in human plasma. The compounds were extracted by protein precipitation and samples were analyzed with a triple quadrupole mass spectrometer. The method showed good selectivity and specificity for all compounds. No carryover was observed, and dilution integrity was demonstrated. No matrix effect could be retrieved; intra-day and inter-day precision and accuracy values met the acceptance criteria. Reinjection reproducibility was assessed. The described method was successfully applied to a 45-year-old male patient to compare the pharmacokinetic behavior of an L-DOPA-based medical treatment involving commercially available extracts and an LDME/carbidopa (100/25 mg) formulation.
Topics: Male; Humans; Middle Aged; Levodopa; Carbidopa; Tandem Mass Spectrometry; Chromatography, Liquid; Reproducibility of Results
PubMed: 37298741
DOI: 10.3390/molecules28114264 -
Journal of Neurology May 2021Levodopa-Carbidopa Intrajejunal gel (LCIG) infusion is an effective intervention for people with advanced Parkinson's disease (PD). Although age may not be a limiting...
OBJECTIVES
Levodopa-Carbidopa Intrajejunal gel (LCIG) infusion is an effective intervention for people with advanced Parkinson's disease (PD). Although age may not be a limiting factor for LCIG implant, no data are available on late elderly PD (LE-PD) subjects. In this cross-sectional, we aimed to demonstrate if older age may impact on quality of life (QoL), motor and non-motor symptoms severity, and profile of side effects in PD treated with LCIG.
METHODS
Out of 512 PD subjects treated with LCIG at 9 Italian PD centers, we selected 25 LE-PD defined as age ≥ 80 years at last follow-up who were available to attend the study visit. Twenty-five PD patients (Control-PD, defined as age < 75 years at last follow-up) matched to LE-PD by disease and LCIG duration served as control group. The following motor and non-motor variables were ascertained: quality of life (PDQ-8), time spent in ON, wearing-off Questionnaire, Unified PD Rating Scale, freezing of gait questionnaire, Parkinson's disease sleep scale-2, Non Motor Symptoms Scale (NMSS), and MOCA.
RESULTS
No statistically significant differences were found between LE-PD and Control-PD on PDQ-8 and several motor and non-motor variables. LE-PD had less frequent and milder impulsive-compulsive behaviors and milder dyskinesia. At multivariable regression, worse quality of life was associated with UPDRS-III and NMSS scores but not to age at study visit and age at LICG implant. Rate of adverse effects was similar in both groups. Drop-out rate calculated in the whole PD cohort was comparable between the two groups.
CONCLUSION
Our data provide evidence that valuable LCIG infusion might be achieved in late elderly PD.
Topics: Aged; Aged, 80 and over; Antiparkinson Agents; Carbidopa; Cross-Sectional Studies; Drug Combinations; Gait Disorders, Neurologic; Gels; Humans; Italy; Levodopa; Parkinson Disease; Quality of Life
PubMed: 33354739
DOI: 10.1007/s00415-020-10356-x -
American Journal of Obstetrics &... May 2024Despite major advances in the pharmacologic treatment of hypertension in the nonpregnant population, treatments for hypertension in pregnancy have remained largely...
The "Preeclampsia and Hypertension Target Treatment" study: a multicenter prospective study to evaluate the effectiveness of the antihypertensive therapy based on maternal hemodynamic findings.
BACKGROUND
Despite major advances in the pharmacologic treatment of hypertension in the nonpregnant population, treatments for hypertension in pregnancy have remained largely unchanged over the years. There is recent evidence that a more adequate control of maternal blood pressure is achieved when the first given antihypertensive drug is able to correct the underlying hemodynamic disorder of the mother besides normalizing the blood pressure values.
OBJECTIVE
This study aimed to compare the blood pressure control in women receiving an appropriate or inappropriate antihypertensive therapy following the baseline hemodynamic findings.
STUDY DESIGN
This was a prospective multicenter study that included a population of women with de novo diagnosis of hypertensive disorders of pregnancy. A noninvasive assessment of the following maternal parameters was performed on hospital admission via Ultrasound Cardiac Output Monitor before any antihypertensive therapy was given: cardiac output, heart rate, systemic vascular resistance, and stroke volume. The clinician who prescribed the antihypertensive therapy was blinded to the hemodynamic evaluation and used as first-line treatment a vasodilator (nifedipine or alpha methyldopa) or a beta-blocker (labetalol) based on his preferences or on the local protocols. The first-line pharmacologic treatment was retrospectively considered hemodynamically appropriate in either of the following circumstances: (1) women with a hypodynamic profile (defined as low cardiac output [≤5 L/min] and/or high systemic vascular resistance [≥1300 dynes/second/cm]) who were administered oral nifedipine or alpha methyldopa and (2) women with a hyperdynamic profile (defined as normal or high cardiac output [>5 L/min] and/or low systemic vascular resistances [<1300 dynes/second/cm]) who were administered oral labetalol. The primary outcome of the study was to compare the occurrence of severe hypertension between women treated with a hemodynamically appropriate therapy and women treated with an inappropriate therapy.
RESULTS
A total of 152 women with hypertensive disorders of pregnancy were included in the final analysis. Most women displayed a hypodynamic profile (114 [75.0%]) and received a hemodynamically appropriate treatment (116 [76.3%]). The occurrence of severe hypertension before delivery was significantly lower in the group receiving an appropriate therapy than in the group receiving an inappropriately treated (6.0% vs 19.4%, respectively; P=.02). Moreover, the number of women who achieved target values of blood pressure within 48 to 72 hours from the treatment start was higher in the group who received an appropriate treatment than in the group who received an inappropriate treatment (70.7% vs 50.0%, respectively; P=.02).
CONCLUSION
In pregnant individuals with de novo hypertensive disorders of pregnancy, a lower occurrence of severe hypertension was observed when the first-line antihypertensive agent was tailored to the correct maternal hemodynamic profile.
Topics: Humans; Female; Pregnancy; Antihypertensive Agents; Prospective Studies; Adult; Hemodynamics; Pre-Eclampsia; Labetalol; Cardiac Output; Nifedipine; Vascular Resistance; Methyldopa; Blood Pressure; Hypertension, Pregnancy-Induced; Treatment Outcome; Heart Rate; Stroke Volume; Vasodilator Agents
PubMed: 38574856
DOI: 10.1016/j.ajogmf.2024.101368 -
European Journal of Neurology Apr 2021Recent data suggest that imbalances in the composition of the gut microbiota (GM) could exacerbate the progression of Parkinson disease (PD). The effects of levodopa...
BACKGROUND AND PURPOSE
Recent data suggest that imbalances in the composition of the gut microbiota (GM) could exacerbate the progression of Parkinson disease (PD). The effects of levodopa (LD) have been poorly assessed, and those of LD-carbidopa intestinal gel (LCIG) have not been evaluated so far. The aim of this study was to identify the effect of LD and LCIG, in particular, on the GM and metabolome.
METHODS
Fecal DNA samples from 107 patients with a clinical diagnosis of PD were analyzed by next-generation sequencing of the V3 and V4 regions of the 16S rRNA gene. PD patients were classified in different groups: patients on LCIG (LCIG group, n = 38) and on LD (LD group, n = 46). We also included a group of patients (n = 23) without antiparkinsonian medicaments (Naïve group). Fecal metabolic extracts were evaluated by gas chromatography mass spectrometry.
RESULTS
The multivariate analysis showed a significantly higher abundance in the LCIG group of Enterobacteriaceae, Escherichia, and Serratia compared to the LD group. Compared to the Naïve group, the univariate analysis showed a reduction of Blautia and Lachnospirae in the LD group. Moreover, an increase of Proteobacteria, Enterobacteriaceae, and a reduction of Firmicutes, Lachnospiraceae, and Blautia was found in the LCIG group. No significant difference was found in the multivariate analysis of these comparisons. The LD group and LCIG group were associated with a metabolic profile linked to gut inflammation.
CONCLUSIONS
Our results suggest that LD, and mostly LCIG, might significantly influence the microbiota composition and host/bacteria metabolism, acting as stressors in precipitating a specific inflammatory intestinal microenvironment, potentially related to the PD state and progression.
Topics: Antiparkinson Agents; Carbidopa; Drug Combinations; Gastrointestinal Microbiome; Gels; Humans; Levodopa; Metabolome; Parkinson Disease; RNA, Ribosomal, 16S
PubMed: 33185912
DOI: 10.1111/ene.14644