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British Journal of Clinical Pharmacology 19801. A survey is given of the various aspects of centrally acting hypotensive drugs. The majority of centrally acting hypotensive agents act by way of central... (Review)
Review
1. A survey is given of the various aspects of centrally acting hypotensive drugs. The majority of centrally acting hypotensive agents act by way of central alpha-adrenoceptors, probably located in the pontomedullary region of the brain. These central receptors are stimulated by clonidine, guanfacine and various related compounds, and also by alpha-methylnoradrenaline, generated in vivo upon biotransformation of alpha-methyldopa within the brain. The stimulation of the alpha-adrenoceptors induces a decrease in peripheral sympathetic tone and thus a fall in arterial blood pressure and bradycardia. 2. The possibility that presynaptic alpha-adrenoceptors in the brain are involved in the central hypotensive action of clonidine, guanfacine and related compounds is discussed. Also, the possible involvement of central histaminergic and cholinergic receptors in central hypotensive effects is reviewed. 3. Various experimental compounds with a central hypotensive effect different from that of clonidine and related drugs are mentioned. 4. Finally, it is pointed out that the hypotensive effects of various beta-sympatholytic drugs and of prazosin are probably not of central origin.
Topics: Adrenergic alpha-Antagonists; Adrenergic beta-Antagonists; Antihypertensive Agents; Blood Pressure; Brain; Clonidine; Guanfacine; Guanidines; Heart Rate; Humans; Imidazoles; Methyldopa; Phenylacetates; Prazosin; Receptors, Adrenergic; Receptors, Adrenergic, alpha; Receptors, Cholinergic; Yohimbine
PubMed: 6104975
DOI: 10.1111/j.1365-2125.1980.tb04899.x -
PloS One 2023To characterize the drug-related problems (DRPs) in high-risk pregnant women with hypertension and gestational diabetes mellitus according to frequency, type, cause, and... (Observational Study)
Observational Study
OBJECTIVE
To characterize the drug-related problems (DRPs) in high-risk pregnant women with hypertension and gestational diabetes mellitus according to frequency, type, cause, and factors associated with their occurrence in the hospital setting.
METHODOLOGY
This is an observational, longitudinal, prospective study that included 571 hospitalized pregnant women with hypertension and gestational diabetes mellitus using at least one medication. DRPs were classified according to the Classification for Drug-Related Problems (PCNE V9.00). In addition to descriptive statistics, a univariate and multivariate logistic regression model was employed to determine the factors associated with the DRPs.
RESULTS
A total of 873 DRPs were identified. The most frequent DRPs were related to therapeutic ineffectiveness (72.2%) and occurrence of adverse events (27.0%) and the main drugs involved were insulins and methyldopa. These were followed in the first five days of treatment by: the ineffectiveness of insulin (24.6%), associated with underdosage (12.9%) or insufficient frequency of administration (9.5%) and methyldopa associated with the occurrence of adverse reactions (40.2%) in the first 48h. Lower maternal age (OR 0.966, 95% CI 0.938-0.995, p = 0.022), lower gestational age (OR 0.966, 95% CI 0.938-0.996, p = 0.026), report of drug hypersensitivity (OR 2.295, 95% CI 1.220-4.317, p = 0.010), longer treatment time (OR 1.237, 95% CI: 1.147-1.333, p = 0.001) and number of prescribed medications (OR 1.211, 95% CI: 0.240-5.476, p = 0.001) were risk factors for occurrence of DRPs.
CONCLUSION
DRPs are frequent in pregnant women with hypertension and gestational diabetes mellitus, and they are mainly related to therapeutic ineffectiveness and the occurrence of adverse events.
Topics: Pregnancy; Humans; Female; Diabetes, Gestational; Drug-Related Side Effects and Adverse Reactions; Prospective Studies; Methyldopa; Hospitals; Hypertension; Insulin
PubMed: 37027363
DOI: 10.1371/journal.pone.0284053 -
CNS Drugs Feb 2021Infusion of levodopa-carbidopa intestinal gel (LCIG; also designated carbidopa-levodopa enteral suspension) for 16 hours is a standard treatment for patients with... (Review)
Review
Infusion of levodopa-carbidopa intestinal gel (LCIG; also designated carbidopa-levodopa enteral suspension) for 16 hours is a standard treatment for patients with advanced Parkinson's disease, and clinical observations suggest that 24-hour LCIG infusion may further reduce symptoms. This review provides practical advice on the management of patients transitioning to 24-hour LCIG infusion. We review available clinical data for 24-hour infusion and discuss adjustments to dosing, recommendations for monitoring, and management of patient concerns, based on our clinical experience. Data from multiple studies suggest that LCIG may improve non-motor symptoms. Although few studies have examined 24-hour LCIG infusion, available data indicate that certain patients may benefit from around-the-clock treatment. Studies of 24-hour LCIG infusion are limited by small sample sizes and open-label study designs, which may hamper translation to clinical practice. In our experience, we have found that patients may benefit from 24-hour infusion when reductions in nocturnal symptoms and improvements to quality of sleep are needed. Levodopa-unresponsive freezing of gait or poorly controlled troublesome dyskinesias may also indicate a patient may benefit from 24-hour infusion. Dose adjustments, especially of the nocturnal rate, are typically necessary and, as with 16-hour infusion, patients should be monitored for autonomic dysfunction; overnight wearing off symptoms; weight changes; fluctuations in plasma levels of vitamins B/B, folate, and homocysteine; changes in sleep patterns; or worsening of hallucinations, delusions, and/or nightmares. Available data and our clinical experience suggest that 24-hour LCIG may be warranted among selected patients who have poorly controlled nocturnal fluctuations or early morning "off" symptoms.
Topics: Antiparkinson Agents; Carbidopa; Drug Administration Schedule; Drug Combinations; Drug Monitoring; Gels; Humans; Levodopa; Parkinson Disease; Time Factors
PubMed: 33582982
DOI: 10.1007/s40263-020-00782-w -
Ideggyogyaszati Szemle Jan 2019For the treatment of advanced Parkinson's disease the deep brain stimulation (DBS) and the levodopa/carbidopa intestinal gel (LCIG) therapies are available in Hungary.... (Review)
Review
For the treatment of advanced Parkinson's disease the deep brain stimulation (DBS) and the levodopa/carbidopa intestinal gel (LCIG) therapies are available in Hungary. Although they may have similar impact on the health-related quality of life and disabilities associated with the disease, they have different indications, and inclusion- and exclusion criteria. Consequently, the patient population treated with DBS and LCIG may be different. In the present review, the authors try to help the process of selection of the optimal device-aided therapy for the patients with advanced Parkinson's disease.
Topics: Antiparkinson Agents; Carbidopa; Deep Brain Stimulation; Drug Combinations; Gels; Humans; Hungary; Levodopa; Parkinson Disease; Quality of Life
PubMed: 30785241
DOI: 10.18071/isz.72.0005 -
Journal of Neural Transmission (Vienna,... Nov 2023This article provides an overview of the various screening and selection tools which have been developed over the past 25 years to identify patients with Parkinson's... (Review)
Review
This article provides an overview of the various screening and selection tools which have been developed over the past 25 years to identify patients with Parkinson's disease (PD) possibly eligible for device-aided therapies (DATs). For the available screening tools, we describe the target therapies (subtypes of DAT), development methods, validation data, and their use in clinical practice. In addition, the historical background and potential utility of these screening tools are discussed. The challenges in developing and validating these tools are also addressed, taking into account the differences in population, the local health care organization, and resource availability.
Topics: Humans; Parkinson Disease; Antiparkinson Agents; Carbidopa; Levodopa; Drug Combinations; Gels
PubMed: 37500937
DOI: 10.1007/s00702-023-02656-z -
Cells Apr 2022The catechol-O-methyltransferase inhibitors entacapone and opicapone prolong the efficacy of conventional oral levodopa/dopa decarboxylase inhibitor formulations through...
The catechol-O-methyltransferase inhibitors entacapone and opicapone prolong the efficacy of conventional oral levodopa/dopa decarboxylase inhibitor formulations through an increase in levodopa plasma bioavailability. Catechol-O-methyltransferase inhibitors influence the homocysteine metabolism associated with levodopa/dopa decarboxylase application. The objectives of this study were to compare the impact of additional single-day entacapone or opicapone intake on the pharmacokinetic plasma behaviour of levodopa, 3-O-methyldopa and total homocysteine in 15 Parkinson's disease patients, with concomitant scoring of motor symptoms, under standardized conditions. The patients received opicapone plus two doses of 100 mg levodopa/carbidopa and, one week later, two doses of levodopa/carbidopa/entacapone or vice versa. Levodopa, 3-O-methyldopa and total homocysteine were determined with reversed-phase high-performance liquid chromatography. Levodopa bioavailability and its maximum concentration were higher with opicapone. The computed peak-to-trough difference was lower after the second levodopa administration with entacapone. The fluctuation index of levodopa did not differ between both conditions. 3-O-methyldopa decreased on both days. Homocysteine levels did not significantly vary between both conditions. A significant homocysteine decrease occurred with entacapone, but not with opicapone. Motor behaviour improved with entacapone, but not with opicapone. Opicapone baseline scores were significantly better, and thus the potential for the improvement in motor symptoms was lower compared with the entacapone condition. The higher levodopa bioavailability with opicapone suggests that it is more efficacious than entacapone for the amelioration of "off" phenomena in fluctuating patients when co-administered with a levodopa/dopa decarboxylase inhibitor regimen. Both compounds prevented an increase in homocysteine, which is a metabolic marker for an impaired capacity in the performance of methylation processes.
Topics: Antiparkinson Agents; Aromatic Amino Acid Decarboxylase Inhibitors; Carbidopa; Catechol O-Methyltransferase; Catechol O-Methyltransferase Inhibitors; Catechols; Homocysteine; Humans; Levodopa; Nitriles; Oxadiazoles; Parkinson Disease
PubMed: 35563817
DOI: 10.3390/cells11091511 -
Clinical Cardiology 1980The effect of the cardioselective beta-adrenoreceptor blocking compound, metoprolol, was compared with methyldopa in the long-term management of hypertension. Thirty...
The effect of the cardioselective beta-adrenoreceptor blocking compound, metoprolol, was compared with methyldopa in the long-term management of hypertension. Thirty patients given metoprolol and twenty-six given methyldopa were treated for 2 years. The maximum dose of metoprolol was 200 mg twice daily (average 308 mg) and of methyldopa 1,000 mg twice daily (average 1,120 mg). Blood pressure was similar at entry to the study (metoprolol 177/110 mmHg and methyldopa 181/111 mmHg). After 2 years of treatment the blood pressure levels were again similar (metoprolol 149/91 mmHg and methyldopa 148/91 mmHg). Erect pressures were lower in the methyldopa group, but there was no difference between supine and erect blood pressure levels in those on metoprolol. At an exercise load of 300 and 600 kpm the increase in systolic pressure was significantly less in the metoprolol group. The proportional increase in systolic and diastolic pressure in response to a standardized stress situation was reduced by treatment with metroprolol but not by methyldopa. Tolerance to therapy did not develop in either group. The main difference between metoprolol and methyldopa was in the incidence and severity of side effects. Four patients were withdrawn from the metoprolol group. Seventeen were withdrawn from the methyldopa mainly because of side effects including drowsiness, depression, skin rash, and impotence. Six patients on metoprolol and seventeen on methyldopa continued on therapy although side effects were present. It is concluded that metoprolol and methyldopa lower blood pressure to the same extent, but metoprolol is advantageous because of a lower incidence of side effects.
Topics: Adult; Aged; Female; Humans; Hypertension; Male; Methyldopa; Metoprolol; Middle Aged; Propanolamines; Stress, Mechanical
PubMed: 7379374
DOI: 10.1002/clc.4960030106 -
Praxis Dec 2013Parkinson's disease belongs to the most prevalent neurodegenerative disorders and manifests both with motor and non-motor symptoms. Symptomatic treatment of this... (Review)
Review
Parkinson's disease belongs to the most prevalent neurodegenerative disorders and manifests both with motor and non-motor symptoms. Symptomatic treatment of this disorder became more multifaceted over the past years: besides classical dopaminergic drugs and physiotherapy, novel invasive escalation treatment strategies became gold standard in many countries. On the other hand, non-motor symptoms significantly impacts quality of life in many patients which necessitates initiation of adequate therapy.
Topics: Antiparkinson Agents; Carbidopa; Catechol O-Methyltransferase Inhibitors; Combined Modality Therapy; Deep Brain Stimulation; Dopamine Agonists; Drug Combinations; Humans; Levodopa; Monoamine Oxidase Inhibitors; Neurologic Examination; Parkinson Disease; Physical Therapy Modalities
PubMed: 24326048
DOI: 10.1024/1661-8157/a001505 -
Clinical NeuropharmacologyLevodopa (LD) administered with dopa decarboxylase inhibitor is predominantly metabolized in the periphery by catechol- O -methyltransferase (COMT) to 3- O -methyldopa... (Randomized Controlled Trial)
Randomized Controlled Trial
Opicapone Pharmacokinetics and Effects on Catechol- O -Methyltransferase Activity and Levodopa Pharmacokinetics in Patients With Parkinson Disease Receiving Carbidopa/Levodopa.
OBJECTIVES
Levodopa (LD) administered with dopa decarboxylase inhibitor is predominantly metabolized in the periphery by catechol- O -methyltransferase (COMT) to 3- O -methyldopa (3-OMD). Catechol- O -methyltransferase inhibition can improve treatment outcomes by decreasing variability in circulating LD concentrations. Opicapone is a once-daily COMT inhibitor approved in the US adjunctive to carbidopa (CD)/LD in patients with Parkinson disease experiencing "OFF" episodes. This study aimed to evaluate the pharmacokinetics and pharmacodynamics of once-daily opicapone 50 mg adjunctive to CD/LD in patients with stable Parkinson disease.
METHODS
Once-daily opicapone 50 mg was administered the evenings of days 1 to 14. Participants were randomized to receive CD/LD (25/100 mg) every 3 or 4 hours (Q3H or Q4H). Participants received Q3H or Q4H CD/LD on days 1, 2, and 15 and their usual CD/LD regimen on other days. Serial blood samples were collected to determine plasma opicapone, LD, and 3-OMD concentrations and erythrocyte soluble COMT (S-COMT) activity. The effects of opicapone on S-COMT, LD, and 3-OMD were assessed. Mean (SD) values are presented.
RESULTS
Sixteen participants were enrolled. At steady-state (day 14), opicapone Cmax (peak plasma concentration) and AUC 0-last (area under the curve-time curve) were 459 ± 252 ng/mL and 2022 ± 783 ng/mL·h, respectively. Maximum COMT inhibition was 83.4 ± 4.9% of baseline on day 14. After opicapone administration, LD total AUC, peak concentration, and trough concentration increased; peak-to-trough fluctuation index decreased. Correspondingly, 3-OMD total AUC, peak concentration, and trough concentration decreased.
CONCLUSIONS
Adding once-daily opicapone 50 mg to LD resulted in marked and extended COMT inhibition, which increased systemic exposure to LD. These changes translated into higher trough concentrations and decreased peak-to-trough fluctuations for LD.
Topics: Humans; Levodopa; Carbidopa; Parkinson Disease; Antiparkinson Agents; Catechol O-Methyltransferase Inhibitors; Catechol O-Methyltransferase
PubMed: 36688497
DOI: 10.1097/WNF.0000000000000538 -
Journal of Parkinson's Disease 2023Tablet formulations of Parkinson's disease (PD) medications may become ineffective at managing motor fluctuations in advanced PD. The liquid formulation, levodopa... (Review)
Review
BACKGROUND
Tablet formulations of Parkinson's disease (PD) medications may become ineffective at managing motor fluctuations in advanced PD. The liquid formulation, levodopa carbidopa ascorbic acid solution, or LCAS, is an effective and inexpensive treatment for motor fluctuations however it remains underutilized.
OBJECTIVE
We compared the efficacy of LCAS with tablet formulations and Duodopa jejunal infusion through routine inpatient management using hourly functional status measures, the Timed Up and Go Test (TUG). The TUG differentiates between 'off' and 'on' states and quantifies motor fluctuations.
METHODS
Experienced nurses used the TUG times and functional observations recorded hourly throughout the waking day to optimize the LCAS hourly dose and the Duodopa flow rate over several days. When patients were stabilized on each of the interventions, the TUG measures were then recorded to compare the outcomes of the interventions.
RESULTS
Twenty-six participants had TUG times recorded while on one or more of the formulations: 19 had TUG times recorded on tablets, 23 on LCAS and 10 on Duodopa. TUG times on LCAS and Duodopa were significantly faster compared to tablets (p < 0.0001, p = 0.001 respectively). Severity of dyskinesia was not significantly different between formulations (p = 0.35). Daily dose for the three formulations and the hourly doses for LCAS and Duodopa did not differ significantly (p = 0.37, p = 0.19 respectively).
CONCLUSION
This report demonstrated the efficacy of LCAS for improving motor complications and its equivalency with Duodopa jejunal infusion.
Topics: Humans; Carbidopa; Levodopa; Parkinson Disease; Antiparkinson Agents; Postural Balance; Time and Motion Studies; Drug Combinations
PubMed: 37092237
DOI: 10.3233/JPD-225117