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Hypertension
Published in Jahangir Moini, Matthew Adams, Anthony LoGalbo, Complications of Diabetes Mellitus, 2022
Jahangir Moini, Matthew Adams, Anthony LoGalbo
Malignant hypertension must be treated in an intensive care unit (ICU). The BP is slowly and continually reduced by using a short-acting titratable intravenous medication. Based on the involved target organ, drug choice and the method of BP reduction are varied. Usually, the goal is a 20%–25% reduction in mean arterial pressure over about 1 hour. Additional titration is used based on the patient’s symptoms. It is not necessary to achieve a normal BP quickly. First-line agents usually include fenoldopam, nitroprusside, labetalol, and nicardipine. Methyldopa, an aromatic-amino-acid decarboxylase inhibitor, is also used. Nitroglycerin used on its own is not as potent as these drugs. Oral drugs have varied onset and are difficult to titrate. Though short-acting nifedipine reduces BP quickly, it can cause potentially fatal cardiovascular and cerebrovascular events. Thiazide diuretics such as hydrochlorothiazide are also used. Cardiac glycosides include drugs such as digoxin.
Movement disorders
Published in Henry J. Woodford, Essential Geriatrics, 2022
The rationale for the use of levodopa is that it is converted to dopamine within the surviving neurons of the basal ganglia to help compensate for the loss of dopaminergic cells (giving dopamine would be ineffective because it cannot cross the blood-brain barrier). It is always given with a decarboxylase inhibitor (carbidopa or benserazide) to prevent excessive peripheral conversion of levodopa to dopamine, which would reduce cerebral availability and produce excessive adverse effects (mainly nausea, vomiting and orthostatic hypotension) (seeFigure 9.8).
Drug therapy
Published in Jeremy Playfer, John Hindle, Andrew Lees, Parkinson's Disease in the Older Patient, 2018
There is, however, a rule of thumb which – although crude – is practical, namely that the frailer the patient is, the more likely one is to initiate with levodopa rather than a dopamine agonist. In starting a patient on a dopamine agonist as initial therapy, it has to be recognised that most patients will require levodopa within the first two years. Combined preparations of levodopa and decarboxylase inhibitor are effective for symptom relief, easy to titrate, well tolerated and inexpensive. Dopamine agonists have the promise of reducing long-term motor complications but have slightly less efficacy and tolerability than levodopa and can require more complicated titration to achieve a therapeutic dose. They may, however, modify the disease process.93 They are significantly more expensive than levodopa. Given life expectancy and a reduced propensity to develop motor complications, with low doses of levodopa, most patients over 75 can avoid the long-term levodopa syndrome. Where there is any degree of frailty, co-morbidity or psychiatric complications, there is a strong argument for initiating treatment with levodopa.
Practical pearls to improve the efficacy and tolerability of levodopa in Parkinson’s disease
Published in Expert Review of Neurotherapeutics, 2022
Abhishek Lenka, Gianluca Di Maria, Guillaume Lamotte, Laxman Bahroo, Joseph Jankovic
As of now, there is insufficient evidence to prefer either of the dopa decarboxylase inhibitor above other. Studies in healthy individuals have reported differences in the pharmacokinetics of carbidopa and benserazide [39]. The latter has a rapid increase and decrease in its plasma concentration compared to carbidopa. This led to a speculation that benserazide/levodopa would possibly be ideal for patients requiring immediate treatment because of its higher maximum observed plasma concentration (Cmax) and stronger dopa decarboxylase inhibitory property. On the other hand, carbidopa/levodopa might be better suited for patients with motor complications, especially dyskinesias, as its pharmacokinetics is relatively stable [39]. A recent retrospective study suggested that, compared to benserazide/levodopa (1:4 formulation), carbidopa/levodopa (1:10 formulation) was associated with delayed onset of motor fluctuations [40]. However, due to lack of head-to-head comparison studies between benserazide/levodopa and carbidopa/levodopa at 1:4 formulation, there are no guidelines regarding the use of these two dopa decarboxylase inhibitors.
What are the main considerations when prescribing pharmacotherapy for Parkinson’s disease?
Published in Expert Opinion on Pharmacotherapy, 2022
MAO-B-I are generally well tolerated. They are less potent than dopamine agonists. They are applied with varying dosages even in a transdermal fashion [16]. Introduction of dopamine agonists and amantadine is generally performed cautiously and slowly. This kind of drug titration avoids or reduces onset of leg edema, nausea, and vertigo particularly in the case of dopamine agonists. Supplementation with the peripheral dopamine receptor blocker domperidone, if available, for amelioration of nausea, or i.e. midodrine for compensation of dopamine replacement induced orthostatic blood pressure, if reimbursed, counteracts these common frequent side effects of dopamine replacement. Application of peripheral acting COMT-I’s only makes sense in combination with L-dopa/dopa decarboxylase inhibitor formulations.
Targeting glucose metabolism to develop anticancer treatments and therapeutic patents
Published in Expert Opinion on Therapeutic Patents, 2022
Yan Zhou, Yizhen Guo, Kin Yip Tam
Benserazide [15,41] (1–8) is an approved drug in the UK for the treatment of Parkinson’s disease. It is a peripheral aromatic L-amino acid decarboxylase inhibitor and is often combined with levodopa in clinical practice. Li et al. used a structure-based virtual ligand screening method to screen the FDA-approved drug database and found that 1–8 was a selective HK2 inhibitor [42] (Enzyme inhibition IC50: 5.52 ± 0.17 μM). As a clinically used drug, 1–8 has clear pharmacokinetics, pharmacodynamics, and low toxicity, which greatly facilitates the development of 1–8 and its derivatives as anti-tumor drugs. Moreover, 1–8 was found to reduce the glucose uptake rate, lactate production, and intracellular ATP levels of cancer cells, as well as depolarize the cancer cell mitochondrial membrane potential leading to apoptosis. These results suggested 1–8 might be a very promising anticancer drug candidate.