Effects of Antithrombotic and Results of Drug Screening
Josef Hladovec in Antithrombotic Drugs in Thrombosis Models, 2020
There exists apparently the multiplicity of effects mentioned already with other drugs. Provided we support a “monistic” theory we could forcibly attempt to reduce all these activities to one common for all situations, or we can simply accept that this multiplicity of effects is a matter of fact. The monistic theory could operate, for example, with the prostaglandin theory, but why then is the effect of aspirin so different? Or else we could suppose the existence of some vague mechanism such as a “membrane” effect caused by some physicochemical changes in the membrane properties. The drug unquestionably has many activities other than antithrombotic; it is a uricosuric, to some extent an antiphlogistic, it affects some immune reactions, arrhythmias, etc. For the time being, it may be concluded that the mechanism decisive for its antithrombotic activity is unknown, but that the interference with the interaction platelets-vessel wall or even with other surfaces may be important with both components influenced relatively more or less according to the actual situation.
Classifications
Fazal-I-Akbar Danish, Ahmed Ehsan Rabbani in Pharmacology in 7 Days for Medical Students, 2018
Drugs for chronic goutDrugs which increase excretion of uric acid (uricosuric agents)Aspirin (in high doses)OxyphenbutazonePhenylbutazoneProbenecidSulfinpyrazoneDrugs which decrease synthesis of uric acid (xanthine oxidase inhibitors)Allopurinol
Purine and urate metabolism
Martin Andrew Crook in Clinical Biochemistry & Metabolic Medicine, 2013
Increasing the renal excretion of urate with uricosuric drugs, such as probenecid or sulfinpyrazone. These drugs may be effective if renal function is normal, but are less so if there is renal glomerular dysfunction. Fluid intake is usually kept high. Low doses of most uricosuric drugs reduce urate secretion; they are rarely used unless allopurinol is contraindicated.
Advances in pharmacotherapies for hyperuricemia
Published in Expert Opinion on Pharmacotherapy, 2023
Federica Piani, Davide Agnoletti, Claudio Borghi
As seen in the previous paragraphs, hyperuricemia may occur from ‘overproduction’ or ‘underexcretion.’ The ‘underexcretion’ type is the most common form of hyperuricemia and is mainly caused by a reduced renal secretion of uric acid. Uric acid is readily filtered, and up to 90% is reabsorbed in the proximal tubular cells by the apical transporters URAT1 and OAT4, and the basolateral GLUT9. Furthermore, uric acid can also be secreted in variable amounts into the proximal tubular lumen by the apical transporters ABCG2, NPT1 and NPT4, GLUT9, and the basolateral OAT1 and OAT3 [13]. The uricosuric agents act on the proximal tubule of the kidney inhibiting uric acid reabsorption and/or increasing uric acid secretion. Uricosuric drugs are second-line agents indicated in refractory hyperuricemia in combination with XO inhibitors, or in patients who cannot tolerate XO inhibitors [59].
Effect of Curcumin on Serum Urate in Asymptomatic Hyperuricemia: A Randomized Placebo-Controlled Trial
Published in Journal of Dietary Supplements, 2021
Pannipa Bupparenoo, Rattapol Pakchotanon, Pongthorn Narongroeknawin, Paijit Asavatanabodee, Sumapa Chaiamnuay
Three types of drugs are currently used in practice to lower the SU level. These include uricostatic (allopurinol and febuxostat), uricosuric (probenecid, benzbromarone, sulfinpyrazone, and lesinurad), and uricolytic drugs (rasburicase and plegoticase). According to recommendation of the Thai Rheumatism Association, the first-line drug is allopurinol (Thai Rheumatism Association 2012), which inhibits xanthine oxidase, resulting in decreasing urate production. However, allopurinol-related severe cutaneous drug reaction was reported at 0.1% to 0.4%, leading to a high mortality rate of 30%. There were reports of allopurinol-induced recurrent meningoencephalitis, acute febrile neutrophilic dermatosis, and severe cholestatic liver failure (Baker and Schumacher 2010; Strilchuk et al. 2019). On the other hand, febuxostat has a high cost and is inaccessible in some circumstances. This drug also has a similar incidence of skin rashes to allopurinol and may cause elevation of liver enzymes (Strilchuk et al. 2019). In addition, uricosuric agents have limitations to use in patients with chronic kidney disease or preexisting uric acid stone. Finally, uricolytic drugs are not available in Thailand. Therefore, there is undoubtedly a treatment gap in the management of gout. A safe and lower-cost drug that can reduce SU is needed to fill this gap.
Safety and tolerability of available urate-lowering drugs: a critical review
Published in Expert Opinion on Drug Safety, 2019
Larysa Strilchuk, Federica Fogacci, Arrigo Fg Cicero
At the best of the current available evidence, XO-inhibitor administration is the first choice to treat hyperuricemia and gout. Besides effectiveness in reducing SU levels, antioxidant effects of allopurinol (at high doses) and febuxostat and their ability to improve endothelial function have been already shown in patients with chronic heart failure and type 2 diabetes, with a usually acceptable safety profile. Recent evidence, however, supports a relevant role also for uricosuric drugs such as lesinurad, whose efficacy and safety profile seems to be optimal. On the other side, we yet need more long-term data on safety and clinical risk of pharmacological interaction of the available SU lowering drugs, in particular in specific subgroup of patients such as elderly and very elderly, patients in secondary prevention for cardiovascular disease and the ones affected by different degrees of chronic renal failure. All these data will allow the physician to prescribe a patient-tailored SU lowering treatment able to minimize the eventual safety risk while maximizing its efficacy. To sum up, approved urate-lowering agents are usually well tolerated, but the physician must always know the list of the most often side effects, because as the Latin saying goes, ‘Praemonitus, praemunitus’ (forewarned is forearmed).
Related Knowledge Centers
- Contraindication
- Hyperuricosuria
- Proximal Tubule
- Uric Acid
- Urine
- Medication
- Drug
- Blood Plasma
- Kidney
- Kidney Stone Disease