Americangeriatrics.org

G2 Sica DA, Gehr TW. Triamterene and the kidney. Nephron 1989;51(4):454-461. Summary (continued)
Summary (continued)
Sica 1989
Search methodology / Databases searched
Pharmacokinetics in disease states (continued)
Renal effects
Biliary excretion also significantly retarded in the Urinary sediment abnormalities
Urine sediment characterized by deeply pigmented Pharmacokinetics
-suggests hepatic disease alters the pharmaco- brown casts and abundant hyaline casts containing The bioavailability is formulation-dependent and it is kinetics by a number of different pathophysiologic and/or coated with birefringent crystals important to distinguish the formulation prior to the determination of either its relative or absolute bio- These abnormalities were present in acid (pH <6.0) TA accumulation is negligible in renal failure since its most important route of elimination is nonrenal These abnormalities disappeared within 48 hours of Triamterene undergoes a significant first pass The predominant route of elimination of OH-TA ester is renal and substantial accumulation of this metabolite TA solubility increases in alkaline urine OH-TA ester progressively accumulates in renal Although the presence of urinary sediment p-OH-TA extremely active pharmacologically abnormalities appears to be common among -if total urinary excretion of TA and it main metabolite individuals receiving TA, their exact clinical relevance There is limited correlation between creatinine clearance and the renal clearance of either TA or OH- Nephrolithiasis
This significant first-pass effect for TA with It has been proposed that TA promotes stone growth subsequent formation of a biologically active by- A number of age-related abnormalities occur in the product alters the perception of limited systemic -concentrations formed are composed almost -elderly subjects achieve higher concentrations of TA entirely of the drug and/or its metabolites -TA crystals provide a nucleus upon which other The renal clearance of TA (220 ml/min) exceeds that -the time to maximum concentration for OH-TA ester of OH-TA ester (180 ml/min) in part due to the fact is prolonged, suggesting the hydroxylation capacity -TA may increase the size of existing stones by that 55% of TA is protein-bound while OH-TA ester is virtue of being laid down as lamina or incrustations on -systemic clearance of both TA and OH-TA ester Since the renal clearance of TA and OH-TA ester -relates in part to renal impairment accompanying These stones typically contain not only pure TA but exceeds the glomerular filtration rate, both also significant amounts of its primary metabolites compounds must undergo net tubular secretion. Pharmacodynamics
Pharmacokinetics in disease states
TA inhibits passive sodium transport resulting in TA and its metabolites fail to promote crystal Alterations in TA pharmacokinetics occur in impaired movement of potassium from cell to lumen nucleation, growth or aggregation in crystal systems TA produces these effects when aldosterone is physiologically suppressed or when it is completely In patients with cirrhosis, the elimination half life for TA is not routinely incorporated into developing TA has only mild antihypertensive properties when administered alone or when utilized in a -TA and its metabolites are assimilated into existing complementary fashion with thiazide-type diuretics stones or stone nidi by adsorption to the protein -not clear whether increase in elimination half-life is The major pharmacodynamic consideration for TA paralleled by an exaggeration of its pharmacologic relates to its dose proportionally relative to potassium TA participates in the stone building process supplements and other potassium-sparing diuretics in dependent upon its mass amount and urine normalizing extra- and intracellular potassium concentration as long as an appropriate incrustation There is no consensus concerning dose proportionality for potassium-sparing agents
Page 2 Sica 1989
Summary (continued)
Summary (continued)
Comments
Renal effects (continued)
Renal effects (continued)
The following patients may potentially experience an adverse Renal failure
Renal failure (continued)
TA associated with transient declines in renal function as well as with the development of frank acute renal failure Reports supporting intrinsic nephrotoxicity of TA independent of -patients with renal and/or hepatic dysfunction Use of TA in the management of edematous conditions (alone or -intrarenal obstruction secondary to crystalline deposits Physicians should be aware of these adverse effects and -hemodynamic events which accompany the coadministration of -can result in substantial deterioration in renal function thus monitor patients closely if they prescribe TA -may prove to have very slow and limited reversibility -appears that certain renal hemodynamic adaptations unique to edematous conditions might be unfavorably affected by the -TA rarely implicated alone or in combination with HCT -if implicated, occurred with routinely prescribed doses of TA or -renal blood flow is frequently diminished -renal blood flow becomes susceptible to additional, sometimes precipitous declines if other indirect vasoconstrictors -only 1 case report suggests that intracellular sequestration of are added to the system or vasodilators are removed from the TA could exert a direct toxic effect on tubules Significant deterioration in renal function attributed to TA have -a number of potassium-sparing diuretics have been implicated occurred in subjects simultaneously ingesting NSAIDs in the development of acute renal failure (including TA-HCT) -common theme has been its occurrence in the elderly with a -events would seem to have been additive and/or synergistic for Studies of the effects of TA on the renin-angiotensin-aldosterone -volume contraction secondary to the thiazide component and renal prostaglandin systems as potential mediators/ -TA administered to normal volunteers or essential Reports supporting intrinsic nephrotoxicity of TA independent of hypertensives predictably stimulates both plasma renin activity -increase in renal prostaglandin production is abolished when and if TA is administered in combination with NSAIDs These observations suggest that combined therapy with TA and an NSAID carries a real risk for the development of renal failure Indices of renal function employed as markers for TA’s -this phenomenon is unpredictable and thus has been poorly -it undoubtedly relates to the limited bioavailability of certain TA formulations as well as to the fact that it is unknown whether the -observed declines in glomerular filtration rate and renal blood NSAID use would seem to presage an increased chance of this flow have occurred in the dose range of 100-200 mg/d (with or without concurrent HCT)

Conclusion:
Although the overall incidence of nephrotoxicity is quite low, certain patient populations presumably would have an increased risk of developing an adverse renal effect from TA.

Source: http://www.americangeriatrics.org/files/documents/beers/Sica1989.pdf

mms.businesswire.com

Otsuka Pharmaceutical Co., Ltd. is a global healthcare company with the corporate philosophy: 'Otsuka-people creating new products for better health worldwide.' Otsuka researches, develops, manufactures and markets innovative and original products, QUICK FACTS with a focus on pharmaceutical products for the treatment of diseases and nutraceutical products for the maintenance of everyday

Antikonvulsiva

PSYCHIATRIE NEUROLOGIE DERMATOLOGIE AUGENHEILKUNDE HALS-NASEN-OHREN-HEILKUNDE RECHTSMEDIZIN PHARMAKOLOGIE UMWELTMEDIZIN Copyright © 2005 Michael Schütz, Michael Berger, Fachschaft Medizin München Das Werk einschließlich aller seiner Teile ist urheberrechtlich geschützt. Jede Verwertung außerhalb der engen Grenzen des Urheberrechtsgesetzes ist ohne Zustimmung

© 2010-2014 Pdf Medical Search