vasopressin receptor antagonist

WordNet

1. a drug that neutralizes or counteracts the effects of another drug
2. a muscle that relaxes while another contracts; "when bending the elbow the triceps are the antagonist"
3. hormone secreted by the posterior pituitary gland (trade name Pitressin) and also by nerve endings in the hypothalamus; affects blood pressure by stimulating capillary muscles and reduces urine flow by affecting reabsorption of water by kidney tubules (同)antidiuretic_hormone, ADH, Pitressin
4. a cellular structure that is postulated to exist in order to mediate between a chemical agent that acts on nervous tissue and the physiological response

PrepTutorEJDIC

1. 対立する人,敵対者,競争相手(opponent)
2. =sense organ / 受信装置

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/02/02 19:33:59」(JST)

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A vasopressin receptor antagonist (VRA) is an agent which interferes with action at the vasopressin receptors. Most commonly VRAs are used in the treatment of hyponatremia, especially in patients with congestive heart failure, liver cirrhosis or SIADH.

Types

Tetracyclines

Demeclocycline, a tetracycline antibiotic, is sometimes used to block the action of vasopressin in the kidney in hyponatremia due to inappropriately high secretion of vasopressin (SIADH), when fluid restriction has failed.

Vaptans

A new class of medication, the "vaptan" drugs, act by inhibiting the action of vasopressin on its receptors (V_1A, V_1B and V₂). These receptors have a variety of functions, with the V_1A and V₂ receptors are expressed peripherally and involved in the modulation of blood pressure and kidney function respectively, while the V_1A and V_1B receptors are expressed in the central nervous system. V_1A is expressed in many regions of the brain, and has been linked to a variety of social behaviors in humans and animals.

The vaptan class of drugs contains a number of compounds with varying selectivity, several of which are either already in clinical use or in clinical trials as of 2009.

Unselective (mixed V_1A/V₂)

• Conivaptan

V_1A selective (V₁RA)

• Relcovaptan

V_1B selective (V₃RA)

• Nelivaptan

V₂ selective (V₂RA)

• Lixivaptan
• Mozavaptan
• Satavaptan
• Tolvaptan

Uses of Vasopressin receptor antagonists

Hyponatremia

V₂R antagonists have become a mainstay of treatment for euvolemic (i.e., SIADH, postoperative hyponatremia) and hypervolemic hyponatremia (i.e., CHF and cirrhosis). V₂RAs predictably cause aquaresis leading to increased [Na⁺] in majority of patients with hyponatremia due to SIADH, CHF, and cirrhosis. The optimum use of VRAs has not yet been determined, but some predictions can be made with reasonable certainty. For hyponatremia in hospitalized patients, who are unable to take medication orally or for those in whom a more rapid correction of hyponatremia is desired, conivaptan (V₁/V₂R antagonist) will likely be the preferred agent. Selective V₂R antagonists such as tolvaptan, lixivaptan etc. will likely be useful in patients for whom oral therapy is suitable and for more chronic forms of hyponatremia.

Congestive heart failure

Neurohormonal activation characteristic of CHF, including increased renin, angiotensin, aldosterone, and catecholamines, contributes to progression of CHF. It has been suggested that cardiovascular mortality may be reduced by selective V₂RA such as tolvaptan in the higher risk group with kidney function impairment or severe congestive findings. But until FDA indication is granted for use in CHF with or without accompanying hyponatremia, VRAs are not recommended in patients with CHF.

Cirrhosis

V₂RA may be particularly beneficial in the treatment of patients with advanced liver cirrhosis and ascites. Blockade of V₂R will induce an effective aquaresis and inhibition of V₂-mediated vasodilation. This aquaresis, in combination with a diuresis, may provide a potential therapy for patients with resistant ascites. V₂ receptor antagonism increases plasma vasopressin concentration, which may cause unopposed hyperstimulation of the vasoconstrictor V₁ receptor. Given the potential hyperstimulation of V₁R, V₂RA may have additional secondary preventative benefits in patients with cirrhosis through a reduction in portal pressure and a decreased risk of variceal bleeding.

Polycystic kidney disease

Polycystin defects increase intracellular cAMP, secondary messenger for vasopressin acting at V₂R, leading to cyst development. cAMP-dependent genes promote fluid secretion into developing renal cysts and increase cell proliferation. Studies in several animal models of polycystic kidney disease have shown a reduction in kidney size and cyst volume after treatment with specific V₂ receptor antagonist. Full scale therapeutic trials of V₂RAs in patients with autosomal dominant polycystic kidney disease are currently ongoing.

Nephrogenic diabetes insipidus

Congenital nephrogenic diabetes insipidus (NDI) may result from V₂R or aquaporin-2 (AQP2) mutations. Exogenously administered V₂R antagonists can bind to misfolded intracellular V₂R, and improve transport of V₂R to the cell membrane. Clinical studies in patients with X-linked NDI showed that the selective V₁R antagonist relcovaptan (SR49059, Sanofi-Aventis) significantly increased urine osmolality and decreased 24-hour urine flow. Thus V₁R and/or V₂R antagonists may serve as molecular chaperones to mitigate misfolding defects in selected patients with type 2 NDI.

References

UpToDate Contents

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• 1. 低ナトリウム血症の治療：抗利尿ホルモン不適合分泌（SIADH）症候群およびreset osmostat症候群 treatment of hyponatremia syndrome of inappropriate antidiuretic hormone secretion siadh and reset osmostat
• 2. 成人における低ナトリウム血症の治療の概要 overview of the treatment of hyponatremia in adults
• 3. 肝硬変患者における低ナトリウム血症 hyponatremia in patients with cirrhosis
• 4. 心不全患者における低ナトリウム血症 hyponatremia in patients with heart failure
• 5. 利尿剤の作用機序 mechanism of action of diuretics

English Journal

• Safety of add-on tolvaptan in patients with furosemide-resistant congestive heart failure complicated by advanced chronic kidney disease: a sub-analysis of a pharmacokinetics/ pharmacodynamics study.

• Tominaga N, Kida K, Matsumoto N, Akashi YJ, Miyake F, Kimura K, Shibagaki Y.
• Clinical nephrology.Clin Nephrol.2015 Jul;84(7):29-38. doi: 10.5414/CN108457.
• BACKGROUND: Treatment of congestive heart failure (CHF) with loop diuretics, such as furosemide, may be associated with complications, including worsening renal function and metabolic or electrolyte disturbances. Coadministration of tolvaptan, a selective vasopressin V2 receptor antagonist, can amel
• PMID 25997504

• Oral vasopressin receptor antagonist tolvaptan in right heart failure due to pulmonary hypertension.

• Tamura Y1, Kimura M2, Takei M2, Ono T2, Kuwana M3, Satoh T4, Fukuda K2, Humbert M5.
• The European respiratory journal.Eur Respir J.2015 Jul;46(1):283-6. doi: 10.1183/09031936.00044915. Epub 2015 Apr 30.
• PMID 25929949

Japanese Journal

• バソプレッシンV2アンタゴニストと心不全 (内分泌) -- (臨床分野での進歩)

• 佐藤 直樹
• Annual review. 糖尿病・代謝・内分泌 2012(-) (-), 230-233, 2012-00-00
• NAID 40019175031

• Correction of Hyponatremia by Tolvaptan Before Left Ventricular Assist Device Implantation

• Imamura Teruhiko,Kinugawa Koichiro,Shiga Taro,Kato Naoko,Endo Miyoko,Inaba Toshiro,Maki Hisataka,Hatano Masaru,Yao Atsushi,Hirata Yasunobu,Nishimura Takashi,Kyo Shunei,Ono Minoru,Nagai Ryozo
• International Heart Journal 53(6), 391-393, 2012
• … Tolvaptan, an oral vasopressin-2-receptor antagonist, has been previously reported to improve congestion and correct hyponatremia through increased excretion of free water. …
• NAID 130002528818

Related Links

• Vasopressin receptor antagonist - Wikipedia, the free encyclopedia

A vasopressin receptor antagonist (VRA) is an agent which interferes with action at the vasopressin receptors. Most commonly VRAs are used in the treatment of hyponatremia, especially in patients with congestive heart failure, liver cirrhosis ...

• Therapeutic potential of vasopressin receptor antagonists.

Therapeutic potential of vasopressin receptor antagonists. Ali F, Guglin M, Vaitkevicius P, Ghali JK. Heart Failure Program, Wayne State University, Detroit, Michigan, USA. Arginine vasopressin (AVP) is a neuropeptide hormone that plays an ...

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