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CHD Genetics Part II
Published in Mark C Houston, The Truth About Heart Disease, 2023
CYP4A11. In terms of salt sensitivity and resistant hypertension, one of the most important is CYP4A11 which relates to sodium and water reabsorption and the role of the epithelial sodium channel (ENaC) function in the kidney. These patients have avid reabsorption of sodium in the kidney tubules from the ENaC which increases the blood volume, blood pressure, and risk for CHD. This type of hypertension is best treated with the drug Amiloride, which blocks the ENaC and results in a diuresis of salt and water to lower the blood pressure. Some of these patients may need a short- or long-term treatment with another type of diuretic, Indapamide.
Cardiovascular Drugs during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
No epidemiological studies regarding the use of amiloride in pregnant women are published. No birth defects were noted among 12 infants exposed to amiloride during the first trimester in the Swedish Birth Defects Registry (Kallen, 2019). No increase in malformations in offspring of pregnant hamsters that received small doses of amiloride was found (Storch and Layton, 1973).
Prescribing for a first episode of affective psychosis
Published in Kathy J Aitchison, Karena Meehan, Robin M Murray, First Episode Psychosis, 2021
Kathy J Aitchison, Karena Meehan, Robin M Murray
Polyuria and a compensatory increased thirst are noted by about one-third of patients on lithium (lithium reduces the responsiveness of the distal tubule to antidiuretic hormone, and may occasionally cause a full-blown nephrogenic diabetes insipidus.247 This is a dose-related side-effect and, if troublesome, may therefore be managed by reducing the dose, if possible. For patients in whom a reduction in dose is not appropriate, amiloride may be used with caution. No deterioration in glomerular filtration rate occurs in the majority of patients whose lithium levels are monitored regularly; occasional cases of chronic renal failure have been attributed to lithium, which may be a rare idiosyncratic reaction to lithium. Histological change in the kidney may be found in up to 20% of patients.
Liddle syndrome misdiagnosed as primary aldosteronism is caused by inaccurate aldosterone-rennin detection while a novel SCNN1G mutation is discovered
Published in Blood Pressure, 2022
Yaling Yang, Chenwei Wu, Duoduo Qu, Xinyue Xu, Lili Chen, Quanya Sun, Xiaolong Zhao
This 21-year-old female presented with repeated hypokalaemia and latent hypertension, poor response to spironolactone, gene mutation located in SCNN1G, c.1729 C > T, leading to the diagnosis of Liddle syndrome instead of primary aldosteronism. Treatment was switched to amiloride accordingly. Since pure amiloride tablets are not available in the domestic market [5]. compound amiloride hydrochloride one tablet daily was prescribed which contains amiloride hydrochloride 2.5 mg and hydrochlorothiazide 25 mg. Her BP decrease was noticed in 3 days, regularly measured 6 times daily, and her plasma potassium climbed to normal with 3.8 mmol/L. After 3 weeks’ treatment, the plasma potassium was 4.3 mmol/L without potassium supplement; BP decreased gradually and stabilised at 110–120/70–80mmHg.
A novel nonsense mutation in the β-subunit of the epithelial sodium channel causing Liddle syndrome
Published in Blood Pressure, 2021
Štěpán Mareš, Jan Filipovský, Kateřina Vlková, Martin Pešta, Václava Černá, Jaroslav Hrabák, Jitka Mlíková Seidlerová, Otto Mayer
When the diagnosis of LS is made early, organ complications may be prevented by adequate treatment. It is based on the administration of an ENaC blocker – either amiloride or triamterene. Restriction of salt intake can further enhance the effect of antihypertensives [1,10,27]. Other antihypertensive drugs are less effective. This also applies for spironolactone, which is used for resistant hypertension, since mutated ENaC is not sensitive to aldosterone [9,28]. Amiloride should also be considered in pregnant women with LS if first line treatment such as metyl-dopa, calcium channel blockers or labetalol fails to control BP. Although we lack randomised clinical trials, prescription of amiloride appears to be safe and effective in pregnancy [29]. Serum electrolytes should be monitored during treatment.
Electrolyte handling in the isolated perfused rat kidney: demonstration of vasopressin V2-receptor-dependent calcium reabsorption
Published in Upsala Journal of Medical Sciences, 2020
Krister Bamberg, Lena William-Olsson, Ulrika Johansson, Anders Arner, Judith Hartleib-Geschwindner, Johan Sällström
To further assess that the perfused kidney model replicates in vivo physiological responses, we assessed the response to ENaC inhibition by amiloride. Administration of amiloride caused a prompt decrease in sodium reabsorption accompanied by an increased potassium reabsorption. These are the expected effects of ENaC inhibition (30), which reduces potassium excretion by hyperpolarizing the principal cells in the collecting duct, thus reducing the electrochemical driving force for potassium extrusion into the lumen. ENaC inhibition will also lower the intracellular sodium concentration, thus reducing basolateral potassium entry through the Na-K-ATPase which also most likely contributes to the reduced potassium secretion (31). Given that both ENaC and TRPC3 are expressed in the principal cells (26,32), the normal response confirms that this nephron segment, where the proposed effects of AVP on calcium reabsorption occurs, is functional in this model. Fractional calcium reabsorption was higher in the DDAVP group both during control conditions and during amiloride treatment. The elevated calcium reabsorption by DDAVP supports the findings in the previous series and also indicates that the acute effect of DDAVP on calcium handling is independent of sodium transport through ENaC.