Hydrochlorothiazide¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ As a diuretic, hydrochlorothiazide inhibits active chloride reabsorption at the early distal tubule via the Na-Cl cotransporter, resulting in an increase in the excretion of sodium, chloride, and water. Thiazides like hydrochlorothiazide also inhibit sodium ion transport across the renal tubular epithelium through binding to the thiazide sensitive sodium-chloride transporter. This results in an increase in potassium excretion via the sodium-potassium exchange mechanism. The antihypertensive mechanism of hydrochlorothiazide is less well understood although it may be mediated through its action on carbonic anhydrases in the smooth muscle or through its action on the large-conductance calcium-activated potassium (KCa) channel, also found in the smooth muscle. Losartan¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ Losartan and its longer acting active metabolite (E-3174) interfere with the binding of angiotensin II to the angiotensin II AT1-receptor by, themselves, binding reversibly to the receptors in vascular smooth muscle and the adrenal gland. As angiotensin II is a vasoconstrictor, which also stimulates the synthesis and release of aldosterone, blockage of its effects results in decreases in systemic vascular resistance. Neither Losartan or its metabolite inhibit the angiotensin converting enzyme, other hormone receptors, or ion channels. Potassium¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ Potassium is the major cation (positive ion) inside animal cells, while sodium is the major cation outside animal cells. The concentration differences of these charged particles causes a difference in electric potential between the inside and outside of cells, known as the membrane potential. The balance between potassium and sodium is maintained by ion pumps in the cell membrane. The cell membrane potential created by potassium and sodium ions allows the cell generate an action potential?”a "spike" of electrical discharge. The ability of cells to produce electrical discharge is critical for body functions such as neurotransmission, muscle contraction, and heart function. Potassium is also an essential mineral needed to regulate water balance, blood pressure and levels of acidity.
Pharmacology
Hydrochlorothiazide¿¡ ´ëÇÑ Pharmacology Á¤º¸ Thiazides such as hydrochlorothiazide promote water loss from the body (diuretics). They inhibit Na+/Cl- reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. Thiazides are often used to treat hypertension, but their hypotensive effects are not necessarily due to their diuretic activity. Thiazides have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue. Losartan¿¡ ´ëÇÑ Pharmacology Á¤º¸ Losartan is the first of a class of antihypertensive agents called angiotensin II (AG II) receptor antagonists. It is, along with its longer acting active metabolite (E-3174), a specific and selective AT1 receptor antagonist. Losartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor found in many tissues, (e.g., vascular smooth muscle, adrenal gland). Potassium¿¡ ´ëÇÑ Pharmacology Á¤º¸ Not Available
Hydrochlorothiazide¿¡ ´ëÇÑ Absorption Á¤º¸ 50-60% Losartan¿¡ ´ëÇÑ Absorption Á¤º¸ Well absorbed, the systemic bioavailability of losartan is approximately 33% Potassium¿¡ ´ëÇÑ Absorption Á¤º¸ Not Available
Hydrochlorothiazide¿¡ ´ëÇÑ Biotransformation Á¤º¸ Hydrochlorothiazide is not metabolized. Losartan¿¡ ´ëÇÑ Biotransformation Á¤º¸ Hepatic. Oxidation of the 5-hydroxymethyl group on the imidazole ring results in the active metabolite of losartan.
Toxicity
Hydrochlorothiazide¿¡ ´ëÇÑ Toxicity Á¤º¸ The most common signs and symptoms observed are those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis. If digitalis has also been administered, hypokalemia may accentuate cardiac arrhythmias. The oral LD50 of hydrochlorothiazide is greater than 10 g/kg in the mouse and rat. Losartan¿¡ ´ëÇÑ Toxicity Á¤º¸ Hypotension and tachycardia; Bradycardia could occur from parasympathetic (vagal) stimulation, LD50= 1000 mg/kg (orally in rat) Potassium¿¡ ´ëÇÑ Toxicity Á¤º¸ Not Available
Drug Interactions
Hydrochlorothiazide¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Amantadine The diuretic increases the adverse effect of amantadineDeslanoside Possible electrolyte variations and arrhythmiasDigitoxin Possible electrolyte variations and arrhythmiasDigoxin Possible electrolyte variations and arrhythmiasLithium The thiazide diuretic increases serum levels of lithiumDofetilide Increased risk of cardiotoxicity and arrhythmiasDiazoxide Significant hyperglycemic effect Losartan¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Amiloride Increased risk of hyperkaliemiaDrospirenone Increased risk of hyperkaliemiaPotassium Increased risk of hyperkaliemiaSpironolactone Increased risk of hyperkaliemiaTriamterene Increased risk of hyperkaliemiaIndomethacin Indomethacin decreases the effect of losartanLithium Losartan increases serum levels of lithiumRifampin Rifampin decreases the effect of losartan Potassium¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Amiloride Increased risk of hyperkaliemiaBenazepril Increased risk of hyperkaliemiaCandesartan Increased risk of hyperkaliemiaCaptopril Increased risk of hyperkaliemiaCilazapril Increased risk of hyperkaliemiaDrospirenone Increased risk of hyperkaliemiaEnalapril Increased risk of hyperkaliemiaEplerenone This association presents an increased risk of hyperkaliemiaEprosartan Increased risk of hyperkaliemiaForasartan Increased risk of hyperkaliemiaFosinopril Increased risk of hyperkaliemiaIrbesartan Increased risk of hyperkaliemiaLisinopril Increased risk of hyperkaliemiaLosartan Increased risk of hyperkaliemiaMoexipril Increased risk of hyperkaliemiaPerindopril Increased risk of hyperkaliemiaPolystyrene sulfonate Antagonism of actionQuinapril Increased risk of hyperkaliemiaRamipril Increased risk of hyperkaliemiaSaprisartan Increased risk of hyperkaliemiaSpirapril Increased risk of hyperkaliemiaSpironolactone Increased risk of hyperkaliemiaTasosartan Increased risk of hyperkaliemiaTelmisartan Increased risk of hyperkaliemiaTrandolapril Increased risk of hyperkaliemiaTriamterene Increased risk of hyperkaliemiaValsartan Increased risk of hyperkaliemia
Hydrochlorothiazide¿¡ ´ëÇÑ Description Á¤º¸ A thiazide diuretic often considered the prototypical member of this class. It reduces the reabsorption of electrolytes from the renal tubules. This results in increased excretion of water and electrolytes, including sodium, potassium, chloride, and magnesium. It has been used in the treatment of several disorders including edema, hypertension, diabetes insipidus, and hypoparathyroidism. [PubChem] Losartan¿¡ ´ëÇÑ Description Á¤º¸ An antagonist of angiotensin type 1 receptor with antihypertensive activity due to the reduced pressor effect of angiotensin II. [PubChem] Potassium¿¡ ´ëÇÑ Description Á¤º¸ Potassium is the major cation (positive ion) inside animal cells, while sodium is the major cation outside animal cells. The concentration differences of these charged particles causes a difference in electric potential between the inside and outside of cells, known as the membrane potential. The balance between potassium and sodium is maintained by ion pumps in the cell membrane. The cell membrane potential created by potassium and sodium ions allows the cell generate an action potential?”a "spike" of electrical discharge. The ability of cells to produce electrical discharge is critical for body functions such as neurotransmission, muscle contraction, and heart function. Potassium is also an essential mineral needed to regulate water balance, blood pressure and levels of acidity.
Drug Category
Hydrochlorothiazide¿¡ ´ëÇÑ Drug_Category Á¤º¸ Antihypertensive AgentsDiureticsSodium Chloride Symporter Inhibitors Losartan¿¡ ´ëÇÑ Drug_Category Á¤º¸ Angiotensin II Receptor AntagonistsAngiotensin II Type 1 Receptor BlockersAnti-Arrhythmia AgentsAntiarrhythmic AgentsAntihypertensive Agents
Smiles String Canonical
Hydrochlorothiazide¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸ NS(=O)(=O)C1=C(Cl)C=C2NCNS(=O)(=O)C2=C1 Losartan¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸ CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=C1)C1=CC=CC=C1C1=NNN=N1 Potassium¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸ Not Available
Smiles String Isomeric
Hydrochlorothiazide¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸ NS(=O)(=O)C1=C(Cl)C=C2NCNS(=O)(=O)C2=C1 Losartan¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸ CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=C1)C1=CC=CC=C1C1=NNN=N1 Potassium¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸ Not Available
InChI Identifier
Hydrochlorothiazide¿¡ ´ëÇÑ InChI_Identifier Á¤º¸ InChI=1/C7H8ClN3O4S2/c8-4-1-5-7(2-6(4)16(9,12)13)17(14,15)11-3-10-5/h1-2,10-11H,3H2,(H2,9,12,13)/f/h9H2 Losartan¿¡ ´ëÇÑ InChI_Identifier Á¤º¸ InChI=1/C22H23ClN6O/c1-2-3-8-20-24-21(23)19(14-30)29(20)13-15-9-11-16(12-10-15)17-6-4-5-7-18(17)22-25-27-28-26-22/h4-7,9-12,30H,2-3,8,13-14H2,1H3,(H,25,26,27,28)/f/h27H Potassium¿¡ ´ëÇÑ InChI_Identifier Á¤º¸ Not Available
Chemical IUPAC Name
Hydrochlorothiazide¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸ 6-chloro-1,1-dioxo-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine-7-sulfonamide Losartan¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸ [2-butyl-5-chloro-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Potassium¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸ Not Available