Xipamide
Encyclopedia
Xipamide is a sulfonamide diuretic
drug marketed by Eli Lilly
under the trade names Aquaphor (in Germany) and Aquaphoril (in Austria). It is used for the treatment of oedema and hypertension
.
reabsorption in the distal convoluted tubule. This increases the osmolarity in the lumen, causing less water to be reabsorbed by the collecting ducts. This leads to increased urinary output. Unlike the thiazides, xipamide reaches its target from the peritubular side (blood side).
Additionally, it increases the secretion of potassium
in the distal tubule and collecting ducts. In high doses it also inhibits the enzyme carbonic anhydrase
which leads to increased secretion of bicarbonate and alkalizes the urine.
Unlike with thiazides, only terminal renal failure
renders xipamide ineffective.
One third of the dose is glucuronidized
, the rest is excreted directly through the kidney (1/3) and the faeces (2/3). The total plasma clearance is 30-40 ml/min. Xipamide can be filtrated by haemodialysis but not by peritoneal dialysis
.
The lowest effective dose is 5 mg. More than 60 mg have no additional effects.
Diuretic
A diuretic provides a means of forced diuresis which elevates the rate of urination. There are several categories of diuretics. All diuretics increase the excretion of water from bodies, although each class does so in a distinct way.- Medical uses :...
drug marketed by Eli Lilly
Eli Lilly and Company
Eli Lilly and Company is a global pharmaceutical company. Eli Lilly's global headquarters is located in Indianapolis, Indiana, in the United States...
under the trade names Aquaphor (in Germany) and Aquaphoril (in Austria). It is used for the treatment of oedema and hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
.
Mechanism of action
Like the structurally related thiazide diuretics, xipamide acts on the kidneys to reduce sodiumSodium
Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...
reabsorption in the distal convoluted tubule. This increases the osmolarity in the lumen, causing less water to be reabsorbed by the collecting ducts. This leads to increased urinary output. Unlike the thiazides, xipamide reaches its target from the peritubular side (blood side).
Additionally, it increases the secretion of potassium
Potassium
Potassium is the chemical element with the symbol K and atomic number 19. Elemental potassium is a soft silvery-white alkali metal that oxidizes rapidly in air and is very reactive with water, generating sufficient heat to ignite the hydrogen emitted in the reaction.Potassium and sodium are...
in the distal tubule and collecting ducts. In high doses it also inhibits the enzyme carbonic anhydrase
Carbonic anhydrase
The carbonic anhydrases form a family of enzymes that catalyze the rapid interconversion of carbon dioxide and water to bicarbonate and protons , a reversible reaction that occurs rather slowly in the absence of a catalyst...
which leads to increased secretion of bicarbonate and alkalizes the urine.
Unlike with thiazides, only terminal renal failure
Renal failure
Renal failure or kidney failure describes a medical condition in which the kidneys fail to adequately filter toxins and waste products from the blood...
renders xipamide ineffective.
Uses
Xipamide is used for- cardiac oedema caused by decompensation of heart failure
- renal oedema, chronic renal disease (but not with anuriaAnuriaAnuria means nonpassage of urine, in practice is defined as passage of less than 50 milliliters of urine in a day. Anuria is often caused by failure in the function of kidneys. It may also occur because of some severe obstruction like kidney stones or tumours. It may occur with end stage renal...
) - hepatic oedema caused by cirrhosisCirrhosisCirrhosis is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrosis, scar tissue and regenerative nodules , leading to loss of liver function...
- ascitesAscitesAscites is a gastroenterological term for an accumulation of fluid in the peritoneal cavity.The medical condition is also known as peritoneal cavity fluid, peritoneal fluid excess, hydroperitoneum or more archaically as abdominal dropsy. Although most commonly due to cirrhosis and severe liver...
- lymphoedema
- hypertension in combination with chronic renal disease
Pharmacokinetics
After oral administration, 20 mg of xipamide are resorbed quickly and reach the peak plasma concentration of 3 mg/l within an hour. The diuretic effect starts about an hour after administration, reaches it speak between the third and sixth hour, and lasts for nearly 24 hours.One third of the dose is glucuronidized
Glucuronidation
Glucuronidation is the addition of glucuronic acid to a substrate. Glucuronidation is often involved in xenobiotic metabolism of substances such as drugs, pollutants, bilirubin, androgens, estrogens, mineralocorticoids, glucocorticoids, fatty acid derivatives, retinoids, and bile acids...
, the rest is excreted directly through the kidney (1/3) and the faeces (2/3). The total plasma clearance is 30-40 ml/min. Xipamide can be filtrated by haemodialysis but not by peritoneal dialysis
Peritoneal dialysis
Peritoneal dialysis is a treatment for patients with severe chronic kidney disease. The process uses the patient's peritoneum in the abdomen as a membrane across which fluids and dissolved substances are exchanged from the blood...
.
Dosage
Initially 40 mg, it can be reduced to 10-20 mg to prevent a relapse.The lowest effective dose is 5 mg. More than 60 mg have no additional effects.
Adverse effects
- more than 1/10 of all patients
- hypokalaemia, which can lead to nausea, muscular weakness or cramps, and ECG abnormities
- 1/100 to 1/10
- hyponatraemia, which can lead to headache, nausea, drowsiness or confusion
- orthostatic hypotensionOrthostatic hypotensionOrthostatic hypotension, also known as postural hypotension, orthostasis, and colloquially as head rush or dizzy spell, is a form of hypotension in which a person's blood pressure suddenly falls when the person stands up or stretches. The decrease is typically greater than 20/10 mm Hg, and may be...
- initially increase of ureaUreaUrea or carbamide is an organic compound with the chemical formula CO2. The molecule has two —NH2 groups joined by a carbonyl functional group....
, uric acidUric acidUric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates such as ammonium acid urate. Uric acid is created when the body breaks down purine nucleotides. High blood concentrations of uric acid...
and creatinineCreatinineCreatinine is a break-down product of creatine phosphate in muscle, and is usually produced at a fairly constant rate by the body...
, wchich can lead to a goutGoutGout is a medical condition usually characterized by recurrent attacks of acute inflammatory arthritis—a red, tender, hot, swollen joint. The metatarsal-phalangeal joint at the base of the big toe is the most commonly affected . However, it may also present as tophi, kidney stones, or urate...
attack in predisposed patients
- 1/1000 to 1/10,000
- allergic reactions of the skin
- hyperlipidaemia
- less than 1/10,000
- haemorrhagic pancreatitisPancreatitisPancreatitis is inflammation of the pancreas. It occurs when pancreatic enzymes that digest food are activated in the pancreas instead of the small intestine. It may be acute – beginning suddenly and lasting a few days, or chronic – occurring over many years...
- acute interstitial nephritisInterstitial nephritisInterstitial nephritis is a form of nephritis affecting the interstitium of the kidneys surrounding the tubules...
- thrombocytopeniaThrombocytopeniaThrombocytopenia is a relative decrease of platelets in blood.A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. These limits are determined by the 2.5th lower and upper percentile, so values outside this range do not necessarily indicate disease...
, leucopenia
- haemorrhagic pancreatitis
Contraindications
- anuria
- praecoma and coma hepaticum
- hypovolemiaHypovolemiaIn physiology and medicine, hypovolemia is a state of decreased blood volume; more specifically, decrease in volume of blood plasma...
, hyponatremia, hypokalemia - hypercalcemia
- gout
- sulfonamideSulfonamide (medicine)Sulfonamide or sulphonamide is the basis of several groups of drugs. The original antibacterial sulfonamides are synthetic antimicrobial agents that contain the sulfonamide group. Some sulfonamides are also devoid of antibacterial activity, e.g., the anticonvulsant sultiame...
hypersensitivity - pregnancy, lactation period
Not recommended combinations
- Xipamide lowers the renal clearance of lithiumLithium pharmacologyLithium pharmacology refers to use of the lithium ion, Li+, as a drug. A number of chemical salts of lithium are used medically as a mood stabilizing drug, primarily in the treatment of bipolar disorder, where they have a role in the treatment of depression and particularly of mania, both acutely...
which can lead to lithium intoxication. (This interaction is classified as medium.)
Combinations requiring special precautions
The product information requests special precautions for these combinations:- The antihypertensive effect can be increased by ACE inhibitorACE inhibitorACE inhibitors or angiotensin-converting enzyme inhibitors are a group of drugs used primarily for the treatment of hypertension and congestive heart failure...
s, barbiturateBarbiturateBarbiturates are drugs that act as central nervous system depressants, and can therefore produce a wide spectrum of effects, from mild sedation to total anesthesia. They are also effective as anxiolytics, as hypnotics, and as anticonvulsants...
s, phenothiazinePhenothiazinePhenothiazine is an organic compound that occurs in various antipsychotic and antihistaminic drugs. It has the formula S2NH. This yellow tricyclic compound is soluble in acetic acid, benzene, and ether. The compound is related to the thiazine-class of heterocyclic compounds...
s, tricyclic antidepressantTricyclic antidepressantTricyclic antidepressants are heterocyclic chemical compounds used primarily as antidepressants. The TCAs were first discovered in the early 1950s and were subsequently introduced later in the decade; they are named after their chemical structure, which contains three rings of atoms...
s, alcoholAlcoholIn chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....
, etc. (Classified as minor.)
- NSAIDs can reduce the antihypertensive and diuretic effects. Xipamide increases the neurotoxicity of high doses of salicylates. (Classified as minor.)
- Toxicity of cardiac glycosideCardiac glycosideCardiac glycosides are drugs used in the treatment of congestive heart failure and cardiac arrhythmia. These glycosides are found as secondary metabolites in several plants, but also in some animals, such as the milkweed butterflies. -Function:...
s is increased due to hypokalemia and hypomagnesemiaHypomagnesemiaHypomagnesemia is an electrolyte disturbance in which there is an abnormally low level of magnesium in the blood. Usually a serum level less than 0.7 mmol/L is used as reference. The prefix hypo- means low . The middle 'magnes' refers to magnesium...
.(Classified as minor.)
- Antiarrhythmic agentAntiarrhythmic agentAntiarrhythmic agents are a group of pharmaceuticals that are used to suppress abnormal rhythms of the heart , such as atrial fibrillation, atrial flutter, ventricular tachycardia, and ventricular fibrillation....
s (classes Ia and III), phenothiazines and other antipsychotics increase the risk of torsade de pointes due to hypokalemia.
Interactions not included in the product information
- Xipamide can reduce the effect of antidiabetics. (Classified as minor.)