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Amipramidin

Amipramidin - General Information

A pyrazine compound inhibiting sodium reabsorption through sodium channels in renal epithelial cells. This inhibition creates a negative potential in the luminal membranes of principal cells, located in the distal convoluted tubule and collecting duct. Negative potential reduces secretion of potassium and hydrogen ions. Amipramidin is used in conjunction with diuretics to spare potassium loss. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p705)

 

Pharmacology of Amipramidin

Amipramidin, an antikaliuretic-diuretic agent, is a pyrazine-carbonyl-guanidine that is unrelated chemically to other known antikaliuretic or diuretic agents. It is an antihypertensive, potassium-sparing diuretic that was first approved for use in 1967 and helps to treat hypertension and congestive heart failure. The drug is often used in conjunction with thiazide or loop diuretics. Due to its potassium-sparing capacities, hyperkalemia (high blood potassium levels) are occasionally observed in patients taking amiloride. The risk is high in concurrent use of ACE inhibitors or spironolactone. Patients are also advised not to use potassium-containing salt replacements.

 

Amipramidin for patients

 

WARNINGS

Hyperkalemia

Like other potassium-conserving agents, amiloride may cause hyperkalemia (serum potassium levels greater than 5.5 mEq per liter) which, if uncorrected, is potentially fatal. Hyperkalemia occurs commonly (about 10%) when amiloride is used without a kaliuretic diuretic. This incidence is greater in patients with renal impairment, diabetes mellitus (with or without recognized renal insufficiency), and in the elderly. When MIDAMOR is used concomitantly with a thiazide diuretic in patients without these complications, the risk of hyperkalemia is reduced to about 1-2 percent. It is thus essential to monitor serum potassium levels carefully in any patient receiving amiloride, particularly when it is first introduced, at the time of diuretic dosage adjustments, and during any illness that could affect renal function.

The risk of hyperkalemia may be increased when potassium-conserving agents, including MIDAMOR, are administered concomitantly with an angiotensin-converting enzyme inhibitor. Warning signs or symptoms of hyperkalemia include paresthesias, muscular weakness, fatigue, flaccid paralysis of the extremities, bradycardia, shock, and ECG abnormalities. Monitoring of the serum potassium level is essential because mild hyperkalemia is not usually associated with an abnormal ECG.

When abnormal, the ECG in hyperkalemia is characterized primarily by tall, peaked T waves or elevations from previous tracings. There may also be lowering of the R wave and increased depth of the S wave, widening and even disappearance of the P wave, progressive widening of the QRS complex, prolongation of the PR interval, and ST depression.

Treatment of hyperkalemia: If hyperkalemia occurs in patients taking MIDAMOR, the drug should be discontinued immediately. If the serum potassium level exceeds 6.5 mEq per liter, active measures should be taken to reduce it. Such measures include the intravenous administration of sodium bicarbonate solution or oral or parenteral glucose with a rapid-acting insulin preparation. If needed, a cation exchange resin such as sodium polystyrene sulfonate may be given orally or by enema. Patients with persistent hyperkalemia may require dialysis.

Diabetes Mellitus

In diabetic patients, hyperkalemia has been reported with the use of all potassium-conserving diuretics, including MIDAMOR, even in patients without evidence of diabetic nephropathy. Therefore, MIDAMOR should be avoided, if possible, in diabetic patients and if it is used, serum electrolytes and renal function must be monitored frequently.

MIDAMOR should be discontinued at least three days before glucose tolerance testing.

Metabolic or Respiratory Acidosis

Antikaliuretic therapy should be instituted only with caution in severely ill patients in whom respiratory or metabolic acidosis may occur, such as patients with cardiopulmonary disease or poorly controlled diabetes. If MIDAMOR is given to these patients, frequent monitoring of acid-base balance is necessary. Shifts in acid-base balance alter the ratio of extracellular/intracellular potassium, and the development of acidosis may be associated with rapid increases in serum potassium levels.

 

Amipramidin Interactions

When amiloride HCl is administered concomitantly with an angiotensin-converting enzyme inhibitor, the risk of hyperkalemia may be increased. Therefore, if concomitant use of these agents is indicated because of demonstrated hypokalemia, they should be used with caution and with frequent monitoring of serum potassium.

Lithium generally should not be given with diuretics because they reduce its renal clearance and add a high risk of lithium toxicity. Read circulars for lithium preparations before use of such concomitant therapy.

In some patients, the administration of a non-steroidal anti-inflammatory agent can reduce the diuretic, natriuretic, and antihypertensive effects of loop, potassium-sparing and thiazide diuretics. Therefore, when MIDAMOR and non-steroidal anti-inflammatory agents are used concomitantly, the patient should be observed closely to determine if the desired effect of the diuretic is obtained. Since indomethacin and potassium-sparing diuretics, including MIDAMOR, may each be associated with increased serum potassium levels, the potential effects on potassium kinetics and renal function should be considered when these agents are administered concurrently.

 

Amipramidin Contraindications

Hyperkalemia

MIDAMOR should not be used in the presence of elevated serum potassium levels (greater than 5.5 mEq per liter).

Antikaliuretic Therapy or Potassium Supplementation

MIDAMOR should not be given to patients receiving other potassium-conserving agents, such as spironolactone or triamterene. Potassium supplementation in the form of medication, potassium-containing salt substitutes or a potassium-rich diet should not be used with MIDAMOR except in severe and/or refractory cases of hypokalemia. Such concomitant therapy can be associated with rapid increases in serum potassium levels. If potassium supplementation is used, careful monitoring of the serum potassium level is necessary.

Impaired Renal Function

Anuria, acute or chronic renal insufficiency, and evidence of diabetic nephropathy are contraindications to the use of MIDAMOR. Patients with evidence of renal functional impairment (blood urea nitrogen [BUN] levels over 30 mg per 100 mL or serum creatinine levels over 1.5 mg per 100 mL) or diabetes mellitus should not receive the drug without careful, frequent and continuing monitoring of serum electrolytes, creatinine, and BUN levels. Potassium retention associated with the use of an antikaliuretic agent is accentuated in the presence of renal impairment and may result in the rapid development of hyperkalemia.

Hypersensitivity

MIDAMOR is contraindicated in patients who are hypersensitive to this product.

 

Additional information about Amipramidin

Amipramidin Indication: For use as adjunctive treatment with thiazide diuretics or other kaliuretic-diuretic agents in congestive heart failure or hypertension.
Mechanism Of Action: Amipramidin works by inhibiting sodium reabsorption in the distal convoluted tubules and collecting ducts in the kidneys by binding to the amiloride-sensitive sodium channels. This promotes the loss of sodium and water from the body, but without depleting potassium. Amipramidin exerts its potassium sparing effect through the inhibition of sodium reabsorption at the distal convoluted tubule, cortical collecting tubule and collecting duct; this decreases the net negative potential of the tubular lumen and reduces both potassium and hydrogen secretion and their subsequent excretion. Amipramidin is not an aldosterone antagonist and its effects are seen even in the absence of aldosterone.
Drug Interactions: Benazepril Increased risk of hyperkaliemia
Candesartan Increased risk of hyperkaliemia
Captopril Increased risk of hyperkaliemia
Enalapril Increased risk of hyperkaliemia
Eplerenone The association presents an ncreased risk of hyperkaliemia
Eprosartan Increased risk of hyperkaliemia
Fosinopril Increased risk of hyperkaliemia
Irbesartan Increased risk of hyperkaliemia
Lisinopril Increased risk of hyperkaliemia
Losartan Increased risk of hyperkaliemia
Moexipril Increased risk of hyperkaliemia
Quinapril Increased risk of hyperkaliemia
Quinidine Decreases the antiarrhythmic effect of quinidine
Ramipril Increased risk of hyperkaliemia
Telmisartan Increased risk of hyperkaliemia
Trandolapril Increased risk of hyperkaliemia
Valsartan Increased risk of hyperkaliemia
Cilazapril Increased risk of hyperkaliemia
Dihydroquinidine barbiturate Decreases the antiarrhythmic effect of quinidine
Forasartan Increased risk of hyperkaliemia
Perindopril Increased risk of hyperkaliemia
Polystyrene sulfonate Antagonism of action
Potassium Increased risk of hyperkaliemia
Quinidine barbiturate Decreases the antiarrhythmic effect of quinidine
Saprisartan Increased risk of hyperkaliemia
Spirapril Increased risk of hyperkaliemia
Tasosartan Increased risk of hyperkaliemia
Food Interactions: Avoid drastic changes in dietary habit.
Avoid salt substitutes containing potassium.
Take with food to reduce irritation.
Avoid natural licorice.
Generic Name: Amiloride
Synonyms: Amiloridum [INN-Latin]; Amiloride hydrochloride hydrate; Amiloride hydrochloride; Amiloride HCL; Amilorida [INN-Spanish]; AMR; Amyloride
Drug Category: Diuretics
Drug Type: Small Molecule; Approved
Other Brand Names containing Amiloride: Amipramidin; Amipramizid; Amipramizide; Amiprazidine; Guanamprazin; Guanamprazine; Midamor;
Absorption: Readily absorbed following oral administration.
Toxicity (Overdose): No data are available in regard to overdosage in humans. The oral LD50 of amiloride hydrochloride (calculated as the base) is 56 mg/kg in mice and 36 to 85 mg/kg in rats, depending on the strain. The most likely signs and symptoms to be expected with overdosage are dehydration and electrolyte imbalance.
Protein Binding: Not Available
Biotransformation: Amiloride is not metabolized by the liver but is excreted unchanged by the kidneys.
Half Life: Plasma half-life varies from 6 to 9 hours.
Dosage Forms of Amipramidin: Tablet Oral
Chemical IUPAC Name: 3,5-diamino-6-chloro-N-(diaminomethylidene)pyrazine-2-carboxamide
Chemical Formula: C6H8ClN7O
Amiloride on Wikipedia: http://en.wikipedia.org/wiki/Amiloride
Organisms Affected: Humans and other mammals