Pirolacton
Pirolacton Uses, Dosage, Side Effects, Food Interaction and all others data.
Pirolacton is a specific pharmacologic antagonist of aldosterone, acting primarily through competitive binding of receptors at the aldosterone-dependent sodium-potassium exchange site in the distal convoluted renal tubule. Pirolacton causes increased amounts of sodium and water to be excreted, while potassium is retained. Pirolacton acts both as a diuretic and as an antihypertensive drug by this mechanism. It may be given alone or with other diuretic agents which act more proximally in the renal tubule. Aldosterone interacts with a cytoplasmic mineralocorticoid receptor to enhance the expression of the Na+ K+ ATPase and the Na+ channel involved in a Na+ K+transport in the distal tubule . Pirolacton bind to this mineralcorticoid receptor, blocking the actions of aldosterone on gene expression. Aldosterone is a hormone; its primary function is to retain sodium and excrete potassium in the kidneys.
Originally spironolactone was only studied for its potassium sparing diuretic effect. Pirolacton competitively inhibits mineralocorticoid receptors in the distal convoluted tubule to promote sodium and water excretion and potassium retention.. Inhibition of this receptor leads to increased renin and aldosterone levels.
Pirolacton is structurally similar to progesterone and as a result is associated with progestogenic and antiandrogenic effects.
| Trade Name | Pirolacton |
| Availability | Prescription only |
| Generic | Spironolactone |
| Spironolactone Other Names | Espironolactona, Spironolactone, Spironolactonum, Spironolattone |
| Related Drugs | amlodipine, lisinopril, metoprolol, losartan, furosemide, carvedilol, hydrochlorothiazide, warfarin, Lasix, chlorthalidone |
| Type | |
| Formula | C24H32O4S |
| Weight | Average: 416.573 Monoisotopic: 416.202130202 |
| Protein binding | >90%. Canrenone is as much as 98% protein bound. |
| Groups | Approved |
| Therapeutic Class | Potassium-sparing diuretics, Potassium-sparing diuretics & Aldosterone antagonists |
| Manufacturer | |
| Available Country | Japan |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Pirolacton is used for Congestive heart failure, Hepatic cirrhosis with ascites and oedema, Nephrotic syndrome, Primary hyperaldosteronism, Essential hypertension, For the treatment of patients with hypokalemia
Pirolacton is a long-acting aldosterone antagonist. Pirolacton is a specific pharmacologic antagonist of aldosterone, acting primarily through competitive binding of receptors at the aldosterone dependent sodium-potassium exchange site in the distal convoluted renal tubule. Pirolacton causes increased amounts of sodium and water to be excreted, while potassium and magnesium is retained.
Pirolacton is also used to associated treatment for these conditions: Acne, Ascites, Congestive Heart Failure (CHF), Edema, High Blood Pressure (Hypertension), Hypokalemia, Idiopathic Hirsutism, Nephrotic Syndrome, Primary Hyperaldosteronism, Secondary hyperaldosteronism, Chronic heart failure with reduced ejection fraction (NYHA Class III), Chronic heart failure with reduced ejection fraction (NYHA Class IV), Idiopathic hyperaldosteronism
How Pirolacton works
Pirolacton competitively inhibits aldosterone dependant sodium potassium exchange channels in the distal convoluted tubule. This action leads to increased sodium and water excretion, but more potassium retention. The increased excretion of water leads to diuretic and also antihypertensive effects.
Dosage
Pirolacton dosage
Edema in adults (congestive heart failure, hepatic cirrhosis, or nephrotic syndrome): An initial daily dosage of 100 mg of Pirolacton administered in either single or divided doses is recommended, but may range from 25 to 200 mg daily. Combined therapy with other diuretics is indicated when more rapid diuresis is desired.
Primary hyperaldosteronism: After the diagnosis of hyperaldosteronism has been established, Pirolacton may be administered in doses of 100 to 400 mg daily in preparation for surgery. For patients who are considered unsuitable for surgery, Pirolacton may be employed for long-term maintenance therapy at the lowest effective dosage determined for the individual patient.
Essential hypertension: For adults, an initial daily dosage of 50 to 100 mg of Pirolacton administered in either single or divided doses is recommended.
Hypokalemia: Pirolacton in a dosage ranging from 25 mg to 100 mg daily is useful in treating a diuretic-induced hypokalemia.
Side Effects
Gynaecomastia may develop in association with the use of Pirolacton. Other adverse reactions are: GI symptoms including cramping and diarrhoea, drowsiness, lethargy, headache, urticaria, mental confusion, impotence, irregular menses or amenorrhoea and post-menopausal bleeding.
Toxicity
Patients experiencing an overdose may present with drowsiness, mental confusion, maculopapular or erythematous rash, nausea, vomiting, dizziness, or diarrhea. Vomiting is generally induced or a gastric lavage is performed. Supportive treatment involves maintining hydration, electrolyte balance, and vital functions.
The oral LD50 in mice, rats, and rabbits is >1g/kg.
Pirolacton should be avoided in pregnancy due to reports of feminization of male fetuses in animal studies. Active metabolites of spironolactone are present in breast milk and levels that are likely inconsequential, though the long term effects have not been studied.
In animal studies, spironolactone slowed follicle development, ovulation, and implantation. Pirolacton increased the incidence of benign adenomas in the testes of male rats, benign uterine endometrial stromal polyps in female rats, and thyroid follicular cell adenomas in both sexes of rats. Pirolacton and canrenone are generally not considered to be mutagenic in tests but canrenone occasionally tests positive for mutagenicity with metabolic activation and spironolactone has occasionally tested inconclusive though slightly positive for mutagenicity.
Precaution
All patients receiving diuretic therapy should be observed for evidence of fluid or electrolyte imbalance. Hyperkalemia may occur in patients with impaired renal function or excessive potassium intake and can cause cardiac irregularities, which may be fatal.
Interaction
ACE inhibitors: Concomitant administration of ACE inhibitors with potassium-sparing diuretics has been associated with severe hyperkalemia.
Alcohol, barbiturates, or narcotics: Potentiation of orthostatic hypotension may occur.
Corticosteroids, ACTH: Intensified electrolyte depletion, particularly hypokalemia, may occur.
Lithium: Lithium generally should not be given with diuretics. Diuretic agents reduce the renal clearance of lithium and add a high risk of lithium toxicity.
Digoxin: Pirolacton has been shown to increase the half-life of digoxin.
Food Interaction
- Avoid alcohol.
- Avoid potassium-containing products. Potassium products increase the risk of hyperkalemia.
- Take with or without food. Food increases the bioavailability of spironolactone by nearly 100%. It should be taken at a consistent time in regards to food.
Pirolacton Alcohol interaction
[Moderate]
Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation.
Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.
Caution and close monitoring for development of hypotension is advised during coadministration of these agents.
Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs.
Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.
Pirolacton Drug Interaction
Major: sacubitril / valsartanModerate: duloxetine, apixaban, metoprolol, metoprolol, alprazolamMinor: aspirin, aspirinUnknown: omega-3 polyunsaturated fatty acids, furosemide, atorvastatin, pregabalin, clopidogrel, montelukast, levothyroxine, acetaminophen, cyanocobalamin, ascorbic acid, cholecalciferol, cetirizine
Pirolacton Disease Interaction
Major: acidosis, diabetes, electrolytes/fluid, hyperkalemia, liver disease, renal dysfunctionModerate: hyperuricemia
Volume of Distribution
Volume of distribution data is not readily available.
Elimination Route
Pirolacton reaches a maximum concentration in 2.6 hours and an active metabolite (canrenone) reaches a maximum concentration in 4.3 hours. When taken with food, the bioavailability of spironolactone increases to 95.4%.
Giving spironolactone with food increases the maximum concentration from 209ng/mL to 301ng/mL. The time to maximum concentration also increases from 2.28 hours to 3.05 hours. The area under the curve varies from 2103ng/mL*hr to 4544ng/mL*hr.
Half Life
1.4 hours.
Canrenone has a half life of 16.5 hours, 7-α-thiomethylspirolactone has a half life of 13.8 hours, and 6-ß-hydroxy-7-α-thiomethylspirolactone has a half life of 15 hours.
Clearance
Clearance data is not readily available.
Elimination Route
Metabolites of spironolactone are excreted 42-56% in urine, and 14.2-14.6% in the feces. No unmetabolized spironolactone is present in the urine.
Pregnancy & Breastfeeding use
Pregnancy: Pirolacton should not be used during pregnancy
Lactation: Canrenone, an active metabolite of Pirolacton, appears in breast milk. If use of the drug is deemed essential an alternative method of infant feeding should be instituted.
Contraindication
Pirolacton is contraindicated in patients with acute renal insufficiency, significant impairment of renal function, anuria, hyperkalaemia or sensitivity to Pirolacton.
Acute Overdose
Symptoms of overdosage include drowsiness, mental confusion, dizziness, diarrhea and vomiting etc. Patients should induce vomiting or evacuate the stomach by lavage during Pirolacton overdoasge.
Storage Condition
Store in a cool and dry place protected from light. Keep out of reach of children.
Innovators Monograph
You find simplified version here Pirolacton
Pirolacton contains Spironolactone see full prescribing information from innovator Pirolacton Monograph, Pirolacton MSDS, Pirolacton FDA label
FAQ
What is Pirolacton used for?
Pirolacton is used to treat or prevent hypokalemia.It prevents your body from absorbing too much salt and keeps your potassium levels from getting too low.
How safe is Pirolacton?
Pirolacton is generally considered safe for healthy women. Taking both Pirolacton and the pill can increase effectiveness. This combination has another advantage. It's essential to use birth control while taking Pirolacton.
How does Pirolacton work?
Pirolacton works to protect the heart, lower blood pressure, and help with any leg swelling that a weak heart can cause.
What are the common side effects of Pirolacton?
Common side effects of Pirolacton drowsiness, dizziness, lightheadedness, stomach upset, diarrhea, nausea, vomiting, or headache may occur. To minimize lightheadedness, get up slowly when rising from a seated or lying position. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.
Is Pirolacton safe during pregnancy?
Women should not take Pirolacton if they are pregnant.Because of the potential risk to the male fetus due to anti-androgenic properties of Pirolacton and animal data, avoid Pirolacton in pregnant women or advise a pregnant woman of the potential risk to a male fetus.
Is Pirolacton safe during breastfeeding?
Pirolacton appears acceptable to use during breastfeeding.
Can I drink alcohol with Pirolacton?
It is best to limit your intake of alcohol while taking Pirolacton. Alcohol can increase the risk for low blood pressure and dizziness. If the blood pressure drops too low, you may feel dizzy or faint, in some cases falls or fainting may occur.
Can I drive after taking Pirolacton?
Do not drive or operate machinery if Pirolacton makes you drowsy or impairs your judgment. Your doctor may need to periodically monitor electrolyte levels in your blood while you are taking Pirolacton.
When is the best time to take Pirolacton?
It is best to take your dose early in the day to prevent having to get up during the night to urinate.Take the tablets with or just after a meal.
Should I take Pirolacton before or after eating?
You may take this medicine with or without food, but it should be taken the same way (with or without food) each day.
When should not I take Pirolacton?
You should not use Pirolacton if you Addison's disease, high levels of potassium in your blood, if you are unable to urinate, or if you are also taking eplerenone.
Can you take spironolactone before bed?
You can take Pirolacton with or without food, but make sure you pick one way and stick to it. Also avoid taking it before bedtime since it can make you go to the bathroom.
Does Pirolacton affect sleep?
Pirolacton oral tablet may cause drowsiness.
How long can I stay on Pirolacton?
Pirolacton usually needs to be continued for up to six months before the benefit can be seen.
Can Pirolacton be taken long-term?
long-term use of Pirolacton in the treatment of acne in women appears to be safe.
What are the benefits of taking Pirolacton?
benefits of taking Pirolacton to protect the heart, lower blood pressure, and help with any leg swelling that a weak heart can cause.
What happens if I stop taking Pirolacton for hair loss?
Some women will find that if they stop taking the Pirolacton, the follicles will shrink once again, and the hair loss may resume. If you are worried about hair loss.
Does Pirolacton increase estrogen?
Pirolacton showed no significant effects on levels of estrogen,
Who should not take Pirolacton?
You should not use Pirolacton with caution if you have kidney problems, high levels of potassium in your blood, Addison's disease, if you are unable to urinate, or if you are also taking eplerenone.
What happens if I take too much Pirolacton?
If too much Pirolacton is taken, the symptoms are similar to Pirolacton side effects: sleepiness, dizziness, mental confusion, drug rash, nausea, vomiting, or diarrhea. If a Pirolacton overdose is suspected, go to an emergency room.
