Potassium Sparing Diuretics

TOPICS: 

*  Introduction ( What are potassium-sparing diuretics ?

* How are Potassium-sparing diuretics used ?

*What are side effects of Potassium-Sparing Diuretics? 

       * What are drug names of Potassium-Sparing Diuretics ?

* Warning

* Before taking this medicine 

* Mechanism of action

* Adverse effect 

* Drug interaction 

* Who cannot take Potassium-Sparing Diuretics 

* Diuretics combination preparations

* Pharmacokinetics

*  Monographs

WHAR ARE POTASSIUM-SPARING DIURETICS ?

HOW ARE POTASSIUM-SPARING DIURETICS USED?

WHAT ARE SIDE EFFECTS OF POTASSIUM-SPARING DIURETICS? 

The side effects associated with potassium-sparing diuretics include:

• Hyperkalemia (increased levels of potassium in the blood)

• Nausea and vomiting

• Abdominal discomfort

• Headache

• Drowsiness

• Confusion

• Ataxia (loss of control on bodily movements due to lack of coordination between muscles and brain)

• Kidney stones

• Gynecomastia (enlargement of breasts in males)

• Impotence

• Hyperchloremic metabolic acidosis (caused by loss of bicarbonate)

• Menstrual irregularities

• Hypersensitivity reaction

The information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

WARNING !! 

You should use spironolactone 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.

Spironolactone has caused tumors in animals but it is not known whether this could occur in people. Do not use this medicine for any condition that has not been checked by your doctor.

BEFORE TAKING THIS MEDICINE 

You should not use spironolactone if you are allergic to it, or if you have:

• Addison's disease (an adrenal gland disorder);

• high levels of potassium in your blood (hyperkalemia);

• if you are unable to urinate

• if you are also taking eplerenone.

To make sure spironolactone is safe for you, tell your doctor if you have:

• an electrolyte imbalance (such as low levels of calcium, magnesium, or sodium in your blood);

• kidney disease

• liver disease

• heart disease.

Tell your doctor if you are pregnant or plan to become pregnant. Having congestive heart failure, cirrhosis, or uncontrolled high blood pressure during pregnancy may lead to medical problems in the mother or the baby. Your doctor should decide whether you take spironolactone if you are pregnant.

It may not be safe to breastfeed while using spironolactone. Ask your doctor about any risk.

MECHANISM OF ACTION 

Normally, sodium is reabsorbed in the collecting tubules of a renal nephron. This occurs via epithelial sodium channels or ENaCs, located on the luminal surface of principal cells that line the collecting tubules. Positively-charged Na+ entering the cells during reabsorption leads to an electronegative luminal environment causing the secretion of potassium (K+) into the lumen/ urine in exchange. Sodium reabsorption also causes water retention.

When the kidneys detect low blood pressure, the renin–angiotensin–aldosterone system (RAAS) is activated and eventually, aldosterone is secreted. Aldosterone binds to aldosterone receptors (mineralocorticoid receptors) increasing sodium reabsorption in an effort to increase blood pressure and improve fluid status in the body. When excessive sodium reabsorption occurs, there is an increasing loss of K+ in the urine and can lead to clinically significant decreases, termed hypokalemia. Increased sodium reabsorption also increases water retention.

Potassium-sparing diuretics act to prevent sodium reabsorption in the collecting tubule by either binding ENaCs (amiloride, triamterene) or by inhibiting aldosterone receptors (spironolactone, eplerenone). This prevents excessive excretion of K+ in urine and decreased retention of water, preventing hypokalemia.

Because these diuretics are weakly natriuretic, they do not cause clinically significant blood pressure changes and thus, are not used as primary therapy for hypertension. They can be used in combination with other anti-hypertensives or drugs that cause hypokalemia to help maintain a normal range for potassium. For example, they are often used as an adjunct to loop diuretics (usually furosemide) to treat fluid retention in congestive heart failure and ascites in cirrhosis. 

ADVERSE EFFECT

On their own this group of drugs may raise potassium levels beyond the normal range, termed hyperkalemia, which risks potentially fatal arrhythmias. Triamterene, specifically, is a potential nephrotoxin and up to half of the patients on it can have crystalluria or urinary casts. Due to its activity as an androgen receptor antagonist and progesterone receptor agonist, spironolactone causes adverse effects, including gynecomastia or decreased libido in males and menstrual abnormalities in females. Spironolactone also causes hyperkalemia and renal insufficiency.

DRUG INTERACTION

Spironolactone interacts with the following medications:

- ACE inhibitors/ARBs: increases hyperkalemia risk.

- Alcohol: risk of orthostatic hypotension.

- Barbiturates: risk of orthostatic hypotension.

- Narcotics: risk of orthostatic hypotension.

- NSAIDs: increases hyperkalemia risk and decreases diuretic effect of potassium-sparing diuretics.

- Digoxin: increases digoxin plasma concentrations, leading to increased toxicity.

WHO CANNOT TAKE POTASSIUM-SPARING DIURETICS?

There are very few people who are not able to take these medicines. They should not be taken by anyone who has high levels of potassium in their blood, severe kidney problems, or Addison's disease.

In addition, potassium supplements should not be taken with these medicines. Some salt substitutes that you can buy are high in potassium. These should be avoided if you take a potassium-sparing diuretic.

Taking a potassium-sparing diuretic at the same time as an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor antagonist medicine (eg, valsartan, losartan) can also cause very high blood potassium levels.

Examples:  Doctor said u just need to understand the concept:

1) DyazideR = Triametrene 50 mg + Hydrochlorothiazide HCT 25 mg 

2) AldactazideR= Spironolactone 25 mg + HCT 25 mg 

3) ModureticR = Amiloride 5 mg + HCT 50 mg 

Why? 

because other diuretics is potassium wasting diuretics = hypokalemia to avoid that we combine these drugs with potassium sparing diuretics. Note : thiazides should always be the 

QUESTIONS:

1- An alcoholic male has developed hepatic cirrhosis. To control the ascites and edema, he is prescribed which one of the following ?

 a) Hydrochlorothiazide.

 b) Acetazolamide. 

c) Spironolactone. 

2- Patient with Chronic renal failure. He was given B-blocker drug .which group of diuretic it is contraindication to use it? 

a) Loop diuretics 

b) Thiazide diuretics

 c) K-sparing diuretics

 3- What are the Side Effects of K-sparing diuretics?

 a) Metabolic alkalosis

 b) Hyperuricaemia (gout).

 c) Gynaecomastia 

Answers: 1- c, 2-c, 3-c. 

MY MONOGRAPH

MADE BY : RAWAN MOHEB ELSHAFEY