DRUGS ACTING ON THE KIDNEY

 

DRUGS ACTING ON THE KIDNEY

PREPARED BY MR. ABHIJIT DAS

DIURETICS

Diuretics are drugs that increase urine production in the body, aiding in the elimination of excess water and salt. They are commonly prescribed to manage conditions such as hypertension, heart failure, and edema.

CLASSIFICATION:

1.    Carbonic Anhydrase Inhibitors:

·        Example: Acetazolamide

2.    Loop Diuretics:

·        Examples: Furosemide, Bumetanide, Torsemide

3.    Thiazide Diuretics:

·        Examples: Hydrochlorothiazide, Chlorthalidone, Indapamide

4.    Potassium-Sparing Diuretics:

·        Examples:

·        Aldosterone Antagonists: Spironolactone, Eplerenone

·        Non-aldosterone Antagonists: Amiloride, Triamterene

5.    Osmotic Diuretics:

·        Examples: Mannitol, Glycerin

CARBONIC ANHYDRASE INHIBITORS:

MOA:

Carbonic anhydrase inhibitor works by blocking an enzyme called carbonic anhydrase in the proximal convoluted tubule (PCT) of the kidney. By doing this, it helps more sodium ions (Na⁺) to be flushed out in the urine. When there's more sodium in the urine, it pulls more water along with it from the nephron, leading to increased urine production.

ADVERSE EFFECTS:

1.    Acid Buildup: Can cause body acidity, leading to confusion and rapid breathing.

2.    Electrolyte Problems: Imbalance in minerals like sodium can cause weakness and irregular heartbeat.

USES:

1.    Glaucoma: Helps reduce pressure inside the eye by decreasing the production of aqueous humor, easing symptoms like eye pain and vision problems.

2.    Edema and Hypertension: Helps to reduce swelling and lower blood pressure by increasing the removal of excess fluid and sodium through urine.

3.    High Altitude Sickness: Can alleviate symptoms of altitude sickness by stimulating breathing and improving oxygen levels in the blood.

LOOP DIURETICS:

MOA:

Loop diuretics inhibit the sodium-potassium-chloride cotransporter (Na⁺K⁺2Cl^-) in the thick ascending limb of the loop of Henle in the kidney, preventing reabsorption of sodium, potassium, and chloride ions. This leads to increased excretion of these ions in urine, along with water, causing diuresis.

ADVERSE EFFECTS:

1.    Electrolyte Imbalance: Can lead to low levels of potassium, sodium, and chloride, causing weakness and irregular heartbeat.

2.    Dehydration: Excessive urination may cause dry mouth, thirst, and dizziness.

3.    Hypotension: May result in low blood pressure, leading to lightheadedness and fainting.

USES:

1.    Edema: Used to reduce swelling caused by conditions like heart failure or kidney disease.

2.    Hypertension: Helps lower blood pressure by decreasing fluid volume in the body.

THIAZIDE DIURETICS:

MOA:

Thiazide diuretics work primarily by inhibiting the sodium-chloride cotransporter (Na⁺Cl^- Cotransporter) in the distal convoluted tubule (DCT) of the kidney. By doing so, they decrease the reabsorption of sodium and chloride ions, leading to increased excretion of these ions in the urine. This results in diuresis.

ADVERSE EFFECTS:

1.    Electrolyte Imbalance: Can cause low sodium levels, leading to weakness and irregular heartbeat. Kaliuresis exacerbates potassium loss.

2.    Hyperglycemia: May raise blood sugar levels, especially in people with diabetes.

3.    Hyperuricemia and Gout: Can increase uric acid levels, triggering or worsening gout attacks in some individuals.

USES:

1.    Edema: Helps reduce swelling caused by conditions like heart failure or kidney disease.

2.    Hypertension: Lowers blood pressure by reducing fluid volume in the body.

POTASSIUM-SPARING DIURETICS:

MOA:

Potassium-sparing diuretics work by blocking the sodium channels in the distal convoluted tubule (DCT) and collecting ducts of the kidney. This action prevents the reabsorption of sodium ions, leading to increased excretion of sodium in the urine.

ADVERSE EFFECTS:

1.    High Potassium: These diuretics can raise potassium levels in the blood, causing muscle weakness, irregular heartbeats, and dangerous heart rhythm issues.

2.    Acid-Base Imbalance: Sometimes they can upset the body's acid-base balance, leading to confusion, fatigue, and rapid breathing.

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USES:

1.    Heart Failure: Potassium-sparing diuretics are often used in the management of heart failure to help reduce fluid buildup and ease the workload on the heart.

2.    Hypertension: They can be used as part of a treatment plan for high blood pressure, helping to lower blood pressure without causing potassium loss.

3.    Hypokalemia Prevention: In some cases, they may be prescribed alongside other diuretics to counteract potassium loss and prevent hypokalemia (low potassium levels).

OSMOTIC DIURETICS:

MOA:

Osmotic diuretics work primarily by increasing the osmotic pressure in the renal tubules, specifically in the proximal convoluted tubule and descending loop of Henle. This prevents the reabsorption of water, leading to increased urine production.

ADVERSE EFFECTS:

1.    Dehydration: Excessive urine production caused by osmotic diuretics can lead to dehydration, which may manifest as symptoms such as dry mouth, thirst, decreased urine output, and dizziness.

2.    Electrolyte Imbalance: Osmotic diuretics can disrupt the balance of electrolytes such as sodium and potassium, leading to abnormalities in the body's electrolyte levels. This imbalance can result in symptoms like weakness, muscle cramps, and irregular heartbeat.

USES:

1.    Cerebral Edema: Reduces brain swelling in conditions like head injuries or strokes.

2.    Acute Kidney Injury: Helps improve kidney function by increasing urine output.

3.    Glaucoma: Lowers pressure in the eyes during certain eye conditions or surgeries.

ANTIDIURETIC DRUGS

DEFINITION

Antidiuretic drugs, also known as vasopressin or antidiuretic hormone (ADH) agonists, are medications that mimic the action of vasopressin in the body. Vasopressin is a hormone produced by the hypothalamus and released from the posterior pituitary gland. Its primary function is to regulate water balance in the body by controlling the reabsorption of water in the kidneys. Antidiuretic drugs are used to treat conditions characterized by excessive urination and water loss, such as diabetes insipidus.

CLASSIFICATION OF ANTIDIURETIC DRUGS:

1.    Synthetic Vasopressin Analogues:

·        Desmopressin (DDAVP): Used for diabetes insipidus, nocturnal enuresis (bedwetting), and certain bleeding disorders like hemophilia.

2.    Vasopressin Receptor Agonists:

·        Conivaptan: Used in hospitalized patients to manage hyponatremia (low sodium levels).

·        Tolvaptan: Used to treat hyponatremia associated with heart failure and certain other conditions.

MECHANISM OF ACTION OF VASOPRESSIN

Vasopressin acts on V₂ receptors in the DCT and Collecting Tubule of the kidney, increasing water permeability. This leads to water reabsorption and concentrated urine.

ADVERSE EFFECTS OF ANTIDIURETIC DRUGS:

1.    Fluid Retention: Excessive use or improper dosage of antidiuretic drugs can cause fluid retention, leading to edema (swelling) and potential cardiovascular complications.

2.    Headache: Some individuals may experience headaches as a side effect of antidiuretic drugs.

3.    Gastrointestinal Disturbances: Nausea, vomiting, and abdominal cramps may occur in some cases.

4.    Hypertension: In certain situations, antidiuretic drugs may cause an increase in blood pressure.

THERAPEUTIC USES OF ANTIDIURETIC DRUGS:

1.    Diabetes Insipidus: Antidiuretic drugs, particularly desmopressin, are the primary treatment for central diabetes insipidus, a condition characterized by excessive thirst and urination due to inadequate vasopressin secretion.

2.    Nocturnal Enuresis: Desmopressin nasal spray is used to treat bedwetting in children and adults.