Module 1: Fluid Therapy and Diuretics

1. osmotic diuretics

2. carbonic anhydrase

3. loop of henle

4. benzothiadiazides / thiazides

5. triazine derivative

6. aldosterone antagonist

7. potassium - retaining agent

8. aquaretics

9. neural endopeptidase inhibitors

10. xanthine / aminouracils

11. dopamine (d1) receptor agonist

DIURETICS

1. osmotic diuretics

   1. Mannitol

   2. Sorbitol’ inositol

   3. Glycerin

   4. Isosorbide

2. carbonic anhydrase

   1. Acetazolamide

   2. Dichlorphenamide

   3. Methazolamide

   4. Ethoxzolamide

3. loop of henle diuretics

   1. Furosemide

   2. Ethacrymic acid

   3. Burmetamide (Bumetanide)

   4. Torsemide

4. benzothiadiazides / thiazides

   1. Chlorothiazide

   2. Polythiazide

   3. Cyclothiazide

   4. Hydrochlorothiazide

5. Triazine derivative

   1. Chlorazanil hydrochloride

6. aldosterone antagonist

   1. Spironolactone

   2. Eplerenone

   3. Heparin

   4. Canrenone

   5. Potassium canrenoate

7. potassium - retaining agent

   1. Triamterene

   2. Amiloride

8. aquaretics

   1. Vasopressin (arginine vasopressin)

   2. Lixivaptan

   3. Tolvaptan

   4. Conivaptan

9. xanthine / aminouracils

   1. Theophylline / Aminophylline

   2. Theobromine (cocoa)

   3. Caffeine (coffee)

   4. Chlorazamil Hydrochloride

10. neural endopeptidase inhibitors (nep)

    1. Ecadotril

11. dopamine (d1) receptor agonist

    1. Fenoldopam

DIURETICS

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acts in the PROXIMAL TUBULE, it increases the osmotic pressure and prevent water from being reabsorbed. The water stays on the tubular lumen and is excreted along with some electrolytes as urine.

MOA of OSMOTIC DIURETICS

1. Tx of nephritis (inflammation of nephron)

2. Tx of renal failure

3. Regulation of CSF

4. Regulation of intra-ocular fluid

5. Induction of polyuria to eliminate toxin

6. Tx of urolithiasis (stones in Urinary tract)

7. Tx of cystitis (inflammation of urinary bladder)

USES of OSMOTIC DIURETICS

 

acts in the PROXIMAL TUBULE, where carbonic anhydrase normally converts CO₂ and H₂O into H⁺ and HCO₃⁻. H⁺ is excreted allowing reabsorption of Na⁺ and HCO₃⁻ . With carbonic anhydrase inhibitors it  block the enzyme. H⁺ excretion decreased so bicarbonate (HCO₃⁻) and sodium stays in the tubular lumen. Along with water it is then is excreted as urine

MOA of CARBONIC ANHYDRASE INHIBITOR

1. Tx of chronic glaucoma

2. Tx of udder edema

3. Reduce Intra-ocular pressure

4. Adjunct to Tx of epilepsy

5. Acute mountain (high-altitude) sickness

USES of CARBONIC ANHYDRASE INHIBITOR

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In the DISTAL CONVOLUTED TUBULE (DCT), sodium and chloride are normally reabsorbed through the Na⁺–Cl⁻ symporter. Thiazide diuretics block this transporter, so both sodium (Na⁺) and chloride (Cl⁻) remain in the tubular lumen, along with water it is excreted as urine.

 

TRIAZINE DERIVATIVE : same MOA but is more potent and can still work even when GFR (renal function) is low, where normal thiazides usually lose effectiveness. Because of this, they’re sometimes combined with loop diuretics for resistant edema.

MOA of BENZOTHIADIAZIDES / THIAZIDES and TRIAZINE DERIVATIVE 

1. Tx of edema associated with congestive heart failure

2. Tx of edema with renal, cardiac and hepatic origin

3. Tx of nephrogenic diabetes insipidus

USES of BENZOTHIADIAZIDES / THIAZIDES

1. Central diabetes insipidus

2. Nephrogenic diabetes insipidus

Types of Diabetes Insipidus

• pituitary

• Thiazides diuretics

in central diabetes insipidus

• (ADH / Vasopressin)

• __________ gland doesn’t produce ADH

• Tx is _________________

• ADH

• Thiazides diuretics

• diet, low protein, low salt, high filtrate

in nephrogenic diabetes insipidus

• produces _____ but when it reaches the kidney it doesn’t function.

• Tx is ______________

• Direct the tx in their _________, (wag pahirapan yung kidney sa filtration) → ___________, _____________, ____________

acts on the LATE DISTAL TUBULE AND COLLECTING DUCT. normally,  aldosterone increases the number of sodium channels and Na⁺/K⁺-ATPase pumps, leading to Na⁺ reabsorption, water retention, and K⁺ excretion. Aldosterone antagonists prevents channel and pump formation. Na⁺ is excreted and water follows, while K⁺ is retained

MOA of ALDOSTERONE ANTAGONIST

1. True competitive antagonist of aldosterone

2. Has some estrogen like activity

3. Tx of hypokalemia

4. Tx of edema associated with renal, liver, and cardiac failure

5. Tx severe ascites

uses of ALDOSTERONE ANTAGONIST: Spironolactone

1. Prevents release of aldosterone

uses of ALDOSTERONE ANTAGONIST: Heparin

1. Inhibit aldosterone receptors

2. Prevent excessive excretion of potassium

uses of ALDOSTERONE ANTAGONIST: Spironolactone, eplerenone

It causes renal vasodilation, which increases renal blood flow and GFR. With increased plasma filtration, more electrolytes and water are excreted as urine.

MOA of XANTHINE / AMINOURACILS

1. Increase heart function

2. Increase pressure

3. Increase filtration

4. Increase water release

USES of XANTHINE / AMINOURACILS

In the COLLECTING TUBULE, normally sodium enters tubular cells via  sodium channels in exchange for potassium. With potassium-retaining agent, potassium is spared, Na⁺ stays in the tubular lumen while K⁺ is retained.

MOA of POTASSIUM – RETAINING AGENT

1. Tx of edema ass, with CHF

2. Tx of edema with liver cirrhosis

3. Tx of edema with nephrotic symptoms

USES of POTASSIUM – RETAINING AGENT

In the THICK ASCENDING LOOP OF HENLE, sodium, potassium, and chloride are normally reabsorbed via the Na⁺–K⁺–2Cl⁻ symporter. Loop of henle diuretics block this symporter, preventing their reabsorption. since water cannot move in this segment, electrolytes stays in tubular lumen, and is excrete as urine

MOA of LOOP OF HENLE DIURETICS

1. Tx of edema

2. Tx of pulmonary congestion

3. Tx of ascites

4. Tx of hydrothorax

5. Contraindicated in anuria, NSAID, aminoglycoside

6. Have ototoxic effect (ear sound, hearing, lead to tinnitus (ringing in the ears))

7. Tx of renal failure

8. Exercise-induce pulmonary hemorrhage (EIPH) in horse treatment of chronic heart failure

USES of LOOP OF HENLE DIURETICS

act in the COLLECTING DUCT  Normally, ADH binds to V₂ receptors, allowing water reabsorption. With, aquaretics, it inhibits the receptor, preventing aquaporin insertion, water is not reabsorbed and is instead excreted as dilute urine.

MOA of AQUARETICS

1. edema associated with liver cirrhosis

2. heart failure

3. nephrogenic syndrome and inappropriate secretion of ADH

USES of AQUARETICS

 

 

Normally, atrial natriuretic factor (ANF) promotes natriuresis and diuresis. By blocking NEP, ANF activity is prolonged, allowing sustained signaling to excrete sodium and water and suppress renin–angiotensin–aldosterone activity

MOA of NEURAL ENDOPEPTIDASE INHIBITORS (NEP)

1. NEP degraded atrial natriuretic factor (ANF)

USES of NEURAL ENDOPEPTIDASE INHIBITORS (NEP)

right atrium, sodium excretion, diuresis

ANF is from the muscle of the ____________ and release in response to blood volume overload leading to __________________ and ________

At low doses, dopamine selectively activates D₁ receptors causing vasodilation. This leads to increased renal blood flow and GFR. With increased plasma filtration, more sodium are excreted as urine

MOA of DOPAMINE

1. increase renal blood flow

2. increase filtration

3. induce natriuresis

USES of DOPAMINE (D1) RECEPTORS AGONIST