RENAL SYSTEM DIURETIC

Diuretics are drugs that primarily increase the excretion of sodium. To some
extent, they also increase the volume of urine produced by the kidneys. They increase
the kidney's output of urine in an effort to lower blood pressure and/or decrease edema.

DISEASE SPOTLIGHT

Diuretics are used in the management of diseases such as:

 Glaucoma

 Hypertension

 Edema in heart failure

 Liver failure

 Renal diseases

Edema is the accumulation of fluids in the interstitial spaces. It can be typically

seen in patients with heart failure (HF). Edema in HF is caused by activation of the
renin-angiotensin system due to an inefficient pumping activity of the heart. As a result,
blood volume increases, and sodium is retained.

Hypertension is persistent higher-than-normal blood pressure and is primarily

idiopathic. Diuretic agents are used in the management of hypertension to reduce blood
pressure by decreasing circulating fluid volume and sodium.

Glaucoma is an eye disease that is characterized by increased intraocular pressure

(IOP), which is the pressure inside the eyes. Diuretic agents are used in the
management of glaucoma by enhancing the osmotic pull to effectively remove some
fluid in the eye, decreasing the IOP.

Nephron

- Functional unit of the kidney

- Each kidney has 1,00,000 nephrons
- Nephron has three main parts:
 - Tubule (PCT & DCT)
- Glomerulus
- Bowman's capsule

DIURETIC SITE OF ACTION IN THE NEPHRON

LOOP DIURETICS

It is a group of medications primarily used to treat edema (and sometimes

hypertension) by inhibiting sodium reabsorption through the NKCC2 cotransporter in the
thick ascending limb of the loop of Henle (TAL), which lead to significant diuresis.

Drugs in the loop diuretic class:

 Furosemide (prototypical drug in the class)

 Bumetanide

 Torsemide

 Ethacrynic acid
PHARMACOKINETICS:

INDICATIONS:

 Edema
- includes:
o Peripheral edema
o Pulmonary edema
o Generalized edema
o Ascites
- resulting from:
o Heart failure
o Hepatic disease/cirrhosis
o Renal disease
 Hypertension
o Not 1st-line agents
o Typically used in combination with other agents
o Most commonly used in heart failure patients with hypertension presenting
with fluid overload
CONTRAINDICATIONS:

 Anuria

 Allergy to sulfa drugs (except to ethacrynic acid

 Hepatic coma

 Severe electrolyte depletion

 Ethacrynic acid in infants

ADVERSE EFFECTS:

“OHH DAANG”

 Ototoxicity

 Hypokalemia

 Hypomagnesemia

 Dehydration

 Allergy (sulfa)

 Alkalosis (metabolic)

 Nephritis (interstitial)

 Gout

PRECAUTIONS:

- Loop diuretics should be used with caution in the following situations:

 In electrolyte, fluid, or acid-base abnormalities, loop diuretics can cause:
o Hypokalemia (K’)
o Hyponatremia (Na)
o Hypocalcemia (Ca2”) (thiazides tend to cause hypercalcemia)
o Hypomagnesemia (Mg2)
 o Metabolic alkalosis
o Prerenal azotemia
o Hypovolemia
 Taken with another medication increasing the risk for hypokalemia:
o Corticosteroids
o Certain antipsychotics drugs
o Amphotericin B
 Taken with another medication increasing the risk for nephrotoxicity and/or
ototoxicity:
o Aminoglycosides
o Probenecid
 Certain medical conditions:
o Hyperuricemia/gout (may precipitate gout)
o Systemic lupus erythematosus (SLE) (may cause a flare)
o Kidney and/or liver disease
o QT prolongation (may worsen secondary to diuretic-induced Hypokalemia)

THIAZIDE DIURETICS

Thiazide and thiazide-like diuretics make up a group of highly important

antihypertensive agents, with some drugs being 1‘st-line agents. These drugs block
sodium reabsorption in the distal convoluted tubule of the kidney by inhibiting the
sodium-chloride cotransporter. As a result, the increased sodium excretion causes
secondary water excretion because water follows the sodium.

Drugs in the thiazide class:

 Hydrochlorothiazide (HCTZ; prototypical drug in this class)

 Chlorothiazide

 Chlorthalidone (1st line agent in the treatment of hypertension)

  Indapamide

 Metolazone

PHARMACOKINETICS:

INDICATIONS:

 Hypertension

 Corticosteroid use

 Estrogen therapy

 Off-label uses:

- Hypercalciuria
- Diabetes insipidus

CONTRAINDICATIONS:

 Hypersensitivity reactions
  Anuria and/or renal failure

 Hypotension

 Hypokalemia

 Allergy to sulfa drugs

 Gout

PRECAUTIONS:

 Diabetes

 Hypercalcemia

 Hepatic impairment

 Pregnancy and lactation

 Certain medications:

- Lithium

- Carbamazepine

- Corticosteroids

- NSAIDs

ADVERSE EFFECTS:

 Hypokalemia

 Hyponatremia and hypovolemia

 Metabolic alkalosis

 Hypomagnesemia

 Hyperuricemia

 Hypercalcemia
  Hyperglycemia
 Dyslipidemia
 Photosensitivity
 Hypersensitivity

POTASSIUM-SPARING DIURETICS

These are the medications that act in the principal cells in the collecting ducts to
induce diuresis that does not result in the excretion of potassium. These diuretics
include 2 subclasses: sodium channel blockers and aldosterone antagonists. These
agents act distally in the nephron, there is no significant potassium wasting associated
with their use.

Drugs in the potassium-sparing diuretic class:

 Aldosterone antagonists:

- Spironolactone
- Eplerenone

 Sodium channel blockers:

- Triamterene
- Amiloride

PHARMACOKINETICS:
INDICATIONS:

General indications

 The potassium-sparing diuretics are most useful for treating edema related to
states of mineralocorticoid excess, which may be either primary or secondary.
Indications include:
 Edema due to primary causes of mineralocorticoid excess:
- Conn syndrome
- Ectopic adrenocorticotropic hormone (ACTH) production
 Edema due to states of depleted intravascular volume resulting in secondary
mineralocorticoid excess:
- Heart failure/post-MI (especially eplerenone)
- Cirrhosis
- Nephrotic syndrome
- Resistant hypertension (typically in addition to 1st-line antihypertensive agents)

Unique indications of spironolactone

 Spironolactone has additional indications owing to its antiandrogenic properties:

 States of hyperandrogenism in females, including:

- Acne vulgaris
- Hirsutism
 - polycystic adrenal hyperplasia
 Hormone therapy for transgender women (male to female)

CONTRINDICATIONS:

 Hyperkalemia
 Addison disease/adrenal insufficiency
 Anuria or severe/progressive CKD
 Severe hepatic disease
 Pregnancy (especially the aldosterone antagonists, which may cause
feminization of a male fetus)

PRECAUTIONS:

 Diabetes (especially triamterene and amiloride)

 Gout
 Lactation

ADVERSE EFFECTS:

 Fluid and electrolyte abnormalities

- Hyperkalemia
- Hyperchloremic metabolic acidosis
- Hyponatremia
- Hypomagnesemia
- Hypocalcemia
- Hypovolemia
 Symptoms:
- Dizziness
- Headache
- Muscle cramps
- GI distress
- Photosensitivity
CARBONIC ANHYDRASE INHIBITORS

It blocks the carbonic anhydrase enzymes in the proximal convoluted tubule,

inhibiting the reabsorption of sodium bicarbonate, which results in diuresis and
metabolic acidosis. Carbonic anhydrase inhibitors are not used for the treatment of
hypertension.

Drugs in the carbonic anhydrase inhibitors:

 Acetazolamide
 Methazolamide

PHARMACOKINETICS:

INDICATIONS:

 Patients with edema who have metabolic alkalosis

 Altitude sickness:
- Hypobaric hypoxia leads to respiratory alkalosis, which requires kidneys to
compensate with ↑ HCO3 excretion and/or H+ excretion
- Acetazolamide leads to ↑ HCO3 excretion, improving acid-base status
- The increased acid load allows the body to take faster, deeper breaths to bring in
enough O₂ without elevating serum pH.

• Glaucoma

• Centrencephalic epilepsy (adjuvant therapy, works via an unknown mechanism)

• Additional off-label uses:

- ° Idiopathic intracranial hypertension and normal pressure hydrocephalus

- °Stable, hypercapnic chronic obstructive pulmonary disease (used as a
respiratory stimulant) metabolic alkalosis
- ° Prevention of cystine renal calculi

CONTRAINDICATIONS:

 Sulfa allergies
 Severe liver and/or kidney disease
 Adrenocortical insufficiency
 Hyponatremia
 Hypokalemia

PRECAUTIONS:

 Carbonic anhydrase inhibitors should be used with caution in the following

populations:

 Patients with respiratory acidosis

 Patients in whom an impairment in mental alertness is not acceptable
(e.g., machine operators)
 Diabetes (may alter glucose control)
 Mild-to-moderate liver or kidney disease
 Elderly patients (may be more sensitive to side effects)
 Pregnancy and lactation (data is limited)

ADVERSE EFFECTS:

 Electrolyte and glucose disturbances:

o Metabolic acidosis
o Hypokalemia
o Hyponatremia
o Hyperglycemia or hypoglycemia
  Myopia/blurry vision
 CNS symptoms:
o Dizziness
o Headache
o Drowsiness/fatigue
o Paresthesias

OSMOTIC DIURETICS

It increases tubular fluid osmolarity, pulling water into the collecting tubules and
preventing water reabsorption, which results in osmotic diuresis.

 The only significant osmotic diuretic used clinically is mannitol

 Glucose can also act as an osmotic diuretic when levels are high enough to
exceed the kidney's capacity for glucose reabsorption

PHARMACOKINETICS

 ABSORPTION:
 Poor oral absorption:
o Typically administered IV as a hypertonic solution
o When given orally, can cause osmotic diarrhea
 Onset of action:
o Diuresis: 1-3 hours
o Reduction in intracranial pressure (ICP): 15-30 minutes
 DISTRIBUTION:
 Confined to the extracellular fluid (ECF) compartment
 Does not penetrate the blood-brain barrier (BBB)
 Freely filtered through the glomerulus
 Not reabsorbed or secreted in the kidneys
 Volume of distribution (VD): 17 L
  METABOLISM: minimal hepatic metabolism to glycogen
 EXCRETION:
 Approximately 80% excreted renally as unchanged drug
 Mannitol clearance approximately equal to GFR
 Half-life:
o 0.5 – 2.5 hours with normal renal function
o 6-36 hours in renal failure

INDICATIONS:

The primary indications for the use of mannitol include:

 Increased ICP due to:

o Cerebral edema
o Brain masses
 Increased intraocular pressure (e.g., acute glaucoma)
 Nephrotoxicity related to rhabdomyolysis (works by maintaining urinary flow)
 As an irrigation fluid during transurethral procedures (e.g., prostatic resection)
 To improve kidney function during kidney transplantation while blood flow is
reduced (off-label use):
o Given to the donor prior to nephrectomy
o Given to the recipient prior to revascularization
 Can also be given to promote diuresis in order to ↑ excretion of toxic substances
and/or metabolites

CONTRAINDICATIONS:

 Anuria
 Severe hypovolemia
 Active intracranial bleeding
 Pulmonary edema
PRECAUTIONS:

 Mannitol may accumulate in the brain, leading to rebound ↑ in ICP

 Use with caution in patients with renal impairment.
 Use with caution in pregnancy and lactation.

ADVERSE EFFECTS:

 Hyperkalemia
 Initially:
o Hypervolemia
o Decompensation in heart failure patients
o Hyponatremia in patients receiving high doses or in those with renal failure
 Over time:
o Dehydration
o Hypovolemic hypernatremia (because over time water losses exceed Na*
losses in patients with normal renal function)
 Other symptoms:
o Pruritus
o Localized erythema, rash, or skin necrosis at the site of injection (mannitol
is a vesicant)
o Myalgias and/or arthralgias

SUMMARY OF DIURETICS
REFERENCE:
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Nurseslabs. https://nurseslabs.com/urinary-system/

Diuretics. (2021, August 13). Mayo Clinic. https://www.mayoclinic.org/diseases-

conditions/high-blood-pressure/in-depth/diuretics/art-20048129

DIURETICS. (n.d.). https://slideplayer.com/slide/10086903/

Drugs used on urinary system. (n.d.). https://www.slideshare.net/diptisorte/drugs-used-

on-urinary-system

Lecturio Login. (n.d.). https://app.lecturio.com/

Tabangcora, D. R. I. N. (2022, May 3). Diuretics. Nurseslabs.

https://nurseslabs.com/diuretics/