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Diuretics - Osmotic and carbonic anhydrase inhibitors: Nursing Pharmacology

Notes

Notes

DIURETICS: OSMOTIC AND CARBONIC ANHYDRASE INHIBITORS
DRUG NAME
mannitol (Osmitrol)
acetazolamide (Diamox), dichlorphenamide (Keveyis), methazolamide, brinzolamide (Azopt), dorzolamide (Trusopt)
CLASS
Osmotic diuretics
Carbonic anhydrase inhibitors
MECHANISM OF ACTION
  • Freely filtered into the tubules → increases osmolality of the tubular fluid → draws water into the tubules for excretion along with mannitol
  • Inhibit carbonic anhydrase enzyme in the renal tubules → decrease absorption of bicarbonate and sodium → diuresis
  • Inhibit carbonic anhydrase enzyme in the eyes  → decrease production of the aqueous humor  → decrease intraocular pressure
INDICATIONS
  • Glaucoma
  • Increased intracranial pressure
  • Induce renal excretion of toxic substances (myoglobin from rhabdomyolysis, hemoglobin from hemolysis)
  • Adjuncts to other diuretics for edematous conditions (e.g., heart failure, pulmonary edema)
  • Cystinuria
  • Gout
  • Open-angle glaucoma
ROUTE(S) OF ADMINISTRATION
  • IV
  • PO
  • IV
  • Opth
SIDE EFFECTS
  • Exacerbation of fluid overload conditions
  • Dehydration
  • Hypotension
  • Confusion
  • Nausea
  • Vomiting
  • Metabolic acidosis
  • Hypokalemia
  • Hyperchloremia
  • Neurological side effects, e.g., headache, seizures, mental status changes, paraesthesia
  • Gastrointestinal side effects, e.g., altered sense of taste, nausea, vomiting and diarrhea
  • Side effects with IV forms: hepatic necrosis, agranulocytosis, aplastic anemia
CONTRAINDICATIONS AND CAUTIONS
  • Renal failure with anuria
  • Fluid overload conditions (e.g., heart failure, pulmonary edema)
  • Dehydration
  • Severe renal or hepatic disease (e.g., cirrhosis)
  • Electrolyte abnormalities (e.g., hyponatremia, hyperkalemia)
  • Respiratory acidosis
  • Chronic obstructive pulmonary disease
  • Sulfa allergy
NURSING CONSIDERATIONS:
DIURETICS: OSMOTIC AND CARBONIC ANHYDRASE INHIBITORS
DRUG NAME
mannitol (Osmitrol)
acetazolamide (Diamox), dichlorphenamide (Keveyis), methazolamide, brinzolamide (Azopt), dorzolamide (Trusopt)
ASSESSMENT AND MONITORING
Baseline assessment
  • Patent IV, indwelling urinary catheter,  ICP monitor
  • Vital signs, lung sounds, SpO2, weight, BUN, creatinine, electrolytes, serum mOsm, urinalysis,  urine out 30–50 mL/hr; neurological status
  • Check the mannitol solution crystals; warm solution to dissolve; use an in-line filter

Monitoring
  • Vital signs, lung sounds, SpO2, electrolytes, BUN, creatinine, I & O
  • Signs of fluid overload; signs of hypovolemia and hypotension
  • Notify the health care provider for serum sodium more than 150 mEq/L or serum osmolality more than 320 mOsm
  • Signs of IV site infiltration
  • Therapeutic response: decreased ICP, improved level of consciousness, increased urine output
  • Rebound increased ICP
  • Patient IV site
  • Baseline assessment:  blood gas analysis, CBC, platelets, glucose, BUN, creatinine, liver function tests
  • Monitor CBC, platelets, blood gas analysis; glucose for diabetic clients
  • Therapeutic response: decreased edema, normal acid-base balance
CLIENT EDUCATION
  • Purpose of medication
  • Report trouble breathing, headache, blurred vision, or pain at the IV site
  • Purpose of medication

Memory Anchors and Partner Content
Transcript

Diuretics, also called water pills, are medications that act on the kidneys to increase diuresis, or the production of urine, to help excrete more water from the body.

Diuretics act on the kidneys’ basic unit, the nephron, to induce salt and water excretion. Zooming into the nephron, it’s made up of a glomerulus, which filters the blood.

The filtered content goes through the renal tubules, which have four parts the proximal convoluted tubule; the U-shaped loop of Henle, with a thin descending, a thin ascending, and a thick ascending limb; and finally, the distal convoluted tubule; and the collecting duct, which drain the urine out of the kidneys.

In this video, we’re going to cover two of the main classes of diuretics, osmotic diuretics and the carbonic anhydrase inhibitors.

Okay, the main osmotic diuretic is mannitol, which is a sugar alcohol that can be administered intravenously. After administration, mannitol travels through the bloodstream and attracts water out of the cells it encounters along the way.

Eventually, mannitol and the extra water reach the kidneys and get secreted by the glomerulus into the renal tubule.

Inside the tubules, mannitol increases the osmolality of the tubular fluid, which makes water stay inside the tubules to be excreted rather than be reabsorbed. Ultimately, both mannitol and water are excreted in the urine.

Osmotic diuretics are primarily used to lower intraocular pressure in glaucoma, or to lower intracranial pressure, such as following head trauma or neurosurgery.

In addition, mannitol can also be used to help excrete harmful substances that may otherwise build up in the body. Examples include myoglobin from the breakdown of muscles, and hemoglobin from the breakdown of red blood cells.

Now, an important side effect is that mannitol also pulls water from cells into the extracellular space, which could worsen edematous conditions like heart failure and pulmonary edema.

In addition, as more water gets pulled into the blood vessels, the concentration of sodium will go down, causing dilutional hyponatremia.

This is especially likely to happen in clients with renal impairment, since they can’t excrete the mannitol, and in heart failure, where the heart can’t handle the increased blood volume.

Other side effects of mannitol are dehydration, hypotension, confusion, headache, nausea and vomiting, which occur due to the rapid fluid shift.

Because of these side effects, mannitol is contraindicated in clients with severe hypovolemia, severe renal impairment and anuria; and should be used with caution in clients with edematous conditions, such as heart failure and pulmonary edema.

Alright, moving on to carbonic anhydrase inhibitors, which usually end in -zolamide, such as acetazolamide that can be administered orally and intravenously; as well as brinzolamide and dorzolamide, which are administered topically in the eyes, and are actually the most commonly used carbonic anhydrase inhibitors.

Now, as the name suggests, these diuretics inhibit the enzyme carbonic anhydrase, which is found at the apical surface of the tubular cells, facing the tubular lumen.

Long story short, this enzyme catalyzes a reaction where bicarbonate is produced and reabsorbed into the tubular cells. Then, a sodium bicarbonate cotransporter snatches up the bicarbonate and a nearby sodium, and shuttles both into the blood, decreasing their excretion in the urine.

Carbonic anhydrase also increases hydrogen secretion into the tubules to ultimately be excreted. Moreover, this enzyme is also present in the eyes, where it stimulates aqueous humor production.

OK, so once administered, carbonic anhydrase inhibitors bind to the carbonic anhydrase enzymes and inhibit them. Now, acetazolamide acts in the kidneys, where it causes more bicarbonate and sodium to get excreted in the urine, along with water that follows sodium.

However, their diuretic effect is pretty weak, so they are only used as adjunct to other diuretics, or to treat edematous states like pulmonary edema or ascites when there’s also alkalosis, where they will help excrete bicarbonate from the blood to decrease its alkalinity.

In addition, carbonic anhydrase inhibitors are given to clients with cystinuria, where there’s too much cystine in the urine, or gout where there’s too much uric acid in the blood and urine.

The use of carbonic anhydrase inhibitors in these clients raises the pH of the urine, which makes it less favorable for the precipitation of cystine and uric acid crystals, therefore preventing the formation of kidney stones.

Now, on the other hand, brinzolamide and dorzolamide act on carbonic anhydrase enzymes in the eyes. This results in a decreased production of the aqueous humor, which helps lower the intraocular pressure in open-angle glaucoma.

The main side effect of carbonic anhydrase inhibitors is metabolic acidosis, since bicarbonate is lost in the urine. In addition, carbonic anhydrase inhibitors can also cause other electrolyte abnormalities, such as hypokalemia and hyperchloremia; as well as altered blood glucose levels, which can lead to hypo- or hyperglycemia.

This can manifest as neurological side effects like headache, seizures, mental status changes, and paraesthesia. Carbonic anhydrase inhibitors can also cause gastrointestinal side effects, such as altered sense of taste, mostly a bitter or rancid taste, as well as nausea, vomiting, and diarrhea.

Finally, acetazolamide can cause more serious side effects like hepatic necrosis, agranulocytosis, or low blood levels of granulocytes, as well as aplastic anemia, where the bone marrow stops producing all blood cells, leading to pancytopenia.

Sources
  1. "Carbonic Anhydrase Inhibitors" StatPearls (2021)
  2. "Mannitol" StatPearls (2021)
  3. "Focus on Nursing Pharmacology" LWW (2019)
  4. "Pharmacology: A patient-centered nursing process approach" Elsevier Health Sciences (2014)
  5. "Mosby's 2021 Nursing Drug Reference" Mosby (2020)
  6. "Saunders Comprehensive Review for the NCLEX-RN Examination" Saunders (2020)
  7. "The Use of Mannitol and Hypertonic Saline Therapies in Patients with Elevated Intracranial Pressure: A Review of the Evidence" Nursing Clinics of North America (2017)