Diuretic Drugs & Renal System

• Diuretic drugs affect the renal system
• The role of the kidneys is to filter toxic waste and conserve essential substances.
• Nephrons are the main structural unit.
• GFR indicates how well the kidneys function as filters and is regulated by the afferent arterioles.
• Daily, 180 Liters of fluid is filtered, with a normal filtration rate of 90-120 ml/min
• The proximal convoluted terminal reabsorbs 60-70% of filtered sodium and water back into the bloodstream, and remaining 5-10% gets reabsorbed in the distal tubule

Diuretic Drugs

• Diuretic drugs accelerate the rate of urine formation, resulting in the removal of sodium and water
• These drugs serve as the foundation for treating hypertension, heart failure, and preventing kidney damage during acute kidney injury.
• Hypertension Canada 2018 guidelines recommend diuretics and thiazides as a first-line treatment option for hypertension.
• Diuretics reduce extracellular fluid volume, plasma volume, and cardiac output to help decrease blood pressure
• In the nephron, sodium flow dictates water flow

Sodium Reabsorption in the Nephron

• 60-70% of sodium and water are returned to the bloodstream by the proximal convoluted tubule.
• 20-25% of sodium is reabsorbed into the bloodstream in the ascending loop of Henle.
• 5-10% is reabsorbed in the distal convoluted tubule.
• The collecting duct is the final common pathway for filtrate originating in the glomerulus
• Water not absorbed in the kidneys is excreted as urine.

Types of Diuretic Drugs

• Diuretics are classified by site of action, chemical structure, and potency
• Loop diuretics are the most potent, followed by mannitol(osmotic), metolazone(thiazide-like), thiazides, and potassium-sparing diuretics.
• The potency of diuretics depends on their action site in the nephron, influencing sodium and water resorption.
• Greater amounts of sodium and water inhibited from resorption lead to greater diuresis and potency
• The main types of diuretics include:
  • Carbonic anhydrase inhibitors
  • Loop diuretics
  • Osmotic diuretics
  • Potassium-sparing diuretics
  • Thiazide and thiazide-like diuretics

Carbonic Anhydrase Inhibitors (CAIs)

• Acetazolamide (Acetazolam®) is the most common carbonic anhydrase inhibitor
• It is available in oral and parenteral forms
• Carbonic anhydrase inhibitors may be beneficial for pregnant women despite potential fetal risks
• Carbonic anhydrase makes H+ ions available for exchange with sodium and water in the proximal tubules
• CAIs block carbonic anhydrase, preventing the exchange of H+ ions with sodium and water
• Inhibition of carbonic anhydrase reduces H+ ion concentration in renal tubules
• Increased excretion of bicarbonate, sodium, water, and potassium occurs with use
• Water resorption is decreased, increasing urine volume
• CAIs manage open-angle glaucoma, secondary glaucoma, edema (secondary to heart failure), high-altitude sickness, and epilepsy
• Contraindications are known drug allergy, hyponatremia, hypokalemia, severe kidney or liver dysfunction, adrenal gland insufficiency, cirrhosis, and acidosis
• Adverse effects are acidosis, hypokalemia, drowsiness, anorexia, paresthesias, hematuria, urticaria, photosensitivity, and melena
• Drug interactions include drugs that cause:
  • Hypokalemia which can increase digoxin toxicity when taken together
  • Increase the effects of amphetamines, carbamazepine, cyclosporine, phenytoin, and quinidine sulphate
  • Use with corticosteroids may also cause hypokalemia

Loop Diuretics

• Loop diuretics include bumetanide, ethacrynic acid, and furosemide (Lasix®)
• Loop diuretics possess kidney, cardiovascular, and metabolic effects by directly acting on the ascending limb of the loop of Henle to block chloride and sodium resorption
• Prostaglandins are increased in the kidney, dilating blood vessels, and reducing kidney, pulmonary, and systemic vascular resistance
• Loop diuretics can treat edema, acute heart failure and edema.
• A rapid onset and lasts for at least 2 hours causing:
  • Potent diuresis and fluid loss
  • Decreased fluid volume
  • Potassium and sodium depletion
  • Small calcium loss
• Decreased fluid volume causes a reduction in:
  • Blood pressure
  • Pulmonary vascular resistance (pulmonary edema)
  • Systemic vascular resistance (pressure inside of artery)
  • Central venous pressure, left ventricular end-diastolic pressure (afterload)
• Loop diuretics treat edema associated with heart failure and liver or kidney disease and hypertension
• Loop diuretics increase kidney excretion of calcium in patients with hypercalcemia and treats heart failure resulting from diastolic dysfunction
• Adverse effects include:
  • Dizziness, headache, tinnitus, blurred vision, nausea, vomiting, diarrhea, agranulocytosis, neutropenia, thrombocytopenia, hypokalemia, hyperglycemia, and hyperuricemia
• Loop diuretics interact negatively with neurotoxic and nephrotoxic substances
  • Increase serum levels of uric acid, glucose, alanine aminotransferase, and aspartate aminotransferase.
  • Thiazides (metolazone) create sequential nephron blockade
  • Nonsteroidal anti-inflammatory drugs (NSAIDs) may decrease the reduction of vascular resistance.
• Furosemide (Lasix) is the most common loop diuretic
• It is used for pulmonary edema and edema associated with heart failure, liver disease, nephrotic syndrome, ascites, and hypertension

Osmotic Diuretics

• Mannitol (Osmitrol®) is the most used osmotic diuretic
• It can increase ICP
• Other drugs include urea, organic acids, and glucose
• Osmotic diuretics work along the entire nephron, mostly in the proximal tubule and descending loop of Henle by nonabsorbable, producing an osmotic effect
• Pull water into the renal tubules inhibiting tubular resorption of water; thus, producing rapid diuresis of water and solutes
• Osmotic diuretics increase glomerular filtration rate and renal plasma flow, which helps to prevent kidney damage
• Osmotic diuretics reduce intracranial pressure or cerebral edema associated with head trauma while also reducing excessive intraocular pressure
• These medicines treat patients in the early, oliguric phase of acute kidney injury, promote the excretion of toxic substances, reduce intracranial pressure, treat cerebral edema, and act as a genitourinary irrigant in patients preparing for transurethral surgical procedures
• Adverse effects are convulsions, thrombophlebitis, pulmonary congestion, headaches, chest pains, tachycardia, blurred vision, chills, and fever.
• Mannitol (Osmitrol) given by IV infusion only and crystallizes when exposed to low temperatures
• Vials are often stored in a warmer and need a filter

Potassium-Sparing Diuretics

• Potassium-sparing diuretics, also known as aldosterone-inhibiting diuretics, include amiloride (Midamor®), spironolactone (Aldactone®), and triamterene (often in combination with hydrochlorothiazide).
• Potassium-sparing diuretics work in collecting ducts and distal convoluted tubules
• These diuretics interfere with sodium-potassium exchange and competitively bind to aldosterone receptors to block aldosterone induced sodium and water resorption
• Potassium-Sparing Diuretics are considered relatively weak
• They competitively block aldosterone receptors and inhibit their action, which promotes the excretion of sodium and water
• Spironolactone and triamterene are indicated for:
  • Hyperaldosteronism, hypertension, reversing potassium loss caused by potassium-wasting diuretics, and certain cases of heart failure for preventing remodelling
• Amiloride is similar to spironolactone and triamterene and less effective long term.
• Adverse effects inclide central nervous, gastrointestinal and other effects such as:
  • Dizziness, headache, cramps, nausea, vomiting, diarrhea, urinary frequency, weakness, and hyperkalemia
• Spironolactone (Aldactone®) specific adverse affects are gynecomastia, amenorrhea, irregular menses, postmenopausal bleeding
• Drug interactions include lithium, angiotensin-converting enzyme inhibitors, potassium supplements, and NSAIDs.

Thiazide and Thiazide-Like Diuretics

• Thiazide diuretics include hydrochlorothiazide (Urozide®) and thiazide-like diuretics including: metolazone (Zaroxolyn®) chlorthalidone indapamide
• Thiazide and Thiazide-Like Diuretics inhibit tubular resorption of sodium, chloride, and potassium ions primarily in the distal convoluted tubule
• The action results in osmotic water loss to dilate the arterioles by direct relaxation, decreasing preload and afterload
• Thiazides should not be used in patients with creatinine clearance is less than 30 to 50 mL/min, a normal value is 125 mL/min.
• Metolazone remains effective to a creatinine clearance of 10 mL/min.
• Diuretics are one of the most frequently prescribed drugs for:
  • Hypertension
  • Edematous states
  • Idiopathic hypercalciuria
  • Diabetes insipidus
  • Heart failure caused by diastolic dysfunction
• Adverse effects include the following:
  • Central nervous system effects like dizziness, headache, and blurred vision;
  • Gastrointestinal issues like anorexia, nausea, vomiting, and diarrhea;
  • Genitourinary issues such as erectile dysfunction;
  • Hematological issues like jaundice, leukopenia, and agranulocytosis;
  • Integumentary effects like urticaria and photosensitivity; and
  • Metabolic imbalances such as hypokalemia, glycosuria, hyperglycemia, hyperuricemia, and hypochloremic alkalosis.

Nursing Implications

• Perform a thorough patient history and physical examination
• Assess baseline fluid volume status, intake and output, serum electrolyte values, weight, and vital signs, especially postural blood pressure.
• Check for disorders that may contraindicate or necessitate cautious use of these drugs, and instruct patients to take the medication in the morning if possible to avoid interference with sleep patterns.
• Monitor serum potassium levels during therapy and teach patients to maintain proper nutritional and fluid volume status
• Teach patients to eat more potassium-rich foods when taking any diuretics but the potassium-sparing drugs
  • These include bananas, oranges, dates, apricots, raisins, broccoli, green beans, potatoes, tomatoes, meats, fish, wheat bread, and legumes.
• Patients taking diuretics with digoxin should be watchful for digoxin toxicity and patients with diabetes mellitus on thiazide, or loop diuretics should monitor blood glucose and watch for elevated levels.
• Teach patients to change positions slowly and to rise slowly after sitting or lying to prevent dizziness and fainting related to orthostatic hypotension, and instruct patients to keep a log of their daily weight.
• Remind patients to return for follow-up visits and laboratory work. Patients who have been ill with nausea, vomiting, or diarrhea should notify their primary care provider.
• Watch for anorexia, nausea, lethargy, muscle weakness, mental confusion, and hypotension are symptoms of hypokalemia.
• Patients should notify their primary care provider immediately if they experience rapid heart rates or syncope, reflecting hypotension or fluid loss.
• Excessive consumption of licorice can lead to additive hypokalemia in patients taking thiazides.
• Monitor for adverse effects, including metabolic alkalosis, drowsiness, lethargy, hypokalemia, tachycardia, hypotension, leg cramps, restlessness, and decreased mental alertness
• Look for hyperkalemia with potassium-sparing diuretics
• Reduce edema, fluid volume overload, manifestations of heart failure, hypertension, and a return to normal intraocular pressures are therapeutic effects

Fluids and Electrolytes

• Total body water is composed of 67% intracellular fluid, 25% interstitial fluid, and 8% plasma volume.
• 60% of the adult human body is water
• Intravascular fluid is fluid inside blood vessels and extravascular fluid is outside blood vessels; like lymph and cerebrospinal fluid.
• Plasma is an extravascular volume, in space between cells, tissues, and organs
• Interstitial and intracellular fluids is both found in extracellular volume

Fluid Balance

• Plasma proteins exert constant osmotic and colloid oncotic pressure at a normal level of 24 mm Hg.
• Interstitial fluid exerts hydrostatic pressure at a normal level of 17 mm Hg.
• Edema indicates too much fluid, and dehydration indicates a fluid loss.
• Sodium is the principal extracellular electrolyte, playing a major role in maintaining water concentration, and potassium is the major intracellular ion.

Crystalloids

• Crystalloids are solutions containing fluids and electrolytes normally found in the body that do not contain proteins.
• Crystalloids pose no risk for viral transmission, anaphylaxis, or alteration in coagulation profile, and are better for treating dehydration instead of expanding plasma volume.
• Crystalloids can compensate for insensible fluid losses, replace fluids, manage specific fluid and electrolyte disturbances, and promote urinary flow
• Normal saline (NS) is 0.9% sodium chloride which is isotonic, however 0.45% "half-normal" is hypotonic
• Hypertonic saline is 3% sodium chloride
• The following are isotonic fluids:
  • 3.3% dextrose and 0.3% NS (two thirds and one third)
  • Lactated Ringer's solution
  • Dextrose 5% in water (DW)
  • Plasma-Lyte
• D5W and 0.45% NS is hypertonic
• Crystalloids treat acute liver failure, acute nephrosis, adult respiratory distress syndrome, burns, cardiopulmonary bypass, hypoproteinemia, hemodialysis, deep vein thrombosis (reduction of risk), and shock.
• However, crystalloids may cause edema, especially peripherally or pulmonary, as they contain no large particles which leak out causing edema, and dilute plasma proteins, reducing colloid oncotic pressure.
• The effects may be short-lived, and prolonged infusions may worsen alkalosis or acidosis.
• Adverse effects of Crystalloid therapy May cause edema Especially peripheral or pulmonary Contain no large particles- leak ȧout into The tissues and Cells which causes Edema May dilute plasma proteins Reducing colloid oncotic pressure May be short-lived

Colloids

• Colloids are protein substances of big particles to increase colloid oncotic pressure
• Colloids move fluid from the interstitial compartment to the plasma compartment (when plasma protein levels are low) and are longer-lived.
• Colloids are:
  • Albumin 5% and 25% (from human donors)
  • Blood
  • Dextran 40 or 70 (available in sodium chloride and 5% dextrose) Hetastarch (synthetic)
• Adverse effects of colloids are usually safe, but may cause altered coagulation, resulting in bleeding.
• There are no clotting factors or oxygen-carrying capacity; rarely dextran therapy causes anaphylaxis or kidney failure.
• Albuminis a natural protein formed by the liver to generate approximately 70% of colloid oncotic pressure.
• Sterile solution of serum albumin prepared from pooled blood, plasma, serum, or placentas collected from healthy human donors, after pasteurization to destroy any contaminants.
• For blood to increase the plasma volume by 1L, one would administer a 5-6L 0.9% NS solution vs a 0.5L of 25% Colloid solution

Blood Products

• Blood products carries oxygen, increase tissue oxygenation and plasma volume
• Blood products are the most expensive and least available fluid because they require human donors.
• Blood products increase colloid osmotic pressure and plasma volume, which results in pulling fluid from extravascular space into the intravascular space thereby acting as plasma expanders
• Derived from human donors and benefits (and hazards) of human blood products
• Cryoprecipitate and plasma protein factors are indicated to manage acute bleeding of +50% slow blood loss or +20% acutely
• Fresh frozen plasma indication is to increase clotting factor levels in patients with demonstrated deficiency
• Packed red blood cells increase oxygen-carrying capacity in patients with anemia, substantial hemoglobin deficits, and those who have lost up to 25% of their total blood volume
• Whole blood is the same as packed red blood cells benefits except that whole blood is more beneficial in cases of extreme (+25%) loss of blood volume, including plasma proteins, which help draw fluid back into blood vessels from surrounding tissues
• Adverse effects may include:
  • Incompatibility with recipient's immune system that may cause reactions:
  • Incompatibility necessitates cross-match testing is required
  • Transfusion reaction
  • Anaphylaxis
  • Transmission of pathogens (i.e., hepatitis or HIV)

Electrolytes

• Sodium cations are the principal extracellular fluid electrolytes, and chloride anions.
• Potassium cation is the principal intracellular fluid electrolyte.
• Others are calcium, magnesium, and phosphorus.

Potassium

• Potassium is the most abundant positively charged (cationic) electrolyte
• 95% of the body's potassium resides inside cells.
• Extracellular K+ levels range from 3.5-5 mmol/L and are critical to normal body function.
• Dietary sources are bananas, oranges, apricots, dates, raisins, broccoli, green beans, potatoes, tomatoes, meats, fish, wheat bread, and legumes.
• Excess dietary potassium is excreted via the kidneys, but impaired kidney function leads to higher serum levels, causing possible toxicity.
• Hyperkalemia manifests as serum potassium level over 5.5 mmol/L
• Factors causing hyperkalemia includes:
  • Potassium supplements
  • Angiotensin-converting enzyme inhibitors
  • Kidney failure
  • Excessive loss from cells
  • Burns, trauma, metabolic acidosis, and infections
  • Potassium-sparing diuretics
• In the presence of digoxin therapy, hypokalemia can cause digoxin toxicity, resulting in serious ventricular dysrhythmias.
• Potassium is responsible for:
  • Muscle contraction, transmission of nerve impulses, regulation of heartbeat, maintenance of acid-base balance, isotonicity, and electrodynamic characteristics of the cell
• Therapeutically, potassium assists the treatment or prevention of potassium depletion when dietary means are inadequate, stops irregular heartbeats, and manages tachydysrhythmias after cardiac surgery.
• Adverse effects include diarrhea, nausea, vomiting, gastrointestinal bleeding, and ulceration but IV potassium administration can be even more dangerous and should be highly controlled.
• Potassium IV effects:
  • Pain at injection Site, phlebitis and excessive administration causes hyperkalemia, toxic effects, and cardiac arrest.
• The manifestations of hyperkalemia: muscle weakness, paresthesia, paralysis, and cardiac rhythm irregularities
• Severe hyperkalemia is treated with IV sodium bicarbonate, calcium gluconate or calcium chloride, dextrose with insulin, sodium polystyrene sulphonate (Kayexalate®) or hemodialysis.

Sodium

• Sodium maintains water concentration and is the most abundant positively charged electrolyte outside cells having a normal concentration of 135 - 145 mmol/L
• Found in salt, fish, meats, and flavored goods.
• Hyponatremia is a sodium loss or deficiency evidenced by serum levels drop to below 135 mmol/L
  • Symptoms include: lethargy, stomach cramps, hypotension, vomiting, diarrhea, and seizures.
  • Factors include same potassium issues: excessive perspiration, kidney disorders, and adrenocortical impairment, prolonged diarrhea or vomiting
• Hypernatremia represents sodium excess; serum levels over 145 mmol/L with:
  • Symptoms include: water retention (edema), hypertension, red, flushed skin, dry, sticky mucous membrane, increased thirst, elevated temperature; decreased cardiac output, decreased or absent urinary output.
  • A root cause is poor kidney excretion; inadequate water consumption and dehydration.
• Sodium is responsible for: control of water distribution, fluid and electrolyte balance, osmotic pressure of body fluids, and acid-base balance.
• The main indication is sodium depletion when dietary measures are inadequate
• Mild sodium depletion can be treated with oral sodium chloride, restricting fluids and severe cases, a treated oral IV with NS or lactated Ringer's solution.
• Dual arginine vasopressin V1A- and V2-receptor antagonists are a new drug class for euvolemic hyponatremia, tolvaptan (Samsca®) is often referred –vaptans often treat low sodium
• Adverse effects are nausea, vomiting, cramps from oral and venous phlebitis from I.V.

Nursing Implications of Electrolytes

• Assess baseline fluid volume and electrolyte status.

• Assess baseline vital signs as well as skin, mucous membranes, daily weights, and input and output.

• Before giving potassium, assess electrocardiogram.

• Assess for contraindications to therapy

• Assess transfusion history and establish venous access as needed as well as monitor serum electrolyte levels during therapy.

• Note the infusion rate, appearance of fluid or solution, and infusion site

• Observe infiltration and other complications of IV therapy; monitor the IV infusion due to the toxicity of the drug, never give as an IV bolus

• Note oral K additives are highly irritating to the gut and should be taken after eating with water or juice to help speed adsorption and mitigate N/V

• Administer colloids slowly, monitoring for fluid overload and possible heart failure.

• For blood products, follow administration procedures closely, and monitor closely for signs of transfusion reactions.

• Monitor therapeutic response based on normal laboratory values for:

  • Red blood cells
  • Electrolyte levels
  • White blood cells

• Improve fluid volume status, increased tolerance for activity, and note all adverse effects