Pharmacology Chapter 24 Diuretic Therapy and Drugs for Renal Failure

Kidney regulation affects

Fluid volume
Electrolytes
Acid base balance

Kidney secretions

Renin
Erthropoietin
Calcitrol

Renin

For blood pressure regulation

Erythropoietin

Stimulate RBC production

Calcitriol

Active vitamin D for bone homeostasis

Urinary system consists of how many kidneys

2

Urinary system consists of how many ureters

2

Urinary system consists of how many bladders

1

Urinary system consists of how many urethras

1

Nephron

Functional units of the kidney

Blood that enters the nephrons is filtered through

The glomerulus

Water and small molecules that enter the nephron pass into

The proximal tubule

What materials are reabsorbed in the urinary system

Glucose
AAs
Na
Cl
Ca
Bicarbonate

What materils are secreted into the filtrate

K
PO4
H+
NH4
Acidic drugs

Renal failure

Decrease in kidney's ability to function
Drugs can accumulate to high lvls

What changes must be done to meds for those with renal failure

Doses are to be adjusted

Administering an average dose to those with renal failure can cause

Fatality

How can renal failure be diagnosed?

Urinalysis
Serum creatinine
Diagnostic imaging
Renal biopsy

Glomerular filtration rate (GFR)

Best marker for estimating renal function
Measure volume of filtrate passing through Bowman's capsule per minute

Acute renal failure

requires immediate treatment
Accumulation of wastes can be fatal
Most common cause is hypoperfusion

Acute renal failure can be caused by

Heart failure
Dysrhythmias
Hemorrhage
Dehydration

Chronic renal failure

Occurs over months or years
Usually includes history of diabetes mellitus or hypertension
Nephrotoxic drugs can be a cause of acute or chronic renal failure

Anemia pathogenesis

Kidneys unable to synth enough erythropoietin for RBC production

Hyperkalemia

Kidneys are unable to adequately excrete K

Hyperphosphatemia

Kidneys are unable to adequately ecrete PO4

Hypervolemia

Kidneys are unable to excrete sufficient Na and H2O = water retention

Hypocalcemia

Hyperphosphatemoa = Ca loss

Metabolic acidosis

Kidneys unable to excrete metabolic acids well

Diuretics

Increase rate of urine flow

Diuretics are used to treat

Hypertension, heart failure, kidney failure
Liver failure/cirrhosis, pulmonary edema

Carbonic anhydrase inhibitors

Inhibit reabsorption of bicarbonate ions in proximal tubule

Carbonic anhydrase adverse effects

Allergies(for those allergic to sulfa)
Fluid and electrolyte imbalances

Carbonic anhydrase primary use

Decrease intraocular fluid pressure in patients with open angle glaucoma

Carbonic anhydrase inhibitor mechanism of action

Inhibit carbonic acid formation

Osmotic diuretics

Act on proximal tubule & Henle loop
Creates osmotic force that pulls water into nephron= Increases electrolyte excretion

Osmotic diuretic primary use

Reduce intracranial pressure due to cerebral edema

Osmotic diuretic mechanism of action

Inhibits carbonic anhydrase

Loop diuretics

Act on ascending loop of Henle
Block Na, Cl, H2O reabsorption
Increased K excretion

Thiazide diuretics

Act on early distal tubule
Block Na, Cl, H2O reabsorption
Increased K excretion

Potassium sparring diuretics

Act on late distal tubule and collecting ducts
Block NA reabsorption
Reduce K secretion

Adverse effects of diuretic therapy

Fluid & electrolyte disturbances
Dehydration
Orthostatic hypotension
K and Na imbalances

Loop diuretics mechanism of action

Block Na and Cl reabsorptionin loop of Henle

Primary use of loop diuretics

Reduce edema assoc w heart, hepatic cirrhosis, renal failure
Furosemide and torsemide also approved for hypertension

Loop type diuretic prototype drug

Furosemide (Lasix)

Furosemide uses

Acute heart failure treatment (has ability to remove large amounts of excess fluid from patient)
Beneficial when cardiac output and renal flow are severly diminished

Furosemide (Lasix) when given IV, diuresis begins within

5 minutes, giving patient quick symptom relief

Furosemide (Lasix) action

Preventing reabsorption of Na and Cl in loop of Henle region of the nephron

Furosemide (Lasix) administration alerts

Check patient's serum potassium lvls before administering the drug
If potassium lvls are below normal, contact doctor before administering
Older adults need less of a dose

Furosemide (Lasix) administration alerts in neonates and premature infants

Handle drug with caution due to the drug's prolonged half life

Furosemide (Lasix) adverse effects

Potential electrolyte imbalances
Hypokalemia
Fluid loss/ dehydration and hypotension (MONITOR)
Hypovolemia= orthostatic hypotension and syncope
Ototoxicity= hearing deficit

Furosemide (Lasix) black box warnings

If given in excessive amounts, may lead to profound diuresis with water and electrolyte depletion

Furosemide (Lasix) contraindications

Hypersensitivity to furosemides/ sulfonamides,
anuria
hepatic coma
severe fluid/electrolyte depletion

Furosemide (Lasix) overdose treatment

Overdose= Hypotension and severe fluid/electrolyte loss
Supportive treatment
Replacement of fluids and electrolytes
Possible administration of a vasopressor

Thiazide diuretics mechanism of action

Block Na+ reabsorption and increase K+ & H2O excretion

Thiazide diuretic primary use

Treat mild to moderate hypertension
Also indicated to reduce edema assoc w heart, hepatic and renal failure

Thiazide diuretics are not effective for

Patients with severe renal failure

Thiazide diuretic prototype drug

Hydrochlorothiazide (Microzide)

Hydrochlorothiazide (Microzide) action

Decreases Na+ reabsorptionin kidney tubule
More Na+, and water is sent to the urine= blood volume decreases and blood pressure falls

Using Hydrochlorothiazide (Microzide), the volume of urine produced is directly proportional to

The amount of sodium reabsorption blocked by the diuretic

Hydrochlorothiazide (Microzide) administration alers

Administer early in day to prevent nocturia
Pregnancy category B

Hydrochlorothiazide (Microzide) adverse effects

Potential electrolyte imbalance due to excessive K+ and Na+
Gout attacks
Hyperuricemia
Cardiac conduction abnormalities

Hydrochlorothiazide (Microzide) contraindications

Anuria
Prior hypersensitivity to thiazides and sulfonamides
Pre-eclampsia
Pregnancy induced HTN

Hydrochlorothiazide (Microzide)- antihypertensive interactions

Additive/synergistic effects on blood pressure

Hydrochlorothiazide (Microzide)- anticoagulants, sulfonylureas, and antidiabetic drugs (ex. insulin) interactions

Decrease effectiveness

Hydrochlorothiazide (Microzide)- cholestyramine and colestipol interactions

Decrease hydrochlorothiazide absorption and effectiveness

Hydrochlorothiazide (Microzide)- NSAIDs interactions

Increased risk of renal toxicity

Hydrochlorothiazide (Microzide)- Corticosterioids and amphotericin B interactions

Increase K+ loss when given with Hydrochlorothiazide (Microzide)

Hydrochlorothiazide (Microzide)-Lithium interactions

Lithium excretion decreases= Li toxicity

Hydrochlorothiazide (Microzide) overdose treatment

Overdose manifests as electrolyte depletion
Treated with infusions of fluids containing electrolytes to prevent dehydration and hypotension

Advantage of potassium-sparring diuretics

Diuresis without affecting blood potassium lvls

Potassium-sparing diuretic mechanism of action

Either by:
Blocking Na+ or by blocking aldosterone

Aldosterone

Hormone that controls renal reabsorption of sodium and potassium, causing water retention
Secreted by adrenal cortex

Potassium-sparing diuretic prototype drug

Spironolactone (Aldactone)

Spironolactone (Aldactone) uses

Treat mild hypertension in combo with other antihypertensives
Reduce edema assoc w kidney or liver disease
Slowing progrssion of heart failure

Spironolactone (Aldactone) action

Inhibits aldosterone , increasing Na+ and water excretion and body retains more K+

Spironolactone (Aldactone) administration alerts

Give with food to increase drug absorption
Do not give K+ supplements
Pregnancy category C

Spironolactone (Aldactone) adverse effects

Hyperkalemia (increased risk with K+ supplements or concurrent use with ACE inhibitors)
Gynecomastia impotence and diminished libido (men)
Menstrual irregularities, hirsutism, breast tenderness (women)

Signs/ symptoms of hyperkalemia

Muscle weakness
Fatigue
Bradycardia

Spironolactone (Aldactone) black box warnings

Causes tumors in animals in clinical studies

Spironolactone (Aldactone) contraindications

Anuria
Renal function impairment
Hyperkalemia
Pregnancy and lactation

Spironolactone (Aldactone)- ammonium chloride interaction

Acidosis

Spironolactone (Aldactone)- aspirin and other salicylates interactions

Increased half life= digoxin toxicity

Spironolactone (Aldactone)- concurrent digoxin use interactions

Decreased digoxin effects

Spironolactone (Aldactone)- potassium supplements, ACE inhibitors and angiotension receptor blockers (ARBs) interactions

Hyperkalemia

Spironolactone (Aldactone)-concurrent antihypertensive use interactions

Hypotensive effect

Spironolactone (Aldactone) overdose treatment

Supportive therapy
Agents to replace fluid and electrolyte loss for diuresis to raise blood pressure

Carbonic anhydrase inhibitors

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