week 8 pharm Flashcards
what is a diuretic
- Drugs that accelerate the rate of urine formation
- Effective treatment of hypertension and heart failure
- Result: removal of sodium and water
- Medications that augment “diuresis”
- Commonly known as “water pills”
- Used to treat heart failure, liver cirrhosis,
hypertension and certain kidney diseases
where is most sodium reabsorbed
- 20 to 25% of all sodium is reabsorbed into the bloodstream in the ascending loop of Henle
- 5 to 10% of sodium reabsorption takes place in the distal convoluted tubules
- 3% takes place in the collecting ducts
- If water is not absorbed, it is excreted as urine
MOA of most diuretics
- Most diuretics share the same basic mechanism of action which is the
blockade of sodium and chloride reabsorption - By blocking the reabsorption of these prominent solutes, diuretics
create osmotic pressure within the nephron that prevents the passive reabsorption of water - The increase in urine flow that a diuretic produces is directly related
to the amount of sodium and chloride reabsorption that it blocks
drugs that act early on the nephron do what
- Drugs that act early in the nephron have the opportunity to block the
greatest amount of solute (Na+) reabsorption and produce the
greatest amount of diuresis - Cause direct arteriolar dilation, decreasing peripheral vascular
resistance & reduce: - extracellular fluid volume
- plasma volume
- cardiac output
severe side effects of diuretics
- Severe potassium deficiencies
- Electrolyte imbalance
- Extreme Weakness
- Fatigue
Loop Diuretics (Furosemide, Lasix):
Mechanism of Action
Act directly on the ascending limb of
the loop of Henle to inhibit chloride and
sodium reabsorption
Increase kidney prostaglandins,
resulting in the dilation of blood
vessels and reduced peripheral
vascular resistance
- significant amount of diuresis
- Results in:
- Reduces blood pressure
- Reduces pulmonary vascular
resistance - Reduces systemic vascular
resistance - Reduces central venous pressure
- Reduces LVED pressure
Loop Diuretics:
Indications
- Edema associated with heart failure or hepatic or renal disease
- Control of hypertension
- Hypercalcemia (increase renal excretion of calcium)
- Certain cases of heart failure resulting from diastolic dysfunction
Loop Diuretics:
Contraindications
- Known drug allergy
- Allergy to sulfonamide antibiotics (caution; crosssensitivity is rare)
- Hepatic coma
- Severe electrolyte loss (especially K+ which may require potassium replacement)
loop diuretic advantage over thiazide diuretics
Can be given with renal failure
Still work when CrCl falls below 25 ml/min
K needs to be in normal range for which loop diuretic
dogoxin
Loop Diuretics: Adverse
Effects
- Central nervous Dizziness, headache, system (CNS) tinnitus, blurred vision
- Gastrointestinal (GI) Nausea, vomiting, diarrhea
- Hematological Agranulocytosis, neutropenia, thrombocytopenia
- Metabolic Hypokalemia,
hyperglycemia, hyperuricemia
Carbonic Anhydrase
Inhibitors (CAIs) -
Acetazolamide MOA
- Inhibits the enzyme carbonic anhydrase
found in kidneys, eyes and other areas of
the body - Acts in the proximal tubule
- Reduces the formation of HCO3 & H+
- Results in the release of H20 & sodium
– diuresis
indications of CAIs
- Primarily high-altitude sickness (Sx
include H/A, nausea, SOB, dizziness,
drowsiness & fatigue) - Glaucoma
- Edema secondary to heart that has
become resistant to other drugs
Adverse effects &
interactions of CAI
- Metabolic acidosis
- Hypokalemia
- Contraindicated in sever liver or kidney dysfunction
Osmotic Diuretics
[mannitol
(Osmitrol)]:
Mechanism of
Action
- primarily act in the proximal tubule and throughout the nephron.
-They are nonabsorbable, creating an osmotic effect that pulls water into the renal tubules, leading to rapid diuresis.
-They can also shift fluid from intracellular to intravascular spaces.
-These diuretics result in minimal loss of electrolytes, particularly sodium, making them unsuitable for treating peripheral edema.
Osmotic Diuretics:
Indications
- Treatment of patients in the early, oliguric
phase of acute renal failure - To promote the excretion of toxic substances
- Reduction of intracranial pressure (important)
- Treatment of cerebral edema (important)
- Elevated intraocular pressure (glaucoma)
- administered IV only
Osmotic Diuretics:
Contraindications
- Contraindications:
- Known drug allergy
- Severe kidney disease
- Pulmonary edema (loop diuretics are used
instead) - Active intracranial bleeding (imporant)
Osmotic Diuretics:
Adverse effects
- Adverse Effects
- Convulsions
- Thrombophlebitis
- Pulmonary congestion
- Headaches, chest pains, tachycardia, blurred vision, chills, and fever
Potassium-Sparing
Diuretics [spironolactone
(Aldactone)]:
Mechanism of Action
-Potassium-sparing diuretics work primarily in the collecting ducts and distal convoluted tubules.
-They interfere with sodium-potassium exchange by competitively binding to aldosterone receptors, which blocks sodium and water resorption normally induced by aldosterone.
-This promotes the excretion of sodium and water while retaining potassium, making them useful for conditions where potassium preservation is desired.
-Low diuresis
Potassium-Sparing
Diuretics: Indications
- Hyperaldosteronism
- Hypertension (generally once 3 drugs haven’t controlled blood pressure)
- To reverse the potassium loss caused by
potassium-losing drugs - Heart failure (most heart failure guidelines have indications for this drug class) – there are exception
Potassium-Sparing
Diuretics: contradictions
- Known drug allergy
- Hyperkalemia
- Severe kidney failure or anuria
Potassium-Sparing
Diuretics: adverse effects
- Hyperkalemia
- Gynecomastia (enlarged breasts in men)
- Amenorrhea
- Irregular menses
- Postmenopausal bleeding
- Sexual dysfunction (?)
Potassium-Sparing
Diuretics drug interactions
- lithium
- angiotensin-converting enzyme (ACE) inhibitors
- Potassium supplements
Thiazide and
Thiazide-Like
Diuretics
hydrochlorothiazide
or indapamide:
Mechanism of
Action
- low diuresis
-Thiazide diuretics inhibit the tubular reabsorption of sodium, chloride, and potassium ions
-primarily acting in the distal convoluted tubule.
-They promote the excretion of water, sodium, and chloride, with some potassium loss.
-Additionally, they cause direct relaxation of arterioles, leading to lowered peripheral vascular resistance and contributing to their antihypertensive effects.
