Diuretics Flashcards
GFR can be preserved by autoregulation within a MAP range of…
50-150 mmHg
Hypertensive patients have a _______ GFR when RBF is constant.
higher
What are the two mechanisms of autoregulation of RBF and GFR?
Myogenic and tubuloglomerular
Explain myogenic autoregulation
Increased arterial pressure stretches afferent arteriolar wall causing reflex constriction. Conversely, decreased arterial pressure causes arteriolar dilation.
Explain tubuloglomerular autoregulation.
Decreased renal blood flow causes decreased GFR which results in afferent arteriolar dilation, increasing GFR and RBF, restoring filtration
Causes renin to be released which stimulates angiotensin II which increases GFR
What are the components of urine?
Water, electrolytes, waste products, pharmacologic metabolites
Indications for diuretics
Hypertension; pulmonary/peripheral edema; electrolyte and pH imbalances; high ICP/brain bulk; prevent acute renal failure due to ischemic insult; drug clearance
Name classification of diuretics
Thiazide Loop Osmotic Potassium-sparing Carbonic anhydrase inhibitors
Name 4 loop diuretics
Furosemide
Torsemide
Bumetanide
Ethacrynic Acid
Loop diuretic MOA
Inhibit reabsorption of NaCl in ascending loop; water follows NaCl, leading to a decrease in intravascular volume
What is the most effective diuretic class?
Loop diuretics
Which works faster, loop or thiazide diuretics?
Loop
Loop diuretics can be used to speed the…
excretion of drugs
Loop diuretics stimulate production of…
prostaglandins which lead to vasodilation and increase RBF; does NOT increase GFR
Indications for loop diuretics
Rapid intravascular fluid removal; hyperkalemia treatment; acute pulmonary edema; kidney stone extraction; reduce ICP (diuresis and decrease CSF production), sometimes with mannitol
Loop diuretic adverse effects
Hypokalemia
Digoxin toxicity
Large doses increase cAMP, patients RESISTANT to NMB
Small doses decrease cAMP, patients SENSITIVE to NMB
Ototoxicity (deafness)
Clinical implications of loop diuretic use
K+/fluid volume replacement may be needed
Cardiac dysrhythmias
Mild hyperglycemia
Name some thiazide diuretics
Chlorothiazide Chlorthalidone Indapamide Hydrochlorothiazide Benzthiazide Cyclothiazide Metolazone
MOA of thiazide diuretics
Inhibits reabsorption of NaCl in loop, proximal, and distal tubules; reduces edema and intravascular fluid volume; vasodilation by decrease in SNS in peripheral smooth muscles by decreasing total body Na+ stores; excretion of Na+, Cl-, Bicarb, Mg+, and K+
Indications for thiazide diuretics
Hypertension, edema from CHF, renal failure
Thiazide diuretics are often used in combination with…
antihypertensive drugs
Which causes more K+ excretion, loop or thiazide diuretics?
Loop
Clinical concerns with thiazide diurectics
Low K+, Mg+, Cl-, and hypochloremic metabolic alkalosis
Hyperglycemia, hyperuricemia (gout)
Dig toxicity, dysrhythmias, muscle weakness, neuropathy, NMB potentiation caused by hypokalemia
K+ and fluid volume replacement may be indicated
Name two osmotic diuretics
Mannitol and urea
Osmotic diuretic MOA
Osmotic diuresis by increased plasma osmolarity in proximal convoluted tubule and Loop of Henle; does NOT alter GFR
Large MW molecule is filtered but too large to reabsorb back
Causes acute osmotic expansion of intravascular fluid volume which is then filtered
Osmotic diuretic adverse effects
Mostly resolved when water is eliminated: Rebound hypertension with non-intact BBB Pulmonary edema Exacerbated CHF Electrolyte disturbances
Indications for mannitol
Reduce ICP and brain bulk
Reduce refractory intraocular hypertension
Urinary excretion of toxic materials
What kind of diuretic is spironolactone?
Aldosterone antagonist
Spironolactone MOA
Competes with aldosterone, secrete Na+ and Cl-
Aldosterone antagonists are often used in conjunction with…
thiazide diuretics
Indications for aldosterone antagonist/spironolactone
CHF, liver cirrhosis edema (which are caused by increased aldosterone)
SE of aldosterone antagonist
Hyperkalemia
Name two potassium sparing diuretics
Triamaterene
Amiloride
Potassium sparing diuretic MOA
Spares potassium independent of aldosterone
Weak diuresis via distal tubules and collecting ducts
Increased excretion of Na+, Cl+, Bicarb
Potassium sparing diuretics are NOT used alone but in combination with…
Loop diuretics to limit K+ losses in the distal tubule
Potassium sparing diuretic SE
Hyperkalemia - caution with ACEI and NSAIDs which cause increased K+
Name two carbonic anhydrase inhibitors
Acetazolamide
Methazolamide
MOA of carbonic anhydrase inhibitors
Works in proximal tubules blocking Na+ and bicarb and causing diuresis
Carbonic anhydrase inhibitor indication
Glaucoma - reduce intraocular pressure by decreasing aqueous humor
Carbonic anhydrase inhibitor side effects
Hyperchloremic metabolic acidosis
Drowsiness
Paresthesia
Renal calculi
Vasopressin receptor antagonist “vaptan” MOA
Selective V2 receptor antagonist in renal collecting duct
Treat SIADH, CHF, liver cirrhosis; hyponatremia associated with normal volume status
Tolvaptan only FDA approved drug
Dopamine receptor agonist MOA
D1 receptors in proximal renal tubule and loop of Henle cause increased RBF and GFR and natriuresis (Na+ excretion)
Dopamine and Fenoldopam
Low dose only (large dose causes sympathetic outflow)
Atrial natriuretic peptide antagonist MOA
ANP produced in atria, ventricles, and renal system in response to atrial and ventricular distension;
Blocks basal Na-K-ATPase channel causing arterial/venous dilation, decreased venous return, decreased CO and natriuresis
Nasiritide only FDA approved drug
MOA of neprilysin antagonist
Since Neprilysin metalloproteinase breaks down BNP and ANP, antagonist increases circulating levels of BNP and ANP, indirectly causing natriuresis
Used in combo with ACEI for natriuresis and dec BP in CHF patients
Entresto: sacubritril/valsartan
- SE: hypotension & hyperkalemia
