renal pharm Flashcards
Acetazolamide, methazolamide, and dichlorphenamide are what class of diuretics?
MOA?
Carbonic anhydrase inhibitors
Decreases HCO3 and Na+ ( and water) reabsorption by inhibiting luminal carbonic anhydrase at the proximal tubule, causing less activity in the Na/H antiporter
What type of diuretic drugs work in the proximal tubule?
Carbonic anhydrase inhibitors
Acetazolamide, methazolamide, and dichlorphenamide
Osmotic diuretics-mannitol
What types of drugs fcn by decreasing HCO3 and Na+ ( and water) reabsorption by inhibiting luminal carbonic anhydrase at the proximal tubule, causing less activity in the Na/H antiporter
Carbonic anhydrase inhibitors
Acetazolamide, methazolamide, and dichlorphenamide
What are the main clinical complications of using CAI?
Hypokalemia resulting from potassium loss in the urine
Metabolic acidosis resulting from bicarb (HCO3) loss in urine
What drugs are used to decrease intraocular volume/pressure and the prevention and treatment of mountain sickness?
Carbonic anhydrase inhibitors
Acetazolamide, methazolamide, and dichlorphenamide
What are the 3 carbonic anhydrase inhibitors?
Acetazolamide, methazolamide, and dichlorphenamide
What is the MOA of mannitol?
Major use?
Osmotic diuretic: Opposes water and sodium reabsorption at proximal tubule to increase the overall osmolarity of tubular fluid
Major use: increased clearance of drugs, minimize renal failure (shock or surgery), decrease IOP or intracranial pressures, diagnose oliguria
What is the major side effect of osmotic diuretics?
Risk of pulmonary hypertension
________ increase the rate and volume of urine due to the filtration and presence of non-reabsorpable solute in the tubular fluid
Osmotic diuretic like mannitol or glucose
Furosemide, bumetanide, torsemide, and ethacrynic acid are what class of diruetic? MOA?
Loop diuretics-most efficacious of the diuretics
MOA: Inhibits the Na-K-2Cl cotransporter in the luminal membrane at medullary and cortical (proximal) talH (thin ascending loop)–> decreased K+, Ca++, an Na+ reabsorption, resultant K+ loss
Which diuretics act in the early distal tubule?
Thaizide diuretics
Chlorothiazide, hydrochlorothiazide,
Chlorothiazide, hydrochlorothiazide are what class of diuretic? MOA?
Thiazide diuretics
MOA: Inhibits the Cl portion of the Na-Cl cotransporter in the luminal membrane at the early distal tubule –> deceased Na+ (and water) reabsorption, increased Ca++ reabsorption, resultant K+ loss
Which of the following diuretics would be most useful in the acute treatment of a comatose patient with traumatic brain injury and cerebral edema?
Acetazolamide Amiloride Chlorothiazide Furosemide Mannitol
Answer: Mannitol
Giving an IV infusion of an osmotic diuretic is used acutely to raise the osmolarity of the plasma and drive water out of the cells of the edematous brain. This will serve to reduce the intracranial pressure rapidly, possibly before irreversible damage to the brain occurs. Furosemide may also be used to achieve the same clinical objective, but the onset of action to increase plasma osmolarity would be less rapid than giving mannitol intravenously.
A 60 year-old patients complains of paresthesis and occasional nausea associated with one of her drugs. She is found to have hyperchloremic metabolic acidosis. She is most likely taking which one of the following drugs?
Acetazolamide for glaucoma
Amiloride for edema associated with hyperaldosteronism
Furosemide for severe hypertension and heart failure
Hydrochlorthiazide for for hypertension
Mannitol for cerebral edema
Answer: acetazolamide for glaucoma
Paresthesia is an abnormal sensation such as tingling, tickling, pricking, numbness or burning of a person’s skin. Paresthesia and gastrointestinal distress are common adverse effects of acetazolamide, especially when taken chronically for treatment of glaucoma. The observation that the patient has metabolic acidosis also suggests the use of acetazolamide.
Metabolic acidosis is a side effect of which class of diuretic drugs?
Carbonic Anhydrase Inhibitors
Acetazolamide
Methazolamide
Dichlorphenamide
Deceases Na+ (and water) and HCO3 reabsorption to the blood…therefore causing acidosis
A 70 year-old retired businessman is admitted with a history of recurrent heart failure and metabolic derangements. He has marked peripheral edema and metabolic alkalosis. Which one of the following drugs is the best treatment option for his edema?
Acetazolamide Digoxin Dobutamine Eplerenone Hydrochlorothiazide
Answer: Acetazolamide
Although acetazolamide is rarely used in patients with heart failure, carbonic anhydrase inhibitors are an effective therapy in patients with edema and metabolic alkalosis. The high bicarbonate levels in these patients make them particularly susceptible to the action of CAI’s. Digoxin is useful in chronic systolic failure but is not a first line therapy. Dobutamine is appropriate only when diuresis has already been accomplished in severe acute failure. Hydrochlorothiazide and spironolactone are not sufficiently effective for treatment of the edema in heart failure to be the diuretic of choice.
A 58 year-old man with lung cancer has abnormally low serum osmolarity and hypo-natremia. A drug that increases the formation of dilute urine and is used to treat SIADH is?
Acetazolamide Amiloride Desmopressin Ethacrynic acid Hydrochlorothiazide Mannitol Spironolactone Triamterene Tolvaptan
Answer: tolvaptan
The Syndrome of Inappropriate Anti-Diuretic Hormone (SIADH) causes an inappropriately high negative free water clearance manifested by retention of water in excess of solute, diluting the plasma Na concentration (hyponatremia) and an inability to form dilute urine in the fully hydrate patient. Competitive antagonists of ADH are useful in these patients to block the effect of inappropriately high circulating levels of ADH and thus reduce and prevent an expanded ECF volume, hypo-natremia and hypo-osmolarity. SIADH patients taking the vaptan class of aquaretic drug will excrete a larger volume of dilute urine, returning plasma volume, Na concentration and plasma osmolarity towards normal levels.
A 62 year-old man with advanced prostate cancer is admitted to the ED with mental obtundation. An electrolyte panel shows a serum Ca++ well above normal levels. Saline infusion and which one of the following drugs would be most useful in the management of his severe hypercalcemia?
Acetazolamide Furosemide Hydrochlorothiazide Mannitol Spironolactone
Answer: Furosemide
The clinical objective of diuretic drug therapy for treatment of hypercalcemia is to decrease the renal reabsorption of calcium in the nephron and thus increase calcium excretion in the urine. Loop diuretics decrease calcium reabsorption in the thick ascending limb of the loop of Henle. To offset the effect of the diuretic to reduce ECF and blood volume, which would limit the reduction in plasma calcium concentration, an infusion of saline together with the diuretic will be most effective in correcting the hypercalcemia.
Which two drugs can be used to treat SIADH? Ethacrynic acid Hydrochlorothiazide Mannitol Conivaptan Spironolactone Triamterene Tolvaptan
Conivaptan
Tolvaptan
Vasopressin (ADH) receptor antagonist working at the collecting duct to increase free water clearance
Which class of diuretic can be used to treat hypercalcemia?
Loop diuretics
Loop diuretics decrease calcium reabsorption in the thick ascending limb of the loop of Henle. To offset the effect of the diuretic to reduce ECF and blood volume, which would limit the reduction in plasma calcium concentration, an infusion of saline together with the diuretic will be most effective in correcting the hypercalcemia.
A medical student is planning to make a high-altitude climb in South America while on vacation and she will not have time to acclimate to altitude slowly. A drug useful in prevention of high-altitude sickness is?
Acetazolamide Triamterene Demeclocycyline Desmopressin Ethacrynic acid
Answer: Acetazolamide
Carbonic anhydrase inhibitors are indicated for the prevention of altitude sickness. How carbonic anhydrase inhibitors prevent altitude sickness is unknown.
A 70 year-old women is admitted to the ED because of a “fainting spell” at home. She appears to have suffered no trauma, but her BP is 120/60 when lying down and 60/20 when she sits up. Neurological exam and ECG are normal when she is lying down. Questioning reveals that she has recently started taking “water pills” for a heart condition. Which one of the following drugs most likely caused her fainting spell?
Acetazolamide Amiloride Furosemide Hydrochlorothiazide Spironolactone
Answer: Furosemide
The case history suggests that the syncope (fainting) is associated with diuretic use. Complications of diuretics that can result in syncope include both postural hypotension (as described) due to excessive reduction of blood volume and arrhythmias due to excessive potassium loss in the urine. Potassium wasting is more common with thiazides because of their long duration of action, but these drugs rarely cause a reduction in blood volume sufficient to induce orthostatic hypotension.
Loop diuretics are the most potent and can cause rapid fluid loss
Which one of the following is an important effect of chronic therapy with loop diuretics?
Decrease urinary excretion of Ca++ Elevated blood pressure Elevated pulmonary vascular pressure Metabolic alkalosis Teratogenicity in pregnancy
Loop diuretics increase urinary calcium excretion and decrease blood pressure in hypertensive patients and pulmonary vascular pressure in congestive heart failure patients. Loop diuretics have no teratogenic effects on the normal development of the fetus. The important side effects of loop diuretics are “contraction” alkalosis, hypokalemia and ototoxicity.
What two classes of diuretic drugs can cause contraction alkalosis?
Loop diuretics
Thaizide diuretics
What diuretics are the most potent?
Loop diuretics…may cause rapid fluid loss and lead to syncope or orthostatic hypotension
The important side effects of ________ are “contraction” alkalosis, hypokalemia and ototoxicity.
loop diuretics Furosemide Bumetanide Torsemide Ethacrynic Acid
Which of the following drugs is correctly associated with its site of action and maximal diuretic efficacy?
Thiazide – distal convoluted tubule – 7% of filtered Na+
Spironolactone – proximal convoluted tubule – 40% of filtered Na+
Bumetanide – thick ascending limb of Loop of Henle – 15% of filtered Na+
Metolazone – collecting tubule – 2% of filtered Na+
Mannitol – distal convoluted tubule – 18% 0f filtered Na+
Thiazide – distal convoluted tubule – 7% of filtered Na.
Spironolactone acts in the collecting tubule not the proximal convoluted tubule and does not increase the excretion of Na to 40% of the filtered load of Na. The loop diuretic Bumetanide is a highly effective saluretic, increasing Na excretion to levels much more than 15% of the filtered load of Na. Metolazone, a thiazide-like diuretic, acts in the distal convoluted tubule, not the collecting tubule. Mannitol’s action to induce diuresis is attributed mostly to an effect of decreasing fluid reabsorption in the proximal tubule and induces a small increase the fractional excretion of Na, due mostly to downstream compensatory Na reabsorption.
Where does the following class of drug fcn in the nephron? Carbonic anhydrase inhibitors
Proximal tubule
Acetazolamide
Methazolamide
Dichlorphenamide
