Pharmacology-Diuretics Flashcards
A 59 year old male presents to your clinic complaining of increasing peripheral edema. History reveals stage IV renal failure and CHF. Why might this patient lose his hearing if you prescribe him loop diuretics?
Diuretics (except spironolactone) have lumenal activity. If GFR is decreased, the diuretic cannot be delivered and may build up in the blood. Loop diuretics inhibit Cl pumps, which also exists in the inner ear. Blocking these pumps can cause deafness.
What renal structures must be intact if you are going to prescribe a diuretic (not spironolactone)?
The PCT (where most drugs are secreted into the lumen) and GFR.
What diuretic classes act on the section of the nephron shown below?
Proximal Tubule: 1=Acetazolamide, 2=Osmotic agents, 3=Loop agents, 4=Thiazides
What diuretic classes act on the section of the nephron shown below?
Henle’s Loop: 2=Osmotic agents, 3=Loop agents.
What diuretic classes act on the section of the nephron shown below?
Distal Tubule: 3=Loop agents, 4=Thiazides
What diuretic classes act on the section of the nephron shown below?
Collecting duct: 5=Aldosterone antagonists, 6=ADH antagonists, 2=Osmotic agents.
What portion of the nephron reabsorbs the majority of the salt and water that is filtered through the glomerulus? How much?
65-70% filtered NaCl and 60% filtered H2O.
What enzyme is required at the proximal tubule in order to secrete H+?
Carbonic acid
What are the major mechanisms of sodium entry in the proximal tubule?
Exchange pump: Na+/H+. Cotransporter: Na+/Glucose, Na+/Amino Acids, Na+/Phosphate and Na+/Organic Solutes (Urate)
How do we know the proximal tubule is the major site of ammonia production in the nephron?
It is the major site of Glutamine metabolism.
What solutes are reabsorbed in the Loop of Henle? How much?
50% filtered Mg2+, 35-40% filtered NaCl and 20-30% filtered Ca2+.
What is the major mechanism of sodium entry in the Loop of Henle?
Active Na+/K+/2Cl- cotransporter. (Note that NH3 can substitute for K+)
What solute is reabsorbed at the distal tubule? How much?
5-8% filtered NaCl.
What triggers Ca2+ secretion at the distal tubule?
PTH binding to its receptor
What is the major mechanism of sodium entry in the distal tubule?
Cotransport: Na+/Cl-
What is the tonicity of the urine at the thin descending loop of Henle and at the start of the distal tubule?
Thin descending limb = hypertonic. Start of distal tubule = hypotonic. This is because the thick ascending limb reabsorbs 10-20% of the solutes in the urine.
What solutes are reabsorbed in the collecting duct?
Principal cells: reabsorbs Na+ and Cl-. Intercalated cells: reabsorbs K+
What solute are secreted in the collecting duct?
Principal cells: secrete K+. Intercalated cells: secrete H+, K+ and HCO3 in metabolic alkalosis
What factors determine the pH of the urine at the collecting duct?
NH4 & H+
What determines how concentrated the urine will be in the collecting ducts?
ADH controls water and urea reabsorption in the collecting duct. Aldosterone controls Na reabsorption in the collecting duct.
What diuretic is used by mountain climbers?
Acetazolamide. It inhibits carbonic acid, blocking reabsorption of bicarbonate and lowering the pH which will help fix alkalosis caused by hyperventilation at high altitude.
Why is acetazolamide considered a diuretic?
Decreasing the amount of bicarbonate produced decreases the amount of H+ produced. This has an inhibitor effect on Na+ reabsorption because of the Na/H exchanger.
A 34 year old woman comes to see you with a headache and new onset seizure. Optical exam reveals retinal edema indicating increased intracranial pressure. MRI reveals several brain tumors. What drug could you give this patient while she awaits surgery to relieve intracranial pressure? What contraindication do you need to check before prescribing?
Mannitol. This complex carbohydrate will increase the osmolality in the collecting duct and take fluid off, relieving her edema. The only kicker is that she must have good kidney function for mannitol to circulate and work properly.
Why do you sometimes give loop diuretics to patients with bone cancer?
They typically have hypercalcemia. Inhibiting the Na/K/2Cl transporter in the loop of Henle will diminish the electrochemical gradient Ca2+ needs to be reabsorbed and more Ca2+ will be excreted in the urine.
A 65 year old male comes to see you with a history of hypertension with a new onset of congestive heart failure. Physical exam reveals 3+ pitting edema at the ankles. CXR reveals increased vascular markings and fluid in the alveolar spaces. What drugs can you give to this patient for short-term relief of this acute edema?
Loop diuretic. These will inhibit Na+ reabsorption and pull water out.
A 54 year old woman comes to see you with nephrotic syndrome and chronic renal failure secondary to diabetes. Labs reveal hypoalbuminemia. Physical exam reveals 4+ pitting edema at the ankles and retinopathy. What drugs could you give this patient for short-term relief of edema?
Loop diuretics.
What drug might you consider prescribing to a patient with CHF that is not seeing results with Furosemide?
Bumetanide. Patients with CHF have gut edema and decreased GI absorption of drugs. Bumetanide has a higher oral bioavailability than Furosemide.
What pathological conditions tend to decrease overall responsiveness to diuretics?
Anything that increases Na+ reabsorption in the nephron (CHF, nephrotic syndrome and cirrhosis)
What causes the results seen in the graph below?
Over time the kidney becomes resistant to the diuretics.
A 45 year old woman presents with essential hypertension of unknown duration. Physical exam reveals thickened retinal arterioles. What is a good drug to start managing this patient’s hypertension? When would you know if this drug is working or not?
They are vasodilators AND diuretics. They should be working by about 10-14 days as Na+ and K+ re-equilibrate.
Why should you use low-dose thiazides as opposed to high-dose thiazides?
High-dose has shown legation in plasma cholesterol, glucose and insulin resistance. These all contribute to CV disease. Hypokalemia and hypomagnesemia also puts patients at further risk for cardiac events.
Why do diuretic tend to cause hypokalemia?
They increase flow rate which maintains an osmotic gradient toward the tubule that causes increased K+ secretion.
What is the point of using K+ sparing diuretics?
Loop diuretics and thiazides tend to cause hypokalemia. K+ sparing diuretics block Na+ channels so that Na+ entering from the tubule does not displace intracellular K+ out into the tubule.
A 55 year old woman with end stage liver disease, anasarca and ascites comes to your office. Physical exam reveals periorbital edema and spider angiomas. What drug would be a good idea to help this woman get rid of fluid slowly over the next few weeks?
Spironolactone.
What drug is used post-MI to minimize scarring in the heart and damage to the kidneys?
Spironolactone. It diminished the release of cytokines that cause fibrosis.
A 66 year old male comes to see you because he has CHF and is volume overloaded. You are considering use of a loop diuretic for this patient. What should you ask this patient in about in his past medical history that will prevent him from having joint problems?
History of gout. These drugs increase uric acid concentration and can induce gout.
One of your patients is currently on a diuretic and his Mg2+ blood levels are consistently low. Supplementation does not help him at all. What lab value can you look at to determine another way to get Mg2+ up?
K+. Mg2+ and K+ reabsorption are linked.
A 60 year old man presents with flank pain. You determine that he has a calcium oxalate kidney stone. He also has CHF. What diuretic could you put him on that would help with his edema and his stones?
Thiazides. Dissipation of the K+ back leak gradient decreases Ca2+ and Mg2+ reabsorption.
What can the patient do to decrease efficacy of diuretics?
Increased NaCl intake, NSAIDs (decreases GFR)
What can’t the patient change that might decrease efficacy of diuretics?
CHF = decreased GI absorption of drug. Renal failure = decreased GFR. Nephrotic syndrome = albumin in urine binds drug.
What happens to the distal tubular cells when patients take Furosemide for a long period of time?
The distal tubular cells hypertrophy and enhance sodium reabsorption to compensate for decreased reabsorption at the proximal tubule.
A 50 year old female comes to see you. She has been on HCTZ for eight years. Labs reveal an elevated uric acid for the past 5 years and mild metabolic alkalosis. Each the patient tries to stop the diuretic she experiences LE edema and restarts within three days. Why does she develop edema?
She gets the edema because it takes a couple of weeks for Na/K to re-equilibrate.
What drugs are contraindicated with diuretics due to increased risk for hypokalemia?
K-wasting drugs: corticosteroids, amphotericin and cation exchange resins. Laxatives also cause increased K+ loss from the GI tract.
What drugs are contraindicated with diuretics in patients with renal insufficiency due to increased risk for hyperkalemia?
K-sparing drugs: ACE-I, ARBs
What might you have to adjust if you prescribe a diuretic to a diabetic?
Diuretics can cause hyperglycemia. You might have to increase the amount of insulin the patient takes per day.
