Diuretics Flashcards
Thiazide diuretics (increase/decrease) calcium reabsorption
Increase
Loop diuretics (increase/decrease) calcium and magnesium excretion
Increase
What effect do acidic drugs have on uric acid excretion?
They compete for excretion with uric acid, so they may cause hyperuricemia —> gout
What are the 3 Carbonic Anhydrase Inhibitors?
Acetazolamide (Diamox)
Dorzolamide (Trusopt) eyedrop
Brinzolamide (Azopt) eyedrop
What is the MOA of Carbonic Anhydrase Inhibitors?
- Block Carbonic Anhydrase enzyme
- Prevents production of bicarb
- H+ can’t exchange with Na+ in the urine so more Na+ and H2O are lost in the urine
What are the 3 indications for Carbonic Anhydrase Inhibitors?
- Glaucoma- decreases aqueous humor and CSF
- Alkalinization of the urine (more bicarb in urine)
- Alkalosis (metabolic and respiratory/Acute Mountain Sickness)
(WOW WHY ISN’T HTN OR EDEMA ON HERE????? ISNT THIS THE DIURETIC LECTURE!!??)
How long do Carbonic Anhydrase Inhibitors work as diuretics?
Only a few days
Reason we don’t use it as a diuretic
Weak bases are (more/less) ionized in alkaline environments
Less ionized.
Which makes it easier for them to diffuse across membranes
What are the adverse effects of Carbonic Anhydrase Inhibitors?
Hyperchloremic Metabolic Acidosis
Hypokalemia
Hyperuricemia
Why do CA Inhibitors cause hyperchloremic metabolic acidosis?
The Na+ loss is in the form of NaHCO3, not NaCl.
=you’re losing bicarb
Why do CA inhibitors cause hypokalemia?
More Na+ is in the lumen which causes an increased Na/K exchange further down the line
Why do CA inhibitors cause hyperuricemia?
They are acids and compete for uric acid secretion
What are the 4 Loop Diuretics?
Furosemide (Lasix)
Bumetanide
Torsemide
Ethacrynic Acid
What is the MOA of Loop Diuretics?
- Block NKCC2 cotransporter
- Induce kidney prostaglandins which decreases salt reabsorption
- Vasodilation- due to the prostaglandins
What are the indications for Loop Diuretics?
Heart Failure
Pulmonary Edema
Peripheral Edema
Hypercalcemia
How do loop diuretics relieve pulmonary congestion?
By increasing systemic venous capacitance
NOT because of fluid loss!!!**
What are the adverse effects of loop diuretics?
Hypokalemic metabolic alkalosis (induces K+ and H+ loss)
Hypocalcemia and hypomagnesemia
Hyperuricemia (loops are acids)
Irreversible ototoxicity**
Which loop diuretic is the worst at causing ototoxicity?
Ethacrynic acid**
What other drug will make the ototoxicity of loop diuretics even worse?
Aminoglycosides
Streptomycin, tobramycin, neomycin, amikacin, gentamycin in case you forgot
Which loop diuretic is NOT a sulfonamide and is OK for patients with Sulfa allergies?
Ethacrynic acid***
What other drug should not be combined with loop diuretics due to the risk of fatal hypokalemia?
Digoxin
What makes ethacrynic acid (Edecrin) different from the other loop diuretics?
It is not a sulfonamide derivative
It has the highest risk of ototoxicity
*100% chance this is on the test
Your patient has profound edema and your choices are Lasix and Ethacrynic Acid. Which one should you use?
Use lasix unless he has a sulfa allergy
What are the 2 thiazides and the 4 compounds released to thiazides?
Thiazides:
Hydrochlorothiazide
Chlorothiazides
Related compounds: Chlorthalidone Metolazone Quinethazone Indapamide
(You have to know the related compounds too)
What is the MOA of thiazide diuretics?
Inhibition of sodium reabsorption at the early distal tubule.
Also increases ATP-dependent K+ channel opening which hyperpolarizes membranes=vasodilation (as well as decreased insulin release because these K+ channels are in the pancreas too)
What are the indications of thiazides?
Hypertension
Heart failure
What are the effects of thiazides causing increased ATP-dependent K+ channel opening?
Vasodilation
Reduced insulin secretion***** (pancreas also uses those ATP dependent K+ channels)BAD THING
What effect do thiazides have on Calcium reabsorption?
Increased calcium reabsorption
How could thiazides help prevent kidney stones?
They increase calcium reabsorption= less calcium in the urine
Which thiazide drug is NOT metabolized by the kidneys?
Indapamide
***
Which thiazide has the longest duration of action due to its slow absorption?
Chlorthalidone** this apparently makes it the ~preferred~ thiazide
What are the sided effects of thiazides?
Hypokalemic metabolic alkalosis (induce K+ and H+ loss, and causes volume contraction= aldosterone secretion and more K+ loss)
Hyperuricemia
Magnesium loss
HYPERGLYCEMIA
Elevated serum lipid levels (except indapamide)
Which class of diuretics is NOT ok to give to patients with Type II diabetes?
Thiazides
They decrease insulin release and increase glucose intolerance
Why do thiazides cause elevated lipid levels?
Because they decrease insulin release
Impedes the usage of glucose for energy, so lipid stores get activated
How is indapamide different from the other thiazides?
- excreted by biliary system in addition to kidneys, so its useful for patients with bad kidneys
- does not elevate lipid levels
If a patient is on lithium, what class of diuretics can he not take?
Thiazides- aggravate lithium toxicity
What are the contraindications/precautions to thiazides?
Sulfa allergy
NSAID use may decrease action
Hypokalemia can cause Digitalis toxicity
DIABETES (contraindication**)
Hyperuricemia (may cause gout)
Can thiazides work in patients with low GFR?
Only Metolazone. All others are useless in a low GFR
What are the 2 unique thiazides?
Metolazone- works at low GFR
Indapamide- doesn’t increase lipids and is metabolized by liver and kidneys 50/50
Do loop diuretics work if a patient has a low GFR?
YES
Are potassium sparing diuretics strong or weak diuretics?
Weak. They are used in combo with thiazides or loops.
What are the 4 potassium sparing diuretics?
Amiloride (Midamor)
Triamterene (Dyrenium)
Aldosterone antagonists:
Spironolactone (Aldactone)
Eplerenone (Inspra)
What is the MOA of spironolactone?
Competitive inhibitor of aldosterone**
(Less Na+ channels in the late distal tubule and collecting duct bringing Na+ in from urine, so less K+ will be excreted into the urine=
Leads to decreased K+ excretion)
What is the most effective drug for treating hyperalodteronism
Spironolactone
How does spironolactone affect men and women differently?
Women- cures hirsutism 🧔🏼->👩🏼
Men- gynecomastia 🥥🥥
(Due to spironolactone being an androgen receptor antagonist)
*****this is definitely gonna be on the test)
What are the indications for spironolactone?
Edema
Hyperaldosteronism
Eliminate need for K+ supplements for patients on loops or thiazides
Hirsutism
What are the adverse effects of spironolactone?
Gynecomastia
Hyperkalemia (especially when combined with ACE/ARBs)
NOT TOO BAD
What is the difference between Eplerenone and spironolactone?
Won’t cause Gynecomastia in men
More drug interactions since its metabolized by CYP3A4
True or False:
Amiloride and Triamterene depend on aldosterone
False
They are independent of aldosterone
What is the MOA of Amiloride and Triamterene?
Directly inhibit the aldosterone sensitive Na+ channel (ENaC)
Leads to decreased K+ excretion
What is the main use for Amiloride and Triamterene?
- Combination with K+ losing diuretics
- Amiloride is the DOC for Lithium induced diabetes insipidus
What is the only class of diuretics that are not acids, and will not cause hyperuricemia
Amiloride and Triamterene
What is the only serious toxicity of Amiloride and Triamterene?
Hyperkalemia
Who can NOT have potassium-sparing diuretics?
Burn patients (have hyperkalemia)
What are the 4 osmotic diuretics?
Mannitol
Isosorbide
Glycerin
Urea
How are osmotic diuretics administered?
IV only!!
If you take them orally you get diarrhea 💩
What is the MOA of osmotic diuretics?
Keep water in the tubules and causes diuresis
What are the indications of osmotic diuretics?
Prevents acute renal failure (keeps water flowing through tubules if flow is getting dangerously low)
Decrease intraocular pressure before eye surgery
Decrease intracranial pressure
Protect kidney against nephrotoxic substances
What are the adverse effects of osmotic diuretics?
Dehydration
Large doses cause ECF volume expansion- cellular dehydration and pulmonary edema in heart failure
Who can NOT have osmotic diuretics?
People in heart failure
Because they can cause pulmonary edema via an ECF volume expansion i don’t remember the physiology of this
what is the only ADH agonist we talked about
Desmopressin
It is synthetic ADH
Desmopressin (synthetic ADH) can be used to treat (central/nephrogenic) diabetes insipidus
Central*****
What are the ADH antagonists?
Conivaptan
Tolvaptan
Lithium NOT ON TEST
Demeclocycline NOT ON TEST
What class of diuretics have the strongest diuretic effect?
Loops
