HTN: Diuretics Flashcards
What is mannitol MOA? What are the clinical indications?
MOA: diuretic working on Proximal Tubule & Loop of Henle
- relative H2o diuresis
Indications:
- DEC ICP associated with cerebral edema**
- maintain serum osm 310 to < 320 - GU irrigate in TURP or other transurethral surgical procedures**
How can mannitol increase plasma osmolality? Two mechanisms.
- Water diuresis leading to water deficit & hypernatremia
2. Hypertonic mannitol may be retained in AKI pts
What are the interactions and ADRs for mannitol and acetazolamide?
Interactions: anti-HTN & Vasodilators –> additive effective
ADRs
- fluid/’lyte imbalance
- hypovolemia* or dehydration secondary to rapid diuresis
What is acetazolamide MOA? What’s indication for use?
MOA: reversible inhibition of carbonic anhydrase
- produces both NaCl & NaHCO3 loss
Indication:
- prevention or amelioration of acute mountain sickness**
- edematous pt w/metabolic alkalosis - lose excess bicarb can restore acid-base
What’s the MOA of loop diuretics? Which drug is the big loop banger?
MOA: interferes with Na/K exchange in Thick Segment of Loop of Henle
Furosemide** (Lasix)
What are clinical indications for loop diuretics?
- acute pulmonary edema & other edematous states**
- acute hypercalcemia**
What do you need to monitor for your pt on loop, thiazide diuretics?
BMP - first few weeks, then periodically
Ca & Mg - as needed
Why are loops better than thiazides for HF?
More Na excretion*
“double the dose until the urine flows”
- if more is needed, add aldosterone AAG
- if sxs persist, add thiazide
Besides HF, what else are loops better than thiazides at?
Loops work better than thiazides for GFR < 30**
How do loops impact calcium?
enhances calcium excretion –> improvement in hypercalcemia**
What are three things to know about Ethacrynic acid (loop) ?
- may be useful for pt who have not responded to other diuretics
- causes most ototoxicity
- only loop that is not a sulfonamide
There are 6 specific drug interactions of loop diuretics. What are they?
- NSAIDs antagonize diuretic effect** [via Na retention]
- Antagonizes DM meds** [via hypoK]
- Anti-arrhythmic toxicity [via hypoK]
- Li tox [DEC excretion]
- Antagonize gout meds [via urate reabsorption]
- Anti-HTN & VD [additive effect]
What are loop diuretic ADRs?
- Hypokalemia** / hypomagnesemia *
- Hyperglycemia** [hypoK involved in dysglycemia]
- Volume depletion [orthostatics, AKI]
- hyperuricemia
- SNHL “ringing”
- rash - sulfa
What are the three bolded thiazide diuretics?
- Hydrochlorothiazide
- Chlorthalidone
- Metolazone
What is the only thiazide available as IV?
Outside of knowing the IV, it is not really used clinically.
Chlorothiazide
What are thiazide MOA?
Interfere with K/Na exchange in Early Distal Convoluted Tubule
Effects of most thiazides is an overall DEC in SVR**
Compare and contrast Chlorthalidone to Hydrochlorothiazide in terms of efficacy and general use
Chlorthalidone is 2x as potent w/a much longer duration of action (d/t creating a RBC “depot”)
Despite superiority of chlorthalidone, most fixed-dose combo that include a diuretic use HCTZ**
Which is the main thiazide used in context of altered renal function [CrCl < 30]
Metolazone
- other Thiazides are less effective with this renal level
What effects may thiazide diuretics have on calcium?
All enhance Ca2+ reabsorption**
Improvement in hypercalciuria = DEC kidney stones **
May be beneficial in osteoporosis
Which thiazide may be used with a loop diuretic for synergy in refractory edematous states?
Metolazone
What are ADRs of thiazides?
Hypokalemia / hypomagnesemia –> hyperglycemia **
For the most part otherwise, at the low dose used for thiazides, you don’t really get many ADRs.
[The others listed are the same as loop diuretics]
What is the unique thiazide ADR related to skin?
Increased risk of nonmelanoma skin CA w/HCTZ*
There are two “classes” of K-sparing diuretics. List the class MOA and the two drugs for each class.
- Anti-aldosterone drug
- MOA: antagonize mineralocorticoid receptors at Cortical Collecting Tubule –> DEC transcription of gene for Na/K ATPase
- Spironolactone** and Eplerenone - MOA: interferes with K/Na exchange
- Amiloride** and triamterene
What is the major difference between spironolactone and eplerenone in terms of action
Spironolactone - nonselective
Eplerenone - more selective for aldo than androgen and progesterone
- less gynecomastia and breast tenderness
What is the clinical use of amiloride and triamterene?
Used with other diuretics to prevent or correct hypokalemia
Overall weak diuretic / BP lowering
Less use now as most diuretics combined with ACE/ARB
What is the clinical use of spironolactone and eplerenone?
Mineralocorticoid excess
- Primary aldosteronism*
- Secondary aldosteronism**
- HFrEF, hepatic cirrhosis, nephrotic syndrome - Off-label
- acne vulgaris, hirsutism
As a class, what is the clinical use for Potassium-sparing diuretics?
Relatively weak natiuretic effect –> primarily used in combination with a loop or thiazide diuretic**
DEC degree of K loss or may INC net diuresis in pt w/refractory edema
What monitoring is required with K-sparing diuretics? What are some C.I. values?
Don’t use for K > 5.5 or eGFR < 30
Monitoring
- K and BUN/Cr: baseline, w/in 1wk, monthly x3, quarterly for 1yr, then q 6mo
What are the 3 main drug interactions with potassium-sparing diuretics?
- Avoid K supplements / salt substitutes
- Additive effect with Anti-HTN & vasodilators
- Careful with drugs retaining K
- B-blockers
- TMP-SMX
- NSAIDs, ACE, ARB
Class ADR of potassium-sparing diuretics?
Hyperkalemia
What are the specific ADRs of spironolactone?
- Teratogen**
- Painful gynecomastia, amenorrhea
- ED, DEC libido
What are the specific ADRs of triamterene?
- Potential nephrotoxin leading to crystalluria & cast formation (up to 50% of pt) **
What is the benefit of using 2 diuretics?
Use of 2 drugs acting at different nephron sites may exhibit synergy**
Loops + thiazides produce more diuresis, than either alone
Metolazone + Loop usually used**
