L12- Diuretics Flashcards
PCT has (high/low) water permeability and (2) are the main drug targets / transporters
1- very high
2- Na+/H+ (NHE3), carbonic anhydrase, acid/base transporters
thin descending loop of Henle has (high/low) water permeability and (2) are the main drug targets / transporters
1- high
2- aquaporins
thick ascending loop of Henle has (high/low) water permeability and (2) are the main drug targets / transporters
1- very low
2- Na+/K+/2Cl- symporter (NKCC2)
DCT has (high/low) water permeability and (2) are the main drug targets / transporters
1- very low
2- Na+/Cl- (NCC)
CT has (high/low) water permeability and (2) are the main drug targets / transporters
1- variable
2- ENaC, K+ channels, H+ transporters, aquaporins
In an edematous state there is (inc/dec) NaCl reabsorption, which leads to (2) and (3). Examples that cause this include the following: (4).
1- inc NaCl
2- H2O retention
3- inc blood volume
4- HF, hepatic ascites, nephrotic syndrome, premenstrual edema
list some examples of non-edematous states where diuretics may be required
- HTN
- hypercalcemia
- diabeted insipidus
define natriuretics and the 2 main clinical uses
-inhibits renal ion transported to dec Na+ reabsorption at different sites in the nephron
i) manage abnormal fluid retention (edema)
ii) treat HTN by reducing blood volume
Loop diuretics target (1) part of the nephron, acting on (2) transporter, to have (3) results.
(furosemide)
1- thick ascending LoH
2- inhibit NKCC2 (Na+/K+/2Cl- co-transporter)
3- inc Na, K, Cl in tubular lumen –> inc H2O excretion
Loop diuretic uses
(furosemide)
- manages edema in HF, hepatic/renal disease
- moderate-severe HTN
Loop-diuretic effects on:
(1) [Ca2+]
(2) [Mg2+]
(3) PGs
(4) renal vascular resistance
(5) renal blood flow
(furosemide) 1- inc Ca excretion 2- inc Mg excretion 3- inc PG synthesis 4- dec resistance 5- inc RBF
Loop diuretics are given in (1) fashion and have a (2) half-life
(furosemide)
1- orally, paraenterally
2- 2-4 hrs
loop diuretics have the following adverse effects
(furosemide)
- ototoxicity
- hyperuricemia
- acute hypovolemia
- hypokalemia
- hypomagnesemia
- allergic reactions
Loop Diuretics:
(1) dec urinary excretion of….
(2) inc urinary excretion of….
(furosemide)
1- dec uric acid excretion
2- inc Na, K, Mg, Ca, urine volume excretion
Thiazides target (1) part of the nephron, acting on (2) transporter, to have (3) results.
1- DCT
2- inhibits NCCT (Na+/Cl- co-transporter)
3- inc Na, Cl in tubular lumen –> inc H2O excretion
Thiazide uses (hint: 5)
- HTN (alone or in combination)
- HF (mild-moderate)
- hypercalciuria (inhibits Ca excretion, used for kidney stones)
- Diabetes Insipidus (=> hyperosmolar urine)
- premenstrual edema
Thiazide effects on:
(1) [K+]
(2) [Mg2+]
(3) [Na+ / Cl-]
(4) [Ca+]
(5) PVR
1- inc K excretion 2- inc Mg excretion 3- inc Na/Cl excretion 4- dec Ca excretion 5- dec peripheral vascular resistance (dec blood volume- which will recover although hypotensive effects remain)
Thiazides are given in (1) fashion and have a (2) half-life
1- orally
2- 40 hrs (1-3 wks for stable effects)
list the thiazides
- HCTZ
- Chlorthalidone
- Metolazone
thiazides should replace loop-diuretics in the what condition
moderate to severe CKD (GFR < 30 mL/min)
(1) thiazide has the longest duration of action
(2) is the most potent thiazide
1- chlorthalidone (40-60 hr half life, used qd for HTN)
2- metolazone (–> Na excretion in advance of kidney failure)
thiazides have the following adverse effects
- hypokalemia, hyponatremia
- hyperuricemia, hyperglycemia, hyperlipidemia
- hypersensitivity
- sexual dysfunction
Thiazides:
(1) dec urinary excretion of….
(2) inc urinary excretion of….
1- dec uric acid, Ca excretion
2- inc K, Na, Mg, urine volume excretion
list the K+-sparing diuretics (include categories)
Aldosterone antagonists: Spironolactone, Eplerenone
Na+ channel inhibitors: Triamteren, Amiloride
K+-sparing diuretics (Spironolactone, Eplerenone) target (1) part of the nephron, acting as (2), to have (3) results.
1- CT
2- aldosterone antagonists
3- prevents ENaC (Na in) and ROMK (K out) transporters on lumenal side –> dec Na reabsorption, dec K excretion
K+ sparing diuretic (Spironolactone, Eplerenone) uses
- HF (adjunct, to prevent cardiac remodeling)
- HTN (adjunct)
- primary hyperaldoteronism (for Dx and Tx, only time it is used alone)
- edema (associated with excess aldosterone)
K+ sparing diuretics (Spironolactone, Eplerenone) have the following adverse effects
- gastric upset / peptic ulcers
- endocrine effects (antiandrogen)
- hyperkalemia
- nausea, lethargy, mental confusion (rare)
____ must be monitored in patients using K+-sparing diuretics (Spironolactone, Eplerenone)
potassium levels
K+-sparing diuretics (Triamteren, Amiloride) target (1) part of the nephron, acting as (2), to have (3) results.
1- CT
2- ENaC (Na+ channel) inhibitors
3- dec Na+/K+ exchange –> inc Na+ in lumen –> inc H2O excretion, dec Na reabsorption, dec K excretion
K+ sparing diuretics (Triamteren, Amiloride) have the following adverse effects
- hyperkalemia
- hyponatremia
- leg cramps
- GI upset
- dizziness, pruritus, HA, minor visual changes
K+ sparing diuretics (all):
(1) dec urinary excretion of….
(2) inc urinary excretion of….
1- dec K excretion
2- inc Na, urine volume excretion
Carbonic Anhydrase inhibitors target (1) part of the nephron, acting as (2), to have (3) results.
(acetazolamide)
1- PCT
2- CA inhibitor –> inc HCO3- and Na excretion
3- dec Na+/H+ exchange (basolateral side, Na in, H out) –> dec Na+/K+ ATPase (apical side, Na out, K in) –> more Na+ and HCO3- in the lumen –> more alkaline urine + inc volume
CA inhibitor uses
(acetazolamide)
- glaucoma
- epilepsy (alone or with other antiepileptics)
- mountain sickness prophalaxis
- metabolic alkalosis
CA inhibitors are given in (1) fashion and have a (2) half-life
(acetazolamide)
1- oral (well absorbed) or IV (acute Tx for closed angle glaucoma)
2- 3-6 hrs
CA inhibitors adverse effects
(acetazolamide)
- hyponatremia, hypokalemia
- crystalluria (due to inc HCO3 in urine)
- metabolic acidosis –> malaise, fatigue, depression, HA, GI upset, drowsiness, paresthesia
CA inhibitors:
(1) dec urinary excretion of….
(2) inc urinary excretion of….
(acetazolamide)
1- n/a
2- HCO3-, Na, K, urine volume
osmotic diuretics target (1) part of the nephron, acting as (2), to have (3) results.
(mannitol)
1- everywhere (no specific targets)
2- osmotic agent (inc plasma osmolarity)
3- H2O pulled out of body tissues –> inc urine volume
osmotic diuretic uses
(mannitol)
- inc urine flow in patients with acute renal failure
- reduce intracranial pressure – treats cerebral edema
- promote excretion of toxic substances
osmotic diuretics are given in _____ fashion
(mannitol)
IV due to poor GI absorption
osmotic diuretics adverse effects and contraindications
(mannitol)
- ECW expansion => hyponatremia
- tissue dehydration
-not used in CHF, pulmonary embolism
ADH antagonists target (1) part of the nephron, acting as (2), to have (3) results.
(conivaptan)
1- CT
2- V1/V2 receptor antagonist (normally bind ADH)
3- dec H2O permeability –> dec retention and inc urine volume (dilute urine)
ADH antagonist uses
(conivaptan)
- euvolemic and hypervolemic hyponatremia
- SIADH
- HF (if benefits»_space;> risks, safety not established)
ADH antagonists are given in _____ fashion
(conivaptan)
IV only
-metabolized by and potent inhibitor of CYP3A4
ADH antagonists adverse effects and contraindications
(conivaptan)
- infusion site rxns
- thirst
- AFib
- GI, electrolyte disturbances
- nephrogenic diabetes insipidus
-Not used in renal failure, hypovolemic hyponatremia
