Diuretics & Other Drugs That Act on the Kidney

 Diuretic - is an agent that increases urine volume

 Natriuretic - causes an increase in renal sodium excretion
 Aquaretic - increases excretion of solute-free water
DRUG CLASS Member Drug PK PD Indication Toxicity Contraindication
THIAZIDE Chlorothiazide • not very lipid- • inhibit NaCl reabsorption • Hypertension 1. Hypokalemic Metabolic • Hepatic cirrhosis
soluble from the luminal side of • Heart failure Alkalosis and • Borderline renal
• must be given in epithelial cells in the DCT • Nephrolithiasis due to Hyperuricemia failure
relatively large by blocking the Na+/Cl− idiopathic hypercalciuria 2. Impaired Carbohydrate • Heart failure
doses • Nephrogenic diabetes Tolerance
transporter (NCC)
• only thiazide • enhance Ca2+ insipidus • Hyperglycemia
available for reabsorption from effects 3. Hyperlipidemia
parenteral in both the proximal and 4. Hyponatremia
administration 5. Allergic Reactions
distal convoluted tubules
• • Photosensitivity or
Hydrochlorothiazide more potent • Action depends in part on
(HCTZ) • should be used in generalized
renal prostaglandin
much lower doses dermatitis occurs
production
rarely
Chlorthalidone • slowly absorbed • inhibited by NSAIDs under
• Hemolytic anemia
• has a longer certain conditions
• useful in the treatment of • Thrombocytopenia
duration of action
• Acute necrotizing
Indapamide • excreted primarily kidney stones caused by
pancreatitis
by the biliary system hypercalciuria
• enough of the active
form is cleared by
the kidney to exert
its diuretic effect in
the DCT
POTASSIUM- Spironolactone • Onset and duration • Spironolactone & 1. states of 1. Hyperkalemia 1. Patients with
SPARING of action are Eplerenone mineralocorticoid excess 2. Hyperchloremic chronic renal
DIURETICS determined by the  Inhibition by direct or hyperaldosteronism Metabolic Acidosis insufficiency
kinetics of the pharmacologic  primary 3. Gynecomastia 2. Patients with liver
aldosterone antagonism of hypersecretion (Conn  Spironolactone disease
response mineralocorticoid ’s syndrome, ectopic 4. Acute Renal Failure 3. Concomitant use of
• Substantial receptors  Triamterene + other agents that
adrenocorticotropic
inactivation occurs • Amiloride & Triamterene Indomethacin blunt the renin-
hormone production)
in the liver  inhibition of Na+ influx 5. Kidney Stones angiotensin system
 secondary
• slow onset of action through ion channels in  Triamterene is only 4. Strong CYP3A4
hyperaldosteronism
Eplerenone • greater selectivity the luminal membrane slightly soluble and inhibitors (eg,
(evoked by heart
for the • Ularitide (recombinant may precipitate in erythromycin,
failure, hepatic
mineralocorticoid urodilatin) the urine fluconazole,
cirrhosis, nephrotic
receptor  blunts Na+ uptake and syndrome, or other
diltiazem, and
• less active on Na+/K+ -ATPase in grapefruit juice) can
conditions associated
androgen and markedly increase
 progesterone collecting tubules and with diminished blood levels of
receptors increases GFR through effective eplerenone
Amiloride • direct inhibitors of its vascular effects intravascular volume
Na + influx in the • Nesiritide 2. blunt the K+ secretory
CCT (cortical  commercially available response in enhanced
collecting tubule for intravenous use only mineralocorticoid
Triamterene • metabolized in the  increases GFR and secretion and excessive
liver blunts Na+ delivery of Na+ to distal
• renal excretion is a reabsorption in both nephron sites
major route of proximal and collecting 3. slow the progression of
elimination for the tubules albuminuria in diabetic
active form and the patients
metabolites 4. reduce myocardial
• shorter half-life perfusion defects after
myocardial infarction
OSMOTIC Mannitol  poorly absorbed by • major effect in the 1. Increase of Urine 1. Extracellular Volume
DIURETICS the GI tract, proximal tubule and the Volume Expansion
 Orally; causes descending limb of Henle’ 2. Reduction of Intracranial • complicate heart
osmotic diarrhea and Intraocular Pressure failure
s loop
rather than diuresis • may produce florid
• oppose the action of ADH
 must be given in the collecting tubule
pulmonary edema
intravenously • Headache, nausea,
• prevents the normal
 not metabolized and absorption of water by
and vomiting
is excreted by 2. Dehydration,
interposing a
glomerular filtration Hyperkalemia, and
countervailing osmotic
within 30–60 force; urine volume Hypernatremia
minutes, without 3. Hyponatremia
increases
any important • In patients with
•  urine flow rate:  the
tubular severe renal
contact time between
reabsorption or impairment,
fluid and the tubular
secretion parenterally
epithelium 
administered
reducing Na+ and water
mannitol cannot be
reabsorption
excreted and is
• resulting natriuresis is of
retained
lesser magnitude than the
intravenously
water diuresis 
excessive water loss and
hypernatremia
ANTIDIURETIC Conivaptan 5–10 hours half-life • inhibit the effects of ADH 1. Syndrome of 1. Nephrogenic Diabetes
HORMONE Demeclocycline in the collecting tubule Inappropriate ADH Insipidus
ANTAGONISTS Tolvaptan • Conivaptan and tolvaptan Secretion 2. Renal Failure
Lithium 12–24 hours half-life are direct ADH receptor • Demeclocycline • Lithium and
Demeclocycline antagonists (600–1200 mg/d) Demeclocycline
• lithium and 3. Chronic interstitial
demeclocycline reduce • tolvaptan (15–60 nephritis
ADH-induced cAMP by mg/d) • Long-term
mechanisms that are not 2. Other Causes of lithium therapy
yet completely clarified Elevated Antidiuretic 4. Dry mouth and thirst
Hormone 5. Hypotension
• Patients with heart • Tolvaptan
failure - blockade of 6. Demeclocycline should
V1a receptors by be avoided in patients
conivaptan leads to with liver disease and in
decreased children younger than
peripheral vascular 12 years
resistance and
increased cardiac
output