diuretics Flashcards
carbonic anhydrase inhibitors
Acetazolamide
Methazolamide
Dichlorphenamide
sulfonamides derivatives thus C/I in sulfa allergy
non competitive and reversible inhibitor
uses of CA inhibitors
GAME - Plan
Glaucoma - iv Acetazolamide, eyedrops - Dorzolamide, Brinzolamide - as adjuvant to other ocular hypotensives
Alkalinization of urine due to bicarbonate loss, in weak acidic drug poisoning, acidic stones in urinary tract such as uric acid stones, cysteine stone (AE: increases risk of calcium phosphate stones which are treated by thiazide)
metabolic acidosis in blood which stimulates chemoreceptors leading to increased respiration (Acetazolamide DOC for mountain sickness - prophylaxis as well as symptomatic relief : produces metabolic acidosis and compensates for respiratory alkalosis & decreases formation of CSF and lowers its pH)
Epilepsy (rarely) - as adjuvant ion absence seizures when primary drugs are not fully effective but refractoriness to an antiepileptic action develops
Periodic muscle paralysis due to hyperkalemia
SE of Carbonic anhydrase inhibitors
BASE PAD
Bone marrow suppression/aplastic anemia due to sulfa allergy
Ammonia retention (CI in liver disease and leads to hyperammonemic encephalopathy)
Calcium phosphate renal stones
Electrolyte imbalance in blood (hyperchloremic hypokalemic metabolic acidosis) - acidosis is more likely to occur in COPD patients
Paresthesia
Sulfa Allergy
Abdominal discomfort & diarrhoea due to HCO3- and Na+ loss in urine
drowsiness and fatigue
PK of CA inhibitors
Acetazolamide is well absorbed orally & excreted unchanged in urine. Action of a single dose lasts 8-12 hrs
MoA of loop diuretics
in medullary portion of TAL
1. inhibits NK2C transporter
2. reduces medullary hyperosmolarity and abolishes counter current mechanism leading to water loss
3. increases prostaglandin synthesis and dilates afferent arterioles thus increasing GFR
(thus, aspirin/NSAIDs reduce PG synthesis and reduces the diuretic effect of loop)
diuretic of choice in renal failure
loop diuretics
loop diuretics
- Mersaryl - mercury containing - highly ototoxic (permanent deafness)
- Sulfa containing - Furosemide [most potent] (Lasix), Bumetanide, Torasemide [longest]- less ototoxic
- Phenoxyacetic acid- Ethacrynic acid
uses of loop diuretics
- hypertension (DOC thiazide but not in severe HTN - >160/100, where loop diuretics are used)
- loop looses all positively charged ions in urine - DOC hyperkalemia, hypervalcemia, hyper magnesemia
- DOC for acute LVF - acute pulmonary edema - venodilators - reduce preload
- DOC for refractory edema
Venodilators
DOC loop diuretics (increase PG synthesis)
Morphine (histamine release)
Nitroglycerine (NO production)
oxygen
Prop up (sitting)
DOC for refractory edema
loop diuretics
DOC for edema
- Heart failure (increase in hydrostatic pressure)
LVF - pulmonary edema
RVF - pedal edema
both - anasarca
DOC is loop diuretics - Kidney failure (CKD)
albumin loss in urine - periorbital edema
DOC is loop diuretics - Liver failure (cirrhosis)
ascites
DOC is Spironolactone (K+ sparing) - cerebral edema (increased intracranial pressure)
DOC is mannitol (osmotic diuretics)
mannitol CI in
heart failure
renal failure
SE of loop diuretics
- loop looses all positively charged ions in urine
hyponatremia - hypotension
hypokalemia - muscle weakness, increased Digoxin toxicity
hypocalcemia - least seen because GIT absorbs calcium more
hypomagnesemia
metabolic alkalosis (H+ reduced) - blood osmolarity reduces
so in blood there will be increase in glucose, uric acid, lipids (LDL) - hyperglycemia(bad for DM), hyperuricemia(bad for gout), hyperlipidemia( bad for dyslipidemia)
LOOP and THIAZIDES have same SE
EXCEPT CALCIUM
Loop looses calcium in urine (blood- calcium decreases: hypocalcemia, urine - calcium increases ( hypercalciuria) while thiazides preserve calcium (blood - calcium increases: hypercalcemia, urine - calcium decreases : hypocalciuria)
Diuretics of choice for hypercalcemia and hypercalciuria
hypercalcemia - loop diuretics
hypercalciuria - thiazides (treatment of renal stones)
Thiazides MOA
inhibits Na+-Cl- symporter in cortical TAL and early DCT
Diuretics which are sulpha drugs
all CA inhibitors
all thiazides
3 loops
Thiazides
Chlorothiazide
Hydrochlorothiazide
Benzthiazide
Bendroflumethiazide
Thiazide like diuretics
chlorthalidone (longest)
Metolazone (safe in renal failure and is add on drug to loop)
Indapamide (most potent)
Xipamide
Clopamide
combination of diuretics
synergism due to sequential action
Uses of thiazides
- Mild to moderate hypertension - DOC thiazides (Hydroclorthiazide, Chlorthalidone-best, Indapamide)
MoA: persistent sodium loss in urine -> sodium deficiency -> vasodilation -> reduces DBP - Preserve calcium - used in hypercalciuria (Dent’s disease) and calcium renal stones
thus, increases bone mineral density and reduces risk of osteoporosis in old age
MoA: increases expression of NCX on basolateral side of distal tubule and increase parathyroid activity on NCX
- DOC for treatment of nephrogenic diabetes insipidus - because thiazides become antidiuretic in this disease
K+ sparing diuretics
SEAT
- Aldosterone receptor antagonist(basolateral side - only diuretic)
Spironolactone
Eplerenone - ENaC inhibitor (luminal side)
Amiloride
Triamterene
produce hyperkalemia so combined with loop/thiazide/CA inhibitors
Aldosterone receptor antagonist also called
mineralocorticoid receptor antagonist
active form of Spironolactone
Canrenone - another new drug
Effect of spironolactone not seen with Eplerenone
blocks testosterone receptors
good for females - treatment of hirsutism in PCOD
bad for males- gynecomastia, impotence
uses of Spironolactone and Eplerenone
DOC for hyperaldosteronism
1. Primary (Conn’s disease) - tumour of adrenal gland causing hypertension [no oedema due to escape phenomenon]
- Secondary - chronic heart failure, chronic liver disease
overactivity of RAAS (which stimulates adrenal gland) - hypertension and oedema
new aldosterone antagonist
Finrenone in treatment of diabetic nephropathy(albuminuria)
Add on drug to DOC ACE inhibitors
EnaC inhibitors another name
Amiloride sensitive Na channels
Amiloride
Longer and more potent than Triamterene
DOC for Liddle syndrome
DOC for Li toxicity
Liddle syndrome
genetic disease where there is excess of ENaC channels which are not under control of aldosterone
Triamterene SE
folic acid deficiency
renal stones
photosensitivity
Osmotic diuretics
Mannitol - iv - 20%
Isosorbite - oral, rectal
Glycerol - oral, rectal
Urea - iv
MoA of osmotic diuretics
At blood:
mannitol increases plasma osmolarity - withdraw fluids from the cell and reduce CSF production in brain and reduce ICP (DOC for cerebral oedema) and reduce aqueous production in eye and reduce IOP (DOC for acute congestive glaucoma)
At kidney:
mannitol gets filtered into the kidney and increase tubular osmolarity and hence water will not get reabsorbed and lead to iso-osmotic urine loss & loss of all ions+ water
(DOC for cisplatin and Li toxicity)
SE of mannitol
expand plasma volume -> increases preload -> absolutely CI in heart failure
absolutely CI in renal failure - will not filter - remains in blood- increases plasma volume - increases risk of heart failure and HTN
diuretics in Li toxicity
Mannitol
Amiloride
diuretic of choice to preserve calcium
Thiazides
Diuretic of choice to preserve magnesium
Amiloride
