Module 3.1: DIURETICS Flashcards
Major effect is in the proximal tubule and descending Loop of Henle Prevents normal absorption of water by interposing a countervailing osmotic force
OSMOTIC DIURETICS
[Thiazide Diuretic] only drug available in parenteral admin
CHLOROTHIAZIDE
[CARBONIC ANHYDRASE INHIBITORS] Indications: (what indication is this?) cystinuria – dissolves cysteine crystals by increasing urinary pH, leads to complete reabsorption of cysteine uric acid crystals – same effect ADR: formation of Ca salts
urine alkalinisation
Newer, more selective aldosterone blockers have fewer of the progestational and anti-androgenic effects than…
Spirinolactone
- reduce pulmonary congestion and left ventricular filling pressures in heart failure before a measurable increase in urinary output occurs
FUROSEMIDE
[CARBONIC ANHYDRASE INHIBITORS] PROTOTYPE DRUG:
ACETAZOLAMIDE
ANTIDIURETIC HORMONE ANTAGONISTS in patients with CHF and and SIADH (x’ss ADH)
LITHIUM DEMECLOCYCLINE*
ADVERSE DRUG REACTIONS: ARF caused by …
combination of triamterene and indomethacin (NSAID)
[LOOP DIURETICS] ADVERSE DRUG REACTIONS
- Hypotension - Dehydration losses excess volume [take note of patient’s fluid volume] - HYPOnatremia - HYPOkalemia o more effect than hyponatremia- monitor level] o if given with digoxin = arrhythmia [should be given simultaneously]
DIRECT Na CHANNEL BLOCKER
TRIAMTERENE AMILORIDE
[OSMOTIC DIURETICS] INDICATION
to increase urine volume reduce intracranial and intraocular pressure
[LOOP DIURETICS] ADVERSE DRUG REACTIONS
- ototoxicity (ETHACRYNIC ACID) - hyperuricemia (hypovolemia-associated enhancement of uric acid reabsorption in the proximal tubule) - HYPOmagnesimia - allergic reactions (may be due to sulfur)
[ALDOSTERONE BLOCKERS/K-SPARING DIURETICS] ADVERSE DRUG REACTIONS
HYPERkalemia Hyperchloremic metabolic acidosis
[OSMOTIC DIURETICS] ADVERSE DRUG REACTIONS:
extracellular volume expansion dehydration, HYPERkalemia, and HYPOnatremia
[Thiazide Diuretic] slow absorption, longer duration
CHLORTHALIDONE
- Ineffective in reducing BP in vast majority of individuals with HTN
LOOP DIURETICS
[ALDOSTERONE BLOCKERS/K-SPARING DIURETICS] INDICATIONS
Hyperaldosteronism treatment - due either to primary hypersecretion (Conn’s syndrome, ectopic adrenocorticotropic hormone production) or secondary hyperaldosteronism (evoked by heart failure, hepatic cirrhosis, nephrotic syndrome, or other conditions associated with diminished effective intravascular volume)
decrease pH and increase luminal concentrations of Cl2 and Na sometimes used in combination with high-ceiling diuretics to counteract alkalosis
ACIDIFYING SALTS [AMMONIUM CHLORIDE]
[CARBONIC ANHYDRASE INHIBITORS] ADVERSE DRUG REACTIONS:
- Hyperchloremic Metabolic Acidosis - Renal stone (phosphaturia, hypercalcuria) - Renal K wasting - Drowsiness and paresthesias - CNS toxicities among renal failure patients - Hypersensitivity reactions
USED ONLY IN ACUTE PHASES not for chronic use; due to reduction of circulating volume
LOOP DIURETICS
MOA: Early renal (salt/water excretion) effects – act by inhibiting the Na/Cl reabsorption pump in the DCT; by blocking Na-Cl co-transporter (NCC)
THIAZIDE DIURETICS
[CARBONIC ANHYDRASE INHIBITORS] Indications: By decreasing cerebrospinal fluid formation and by decreasing the pH of the cerebrospinal fluid and brain leading to an increase in ventilation and diminish symptoms of ….
acute mountain sickness
increasing cardiac output and promoting a higher glomerular filtration rate seldom used as diuretics, but diuresis occurs under other clinical applications (e.g., for bronchodilatation) MOA: antagonism of adenosine receptors
XANTHINE DIURETICS
[LOOP DIURETICS] INDICATIONS
Mild HYPERkalemia - enhance urinary excretion of K + Acute Renal Failure (ARF) – inc rate of urine outflow, inc excretion of K Anion overdose
ANTIDIURETIC HORMONE AGONISTS in patients with CENTRAL DIABETES INSIPIDUS (low ADH)
VASOPRESSIN* DESMOPRESSIN
[CARBONIC ANHYDRASE INHIBITORS] Indications:
- treatment of sleep apnea - adjuvant treatment of epilepsy and in some forms of hypokalemic periodic paralysis - treating patient with CSF leak(tumor or head trauma) - increasing urinary phosphate excretion during hyperphosphatemia
- Prevent reabsorption of Cl and Na by blocking NaK2Cl transporter [leading to excretion of Na and Cl]
LOOP DIURETICS
[CARBONIC ANHYDRASE INHIBITORS] Indications: - Glaucoma by reducing aqueous humor production Topically active agents are…
DORZOLAMIDE BRINZOLAMIDE
[ALDOSTERONE BLOCKERS/K-SPARING DIURETICS] INDICATIONS
- chronic liver disease leads to decreased possibility in development of ascites - chronic heart failure [CHF] - usually given with a thiazide diuretic [not as potent if alone]
ADVERSE DRUG REACTIONS: Kidney stone/nephrolithiasis caused by…
triamterene
- Act on membrane ion transport mechanism in the thick ascending limb of the Loop of Henle
LOOP DIURETICS
MOA of Loop Diuretics for patient with…..: - Loop diuretics effectively reduce ECF volume and BP - The renal and antinatriuretic mechanisms are blunted
Patient with renal dysfunction
- These are VENODILATORS and little arteriolar dilator effect
LOOP DIURETICS
mild diuretic
CAFFEINE
Should be given as IV, if given orally can cause osmotic diarrhea rather than diuresis
MANNITOL (non-reabsorbable solute)
ALDOSTERONE ANTAGONISTS – competitive inhibitor of aldosterone
SPIRINOLACTONE EPLENERONE
[OSMOTIC DIURETICS] INDICATION reduce cellular edema in case of hemorrhagic stroke to decrease ICP
MANNITOL (non-reabsorbable solute)
[Thiazide Diuretic] ADVERSE EFFECTS
HYPOkalemic metabolic alkalosis and hyperuricemia impaired CHO tolerance HYPERGLYCEMIA Hyperlipidemia – inc in total cholesterol and LDL levels HYPOnatremia Allergy- photosensitivity, dermatitis; severe could lead to hemolytic anemia, thrombocytopenia, and acute necrotizing pancreatitis
[CARBONIC ANHYDRASE INHIBITORS] CONTRAINDICATION
Liver cirrhosis, may contribute to development of hyperammonemia and hepatic encephalopathy
MOA: They provide effective Anti-HTN treatment especially in low-renin and salt sensitive forms of hypertension Provide additional benefit in the treatment of heart failure (HF) when combined with ACE Inhibitors (ACE-I), digitalis, and loop diuretics
ALDOSTERONE BLOCKERS/K-SPARING DIURETICS
[CARBONIC ANHYDRASE INHIBITORS] Indications: …..due to excessive use of diuretics among HF patients should only be treated with carbonic anhydrase inhibitors
metabolic alkalosis states
ADVERSE DRUG REACTIONS: Gynecomastia, impotence, and benign prostatic hyperplasia caused by….
spironolactone and eplerenone due to steroid like structure
MOA of Loop Diuretics for patient with…..: - Variety of mechanisms blunts the ability to persistently reduce ECF volume or BP - The initial diuresis is typically followed by longer period of Na retention (neutral or positive balance) *another reason why it’s not for chronic use
Normal GFR patient
Predominantly found in the luminal membrane of the PCT Inhibitors that block NaHCO3 reabsorption
CARBONIC ANHYDRASE INHIBITORS {-ZOLAMIDE}
[Thiazide Diuretic] use in combination with loop diuretics
METOLAZONE
- Induces production of COX-2 leading to production of prostaglandins like PGE2 which inhibits salt reabsorption in the TAL
FUROSEMIDE
[OSMOTIC DIURETICS] PROTOTYPE DRUG:
MANNITOL (non-reabsorbable solute)
- If given IV, check BP before and after administration; if hypotensive from the start, given with this would lead to severe hypotension; if normal BP then administered, dramatic decrease in BP
FUROSEMIDE
[Thiazide Diuretic] INDICATIONS
Hypertension – mild; or as adjunct with other anti-HTN Heart failure Nephrolithiasis due to idiopathic hypercalciuria Nephrogenic diabetes insipidus
Topical for glaucoma
Brinzolamide, dorzolamide
MOA:
Inhibition of the enzyme
prevents dehydration of
H2CO3 and hydration of
CO2 in the proximal convoluted
tubule
EFFECTS:
Reduces reabsorption of HCO3−, causing
self-limited diuresis • hyperchloremic
metabolic acidosis reduces body pH,
reduces intraocular pressure
CLINICAL APP:
Glaucoma, mountain sickness,
edema with alkalosis
Acetazolamide
ROA: Oral and topical preparations available
• duration of action ∼
8–12 h
TOXICITY: Metabolic acidosis,
renal stones, hyperammonemia
in cirrhotics
Acetazolamide
Sulfonamide loop agents like furosemide
Bumetanide, torsemide
Not a sulfonamide but has typical loop activity and some uricosuric action
Ethacrynic acid
MOA:
Inhibition of the Na/K/2Cl
transporter in the ascending
limb of Henle’s loop
EFFECTS:
Marked increase in NaCl excretion, some
K wasting, hypokalemic metabolic alkalosis,
increased urine Ca and Mg
Furosemide
CLINICAL APP:
Pulmonary edema, peripheral
edema, hypertension,
acute hypercalcemia or
hyperkalemia, acute renal
failure, anion overdose
ROA: Oral and parenteral preparations
• duration of action 2–4 h
TOXICITY: Ototoxicity, hypovolemia,
K wasting, hyperuricemia,
hypomagnesemia
Furosemide
Thiazide Popular for use with loop agents for synergistic effects
Metolazone
Only parenteral thiazide available (IV)
Chlorothiazide
Long half-life (50–60 h) due to binding to red blood cells
Chlorthalidone
MOA:
Inhibition of the Na/Cl
transporter in the distal
convoluted tubule
EFFECTS:
Modest increase in NaCl excretion • some
K wasting • hypokalemic metabolic
alkalosis • decreased urine Ca
Hydrochlorothiazide
CLINICAL APP:
Hypertension, mild heart failure,
nephrolithiasis, nephrogenic
diabetes insipidus
ROA: Oral • duration 8–12 h
TOXICITY:
Hypokalemic metabolic alkalosis,
hyperuricemia, hyperglycemia,
hyponatremia
Hydrochlorothiazide
Mechanism like amiloride, much less potent, more toxic
Triamterene
Like spironolactone, more selective for aldosterone receptor
Eplerenone
MOA:
Pharmacologic antagonist
of aldosterone • weak
antagonism of androgen
receptors
Spironolactone
EFFECTS:
Reduces Na retention and
K wasting in kidney • poorly
understood antagonism
of aldosterone in heart and
vessels
Spironolactone
CLINICAL APP:
Aldosteronism from any
cause • hypokalemia due to
other diuretics • postmyocardial
infarction
Slow onset and offset of effect
• duration 24–48 h
TOXICITY:
Hyperkalemia, gynecomastia
(spironolactone, not eplerenone)
• additive interaction with other
K-retaining drugs
Spironolactone
MOA:
Blocks epithelial sodium
channels in collecting tubules
EFFECTS:
Reduces Na retention and
K wasting • increases lithium
clearance
Amiloride
CLINICAL APP:
Hypokalemia from other
diuretics • reduces lithiuminduced
polyuria
ROA:
Orally active • duration 24 h
TOXICITY: Hyperkalemic metabolic
acidosis
Amiloride
MOA:
Physical osmotic effect on
tissue water distribution
because it is retained in the
vascular compartment
EFFECTS:
Marked increase in urine
flow, reduced brain volume,
decreased intraocular
pressure, initial hyponatremia,
then hypernatremia
Mannitol
CLINICAL APP:
Renal failure due to increased
solute load (rhabdomyolysis,
chemotherapy), increased
intracranial pressure, glaucoma
ROA: IV administration
TOXICITY:
Nausea, vomiting, headache
Mannitol
