HTZ

chlorthalidone

metolazone

furosemide

bumetanide

spironolactone

amiloride

• types
  • hyperAld
  • renal HTN
  • renovascular HTN

• stenosis of afferent renal A.
• decrease renal perfusion pressure
• activate RAAS
• salt, water rention

• impaired renal excretion
• leads to ECV expansion

• high Ald
• low renin
• hypokalemia

• Na- increase
• K- MARKED increase
• H- decrease
• Ca- NO CHANGE
• Mg- variable
• Cl- increase
• HCO₃- MARKED increase

• RBF- decrease
• GFR- decrease
• TGF- increase

• Na- MARKED increase
• K- increase
• hydrogen- unknown
• Ca- increase
• Mg- MARKED increase
• Cl- increase
• HCO₃- increase

• RBF- increase
• GFR- no change
• TGF- unknown

• Na- marked increase
• K- marked increase
• H- increase
• Ca- marked increase
• Mg- marked increase
• Cl- marked increase
• HCO₃- increase

• RBF- variable increase
• GFR- no change
• TGF- decrease

• Na- increase
• K- marked increase
• H- increase
• Ca- variable decrease
• Mg- variable increase
• Cl- increase
• HCO₃- increase

• Na- increased
• K- decreased
• H- decreased
• Ca- decreased
• Mg- decreased
• Cl- increased
• HCO₃- slight increase

• RBF- no change
• TGF- no change
• GFR- no change

• RBF- no change
• GFR- variabe decrease
• TGF- no change

• Na- increase
• K- decrease
• H- decrease
• Ca- unknown
• Mg- decrease
• Cl- increase
• HCO₃- slight increase

• RBF- no change
• TGF- no change
• GFR- no change

• PCT (major)- major site of bicarb reabsorption
• intercalated cells of CD

Can act anwhere CA is located (ex: gastric mucosa, RBC, eye)

1. inh. CA in lumen and epithelial cells
2. reduce HCO₃ reabsorption and decrease H secretion
   • creates acidosis
   • decreases production of aqueous humor

• decreased HCO₃, Na, K
• increased Cl and H
  • lead to hypercholoremic acidosis (increased reabsorption of Cl into CD as result of increased negative driving charge from HCO₃ in lumen)
• increased CO₂

• second line treatment in open angle glaucoma (apply topically to the eye)
• urinary alkalinization (enahnced excretion of weak acids, but if prolonged therapy, administer bicarbonate)
• metabolic alkalosis (usually due to excessive loop/thiazide diuretic use)
  • esp. good in heart failure patients
• acute mountain sickness- a form of respiratory alkalosis (prophylaxis)
• epilepsy (given with antiepiletic medication)
  • metabolic acidosis slows down synaptic transmission

• in large doses, drowsiness, paresthesia
  • decreased dose for elderly, renal failure patients
• hypercholeremic metabolic acidosis
  • contraindicated in patients with COPD, hepatic cirrhosis
• renal stones (calcium salts less soluble at alkaline pH of urine)
• reduction in urniary excretion of weak organic bases (ex:NH₃) due to increase pH
• crosshypersensitivity with sulfonamides

1. block Na/K/2Cl channel in TAL
2. this will reduce the lumen potential
   • this leads to decreased Ca, Mg reabsorption
   • ABOLISH CORTICOMEDULLARY GRADIENT (we cant conc. the urine now)
3. Also, block same channel in JGA
   • decrease renal vascular resistance
   • increased renal blood flow via PG action
4. When given IV,
   1. dilate large veins, decreasing venous return
5. acts as WEAK CA inh.

• hypochloremic alkalosis
• hypokalemia

• acute pulm. edema
• edema of cardiac, hepatic or renal orgin that does not respond to thiazide
• hyperkalemia, hypercalcemia
• acute renal failure
  • increase urine flow and potassium excretion

• orally absorbed
• IV- act within five minutes
• duration of action: 1-3 hrs (except torsemide which has a loner half life)
• 60% excreted in the urine, the rest is metabolized
• extensively bound to plasma protein and secreted by organic acid transporter

• fluid/electrolyte imbalance
  • hyperuricemia
  • hypokalemia
  • hypomagnesemia
  • hypochloremic alkalosis
• cardiac arrhythmias
  • contraindicated with quinidine, leads to development of vent. tachycardia (torsades de pointes) which are fatal if hypokalemia present
• hypotension (due to volume depletion)
• ototoxicity (esp. ethacrynic acid)
• hypersensitivity reaction in those allergic to sulfonamides (for furosamide is a sulfonamide)

1. act at DCT to inhibit Na/Cl cotransporter
   1. no effect on corticomedullary gradient

• hypokalemia
• hypochloremic alkalosis

• increased excretion of:
  • Na
  • Cl
  • K
• decrease excretion of calcium

Hyperosmolar urine

• HTN (reduce volume, mild vasodil)
• CHF
• hypercalciuria (prevents renal stones)
• nephrogenic diabetes insipidus (thiazides can substitute for ADH)

• fluid and electrolyte imbalance
  • hyponatremia
  • hypochloremic alkalosis
  • hypokalemia
  • hypercalcemia
  • hyperuricemia
  • cardiac arrhythmias
• hypotension due to volume depletion
• hyperglycemia
• increase LDL, total chol., total triglyc.
• hypersensitivity rxn

1. act at collecting duct to compete with Ald for binding to its receptor
2. spironolactones active metabolite, canernone, forms an inactive receptor complex, block Ald action
   • without circulatin Ald, there can be no effect
   • eplerenone is more selective than spironolactone, so less side effects

• plasma- hyperkalemia
• urine
  • increase excretion of Na, Cl, water
  • decreased excretion of K

• take hours to days to reach peak effect
• absorbed orally and induce cyc P450

• either thiazide or loop diuretics
• prevents some K excretion which would occur with the thiazide, loop diuretics

• primary hyperAld
• secondary hyperAld resultin from CHF, hepatic cirrhosis, nephrotic syndrome

• hyperkalemia
  • more at risk if use drug that suppresses RAAS (ex: ACE inh.)
  • must monitor K levels if use both ACE inh. and Ald R blocker
• gynecomastia in males
• menstrual irregularities in females

1. act at CD to block sodium channels, leading to decrease Na/K exchange
   • INDEP. OF ALD PRESENCE

• urine- decreased K excretion
• plasma- hyperkalemia

• given in conj. with thiazide and loop diuretics
• this will prevent loss of K

• bound to plasma proteins and secretd by organic base transporters in PCT

• hyperkalemia (esp. in presence of renal disease)
• triamterne can precipitate in urine causing kidney stones
  • contraindicated with use of indomethacine (cases of acute renal failure)

1. mannitol is a nonelectrolyte that is freely filterable at the glomerulus and poorly reabsorbed by the renal tubule
2. mannitol acts at segments in tubule permeable to water (PCT, DCT, tDL, CD)
   1. increase osmotically active solute in filtrate, leading to decrease water reabsorption, causing increased urine volume
   2. increase renal blood flow, leading to decrease in corticomedullary osmotic gradient, which will decrease reabsorption of water from tDL and CD

• urine
  • increase in volume
  • decrease in osmolality
  • increase electrolyte excretion due to:
    • lowered tubule sodium conc.
    • increased tubular flow rate
• plasma
  • initially produce hyponatremia due to transfer in fluid to extracellular compartment
  • however, since water diuresis with mannitol is greater than increase in natriuresis, this can cause hypernatremia

• maintain urine flow in prophylaxis and treatment of acute renal failure
• short term reduction in intracranial or intraocular P before and after surgery
• acute glaucoma attacks
• dialysis disequilibrium
  • reduce hypotension and CNS symtpoms after over dialysis (decreased plasma osmolality)

• before diuresis, increase ECV lead to pulm. edema and CHF
• initial hyponatremia, cause headache, nausea, vomitting
• prolonged mannitol use without water replacment causes:
  • dehydration
  • free water losses
  • hypernatremia
  • hyperkalemia
• contraindicated for active cranial bleed

• act at collecting duct basolateral membrane by blocking ADH receptors (V_1a and V₂)

• urine- increased volume and decrease osmolality
• plasma- increased sodium concentration

• SIADH (only IV preps available)
• CHF when increased ADH levels present