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233 2nd midterm > Pharm of Diuretics > Flashcards

Pharm of Diuretics Flashcards

1
Q

what is increased sodium excretion
increased potassium excretion

which drugs cause a net loss of Na+ and water in urine

A

Natriuresis
Kaliuresis
Diuretics

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2
Q

Kidney Function (read)

A

• Primary function of the kidney is to maintain constancy of the “interior environment”
– Eliminating waste products (Urea, Uric acid, Creatinine etc.)
– Regulates volume, electrolyte content & pH of the
extracellular fluid
• Filter ~180 L per day (receive 25% of total cardiac
output)
• As filtrate passes through the renal tubule, the vast
majority of filtered water and Na+ is reabsorbed
– ~1.5-1.8 L voided as urine
• The functional unit of the kidney is the nephron

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3
Q

how much Na+, K+, Cl-, HCO3- and water is reabsorbed

A

> 99% of Na+, Cl-, water,
93% K+
100% HCO3-

87% of total solute

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4
Q

prox tubule

what is it permeable to?

A
  • Freely permeable to water and solutes.
  • Na+-K+-ATPase in the basolateral membrane provides the Na+- gradients (low cytoplasmic Na+ concentrations) for passive transporters in the apical membranes which facilitate Na+ entry (reabsorption) from the tubular fluid down a concentration gradient.
  • 60–70% of the filtered Na+ and >90% of HCO3- is absorbed in the proximal tubule.

Na+ is passively transported and will be actively transported through basolateral membrane using sodium potassium ATPase channel

Active transport of chloride, bicarbonate, glucose, aa, organic solutes

Most of where reabs happens

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5
Q

loop of henle (see pic)

which parts are permeable?
permeable to?
what does it reabsorb?

A

• Descending limb is permeable to water
• The TAL (thick ascending limb) is impermeable to water; 20–30% of the filtered NaCl is actively reabsorbed in this segment
• Ions are reabsorbed from tubular
fluid by a Na+/K+/2Cl− cotransporter in the apical
membranes of the TAL

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6
Q

Distal Tubule (see pic)

what does it reabsorb?

A
  • Reabsorbs 5–10% of filtered Na+
  • Active transport of Na+ by Na+/Cl− co-transport in DT
  • Calcium excretion is regulated by parathyroid hormone
  • K+ is secreted into tubular fluid in the distal tubule
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7
Q

Collecting Tubule/Duct (see pic)

what does it reabsorb?

A
  • Reabsorbs (2–5%) coupled to K+/H+ secretion (under Aldosterone control)
  • Vasopressin control water reabsorption in Collecting duct
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8
Q

mineralocorticoids

what is the primary endogenous one?

A

aldosterone

  • increases Na+ reabs in kidney (accompanied via increased excretion of K+ and H+)
  • low plasma Na+ or high plasma K+ influence zona glomerulosa cells, stimulating aldosterone release
  • low Na+ also increases angiotensin II which increases synth and release of aldosterone
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9
Q

summary of nephron func

prox tubule
Thin descending limb of Henle’s loop
Thick ascending limb of Henle’s loop

A

PT: Reabsorbs:
• 60-70% of filtered Na+/K+/ Ca2+/Mg2+ and water (osmotic)
• >90% of HCO3−
• ~100% of glucose and amino acids

Thin descending
Passive reabsorption of water (~20%)

Thick ascending
• Active reabsorption of 20-30% of filtered Na+/K+/Cl−
• Impermeable for water

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10
Q

summary of nephron func

distal tubule (DT)

Collecting Tubule (CT)
Collecting Duct (CD)
A

DT
• Active reabsorption of 5–10% of filtered Na+/Cl−
• Ca2+ reabsorption under parathyroid hormone control

CT
• Reabsorption of 2–5% Na+ coupled to K+/H+ secretion (under Aldosterone)
• Vasopressin control water reabsorption in Collecting duct

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11
Q 
Collecting Tubule (CT)
Collecting Duct (CD)
A
  • Reabsorption of 2–5% Na+ coupled to K+/H+ secretion (under Aldosterone)
  • Vasopressin control water reabsorption in Collecting duct
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12
Q

Loop Diuretics

name 2 drugs

indications? (6)

A

• Furosemide
• Bumetanide
• Most powerful diuretics
- hiogher sodium release and more flow of urine compared to thiazides

Used to treat salt & water overload
associated w/
• Acute pulmonary edema
• Chronic heart failure
• Cirrhosis of the liver
• Nephrotic syndrome
• Renal failure
• Preferred for hypertension with poor renal function
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13
Q

Loop Diuretics

MOA?

A

• Inhibit the Na+/K+/2Cl- carrier in the luminal membrane of the thick ascending limb (bind to the Clbinding site)
– The most powerful diuretics
– Cause excretion of 15-25% of filtered Na+, stay in lumen to be excreted

Also have vascular actions
– Vasodilation independent of the diuresis (may involve reduced responsiveness to angiotensin II (or increase in vasodilation prostaglandins) & noradrenaline)

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14
Q

Loop Diuretics

AE (4 main)

A
  • Excessive Na+ & water loss (especially in elderly people)
  • *Hypovolemia: Increase of blood pH, bicarbonate pH increases as plasma volume is reduced due to loss of water
  • *Hypokalemia: extra care for heart failure, CBD as toxicity is worse
  • Metabolic Alkalosis
  • Hypomagnesaemia
  • *Hyperuricemia: increase urea, lead to gout
  • Reduced renal perfusion
  • *Hearing loss: due to impaired ion transport in inner ear

uncommon
• Rashes
• Bone marrow depression
• Contraindicated in people with sulfa allergy

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15
Q

Thiazides

2 main drugs
compare to loop diuretics

indications? (4)

A
  • Bendroflumethiazide
  • Hydrochlorothiazide
  • Less powerful than loop diuretics
  • Acts synergistically with loop diuretics
  • Related drugs include chlortalidone, indapamide & metolazone
  • Hypertension
  • Mild heart failure
  • Severe resistant edema
  • Nephrogenic diabetes insipidus
  • Preferred for hypertension with normal renal function
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16
Q

Thiazides

MOA?

A

• Bind to the Cl- site of the distal tubular Na+/Cl- co-transport system
– Induce natriuresis with loss of Na+ and Cl- ions (stay in lumen)
– Stimulate renin secretion (leads to angiotensin formation & aldosterone secretion)
• Unlike loop diuretics, thiazides reduce Ca2+ excretion
– Potentially advantageous in elderly patients at risk of osteoporosis

17
Q

Thiazides

AE? (3)

A
  • *Erectile dysfunction (less common with low doses and is reversible)
  • Hypochloremic alkalosis
  • *Impaired glucose tolerance
  • Hyponatremia (especially in the elderly)
  • *Hypokalemia
  • Rashes and blood dyscrasias (uncommon)
18
Q

Potassium Sparing Diuretics

name 2

indication (4)

A

main drugs are aldosterone antagonists
• Spironolactone
• Eplerenone

  • Limited action when used singly
  • These drugs prevent hypokalemia when combined with loop diuretics of thiazides
  • Resistant essential hypertension
  • Heart failure
  • Primary hyperaldosteronism
  • Secondary hyperaldosteronism (hepatic cirrhosis)
19
Q

Potassium Sparing Diuretics

MOA?

A

• Compete with aldosterone for its intracellular receptor

– Inhibit distal Na+ retention and K+ secretion

20
Q

Potassium Sparing Diuretics

AE (2)

A
  • *Hyperkalemia: beneficial if you use potassium sparing diuretics to compensate this effect
  • GI upset
  • *Gynecomastia, menstrual disorders & testicular atrophy (less w/ eplerenone)
21
Q

Other Diuretics
Triamterene/Amiloride

when are they used?
MOA?
AE (1)

A
  • Limited action when used singly
  • These drugs prevent hypokalemia when combined with loop diuretics of thiazides
  • Inhibit Na+ reabsorption in the collecting tubules by blocking lumenal Na+ channels regulated by aldosterone
  • *hyperkalemia and GI upset
22
Q 
Other Diuretics
Osmotic Diuretics (Mannitol)

when are they used?
MOA?
AE (1)

A

inhibits reabsorption of water and sodium

  • Mannitol is a 6-carbon sugar alcohol
  • Pharmacologically inert substances that are filtered in the glomerulus but are not reabsorbed
  • Exert their actions on parts of the nephron that are permeable to water (all parts except ascending loop)
  • Are used in acute renal failure
  • Also used for treating acutely raised intracranial or intraocular pressure
  • *Can increase risk for precipitating left ventricular failure
  • Other adverse effects include headache, nausea & vomiting
23
Q

site of action of loop diuretics

A

Thick Ascending Limb of Loop of Henle

Na+/K+/2Cl- inhibition

24
Q

site of action of thiazides

A

DCT (NaCl)

25
Q

site of action of Potassium Sparing Diuretics

A

CD

26
Q

site of action of Osmotic Diuretics

A

PTC, LOH, DCT, CT

27
Q

which causes hypokalemia, hypocalcemia, hyperuricemia?

A

loop diuretics

28
Q

which causes hypokalemia, hypercalcemia, impaired glucose tolerance?

A

thiazide diuretics

29
Q

which causes hyperkalemia

A

Potassium Sparing Diuretics

30
Q

which causes risk for precipitating left ventricular failure and pulmonary edema?

A

Osmotic Diuretics

233 2nd midterm (13 decks)

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