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Theme 3: The Excretory System and Renal Function > Drugs affecting the kidneys- diuretic agents > Flashcards

Drugs affecting the kidneys- diuretic agents Flashcards

1
Q

What are diuretic agents?

A

A drug that increases the excretion of both fluids and solutes

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2
Q

Natriuretic

A

Increases Na+ excretion

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3
Q

Kaliuretic

A

Increases K+ excretion

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4
Q

Two major applications of diuretic agents

A
  1. Reduce circulating fluid volume

2. Removal of excess body fluids

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5
Q

Site of action of carbonic anhydrase inhibitors

A

Proximal tubule

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6
Q

Site of action of osmotic diuretics

A

Proximal tubule

Descending loop of henle

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7
Q

Site of action of loop diuretics

A

Ascending loop of henle

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8
Q

Site of action of thiazide and thiazide like diuretics

A

Early distal tubule

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9
Q

Site of action of K+-sparing diuretics

  • aldosterone antagonists
  • non- aldosterone antagonists
A

Late distal tubule

Early collecting duct

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10
Q

Loop diuretics

A

Most effective

Inhibit Na+/K+/2Cl- transporters in thick ascending limb (reduces reabsorption)

Increased Na+ delivery to DT, exchanged for K+ which is excreted in urine

Reduced Na+ reabsorption leads to rapid and profound diuresis

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11
Q

Loop diuretics clinical data

A

Oral absorption

  • diuresis in 60 minutes
  • persits for 4-6 hours

IV administation

  • diuresis within 5minutes
  • persists for 2 hours

IM administration
- diuresis in 30 minutes

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12
Q

Clinical uses of loop diuretics

A

MORE ACUTE CASES

Acute pulmonary oedema

Chronic heart failure

Cirrhosis of the liver

Resistant hypertension

REDUCED URINE PRODUCTION

Nephrotic syndrome

Acute renal failure

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13
Q

Unwanted effects of loop diuretics

A

Dehydration

K+ loss leads to hypokalaemia

Metabolic alkalosis due to H+ loss in urine

Hypokalaemia can potentiate effects of cardiac glycosides

Deafness (when used with aminoglycoside antibiotics)

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14
Q

Thiazide diuretics

A

Act in DT to inhibit apical Na+/Cl- co-transporter

Cause moderate but sustained Na+ excretion with increased water excretion

Moderately powerful diuretics

Well absorbed from GI tract and long duration of action (up to 24 hours)

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15
Q

Thiazide diuretics clinical data

A

Prototype is hydrochlorothiazide

Main is benzoflumethiazide

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16
Q

Clinical use of thiazide diuretics

A

Hypertension

Oedema

Mild heart failure

17
Q

Unwanted effects of thiazide diuretics

A

Plasma K+ depletion

Metabolic alkalosis

Increased plasma uric acid- gout

Hyperglycaemia

Increased plasma cholesterol (long term use)

Male impotence (reversible)

18
Q

Hypokalaemia

A

Mild: fatigue, drowsiness, dizziness, muscle weakness

Severe: abnormal heart rhythm, muscle paralysis, death

K+ sparing diuretics

  • act on DT to inhibit Na+ reabsorption
  • K+ is not secreted into distal tubule
19
Q

Subcategories of K+ sparing diuretics

A

Aldosterone antagonists

  • eplerenone
  • spironolactine

Non-aldosterone antagonists

  • amiloride
  • triamterene
20
Q

Aldosterone antagonists

A

Sprironolactone metabolised to canrenone

Competitive antagonist of aldosterone- reduce Na+ channel formation

Reduces Na+ absorption from DT

21
Q

Clinical uses of sprionolactone

A

SHORT TERM

Heart failure

Oedema

22
Q

Unwanted effects of spironolactone

A

Hyperkalaemia

Metabolic acidosis

GI upsets

Gynaecomastia, menstrual disorders, testicular atrophy

Eplerenone produces less effects

23
Q

Triamterene and Amiloride

A

Weak diurects- act on DT to inhibit Na+ reabsorption and decrease K+ excretion

Blocks luminal Na+ channel

Main unwanted effects

  • hyperkalaemia
  • metabolic acidosis
  • GI disturbances
  • skin rashes
24
Q

Combination of diuretics

A

Increases diuretic effect

Avoids unwanted effects of hypokalaemia

25
Q

How to avoid hypokalaemia

A

Loop diuretics with spironolcatone

Loop diuretics with amiloride or triamterene

Thiazides with sprionolactone

Thiazides with amiloride or triamterene

Diuretics containing K+

26
Q

Carbonic anhydrase inhibitors

A

Blocks NaHCO3 reabsorption in PT

Causes weak diuresis

Used for

  • glaucoma
  • epilepsy

Unwanted effects

  • metabolic acidosis
  • enhances renal stone formation
27
Q

Osmotic diuretics

A

Main- mannitol

  • non- reabsorbable solute undergoes glomerular filtration
  • excretion within 30-60 mins
  • diuresis in 30-60 mins persists for 6-8 hours

Clinical uses

  • cerebral oedma
  • glaucoma
  • cause osmotic diarrhoea
  • acute renal failure

Unwanted effects

  • increases plasma volume
  • can’t be used in patients with hypertension
28
Q

Water as a diuretic

A

Process controlled by ADH

Increased fluid intake leads to reduced secretion of ADH from posterior pituitary due to reduced plasma osmolality

Reduced expression of AQP2 channels on apical surface of DT and collecting duct

29
Q

Potential ADH antagonists

A

Investigational drugs which inhibit the effects of ADH at collecting tubule

Two non- selective agents

  • lithium (Li+)
  • demeclocycline
30
Q

Toxicity problem of ADH antagonists

A

Can cause diabetes insipidus

Renal failure

Li+ cause tremors, mental confusion, cardiotoxicity, thyroid dysfunction and leukocytosis

Demeclocycline shouldn’t be used in patients with liver disease

31
Q

Xanthines

A

Caffeine, theophylline, theobromine

Produce weak diuretic effect by increasing cardiac output

Possibly also some vasodilation of glomerular afferent arteriole

Increased renal and glomerular blood flow, increase GFR and urine output

Theme 3: The Excretory System and Renal Function (13 decks)

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