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Renal Pharmacology > Diuretics > Flashcards

Diuretics Flashcards

1
Q

What are diuretics?

A

Drugs inducing a state of increased urine flow and output

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2
Q

What are the main functions of the nephron?

A

Filtration, reabsorption, secretion and excretion

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3
Q

Reabsorption of salt is under control of?

A

aldosterone

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4
Q

Water is under control of?

A

vasopressin

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5
Q

How do diuretics work?

A
  1. diuretics are ion transport inhibitors that decrease the reabsorption of Na+ at different sites in the nephron
    - Other electrolytes involved are Cl-, HCO3-, K+
  2. To maintain an osmotic balance the increased excretion of electrolytes is accompanied by increase in water excretion
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6
Q

What physiological changes do diuretics do to the body?

A
  1. increase the volume of the urine
  2. often change pH of urine
  3. change the ionic composition of the urine and blood
  4. change the levels of Na+, Cl-, HCO3-, K+
    • cause side effects related to changes of
      above electrolytes and others
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7
Q

How much fluid is filtered everyday?

A

180L of fluid

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8
Q

Where does filtration take place?

A

glomerulus

- plasma proteins and lipids are not filtered

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9
Q

Urine formation starts from?

A

glomerular filtration
- More than 99% of the glomerular filtrate is
reabsorbed in the tubules

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10
Q

How much urine is produced in 24 hours?

A

1.5L

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11
Q

Describe the normal amount of urine produced by a person?

A

1–2 litres per 24 hours

- highly variable depending on fluid intake and water loss through the skin and GI tract

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12
Q

What is the colour of normal urine?

A
  1. Straw or amber
    • darker means more concentrated
  2. should be clear
    • not cloudy
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13
Q

Describe the specific gravity of normal urine?

A
  1. 01–1.025
    - a measure of the dissolved material in urine
    - the lower the value, the more dilute the urine
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14
Q

Describe the pH of normal urine?

A

Average 6

  • range 4.6–8.0
  • diet has the greatest effect on urine pH
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15
Q

Describe the composition of normal urine?

A

95% water; 5% salts and waste products

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16
Q

Describe the nitrogenous waste present in normal urine?

A
  1. Urea—from amino acid metabolism
  2. Creatinine—from muscle metabolism
  3. Uric acid—from nucleic acid metabolism
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17
Q

Tubular reabsorption can be divided into 4 sites?

A

Site I: Proximal tubule
Site II: Ascending limb of loop of Henle
Site III: Cortical diluting segment of loop of Henle (descending)
Site IV: Distal tubule (DT) and collecting duct (CD)

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18
Q

What are the main kidney functions?

A
  1. Cleansing of extracellular fluid (ECF) and maintenance of ECF volume and composition
    • affected by diuretics the most
  2. Maintenance of acid-base balance
  3. Excretion of metabolic wastes and foreign substances (eg, drugs, toxins)
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19
Q

Describe the application of diuretics?

A
  1. treatment of hypertension
  2. mobilization of oedematous/interstitial fluid associated with heart failure, cirrhosis, or kidney disease
  3. prevent renal failure
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20
Q

The relative magnitudes of Na+ reabsorption at different tubular sites are?

A
  1. PT 65–70%;
  2. Asc LH 20–25%;
  3. DT 8–9%;
  4. CD 1–2%.
21
Q

Describe the diuretics that act on the proximal tubule?

A

these agents are either too weak or cause distortion of acid-base balance

22
Q

Diuretic agents may include?

A
  1. carbonic acid anhydrase inhibitors
  2. loop diuretics
  3. thiazides
  4. K+ sparing diuretics
  5. osmotic diuretics
  6. Anti-diuretic hormone antagonists
    - These agents work on different sections of the nephron
    - It depends on processes affected and the types of electrolytes involved
23
Q

What is the mechanism of action of diuretics?

A

Increases renal excretion of Na+ & H20

  1. Cellular action of diuretics is to reduce the reabsorption of Na+ with increased H2O loss occurring as a consequence
  2. causing Na+ retention (in lumen): ↓H2O reabsorption (↑urine volume)
24
Q

What is the mechanism of action of carbonic anhydrase inhibitors?

A

inhibit the enzyme carbonic anhydrase in the proximal tubular epithelial cells

25
Q

What is the function of carbonic anyhdrase?

A

is an enzyme which catalyses the reversible reaction H2O + CO2 -> H2CO3

  • which spontaneously ionizes into H+ + HCO3
  • only mild diuresis action
26
Q

Where is carbonic acid anhydrase found?

A
  1. renal tubular cell (especially PT)
  2. gastric mucosa
  3. exocrine pancreas
  4. ciliary body of eye
  5. brain
  6. RBC
27
Q

What are the therapeutic uses of carbonic acid anhydrase inhibitors?

A
  1. glaucoma
  2. epilepsy
  3. mountain sickness
  4. to alkalinise urine
    - for urinary tract infection
    - to promote excretion of certain acidic drugs
28
Q

What are the side effects of carbonic anhydrase inhibitors?

A
  1. metabolic acidosis (mild)
  2. metabolic alkalosis
  3. hypokalemia
  4. renal stone formation
  5. drowsiness
  6. abnormal taste
  7. decreased libido
  8. lethargy
  9. paresthesia
29
Q

What medications interact with carbonic anhydrase inhibitors?

A
  1. Aspirin/ salicylates

2. K+ depleting agents

30
Q

What are the consequences of the interactions between CAAI and aspirin/salicylates?

A

acetazolamide induced acidosis:

  • lethargy
  • confusion
  • coma
31
Q

What is the consequence of the interaction between CAAI and K+ depleting agents?

A

induction of hypokalemia aggravated

32
Q

Loop diuretics are also known as?

A

high ceiling diuretics

33
Q

How much urine can be produced under loop diuretics?

A

up to 10L of urine in 24hrs

34
Q

What is the mechanism of action of loop diuretics?

A

inhibits Na+- K+-2Cl¯ cotransport mainly on the Ascending Loop of Henry, therefore, reabsorption of Na+, K+, and CI- is decreased

35
Q

Name the 4 loop diuretics?

A
  1. Furosemide
  2. Bumetanide
  3. Torsemide
    • Sulphonamides
  4. Ethacrynic acid
    • Not a sulphonamide derivative
    • Derived from azo dyes
36
Q

What are the therapeutic uses of loop diuretics?

A
  1. pulmonary edema - associated with CHF, 2. acute pulmonary edema (cardiac, hepatic or renal)
  2. hypertension
  3. Hypercalcaemia of malignancy
37
Q

What are the side effects of loop diuretics?

A 
1. Hypokalemic metabolic alkalosis 
   (concomitant use of K+ sparing diuretics/ or 
    K+ supplements)
2. Hyperuricemia 
3. Ototoxicity
4. acute hypovolemia
5. hypokalemia (shock, hypotension, 
    arrhythmias)
38
Q

Describe the administration of Lasix?

A

Lasix is rapidly absorbed orally and could be administered both oral and parenteral

39
Q

Describe the pharmacokinetics of loop diuretics?

A
  1. Duration of action is within 6 hrs, and has got rapid onset
  2. Oral route: Onset 60 min; peak 60–120 min + duration 6–8 h
  3. IV : Onset 5 min; peak 30 min + duration 2 h
  4. T½: 120 min - metabolized in the liver and excreted in urine
40
Q

What drugs do loop diuretics interact with?

A

Aminoglycosides, cephalosporines, sulfonamides or quinolones; plasma protein binding displaced by warfarin

41
Q

Describe the contraindications of loop diuretics?

A

Hypersensitivity to sulphonamides
Hepatic coma
Renal failure
Hypokalemia

42
Q

What is the mechanism of action of Thiazides?

A

Inhibitors of Na+-Cl¯ symport

  • moderately efficacious diuretics
  • site of action mostly at segment III
  • they also inhibit urinary calcium excretion
43
Q

What are the therapeutic uses of Thiazides?

A

Hypertension; CHF; hypercalciuria; nephrogenic diabetes insipidus

44
Q

What are the side effects of Thiazides related to diuretic effect?

A 
Hypokalaemia
Metabolic alkalosis
Hyponatremia
Hypovolemia & hypotension
Hypomagnesemia
Hypercalcemia
45
Q

What are the side effects of Thiazides not related to diuretic effect?

A

Hyperuricemia
Hyperglycemia
↑LDL & cholesterol (hyperlipidaemia)
Impotence

46
Q

What are the pharmacokinetics of Thiazides?

A
  1. Take time to produce stable reduction in BP
    • 1 to 3 weeks
  2. prolonged t1/2 about 40 hrs
    • exhibit poor absorption (hydrochlorothiazide)
  3. Oral route: Onset 2 h; peak 4–6 h; duration 6–12 hr
  4. T½: 5.6–14 h
    - metabolized in the liver and excreted in urine
47
Q

What drugs do Thiazides interact with?

A

Cardiac glycosides; Antidiabetic agents; Lithium; Uricosuric agents; NSAIDs; K+ depleting agents

48
Q

What are the contraindications of Thiazides?

A

Severe renal/hepatic impairment
Hypokalemia
Pre-existing hypercalcemia
Hypersensitivity to thiazides /other sulphonamide derivatives

49
Q

What is the mechanism of action for osmotic diuretics?

A

reduce water reabsorption resulting in a subsequent decrease of sodium reabsorption
e.g. mannitol

Renal Pharmacology (2 decks)

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