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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
What is the function of carbonic anyhdrase?
is an enzyme which catalyses the reversible reaction H2O + CO2 -> H2CO3 - which spontaneously ionizes into H+ + HCO3 - only mild diuresis action
26
Where is carbonic acid anhydrase found?
1. renal tubular cell (especially PT) 2. gastric mucosa 3. exocrine pancreas 4. ciliary body of eye 5. brain 6. RBC
27
What are the therapeutic uses of carbonic acid anhydrase inhibitors?
1. glaucoma 2. epilepsy 3. mountain sickness 4. to alkalinise urine - for urinary tract infection - to promote excretion of certain acidic drugs
28
What are the side effects of carbonic anhydrase inhibitors?
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
What medications interact with carbonic anhydrase inhibitors?
1. Aspirin/ salicylates | 2. K+ depleting agents
30
What are the consequences of the interactions between CAAI and aspirin/salicylates?
acetazolamide induced acidosis: - lethargy - confusion - coma
31
What is the consequence of the interaction between CAAI and K+ depleting agents?
induction of hypokalemia aggravated
32
Loop diuretics are also known as?
high ceiling diuretics
33
How much urine can be produced under loop diuretics?
up to 10L of urine in 24hrs
34
What is the mechanism of action of loop diuretics?
inhibits Na+- K+-2Cl¯ cotransport mainly on the Ascending Loop of Henry, therefore, reabsorption of Na+, K+, and CI- is decreased
35
Name the 4 loop diuretics?
1. Furosemide 2. Bumetanide 3. Torsemide - Sulphonamides 4. Ethacrynic acid - Not a sulphonamide derivative - Derived from azo dyes
36
What are the therapeutic uses of loop diuretics?
1. pulmonary edema - associated with CHF, 2. acute pulmonary edema (cardiac, hepatic or renal) 3. hypertension 4. Hypercalcaemia of malignancy
37
What are the side effects of loop diuretics?
``` 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
Describe the administration of Lasix?
Lasix is rapidly absorbed orally and could be administered both oral and parenteral
39
Describe the pharmacokinetics of loop diuretics?
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
What drugs do loop diuretics interact with?
Aminoglycosides, cephalosporines, sulfonamides or quinolones; plasma protein binding displaced by warfarin
41
Describe the contraindications of loop diuretics?
Hypersensitivity to sulphonamides Hepatic coma Renal failure Hypokalemia
42
What is the mechanism of action of Thiazides?
Inhibitors of Na+-Cl¯ symport - moderately efficacious diuretics - site of action mostly at segment III - they also inhibit urinary calcium excretion
43
What are the therapeutic uses of Thiazides?
Hypertension; CHF; hypercalciuria; nephrogenic diabetes insipidus
44
What are the side effects of Thiazides related to diuretic effect?
``` Hypokalaemia Metabolic alkalosis Hyponatremia Hypovolemia & hypotension Hypomagnesemia Hypercalcemia ```
45
What are the side effects of Thiazides not related to diuretic effect?
Hyperuricemia Hyperglycemia ↑LDL & cholesterol (hyperlipidaemia) Impotence
46
What are the pharmacokinetics of Thiazides?
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
What drugs do Thiazides interact with?
Cardiac glycosides; Antidiabetic agents; Lithium; Uricosuric agents; NSAIDs; K+ depleting agents
48
What are the contraindications of Thiazides?
Severe renal/hepatic impairment Hypokalemia Pre-existing hypercalcemia Hypersensitivity to thiazides /other sulphonamide derivatives
49
What is the mechanism of action for osmotic diuretics?
reduce water reabsorption resulting in a subsequent decrease of sodium reabsorption e.g. mannitol

Renal Pharmacology (2 decks)

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