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Renal > Pharmacology > Flashcards

Pharmacology Flashcards

1
Q

What is the general mechanism of action of diuretics?

A

Increase urine flow by inhibiting the reabsorption of electrolytes and enhance salt/water excretion where increased ECF causes tissue swelling

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2
Q

In what circumstance does oedema occur?

A

When formation does not equal absorption of interstitial fluid

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3
Q

Which forces move fluid out of the capillary?

A

Pc - capillary hydrostatic

Pi i - interstitial oncotic

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4
Q

Which forces move fluid into the capillary?

A

Interstitial hydrostatic

Plasma oncotic

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5
Q

What changes to the forces result in oedema?

A

Increase in capillary hydrostatic or decrease in plasma oncotic

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6
Q

Name three disease that can cause oedema

A
  • heart failure
  • cirrhosis
  • nephrotic syndrome
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7
Q

How does decreased plasma oncotic pressure lead to oedema?

A

Increased interstitial fluid
Decreased blood volume, activates RAAS which leads to salt/water retention increasing capillary hydrostatic and reducing plasma oncotic

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8
Q

How does congestive heart failure lead to oedema?

A

Reduced cardiac output leads to renal hypoperfusion activating RAAS causing increased blood volume and increasing venous/capillary pressures

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9
Q

Describe how cirrhosis causes oedema

A

Increased pressure in portal vein and decreased albumin leads to loss of fluid in the peritoneal cavity (ascites)

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10
Q

Which part of the cell do diuretics usually work?

A

Apical membrane

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11
Q

What happens to most salt and water that enters the filtrate?

A

It is reabsorbed

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12
Q

How can diuretics enter the filtrate?

A
  • glomerular filtration

- secretion in proximal tubule (organic anion/cation)

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13
Q

Give examples of drugs that move via organic anion transport

A

Simvastatin
Furosemide
NSAIDs
Penicillin

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14
Q

Describe what happens at the basolateral membrane in organic anion transport

A

OA- enters against the gradient in exchange for alpha ketogluterate which moves against its own gradient by a sodium transporter

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15
Q

Describe what happens at the apical membrane in organic anion transport

A

OA- crosses via multidrug resistance proteins and breast cancer resistance protein and comes from the lumen via OAT 4 in exchange for alpha ketogluterate

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16
Q

Give examples of drugs that move by organic cation transport

A

Triamterene

Amiloride

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17
Q

What happens in the cation transport at the basolateral membrane?

A

Enters by OCT2 which is driven by electrical potentials

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18
Q

What happens in cation transport at the apical membrane?

A

Enters lumen via MATE and MDR1 in a rate limiting manner

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19
Q

Name two loop diuretics

A

Furosemide and bumetanide

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20
Q

Describe the mechanism of action of loop diuretics

A

Inhibits sodium/potassium/chlorine triple transporter by binding to the chloride site

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21
Q

What is the effect of loop diuretics binding to the chloride site?

A

Decrease tonicity of the interstitial and prevents dilution of filtrate in ascending limb
Increased sodium delivered to distal regions, increased calcium and magnesium excretion

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22
Q

State the indications for loop diuretics

A

Reduce salt/water overload (HF/ascites/nephrotic syndrome)
Increases urine volume in AKI
Resistant hypertension
Reduce hypercalcaemia

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23
Q

When are loop diuretics contraindicated?

A

Severe hypovolaemia

Dehydration

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24
Q

Name the side effects of loop diuretics

A
  • hypokalaemia
  • metabolic alkalosis
  • hypocalcaemia
  • hypomagnesaemia
  • hypovolaemia
  • hypotension
  • hyperuricaemia (gout)
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25
Q

Name two thiazide/thiazide like diuretics

A

Bendroflumathiazide

Indapamide

26
Q

Describe the mechanism of action of thiazide diuretics

A

Inhibit the sodium/chloride carrier by binding to the chloride site - this prevents dilution of filtrate and increases sodium delivery to the collecting duct and increases calcium reabsorption

27
Q

Where are most diuretics absorbed?

A

GI tract

28
Q

What are the indications for thiazide diuretics?

A 
Mild heart failure 
Hypertension
Resistent oedema 
Renal stones 
Nephrogenic diabetes insipidus
29
Q

What are the contraindications of thiazide diuretics?

A

Hypokalaemia
Gout
Hyponatraemia

30
Q

State the side effects of thiazide diuretics

A
  • hypokalaemia
  • metabolic acidosis
  • hypovolaemia/hypotension
  • hypomagnaesmia
  • hyperuricaemia
  • erectile dysfunction
  • impaired glucose tolerance
31
Q

How do diuretics cause potassium loss?

A

Increased sodium enhances sodium reabsorption and the charge separation leads to a gradient across the lumen and an increased driving force of potassium secretion

32
Q

Name four potassium sparing diuretics

A
  • amiloride
  • triamterene
  • spironolactone
  • eplerenone
33
Q

Describe the mechanism of action of amiloride and triamterene

A

Block the apical sodium channel and reduce sodium reabsorption by blocking sodium channels in the collecting tubules

34
Q

Describe the mechanism of action of spironolactone and eplerenone

A

Compete with aldosterone for intracellular receipts preventing the action of steroid. Increase sodium excretion and decrease potassium excretion

35
Q

What are the clinical indications fro potassium sparing diuretics?

A

Heart failure
Hyperaldosteronism
Resistant essential hypertension

36
Q

Why are potassium sparing diuretics usually used in conjunction with thiazide/loop diuretics?

A

Alone they can cause hyperkalaemia

37
Q

State the contraindications of potassium sparing diuretics

A

Severe renal impairment
Addison’s
Hyperkalaemia

38
Q

Give an example of an osmotic diuretic

A

Mannitol

39
Q

Describe the mechanism of action of osmotic diuretics

A

Enter the nephron by glomerular filtration but are not reabsorbed - they increase the osmolality of filtrate opposing water and sodium reabsorption

40
Q

State the indications for osmotic diuretics

A
  • prevention of acute pre-renal failure

- increased ICP/intraocular pressure

41
Q

What are the side effect of osmotic diuretics?

A

Transient expansion of blood volume and hyponatraemia

42
Q

What can cause osmotic diuresis?

A

hyperglycaemia, iodine contrast

43
Q

Name a carbonic anhydrase inhibitor

A

Acetazolamide

44
Q

What can carbonic anhydrase inhibitors cause?

A

Alkaline diuresis

Metabolic acidosis

45
Q

When are carbonic anhydrase inhibitors?

A

Glaucoma
Altitude sickness
Infantile epilepsy

46
Q

When is it useful to alkalise urine?

A

Can help with dyuria, decrease stone formation and enhance acid excretion (useful in aspirin overdose)

47
Q

State three things that inhibit vasopressin

A
  • lithium
  • demedocycline
  • vaptans
48
Q

When can synthetic vasopressin be used?

A

To treat neurogenic diabetes insipidus - replaces lack of secretion from the posterior pituitary
Can also be used in bed wetting

49
Q

Can nephrogenic diabetes insipidus be treated?

A

No - it is genetic X linked

50
Q

How do vaptans work?

A

Act as competitive antagonists of vasopressin receptors

51
Q

Name the two types of vasopressin receptor and what they do

A

V1A - vasoconstriction

V2 - water reabsorption by aquaporins

52
Q

Give an example of a vaptan that treats SIADH and explain its mechanism

A

Tolvaptan

Blocking of V2 leads to water excretion and increased plasma sodium

53
Q

Give an example of a vaptan that treats heart failure

A

Conivaptan

Blocks both receptors used in hypervolaemic hyponatraemia

54
Q

Name an SGLT2 inhibitor

A

Canagliflozin

55
Q

Where is SGLT2 found?

A

Proximal tubule and reabsorbs glucose by secondary active transport and facilitated diffusion at the basolateral membrane. Glucose is transported by coupling with sodium influx

56
Q

What does inhibition of SGLT2 cause?

A

Glucosuria - used in T2DM

57
Q

State two types of prostaglandins

A

PGE2 - medulla

PGI2 - glomeruli

58
Q

What is needed for prostaglandins to be produced?

A

COX1/2

59
Q

What are the effects of prostaglandins on the kidneys?

A

They cause vasodilation in the afferent arteriole, releasing renin and causing efferent constriction to increase GFR

60
Q

What drugs inhibit COX?

A

NSAIDs

61
Q

In what cases are NSAIDs detrimental?

A

Conditions that rely on prostaglandins to maintain renal blood flow e.g HF and cirrhosis

62
Q

What drugs act on the kidneys and are useful in gout?

A

Probenecid and sulfinpyrazole - block rate reabsorption in the proximal tubule

Renal (20 decks)

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