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Module 104 - Nutrition, metabolism & excretion > T3 L6 Drugs which affect the kidney > Flashcards

T3 L6 Drugs which affect the kidney Flashcards

1
Q

What type of drugs affect the kidneys?

A 
ACE inhibitors
Anticancer drugs
Antiviral agents
Aminoglycosides
Beta blockers
Lithium
NSAIDs
Radiocontrast media
Vasodilators
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2
Q

What are the 3 types of acute kidney injury?

A

Pre-renal due to blood loss
Intrinsic
Post-renal due to bloackage

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3
Q

What is a diuretic?

A

Drug that increases the excretion of both fluids and solutes

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4
Q

What does a natriuretic do?

A

Increases sodium excretion

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5
Q

What does a kaliuretic do?

A

Increases potassium excretion

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6
Q

What are aquatic agents?

A

Increase urine excretion without increasing sodium excretion

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7
Q

What are the 2 main applications to use diuretics?

A

Reduce circulating fluid volume

Remove excess body fluid (oedema)

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8
Q

What are the reasons to use diuretics for their actions on the kidneys?

A 
Hypertension
Chronic heart failure
Liver cirrhosis
Renal diseases
Premenstrual oedema
Toxic oedema
Increase elimination of drugs
Rapid weight loss
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9
Q

What other conditions are diuretics used in?

A

Glaucoma to reduce intra-occular pressure

Epilepsy to reduce the pressure of CSF

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10
Q

What are the classes of diuretic agents?

A 
Carbonic anhydrase inhibitors
Osmotic diuretics
Loop diuretics
Thiazide & thiazide-like diuretics
Potassium-sparing diuretics
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11
Q

Where do carbonic anhydrase inhibitors act?

A

On the proximal tubule

Old diuretics & aren’t used for hypertension anymore

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12
Q

Where do osmotic diuretics act?

A

Proximal tubule

Descending loop of Henle

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13
Q

Where do loop diuretics act?

A

Ascending loop of Henle

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14
Q

Where do thiazide & thiazide-like diuretics act?

A

Early distal tubule to inhibit apical Na+/Cl- cotransporter

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15
Q

Where do potassium sparing diuretics act?

A

Late distal tubule

Early collecting tubule

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16
Q

What diuretics can cause hypokalaemia?

A

Loop
Thiazide
Thiazide-like
Cause you to excrete more potassium

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17
Q

What is the mechanism of loop diuretics?

A

Inhibit Na+/K+/2Cl- transporters (NKCC2) in thick ascending limb of loop of henle
Reduces reabsorption of Na+, K+ & Cl-
Reduced Na+ reabsorption leads to rapid & profound diuresis

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18
Q

How do loop diuretics cause hypokalaemia?

A

Increased delivery of sodium to distal tubule
Na+ exchanged for K+ in the distal tubule
Excreted in urine

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19
Q

How much increase in urine volume can a single dose of loop diuretics cause?

A

Increase urine volume from 200ml to 1200ml over 3 hours

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20
Q

Give an example of a loop diuretic

A

Furosemide
Bumetanide
Torasemide
Ethacrynic acid - not on market due to hepatic toxicity

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21
Q

What type of diuretic is furosemide?

A

Loop diuretic

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22
Q

Describe the dosing of furosemide

A

Oral absorption - diuresis in 60 min. Last for 4-6 hours
IV administration - diuresis in 5 min. Lasts for 2 hours
IM administration - diuresis in 30 min

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23
Q

What are some clinical uses of loop diuretics?

A 
Acute pulmonary oedema
Chronic heart failure
Cirrhosis of the liver
Resistant hypertension
Nephrotic syndrome
Acute renal failure
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24
Q

What are the unwanted effects of loop diuretics?

A

Dehydration
Hypokalaemia - can potentiate effects of cardiac glycosides
Metabolic alkalosis - due to H+ loss in urine
Deafness if used with aminoglycoside antibiotic

25
Q

What do thiazide diuretics do?

A

Cause moderated by sustained Na+ excretion with increased water excretion
Moderately powerful diuresis - lower than what is produced by loop diuretics
Well absorbed from GI tract
Long duration of action - up to 24h

26
Q

What is the main thiazide diuretic?

A

Bendoflumethiazide - used for mild/moderate heart failure

27
Q

What are some examples of thiazide diuretics?

A 
Bendroflumethiazide
Chlortalidone
Cyclopenthiazide
Benthiazide
Cyclopenthiazide
Hydroflumethiazide
28
Q

What are some examples of thiazide-like diuretics?

A

Indapamide
Metolazone - good combined with loop
Xipamide - lowers BP with less side effects
Clopamide

29
Q

What are the clinical uses of thiazide & thiazide-like diuretics?

A

Hypertension
Oedema
Mild heart failure
Generally used for less acute conditions

30
Q

What are the unwanted effects of thiazide diuretics?

A 
Hypokalaemia
Metabolic alkalosis due to H+ loss
Increased plasma uric acid -  gout
Hyperglycaemia
Increased plasma cholesterol with long-term use
Male impotence - reversible
31
Q

Why does hypokalaemia occur?

A

Due to a loss of K+ in the urine

32
Q

What are the symptoms of mild hypokalaemia?

A

Fatigue
Drowsiness
Dizziness
Muscle weakness

33
Q

What are the symptoms of severe hypokalaemia?

A

Abnormal heart rhythm
Muscle paralysis
Death

34
Q

How do potassium sparing diuretics avoid hypokalaemia?

A

Act on distal tubule to inhibit Na+ reabsorption
K+ is not secreted into distal tubule
Aldosterone antagonists & non-aldosterone antagonists

35
Q

What are aldosterone antagonists?

A

Potassium sparing diuretics
Competitive antagonists of aldosterone - reduce Na+ channel formation –> reduced Na+ absorption from distal tubule
Limited diuretic action - not as potent as loop or thiazide diuretics
Mechanism depends on reduction of protein expression in distal tubular cells

36
Q

What are some examples of aldosterone antagonists?

A

Spironolactone

Eplerenone

37
Q

What are some clinical reasons to use aldosterone antagonists?

A

Heart failure
Oedema
Short term use
Resistant hypertension in the short term - concerns for long term due to possible incidence of cancer in rat studies

38
Q

What are some unwanted effects of aldosterone antagonists?

A

Hyperkalaemia
Metabolic acidosis
GI upsets
Gynaecomastia, menstrual disorders, testicular atrophy
Eplerenone produces less unwanted effects than spironolactone

39
Q

What are triamterene & amiloride?

A

Weak diuretics
Non-aldosterone potassium sparing inhibitors
Act on distal tubule to inhibit Na+ reabsorption & decrease K+ excretion
Blocks luminal Na+ channel which aldosterone uses to produce its main effects
Of little therapeutic use on their own but are useful in combination with potassium-depleting diuretics as they limit hypokalaemia

40
Q

What are the unwanted effects of triamterene & amiloride?

A

Hyperkalaemia
Metabolic acidosis
GI disturbances
Skin rashes

41
Q

What is the purpose of using diuretics in combination?

A

Increase diuretic effect

Avoid unwanted effects of hypokalaemia

42
Q

Give some examples of diuretics that are used in combination

A

Combinations of loop diuretics or thiazides with potassium-sparing diuretics
Diuretic preparations containing K+
Loop diuretics with spironolactone
Loop diuretics with amiloride or triamterene
Thiazides with spironolactone
Thiaxides with amiloride or triamterene

43
Q

Give an example of a carbonic anhydrase inhibitor

A

Acetazolamide

44
Q

What do carbonic anhydrase inhibitors do?

A

Blocks sodium bicarbonate in the proximal tubule

Weak diuresis so is not commonly used

45
Q

What are the clinical uses of carbonic anhydrase inhibitors?

A

Glaucoma

Epilepsy

46
Q

What are some unwanted effects of carbonic anhydrase inhibitors?

A

Metabolic acidosis - due to excretion of HCO3-

Enhances renal stone formation - due to alkaline urine

47
Q

What is mannitol?

A

Osmotic diuretic
Non-reabsorbable solute which undergoes glomerular filtration
Excreted with 30-60min

48
Q

What is mannitol used for?

A

Raised inter cranial pressure
Intraoccular pressure - glaucoma
Can cause osmotic diarrhoea which eliminates toxins
Acute renal failure

49
Q

What are the unwanted effects of osmotic diuretics?

A

Presence in blood exerts an osmotic pressure –> increase in plasma volume

50
Q

How is water as a diuretic controlled?

A

By ADH
Increased fluid intake –> reduced plasma osmolality –> reduced secretion of ADH from posterior pituitary –> reduced expression of AQP2 on apical surface of distal tubule & collecting duct –> more water excreted

51
Q

What are some examples of possible ADH antagonists

A

2 non-selective agents:
Lithium & demeclocycline
Tolvaptan

52
Q

What are the issues with ADH antagonists?

A

Can cause diabetes insipidus
Renal failure
Lithium can cause tremors, mental confusion, cardiotoxicity, thyroid dysfunction & leucocytosis

53
Q

What is tolvaptan?

A

ADH antagonist
V2 receptor antagonist used for treatment of hyponatraemia –> decreased extracellular fluid –> increased plasma sodium concentration

54
Q

What inhibits ADH release

A

Alcohol - tolerance develops rapidly so the diuresis is not sustained
Increases urine excretion

55
Q

What increases ADH release?

A 
Nicotine
Ether
Morphine
Barbiturates
Reduce urine excretion
56
Q

What are some examples of xanthines?

A

Caffeine
Theophylline
Theobromine

57
Q

What do xanthines do?

A

Produce a weak diuretic effect by increasing cardiac output
May cause some vasodilation of glomerular afferent arteriole
Increase renal & glomerular blood flow –> increases GFR & urine output

58
Q

Why aren’t xanthines used clinically?

A

Cause gastric irritant effects

59
Q

What is theophylline used for?

A

Bronchodilator for asthma

Module 104 - Nutrition, metabolism & excretion (31 decks)

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