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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

(59 cards)

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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?

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A

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

25
What do thiazide diuretics do?
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
What is the main thiazide diuretic?
Bendoflumethiazide - used for mild/moderate heart failure
27
What are some examples of thiazide diuretics?
``` Bendroflumethiazide Chlortalidone Cyclopenthiazide Benthiazide Cyclopenthiazide Hydroflumethiazide ```
28
What are some examples of thiazide-like diuretics?
Indapamide Metolazone - good combined with loop Xipamide - lowers BP with less side effects Clopamide
29
What are the clinical uses of thiazide & thiazide-like diuretics?
Hypertension Oedema Mild heart failure Generally used for less acute conditions
30
What are the unwanted effects of thiazide diuretics?
``` Hypokalaemia Metabolic alkalosis due to H+ loss Increased plasma uric acid - gout Hyperglycaemia Increased plasma cholesterol with long-term use Male impotence - reversible ```
31
Why does hypokalaemia occur?
Due to a loss of K+ in the urine
32
What are the symptoms of mild hypokalaemia?
Fatigue Drowsiness Dizziness Muscle weakness
33
What are the symptoms of severe hypokalaemia?
Abnormal heart rhythm Muscle paralysis Death
34
How do potassium sparing diuretics avoid hypokalaemia?
Act on distal tubule to inhibit Na+ reabsorption K+ is not secreted into distal tubule Aldosterone antagonists & non-aldosterone antagonists
35
What are aldosterone antagonists?
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
What are some examples of aldosterone antagonists?
Spironolactone | Eplerenone
37
What are some clinical reasons to use aldosterone antagonists?
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
What are some unwanted effects of aldosterone antagonists?
Hyperkalaemia Metabolic acidosis GI upsets Gynaecomastia, menstrual disorders, testicular atrophy Eplerenone produces less unwanted effects than spironolactone
39
What are triamterene & amiloride?
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
What are the unwanted effects of triamterene & amiloride?
Hyperkalaemia Metabolic acidosis GI disturbances Skin rashes
41
What is the purpose of using diuretics in combination?
Increase diuretic effect | Avoid unwanted effects of hypokalaemia
42
Give some examples of diuretics that are used in combination
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
Give an example of a carbonic anhydrase inhibitor
Acetazolamide
44
What do carbonic anhydrase inhibitors do?
Blocks sodium bicarbonate in the proximal tubule | Weak diuresis so is not commonly used
45
What are the clinical uses of carbonic anhydrase inhibitors?
Glaucoma | Epilepsy
46
What are some unwanted effects of carbonic anhydrase inhibitors?
Metabolic acidosis - due to excretion of HCO3- | Enhances renal stone formation - due to alkaline urine
47
What is mannitol?
Osmotic diuretic Non-reabsorbable solute which undergoes glomerular filtration Excreted with 30-60min
48
What is mannitol used for?
Raised inter cranial pressure Intraoccular pressure - glaucoma Can cause osmotic diarrhoea which eliminates toxins Acute renal failure
49
What are the unwanted effects of osmotic diuretics?
Presence in blood exerts an osmotic pressure --> increase in plasma volume
50
How is water as a diuretic controlled?
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
What are some examples of possible ADH antagonists
2 non-selective agents: Lithium & demeclocycline Tolvaptan
52
What are the issues with ADH antagonists?
Can cause diabetes insipidus Renal failure Lithium can cause tremors, mental confusion, cardiotoxicity, thyroid dysfunction & leucocytosis
53
What is tolvaptan?
ADH antagonist V2 receptor antagonist used for treatment of hyponatraemia --> decreased extracellular fluid --> increased plasma sodium concentration
54
What inhibits ADH release
Alcohol - tolerance develops rapidly so the diuresis is not sustained Increases urine excretion
55
What increases ADH release?
``` Nicotine Ether Morphine Barbiturates Reduce urine excretion ```
56
What are some examples of xanthines?
Caffeine Theophylline Theobromine
57
What do xanthines do?
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
Why aren't xanthines used clinically?
Cause gastric irritant effects
59
What is theophylline used for?
Bronchodilator for asthma

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

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