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3002 > 56 Action of diuretics > Flashcards

56 Action of diuretics Flashcards

1
Q

Where do the main therapeutically useful diuretics act on? (3)

A
  1. Thick ascending loop of Henle
  2. Early distal consulted tubules
  3. Collecting tubules and ducts
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2
Q

What are the general action of diuretics? (3)

A
  1. Direct action on cells of the nephron to alter ionic pumps or indirectly to modify the content of the filtrate
  2. Decrease net absorption of Na+ and Cl+ ions from he filtrate to cause natriuresis causing diuresis
  3. Increase excretion of Na+ and water
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3
Q

What is the most powerful diuretic?

A

Loop diuretics

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4
Q

What are 2 examples of loop diuretics?

A

Furosemide

Bumetanide

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5
Q

How quickly do loop diuretics act?

A

Within 1 hour

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6
Q

Where do loop diuretics act on?

A

Thick ascending limb of loop of Henle

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7
Q

What is the mechanism of action of loop diuretics?

A
  1. Inhibit Na+/K+/2Cl- carrier in luminal membrane
  2. Thereby inhibiting transport of NaCl out of tubule into interstitial tissue
  3. Dissipates osmotic gradient in medulla of kidney: not able to recover water in the collecting tubules and ducts
  4. Increases delivery of Na+ to distal tubule casting loss of H+ and K+
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8
Q

What may loop diuretics produce?

A

Metabolic alkalosis

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9
Q

What are the indications for loop diuretics? (2)

A
  1. Oedema due to heart failure

2. Resistant hypertension

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10
Q

What are the side effects of loop diuretics? (4)

A
  1. Dehydration
  2. Electrolyte disturbances - e.g. hypokalaemia, hyponatraemia
  3. Gout
  4. Renal impairment if dose too high
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11
Q

Where do thiazide diuretics act on?

A

Distal tubule

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12
Q

What are 2 examples of thiazide diuretics?

A

Bendroflumethiazide

Indapamide

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13
Q

What is the mechanism of action of thiazide diuretics?

A
  1. Decrease absorption of Na+ and Cl- by binding to the Na+ / Cl- co-transport system
  2. Thereby inhibit co-transport’s action
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14
Q

Which diuretics also produces vasodilation

A

Thiazide diuretics

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15
Q

What are the indications of thiazide diuretics? (4)

A
  1. Hypertension
  2. Mild heart failure
  3. Severe resistant oedema
  4. Nephrogenic diabetes insipidus
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16
Q

What are the side-effects of thiazide diuretics?

A

Metabolic and electrolyte disturbances:

  • ↑ cholesterol, glucose, uric acid, calcium
  • ↓potassium, sodium, magnesium, BP
  • metabolic alkalosis
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17
Q

Where do potassium sparing diuretics act?

A

Collecting tubules

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18
Q

Which is the weakest diuretic?

A

Potassium sparing diuretic

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19
Q

What are 2 examples of potassium sparing diuretic?

A

Amiloride

Spironolactone

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20
Q

What is the mechanism of action of potassium sparing diuretics? (Amiloride and triamterene)

A

Blocking sodium channels controlled by aldosterone’s protein mediator

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21
Q

What is the mechanism of action of potassium sparing diuretics? (Spironolactone and eplerenone)

A

Antagonists at aldosterone receptor

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22
Q

Which diuretic doesn’t produce hypokalaemia?

A

Potassium sparing diuretic

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23
Q

What are indications of potassium sparing diuretics? (4)

A
  1. Alongside K+ losing diuretics (loop or thiazide) to prevent K+l loss

Spironolactone:

  1. Heart failure
  2. Conn’s (primary hyperaldosteronism)
  3. Secondary hyperaldosteronism
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24
Q

What are the side-effects of K+ sparing diuretics? (3)

A
  1. Hyperkalaemia
  2. GI upset
  3. Metabolic acidosis
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25
Q

What is an example of osmotic diuretics?

A

Mannitol

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26
Q

What are the indications for osmotic diuretics? (2)

A
  1. Cerebral oedema

2. Raised intra-ocular pressure

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27
Q

What is an example of carbonic anhydrase inhibitors?

A

Acetazolamide (very weak diuretic)

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28
Q

What are the indications for carbonic anhydrase inhibitors? (2)

A
  1. Glaucoma

2. Altitude sickness

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29
Q

What is syndrome of inappropriate ADH secretion (SIADH)?

A

Inappropriate ADH secretion from posterior pituitary or from ectopic source despite low serum osmolarity

30
Q

What is SIADH associated with (3)

A
  • ↓ sodium
  • ↑ urine osmolality
  • euvolaemia
31
Q

What is SIADH caused by? (4)

A
  1. Neurological causes - tumour, trauma, infection , GBS, MS, SLE
  2. Pulmonary causes - lung small cell ca, mesothelioma, pneumonia
  3. Malignancy - stomach, pancreatic ca
  4. Drugs - thiazide and loop diuretics , ACE - is, SSRIs and PPIs
32
Q

What is the presentation of SIADH? (6)

A
  1. Nausea
  2. Vomiting
  3. Cramps/ tremors
  4. Depressed mood, irritability, personality change, memory issues, hallucinations
  5. Seizures
  6. Coma
33
Q

What is the treatment of SIADH?

A
  • Correct underlying cause, monitor plasma osmolality, serum Na+ and bodyweight
  • Fluid restrict (500-100ml daily)
  • Drugs - demeclocycline, tolvaptan
  • Hypertonic NaCl in sever cases only
34
Q

How does demeclocyline work? And what does it treat?

A
  • Inhibits action of vasopressin on kidney, anti-ADH action

* SIADH

35
Q

How does tolvaptan work? And what does it treat?

A
  • Vasopressin V2 antagonist in renal collecting ducts

* SIADH

36
Q

What is the function erythropoietin (EPO)?

A

Hormone that promotes RBC formation in bone marrow

37
Q

What is erythropoietin driven by?

A

Anoxia

38
Q

Where is erythropoietin produced?

A
  • Kidney (peritubular interstitial cells)

* Liver (different form from kidney)

39
Q

What occurs in moderate-severe renal impairment regarding EPO?

A

Kidneys produce less EPO resulting in anaemia

40
Q

What is the treatment of less EPO production resulting in anaemia?

A

Artificial versions of EPO - ESAs (erythropoiesis stimulation agents)

-boosts production of RBCs, improve survival, reduce cardiovascular morbidity, enhance quality of life

41
Q

What are 2 examples of ESAs (erythropoiesis stimulating agents)?

A
  • Epoetin Alfa

* Darbapoietin

42
Q

What are 2 examples of vasopressin receptor agonists?

A
  • Desmopressin

* Terlipressin

43
Q

What does demopressin treat?

A

Diabetes insipidus

44
Q

What does terlipressin treat?

A

Oesophageal varices

45
Q

What is an example of sodium-glucose co-transporter-2 (SGLT-2) Inhibitors? And what does it treat?

A
  • Canagliflozin

* Type 2 diabetes mellitus

46
Q

What is an example of uricosuric drug? And what does it treat?

A
  • Sulphinpyrazone

* Gout

47
Q

What are examples of drugs affecting pH of urine? And what does it treat?

A
  • Ascorbic acid (acidify)
  • Potassium citrate(alkalinise):

• for urine infection symptoms or kidney stone formation

48
Q

What is the main organ for drug elimination from body?

A

Kidneys

49
Q

What occurs if kidneys are damaged regarding drugs?

A

Affects pharmacokinetics of many drugs

50
Q

How is the severity of renal impairment gauged?

A
  • Estimate glomerular filtration rate

* Use lab-quoted eGFR

51
Q

What occurs to some renal excreted drugs in renal impairment?

A

Stay in body for longer and can accumulate - toxic

52
Q

What is the management of acute kidney injury (AKI)? (6)

A
  1. Treat any sepsis or uro obstruction
  2. Aim for good fluid/ electrolyte balance
  3. Optimise BP
  4. With-hold/ stop toxins
  5. Review drug doses and side effect profile
  6. Monitor U&Es, refer nephrology/ urology if worsening
53
Q

Nephrotoxic drugs

A
  • Some drugs can help or worsen renal function - e.g. ACE inhibitors
  • Some can help reno-protect - e.g. ACE inhibitors
  • Reduced renal excretion of a drug and its metabolites may cause toxicity
  • Increased risk of adverse drug reactions
54
Q

What are some drug reduced renal impairments?

A
  1. Pre-renal
  2. Obstructive uropathy
  3. Allergic or immunological damage
  4. Direct nephrotoxicity
55
Q

Drug induced renal impairment (pre-renal)?

A
  • Water/ electrolyte loss
  • Increased catabolism
  • Vascular occlusion
  • Altered renal haemodynamics
56
Q

Drug induced renal impairment (obstructive uropathy)?

A

Bleeding/clots

57
Q

Drug induced renal impairment (allergic or immunological damage)?

A
  • Hypersensitivity reactions resulting in vasculitis
  • Interstitial nephritis
  • Glomerulonephritis
58
Q

Drug induced renal impairment (direct nephrotoxicity)?

A
  • Giving rise to acute tubular or interstitial damage

* Renal papillary necrosis

59
Q

Examples of potentially nephrotoxic drugs

use with caution or avoid in renal impairment

A
  1. ACE inhibitors, Angiotensin II blockers
  2. NSAIDs - ibuprofen
  3. Lithium (bipolar disorders)
  4. Digoxin
  5. Aminoglycosides - gentamicin
  6. Vancomycin
  7. Metformin (T2DM)
  8. Iodinated contrast media
  9. Opiods - morphine
60
Q

Examples of drugs that reduce renal perfusion

A
  1. Diuretics (esp. loop diuretics)
  2. NSAIDs
  3. ACE inhibitors
61
Q

How do diuretics reduce renal perfusion?

A

Causing excessive fluid loss

62
Q

How do NSAIDs reduce renal perfusion?

A

Inhibit prostaglandin synthesis leading to vasoconstriction, poor renal blood flow, reduced GFR and urine volume

63
Q

How do ACE inhibitors reduce renal perfusion?

A

Prevent angiotensin II mediated vasoconstriction and cause vasodilation of efferent arteriole leading to a reduction in GFR (important in reno vascular disease)

64
Q

What are “Medicine sick day rules”?

A
  • Help reduce the risk of acute kidney injury through patient education
  • If patient gets dehydrated and on ACE inhibitor/ ARBs/ NSAIDs/ Diuretics/ Metformin - risk of AKI
65
Q

Examples of ACE inhibitors

A

Medicine names ending in “pril”
• Lisinopril
• Ramipril

66
Q

Examples of ARBs

A

Medicine names ending in “sartan”
• Losartan
• Candesartan
• Valsartan

67
Q

Examples of NSAIDs

A

Anti-inflammatory pain killers
• Ibuprofen
• Diclofenac
• Naproxen

68
Q

Examples of diuretics

A 
"Water pills"
• Furosemide
• Spironoloactone
• Indapamide
• Bendeoflumethiazide
69
Q

What is metformin used for?

A

Diabetes

70
Q

Prescribing in renal impairment:

if drug is really excreted or has active metabolites that are really excreted?

A
  • Consider stopping nephrotoxic drugs
  • If continuing, reduce dose or increase dosing interval
  • Use therapeutic drug monitoring to guide dose/ frequency if appropriate
  • Monitor U&Es, eGFR, BP, and clinical response0 adjust subsequent doses accordingly
71
Q

Prescribing in chronic kidney disease (CKD)

A
  • CKD classified stage 1 (mild) –> 5 (severe impairment)
  • Important risk factor for CVD

Aim to:
• Normalise BP with anti-hypertensives
• Prevent or reverse worsening
• Review all meds, check doses appropriate for patient’s eGFR
• Manage concurrent conditions e.g. sepsis, diabetse, heart failure, renal anaemia, bone disease, electrolyte and acid-base disturbances

72
Q

Patients on renal replacement therapy

A
  • Some drugs actively removed during dialysis - will affect dose and timing of drug
  • Many variables - what kind of dialysis?
  • Is drug removed from circulation during dialysis?
  • What is dialysed membrane, blood and dialyse flow rate?
  • Refer to specialist renal team

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