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
What is an example of osmotic diuretics?
Mannitol
26
What are the indications for osmotic diuretics? (2)
1. Cerebral oedema | 2. Raised intra-ocular pressure
27
What is an example of carbonic anhydrase inhibitors?
Acetazolamide (very weak diuretic)
28
What are the indications for carbonic anhydrase inhibitors? (2)
1. Glaucoma | 2. Altitude sickness
29
What is syndrome of inappropriate ADH secretion (SIADH)?
Inappropriate ADH secretion from posterior pituitary or from ectopic source despite low serum osmolarity
30
What is SIADH associated with (3)
* ↓ sodium * ↑ urine osmolality * euvolaemia
31
What is SIADH caused by? (4)
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
What is the presentation of SIADH? (6)
1. Nausea 2. Vomiting 3. Cramps/ tremors 4. Depressed mood, irritability, personality change, memory issues, hallucinations 5. Seizures 6. Coma
33
What is the treatment of SIADH?
* 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
How does demeclocyline work? And what does it treat?
* Inhibits action of vasopressin on kidney, anti-ADH action | * SIADH
35
How does tolvaptan work? And what does it treat?
* Vasopressin V2 antagonist in renal collecting ducts | * SIADH
36
What is the function erythropoietin (EPO)?
Hormone that promotes RBC formation in bone marrow
37
What is erythropoietin driven by?
Anoxia
38
Where is erythropoietin produced?
* Kidney (peritubular interstitial cells) | * Liver (different form from kidney)
39
What occurs in moderate-severe renal impairment regarding EPO?
Kidneys produce less EPO resulting in anaemia
40
What is the treatment of less EPO production resulting in anaemia?
Artificial versions of EPO - ESAs (erythropoiesis stimulation agents) -boosts production of RBCs, improve survival, reduce cardiovascular morbidity, enhance quality of life
41
What are 2 examples of ESAs (erythropoiesis stimulating agents)?
* Epoetin Alfa | * Darbapoietin
42
What are 2 examples of vasopressin receptor agonists?
* Desmopressin | * Terlipressin
43
What does demopressin treat?
Diabetes insipidus
44
What does terlipressin treat?
Oesophageal varices
45
What is an example of sodium-glucose co-transporter-2 (SGLT-2) Inhibitors? And what does it treat?
* Canagliflozin | * Type 2 diabetes mellitus
46
What is an example of uricosuric drug? And what does it treat?
* Sulphinpyrazone | * Gout
47
What are examples of drugs affecting pH of urine? And what does it treat?
* Ascorbic acid (acidify) * Potassium citrate(alkalinise): • for urine infection symptoms or kidney stone formation
48
What is the main organ for drug elimination from body?
Kidneys
49
What occurs if kidneys are damaged regarding drugs?
Affects pharmacokinetics of many drugs
50
How is the severity of renal impairment gauged?
* Estimate glomerular filtration rate | * Use lab-quoted eGFR
51
What occurs to some renal excreted drugs in renal impairment?
Stay in body for longer and can accumulate - toxic
52
What is the management of acute kidney injury (AKI)? (6)
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
Nephrotoxic drugs
* 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
What are some drug reduced renal impairments?
1. Pre-renal 2. Obstructive uropathy 3. Allergic or immunological damage 4. Direct nephrotoxicity
55
Drug induced renal impairment (pre-renal)?
* Water/ electrolyte loss * Increased catabolism * Vascular occlusion * Altered renal haemodynamics
56
Drug induced renal impairment (obstructive uropathy)?
Bleeding/clots
57
Drug induced renal impairment (allergic or immunological damage)?
* Hypersensitivity reactions resulting in vasculitis * Interstitial nephritis * Glomerulonephritis
58
Drug induced renal impairment (direct nephrotoxicity)?
* Giving rise to acute tubular or interstitial damage | * Renal papillary necrosis
59
Examples of potentially nephrotoxic drugs | use with caution or avoid in renal impairment
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
Examples of drugs that reduce renal perfusion
1. Diuretics (esp. loop diuretics) 2. NSAIDs 3. ACE inhibitors
61
How do diuretics reduce renal perfusion?
Causing excessive fluid loss
62
How do NSAIDs reduce renal perfusion?
Inhibit prostaglandin synthesis leading to vasoconstriction, poor renal blood flow, reduced GFR and urine volume
63
How do ACE inhibitors reduce renal perfusion?
Prevent angiotensin II mediated vasoconstriction and cause vasodilation of efferent arteriole leading to a reduction in GFR (important in reno vascular disease)
64
What are "Medicine sick day rules"?
* 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
Examples of ACE inhibitors
Medicine names ending in "pril" • Lisinopril • Ramipril
66
Examples of ARBs
Medicine names ending in "sartan" • Losartan • Candesartan • Valsartan
67
Examples of NSAIDs
Anti-inflammatory pain killers • Ibuprofen • Diclofenac • Naproxen
68
Examples of diuretics
``` "Water pills" • Furosemide • Spironoloactone • Indapamide • Bendeoflumethiazide ```
69
What is metformin used for?
Diabetes
70
Prescribing in renal impairment: | if drug is really excreted or has active metabolites that are really excreted?
* 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
Prescribing in chronic kidney disease (CKD)
* 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
Patients on renal replacement therapy
* 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