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SA Clinical Pharmacology & Therapeutics > S4) Diuretics & Renal Pharmacology > Flashcards

S4) Diuretics & Renal Pharmacology Flashcards

1
Q

yWhat are the four broad functions of the kidney?

A
  • Regulatory
  • Excretory
  • Endocrine
  • Metabolism
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2
Q

What are the three regulatory functions of the kidney?

A
  • Fluid balance
  • Acid-base balance
  • Electrolyte Balance
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3
Q

What does the kidney excrete?

A
  • Waste products
  • Drug elimination (glomerular filtration & tubular secretion)
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4
Q

Identify four endocrine secretions of the kidney

A
  • Renin
  • Erythropoetin
  • Prostaglandins
  • 1-alpha calcidol
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5
Q

Which substances does the kidney metabolise?

A
  • Vitamin D
  • Polypeptides e.g. insulin
  • Drugs e.g. morphine, paracetamol
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6
Q

What are the seven different types of diuretic drugs acting on the kidney?

A
  • Carbonic anhydrase inhibitors
  • Osmotic diuretics
  • Loop diuretics
  • Thiazides
  • K+ sparing diuretics
  • Aldosterone antagonists
  • ADH Antagonists
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7
Q

Describe the actions and effects of carbonic anhydrase inhibitors

A
  • Sodium bicarbonate diuresis
  • Excretion of Na+, K+ and PO3
  • Metabolic acidosis (loss of bicarbonate) / hypokalemia (lose K at RomK channels)
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8
Q

Describe the actions and effects of osmotic agents

A
  • Filtered at glomerulus
  • Increase osmotic gradient throughout nephron
  • Excessive water loss
  • Hypernatraemia
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9
Q

Describe the actions and effects of loop agents

A
  • Thick ascending limb loop of Henle
  • Inhibit NaCl reabsorption
  • Concurrent Ca/Mg excretion
  • Hypokalaemia (CD) because there is an increase in the activation of RomK to increase Enac so more K leaves
  • causes direct dialation of veins that reduce preload
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10
Q

Describe the actions and effects of thiazides

A
  • Inhibits NaCl reabsorption
  • Promotes Ca reabsorption
  • Hypokalaemia
  • Hyperuricaemia
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11
Q

Describe the actions and effects of aldosterone antagonists e.g. spironolactone

A
  • Inhibits Na+ retention (Na-K ATPase / Na+ flux)
  • Blunts K+ and H+ secretion
  • Androgenic cross-reactivity
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12
Q

What is the action of aldosterone on the kidney

A

Aldosterone increases expression of ENaC and Na/K/ATPase in principal cells of the collecting duct

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13
Q

Describe the actions and effects of ADH antagonists ‘ aquaretics’ e.g. lithium

A

ADH antagonists reduce concentrating ability of urine in collecting ducts

  • tolvaptan → diuretic but not natriuretic, treat hyponatremia
  • lithium → diuretic not a natriuretic
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14
Q

Explain how the following substances have diuretic action:

  • Alcohol
  • Caffeine
A
  • Alcohol – inhibits ADH release
  • Caffeine – ↑GFR and ↓ tubular Na+ reabsorption
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15
Q

Identify four generic adverse drug reactions from diuretics

A
  • Anaphylaxis / photosensivity rash
  • Hypovolaemia & hypotension
  • Electrolyte disturbance (Na+, K+, Mg2+, Ca2+)
  • Metabolic abnormalities
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16
Q

Identify 5 common specific ADRs from thiazides

A
  • Gout
  • Hyperglycaemia
  • Erectile dysfunction
  • ↑LDL & TG
  • Hypercalcaemia
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17
Q

Identify 3 common specific ADRs from spironolactone

A
  • Hyperkalaemia
  • Impotence
  • Painful gynaecomastia
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18
Q

Identify 4 common specific ADRs from furosemide (loop diuretic)

A
  • Ototoxicity
  • Alkalosis
  • ↑LDL & TG
  • Gout
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19
Q

Identify a common specific ADRs from bumetanide (loop diuretic)

A

Myalgia

20
Q

Explain the effect of ACE Inhibitors interacting with K+ sparing diuretics

A

Increased hyperkalaemia → cardiac problems

21
Q

What is the effect of aminoglycosides interacting with loop diuretics?

A
  • Ototoxicity
  • Nephrotoxicity
22
Q

Explain the effect of digoxin interacting with thiazide and loop diuretics

A

Hypokalaemia → increased digoxin binding & toxicity

23
Q

What is the effect of β- Blockers interacting with thiazide diuretics?

A
  • Hyperglycemia
  • Hyperlipidemia
  • Hyperuricaemia
24
Q

What is the effect of steroids interacting with thiazide & loop diuretics?

A

Increased risk of hypokalaemia

25
Q

What is the effect of lithium interacting with thiazide & loop diuretics?

A
  • Lithium toxicity (thiazides)
  • Reduced lithium levels (loop)
26
Q

What is the effect of carbamazepine interacting with thiazide diuretics?

A

Increased risk of hyponatraemia

27
Q

Which diuretics are commonly used to treat hypertension?

A
  • Thiazide diuretics (vasodilatation as well as diuresis)
  • Spironolactone
28
Q

Which diuretics are commonly used to treat heart failure?

A
  • Loop diuretics
  • Spironolactone (non-diuretic benefits)
29
Q

Which diuretics are commonly used to treat decompensated liver disease?

A
  • Spironolactone
  • Loop diuretics
30
Q

Which diuretics are commonly used to treat nephrotic syndrome?

A
  • Loop diuretic (often big doses needed)
  • ± Thiazides
  • ± K+ sparing diuretic / K+ supplements
31
Q

Which diuretics are commonly used to treat Chronic Kidney Disease?

A
  • Loop diuretics
  • ± Thiazide-like
  • Generally avoid K+ sparing diuretics
32
Q

Describe the process and requirements for diuretic delivery to renal tubule e.g. furosemide

A
  • Blood flow to proximal tubule must be intact (transport via albumin)
  • Proximal tubule must be functioning to transport furosemide across
  • TAL must be intact to respond to furosemide
33
Q

In four steps, describe the clinical approach to treat a patient with refractory oedema

A

⇒ Check salt intake

⇒ IV furosemide (if gut oedema likely)

⇒ Find minimum effective dose

⇒ Give repeated bolus or infusion (short t1/2)

34
Q

Describe the relationship between diuretic drugs and kidney function in terms of adverse reactions

A
  • Drugs may reduce kidney function by direct/indirect toxicity
  • Drugs may accumulate to toxic levels if they are excreted through the kidneys and renal function is impaired
35
Q

Identify four potentially nephrotoxic drugs

A
  • Aminoglycosides e.g gentamicin
  • Vancomycin (IV only)
  • Aciclovir
  • NSAIDs
36
Q

Identify four drugs which can exacerbate renal dysfunction

A
  • ACE-Inhibitors
  • Diuretics
  • NSAIDs
  • Metformin
37
Q

What are the three steps involved in managing hyperkalaemia?

A

⇒ Identify a cause

⇒ ECG

⇒ Treatment

38
Q

Describe the three steps in the emergency treatment of hyperkalaemia

A

⇒ Protect the heart → calcium gluconate

⇒ Lower serum K+ → insulin / dextrose

⇒ Remove K+ from body → calcium resonium

39
Q

list some conditions diuretics are used for

A
  • nephrotic syndrome
  • odema
  • hypertension
  • chronic heart failure
  • decompensated liver disease → ascites
40
Q

what is the definition of aquaretic

A

loss of water without electrolytes

41
Q

what are some adverse effects of loop diuretics

A
  • dehydration, hypotension, hypokalaemia, hyponatremia,
42
Q

who should you not prescribe loop diuretics to?

A

people with:

  • hypokalaemia
  • hyponatremia
  • gout → can cause a build up of uric acid in joints (arthritis) as less urine so more concentrated
43
Q

which drug interactions occur with loop diuretics

A
  • aminoglycosides (gentamicin) can effect hearing
  • digoxin → blurred yellow vision
  • digoxin and lithium → both excreted via kidney so they compete with the diuretic so more will end up in blood
44
Q

potassium sparing drug

A
  • block Enac, Na not reabsorbed, reduced K excretion.
  • adverse effects: hyperkalemia, potential arrhythmia
  • people to avoid: Addisons (low aldosterone), anuria and hyperkalemia
  • drug interactions: K sparing drugs, ACEi ARB
45
Q

type 2 potassium sparing drug

A
  • aldosterone antagonist/mineralcorticoid receptor antagonist
  • aldosterone increases ENAc and Na/K/ATPase in principal cells of collecting duct so more Na reabsorbed and K excretion
  • if this is antagonised then opposite happens and k gets absorbed
  • adverse effects: gynaecomastia (blocks androgen receptor and reduces testosterone production), hyperkalamia
  • people to avoid giving: Addisons (reduced aldosterone anyway), hyperkalemia
  • drug interactions: alcohol, ACEi, amioride (too much K sparing then), ARBs
46
Q

challenges with multiple drugs

A
47
Q

potential sites where diuretic delivery to the renal tubule can be opposed

A
  • Gut oedema → hard to absorb med (furosemide) decompensated heart failure
  • blood → nephrotic syndrome → low albumin so drug can’t bind
  • PCT → patient has CKD, maybe bad OAT (transports anions across)

SA Clinical Pharmacology & Therapeutics (36 decks)

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