Session 9 - Diuretics Flashcards

1
Q

What are the four functions of the renal system?

A
REEM
Regulatory
Excretory
Endocrine
Metabolism
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2
Q

How is the renal system regulatory?

A

 Fluid balance
 Acid-base balance
 Electrolyte balance

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3
Q

What excretory functions does the renal system have?

A

 Waste products

 Drug Elimination – Glomerular filtration and Tubular secretion

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4
Q

What endocrine functions does the renal system have?

A

 Renin-Angiotensin-Aldosterone System
 Erythropoetin
 Prostaglandins

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5
Q

What does the renal system do in metabolism?

A

 Vitamin D

 Polypeptides – Insulin and PTH

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6
Q

Give 7 drugs that work on the renal tubules

A
o	Carbonic Anhydrase Inhibitors
o	Osmotic Diuretics
o	Loop Diuretics
o	Thiazide Diuretics
o	Potassium Sparing Diuretics
o	Aldosterone Antagonists
o	ADH Antagonists
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7
Q

What do carbonic anhydrases do?

A

o Given systemically it interferes with Na+ and HCO¬¬3- reabsorption, giving it a weak diuretic effect. Danger of metabolic acidosis.

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8
Q

When are carbonic anhydrases used?

A

Glaucoma

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9
Q

Name an osmotic diuretic and when it would be used

A

Mannitol

Raised ICP

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10
Q

What is the mech of action of an OSMOTIC DIURETIC

A

 Freely filtered at the glomerulus, but only partially, if at all, reabsorbed
 Passive water reabsorption is reduced by the presence of this non-reabsorbable solute within the tubule lumen

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11
Q

What are two contraindicative conditions for osmotic diuretics?

A

 Congestive heart failure

 Pulmonary oedema

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12
Q

What is the site of action of osmotic diuretics?

A

 Tubular segments that are water permeable

 Proximal tubule, descending loop of Henle, collecting ducts

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13
Q

Give an adverse drug reaction of osmotic diuretic

A

Chills and fever

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14
Q

Why are osmotic diuretics not used in heart failure?

A

Because expansion of blood volume may be greater than degree of diuresis

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15
Q

Give two examples of thiazide diuretics

A

 Bendroflumethiazide

 Metolazone

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16
Q

Give an indication for thiazide diuretics?

A

 Hypertension

 Oedema secondary to congestive cardiac failure, liver disease or nephrotic syndrome

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17
Q

What is the mech of action of thiazide diuretics?

A

 Thiazide diuretics inhibit the Na+/Cl- co-transporter in the luminal membrane in the distal tubule of the kidney. This blocks the reabsorption of Na+ and therefore water. Result is lower blood volume and pressure.

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18
Q

Give a couple of adverse drug reactions (and thus contra-indications) of thiazide diuretics - think minerallss

A

 Hypokalaemia, hyperuricaemia, impaired glucose tolerance, Hyponatraemia, hypermagnesemia, Hypercalcaemia, metabolic alkalosis

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19
Q

What four drugs should thiazide not be used with?

A

 Steroids – Increased risk of hypokalaemia
 Beta-Blockers – Hyperglycaemia, Hyperlipidaemia, Hyperuricaemia
 Digoxin – Hypokalaemia increases digoxin binding and toxicity
 Carbamazepine – Increased risk of Hyponatraemia

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20
Q

Give an example of a loop diuretic

A

 Furosemide
 Bumetanide
 Torasemide

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21
Q

What is the mech of action of loop diuretics?

A

 Inhibit the Na/K/Cl co-transporter in the luminal membrane

 Blocks reabsorption of Na+ and therefore water.

22
Q

What are three routes of admin in loop diuretic, and why would one be used in a morwe acute situation

A

 Oral, intravenous or intramuscular. Intravenous route used in emergencies as therapeutic effect is much faster (30 mins compared to 4-6 hours orally).

23
Q

Give four indications for loop diuretics

A

 Acute pulmonary oedema
 Oliguria (acute renal failure)
 Resistant heart failure
 Hypertension

24
Q

Give a contraindication for loop diuretics

A

 Severe renal impairment

25
Q

What is the sit of action of a loop diuretic?

A

 Thick Ascending Limb of the loop of Henle

26
Q

Give an adverse drug reaction or 6 of loop diuretics (again, think minerals)

A

 Hypokalaemia, Hyponatraemia, hyperuricaemia, hypotension, hypovolaemia, metabolic alkalosis

27
Q

What can furosemide cause specifically?

A

 Furosemide can cause Ototoxicity

28
Q

Give three drug-drug interactions of furosemide

A

 Cardiac Glycosides – Hypokalaemia caused by loop diuretics potentiates the action of cardiac glycosides, increasing the risk of arrhythmias
 Aminoglycoside Antibiotics – (E.g. Gentamycin) Will interact with loop diuretics and increase risk of ototoxicity and potential hearing loss
 Steroids – Increased risk of hypokalaemia

29
Q

Give two potassiums sparing diuretics

A

 Amiloride (Na+ channel blockers)

 Spironolactone (Aldosterone Antagonist)

30
Q

What are the main indications for potassium sparing diuretics?

A

 In conjunction with other diuretics in managing heart failure or hypertension. They are only mild diuretics.
 Aldosterone antagonists used in the treatment of hyperaldosteronism
 Primary – Conn’s Disease
 Secondary – Result of heart failure, liver disease or nephrotic syndrome

31
Q

What is the mech of action of potassium sparing diuretics?

Na+ AND Aldosterone separately

A

 Na+ channel blockers
 Block Na+ reabsorption by principal cells
 Aldosterone Antagonist
 Competitive antagonist at aldosterone receptor which reduces secretion of Na+

32
Q

What is the site of action of potass sparing diuretics?

A

 Late distal tubule and collecting duct

33
Q

What are four adverse drug reactions to potass sparing diuretics

A

 GI disturbances
 Hyperkalaemia (in patients in renal failure)
 Hyponatraemia
 Spironolactone – Gynaecomastia, menstrual disorders, erectile dysfunction

34
Q

Give a drug-drug interaction of potass sparing diuretic

A

 Interaction with ACE inhibitors, increasing risk of hyperkalaemia

35
Q

Give two other drugs with diuretic activity

A
Digoxin 
ADH antagonists (lithium and demecocycline)
36
Q

What does digoxin do? What does it interact with?

A

 Inhibits tubular Na/K-ATPase

 Drug-Drug interaction with Thiazide Diuretics. Hypokalaemia leads to increased digoxin binding and toxicity.

37
Q

What do ADH antagonists do?

A

blocking the action of Anti-Diuretic Hormone, Aquaporin 2 is not inserted into the apical membrane, meaning less water is able to be reabsorbed

38
Q

Give THREE major indications for diuretic use

A

Heart failure
Hypertension
Decompensated liver disease

39
Q

What diuretics would be used in heart failure?

A

 Loop diuretics
 Thiazide diuretics
 (also ACE inhibitors/Angiotensin Receptor antagonists, β-blockers)

40
Q

What diuretics would be used in hypertension?

A

 Thiazide diuretics
 Spironolactone
 (also ACE inhibitors/Angiotensin Receptor antagonists, β-blockers)

41
Q

What diuretics would be used in decompensated liver disease?

A

 Spironolactone

 Loop diuretics

42
Q

Give a couple reasons why diuretic resistance can come about

A

o Incomplete treatment of primary disorder
o Continuation of high Na+ intake
o Patient non-compliance
o Poor absorption
o Volume depletion decreases filtration of diuretics
o Volume depletion increases serum aldosterone, enhancing Na+ reabsorption
o NSAIDs – Can reduce renal blood flow

43
Q

Give the two key issues of prescribing during renal failure

A
  1. Drugs may reduce kidney function by direct or indirect toxicity
  2. Drugs at normal doses may accumulate to toxic levels if they are excreted through the kidneys and renal function is impaired
44
Q

Give 6 drugs which reduce kidney function

A
	ACE inhibitors
	Aminoglycosides (e.g. Gentamicin) 
	Penicillins
	Cyclosporin A
	Metformin
	NSAIDs
45
Q

What do ACE inhibitors do in Renal Disease?

A

In Renal Artery Stenosis, Glomerular Filtration Pressure falls, leading to a drop in GFR, leading to the activation of RAAS.

This causes vasoconstriction of the efferent arteriole to maintain Glomerular Filtration Pressure.

If ACE inhibitors are given, inhibiting RAAS, the Glomerular Filtration Pressure will drop, causing Acute Renal Failure.

46
Q

What should you try and avoid when prescribing drugs?

A

Nephrotoxins

47
Q

What should be done about dosage?

A

It should be reduced in line with GFR

48
Q

What must one do if a drug has a narrow therapeutic range?

A

Monitor renal function and drug levels

49
Q

How do you manage hyperkalaemia in an emergency?

A
o	Reduce K+ effect on heart
	IV Calcium Gluconate
o	Shift K+ into ICF via glucose and insulin IV
	Remove excess K+
o	Dialysis
50
Q

How do you manage Hyperkalaemia long term?

A
o	Remove excess K+
	Dialysis
	Oral K+ binding resins to bind K+ in the gut
o	Reduce Intake
o	Treat cause