Session 9 - Diuretics Flashcards
What are the four functions of the renal system?
REEM Regulatory Excretory Endocrine Metabolism
How is the renal system regulatory?
Fluid balance
Acid-base balance
Electrolyte balance
What excretory functions does the renal system have?
Waste products
Drug Elimination – Glomerular filtration and Tubular secretion
What endocrine functions does the renal system have?
Renin-Angiotensin-Aldosterone System
Erythropoetin
Prostaglandins
What does the renal system do in metabolism?
Vitamin D
Polypeptides – Insulin and PTH
Give 7 drugs that work on the renal tubules
o Carbonic Anhydrase Inhibitors o Osmotic Diuretics o Loop Diuretics o Thiazide Diuretics o Potassium Sparing Diuretics o Aldosterone Antagonists o ADH Antagonists
What do carbonic anhydrases do?
o Given systemically it interferes with Na+ and HCO¬¬3- reabsorption, giving it a weak diuretic effect. Danger of metabolic acidosis.
When are carbonic anhydrases used?
Glaucoma
Name an osmotic diuretic and when it would be used
Mannitol
Raised ICP
What is the mech of action of an OSMOTIC DIURETIC
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
What are two contraindicative conditions for osmotic diuretics?
Congestive heart failure
Pulmonary oedema
What is the site of action of osmotic diuretics?
Tubular segments that are water permeable
Proximal tubule, descending loop of Henle, collecting ducts
Give an adverse drug reaction of osmotic diuretic
Chills and fever
Why are osmotic diuretics not used in heart failure?
Because expansion of blood volume may be greater than degree of diuresis
Give two examples of thiazide diuretics
Bendroflumethiazide
Metolazone
Give an indication for thiazide diuretics?
Hypertension
Oedema secondary to congestive cardiac failure, liver disease or nephrotic syndrome
What is the mech of action of thiazide diuretics?
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.
Give a couple of adverse drug reactions (and thus contra-indications) of thiazide diuretics - think minerallss
Hypokalaemia, hyperuricaemia, impaired glucose tolerance, Hyponatraemia, hypermagnesemia, Hypercalcaemia, metabolic alkalosis
What four drugs should thiazide not be used with?
Steroids – Increased risk of hypokalaemia
Beta-Blockers – Hyperglycaemia, Hyperlipidaemia, Hyperuricaemia
Digoxin – Hypokalaemia increases digoxin binding and toxicity
Carbamazepine – Increased risk of Hyponatraemia
Give an example of a loop diuretic
Furosemide
Bumetanide
Torasemide
What is the mech of action of loop diuretics?
Inhibit the Na/K/Cl co-transporter in the luminal membrane
Blocks reabsorption of Na+ and therefore water.
What are three routes of admin in loop diuretic, and why would one be used in a morwe acute situation
Oral, intravenous or intramuscular. Intravenous route used in emergencies as therapeutic effect is much faster (30 mins compared to 4-6 hours orally).
Give four indications for loop diuretics
Acute pulmonary oedema
Oliguria (acute renal failure)
Resistant heart failure
Hypertension
Give a contraindication for loop diuretics
Severe renal impairment
What is the sit of action of a loop diuretic?
Thick Ascending Limb of the loop of Henle
Give an adverse drug reaction or 6 of loop diuretics (again, think minerals)
Hypokalaemia, Hyponatraemia, hyperuricaemia, hypotension, hypovolaemia, metabolic alkalosis
What can furosemide cause specifically?
Furosemide can cause Ototoxicity
Give three drug-drug interactions of furosemide
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
Give two potassiums sparing diuretics
Amiloride (Na+ channel blockers)
Spironolactone (Aldosterone Antagonist)
What are the main indications for potassium sparing diuretics?
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
What is the mech of action of potassium sparing diuretics?
Na+ AND Aldosterone separately
Na+ channel blockers
Block Na+ reabsorption by principal cells
Aldosterone Antagonist
Competitive antagonist at aldosterone receptor which reduces secretion of Na+
What is the site of action of potass sparing diuretics?
Late distal tubule and collecting duct
What are four adverse drug reactions to potass sparing diuretics
GI disturbances
Hyperkalaemia (in patients in renal failure)
Hyponatraemia
Spironolactone – Gynaecomastia, menstrual disorders, erectile dysfunction
Give a drug-drug interaction of potass sparing diuretic
Interaction with ACE inhibitors, increasing risk of hyperkalaemia
Give two other drugs with diuretic activity
Digoxin ADH antagonists (lithium and demecocycline)
What does digoxin do? What does it interact with?
Inhibits tubular Na/K-ATPase
Drug-Drug interaction with Thiazide Diuretics. Hypokalaemia leads to increased digoxin binding and toxicity.
What do ADH antagonists do?
blocking the action of Anti-Diuretic Hormone, Aquaporin 2 is not inserted into the apical membrane, meaning less water is able to be reabsorbed
Give THREE major indications for diuretic use
Heart failure
Hypertension
Decompensated liver disease
What diuretics would be used in heart failure?
Loop diuretics
Thiazide diuretics
(also ACE inhibitors/Angiotensin Receptor antagonists, β-blockers)
What diuretics would be used in hypertension?
Thiazide diuretics
Spironolactone
(also ACE inhibitors/Angiotensin Receptor antagonists, β-blockers)
What diuretics would be used in decompensated liver disease?
Spironolactone
Loop diuretics
Give a couple reasons why diuretic resistance can come about
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
Give the two key issues of prescribing during renal failure
- Drugs may reduce kidney function by direct or indirect toxicity
- Drugs at normal doses may accumulate to toxic levels if they are excreted through the kidneys and renal function is impaired
Give 6 drugs which reduce kidney function
ACE inhibitors Aminoglycosides (e.g. Gentamicin) Penicillins Cyclosporin A Metformin NSAIDs
What do ACE inhibitors do in Renal Disease?
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.
What should you try and avoid when prescribing drugs?
Nephrotoxins
What should be done about dosage?
It should be reduced in line with GFR
What must one do if a drug has a narrow therapeutic range?
Monitor renal function and drug levels
How do you manage hyperkalaemia in an emergency?
o Reduce K+ effect on heart IV Calcium Gluconate o Shift K+ into ICF via glucose and insulin IV Remove excess K+ o Dialysis
How do you manage Hyperkalaemia long term?
o Remove excess K+ Dialysis Oral K+ binding resins to bind K+ in the gut o Reduce Intake o Treat cause
