T3 L6: Diuretic agents Flashcards
What is the definition of a diuretic agent?
A drug that increases excretion of both fluids and solutes
What is Natriuretic excretion?
Of Na+
What is Kaliuretic excretion?
Of K+ (usually an unwanted effect)
Where do carbonic anhydrase inhibitors take effect as diuretics on a nephron?
Proximal tubule (not powerful)
Where do osmotic diuretics take effect on a nephron?
Proximal tubule and descending loH (water permeable parts of the nephron)
Where do loop diuretics take effect on a nephron?
Ascending loH
Where do thiazides and thiazide-like diuretics take effect on a nephron?
Early distal tubule
Where do potassium-sparing diuretics (aldosterone antagonists and non-aldosterone antagonists) take effect on a nephron?
Late distal and early collecting tubule (They’re weak)
How do loop diuretics work?
They inhibit NKCC2 transporters in the thick ascending limb of the loH so reabsorption of Na+, K+ and Cl- increases. They are the most effective diuretics available
How does weighing yourself prevent dehydration when using diuretics?
If they gain weight, they need to drink less and if they lose weight then they need to drink more
What are some clinical uses of loop diuretics?
Acute pulmonary oedema, chronic heart failure, cirrhosis of the liver, resistant hypertension, nephrotic syndrome, and acute kidney injury
What are some unwanted effects of loop diuretics?
Dehydration, Hypokalaemia, metabolic alkalosis due to loss of H+ in urine, Hypokalaemia can potentiate effects of cardiac glycosides, and deafness when used with aminoglycoside antibiotics
How do loop diuretics cause hypokalaemia?
They increase the exchange of Na+ for K+ in the distal tubule
How do Thiazide diuretics work?
They inhibit apical Na+/Cl- co-transporters in the distal tubule and therefore cause increased Na+ excretion with increased water excretion. They last up to 24hours
What is the main thiazide diuretic and what is it used for?
Bendroflumethiazide used for mild/moderate heart failure
What is indapamide used for?
Resistant hypertension because it has less side effects
What are thiazide diuretics used for?
Hypertension, oedema, and mild heart failure
What are some unwanted effects of thiazide diuretics?
Hypokalaemia, metabolic acidosis, gout, hyperglycaemia as they have an effect on pancreatic beta-cells, increased plasma cholesterol with long-term use, and male impotence that’s reversible
What’s the mechanism behind metabolic acidosis?
Loss of urinary H+
What is gout?
Increased plasma uric acid
Why do thiazide diuretics cause gout?
They work on the transporter that transports uric acid in the nephron
What are the symptoms of mild hypokalaemia?
Fatigue, drowsiness, dizziness, muscle weakness
What are the symptoms of severe hypokalaemia?
Abnormal heart rhythm, muscle paralysis, and death
How do potassium-sparing diuretics work?
They inhibit Na+ reabsorption on the distal tubules where K+ is not secreted
Eplerenone and Spironolactone are types of what diuretic?
Potassium-sparing aldosterone antagonist diuretics. They are competitive antagonists to aldosterone
Amiloride and Triamterene are types of what diuretic?
Potassium-sparing non-aldosterone antagonist diuretic
What is the active metabolite of Spironalactone?
Canrenone
Why are potassium-sparing aldosterone antagonist diuretics less effective?
They depend on reduction of protein expression is distal tubular cells that take days to develop
What are the clinical uses of spironolactone?
Heart failure, oedema, and resistant hypertension in short-term
Why can’t spironolactone be used in the long-term?
Because there was a reported incidence of cancer in the long term in rats
What are some unwanted effects of spironolactane?
Hyperkalaemia, metabolic acidosis, GI upsets like ulcers, menstrual disorders, testicular atrophy
Why does Spironolactane cause Gynaecomastia, menstrual disorders and testicular atrophy?
Because aldosterone has an effect on sexual characteristics
What is Gynaecomastia?
Man boobs
What are some unwanted side effects of Triamterene and Amiloride?
Hyperkalaemia, metabolic acidosis, GI disturbances, and skin rashes
What are Triamterene and Amiloride usually pared with and why?
With potassium-depleting diuretics as they limit hypokalaemia
What type of diuretic is azetozalamide?
A carbonic anhydrase inhibitor
What are carbonic anhydrase inhibitors used to treat?
Glaucoma (reduces intraocular pressure) and epilepsy (reduces volume and pressure of CSF)
What are some unwanted effects of carbonic anhydrase inhibitors?
Metabolic acidosis, and kidney stones because of alkaline urine
How do carbonic anhydrase inhibitors work?
They inhibit the absorption of sodium bicarbonate (NaHCO3) reabsorption in the proximal tubule
How do osmotic diuretics work?
They act as sponges to remove H2O. They absorb H2O into their chemical structure and are then excreted along with it
What type of diuretic is mannitol?
An osmotic diuretic
What are some clinical uses of osmotic diuretics?
Cerebral oedema, glaucoma, for toxin elimination by ‘osmotic diarrhoea’, acute renal failure
What is glaucoma?
Increased ocular pressure
What are the unwanted effects of osmotic diuretics?
Their presence in blood exerts osmotic pressure leading to increased blood volume so they can’t be given to those with hypertension
How can water act as a diuretic?
It increases the volume of water excreted which leads to reduced secretion of ADH
What are some unwanted effects of ADH antagonists?
Can cause diabetes insipidus, renal failure, tremors
Demeclocycline shouldn’t be given to patients with what?
Liver disease
Lithium, demeclocycline and Amphotericin B are types of what drug?
ADH antagonists
What are some examples of xanthines?
Caffeine (tea and coffee), theophylline, and theobromine
How do xanthines produce an diuretic effect?
They increase cardiac output and therefore increased renal and glomerular blood flow which increases GFR and urine output
