Drugs affecting the kidneys- diuretic agents Flashcards
What are diuretic agents?
A drug that increases the excretion of both fluids and solutes
Natriuretic
Increases Na+ excretion
Kaliuretic
Increases K+ excretion
Two major applications of diuretic agents
- Reduce circulating fluid volume
2. Removal of excess body fluids
Site of action of carbonic anhydrase inhibitors
Proximal tubule
Site of action of osmotic diuretics
Proximal tubule
Descending loop of henle
Site of action of loop diuretics
Ascending loop of henle
Site of action of thiazide and thiazide like diuretics
Early distal tubule
Site of action of K+-sparing diuretics
- aldosterone antagonists
- non- aldosterone antagonists
Late distal tubule
Early collecting duct
Loop diuretics
Most effective
Inhibit Na+/K+/2Cl- transporters in thick ascending limb (reduces reabsorption)
Increased Na+ delivery to DT, exchanged for K+ which is excreted in urine
Reduced Na+ reabsorption leads to rapid and profound diuresis
Loop diuretics clinical data
Oral absorption
- diuresis in 60 minutes
- persits for 4-6 hours
IV administation
- diuresis within 5minutes
- persists for 2 hours
IM administration
- diuresis in 30 minutes
Clinical uses of loop diuretics
MORE ACUTE CASES
Acute pulmonary oedema
Chronic heart failure
Cirrhosis of the liver
Resistant hypertension
REDUCED URINE PRODUCTION
Nephrotic syndrome
Acute renal failure
Unwanted effects of loop diuretics
Dehydration
K+ loss leads to hypokalaemia
Metabolic alkalosis due to H+ loss in urine
Hypokalaemia can potentiate effects of cardiac glycosides
Deafness (when used with aminoglycoside antibiotics)
Thiazide diuretics
Act in DT to inhibit apical Na+/Cl- co-transporter
Cause moderate but sustained Na+ excretion with increased water excretion
Moderately powerful diuretics
Well absorbed from GI tract and long duration of action (up to 24 hours)
Thiazide diuretics clinical data
Prototype is hydrochlorothiazide
Main is benzoflumethiazide
Clinical use of thiazide diuretics
Hypertension
Oedema
Mild heart failure
Unwanted effects of thiazide diuretics
Plasma K+ depletion
Metabolic alkalosis
Increased plasma uric acid- gout
Hyperglycaemia
Increased plasma cholesterol (long term use)
Male impotence (reversible)
Hypokalaemia
Mild: fatigue, drowsiness, dizziness, muscle weakness
Severe: abnormal heart rhythm, muscle paralysis, death
K+ sparing diuretics
- act on DT to inhibit Na+ reabsorption
- K+ is not secreted into distal tubule
Subcategories of K+ sparing diuretics
Aldosterone antagonists
- eplerenone
- spironolactine
Non-aldosterone antagonists
- amiloride
- triamterene
Aldosterone antagonists
Sprironolactone metabolised to canrenone
Competitive antagonist of aldosterone- reduce Na+ channel formation
Reduces Na+ absorption from DT
Clinical uses of sprionolactone
SHORT TERM
Heart failure
Oedema
Unwanted effects of spironolactone
Hyperkalaemia
Metabolic acidosis
GI upsets
Gynaecomastia, menstrual disorders, testicular atrophy
Eplerenone produces less effects
Triamterene and Amiloride
Weak diurects- act on DT to inhibit Na+ reabsorption and decrease K+ excretion
Blocks luminal Na+ channel
Main unwanted effects
- hyperkalaemia
- metabolic acidosis
- GI disturbances
- skin rashes
Combination of diuretics
Increases diuretic effect
Avoids unwanted effects of hypokalaemia
How to avoid hypokalaemia
Loop diuretics with spironolcatone
Loop diuretics with amiloride or triamterene
Thiazides with sprionolactone
Thiazides with amiloride or triamterene
Diuretics containing K+
Carbonic anhydrase inhibitors
Blocks NaHCO3 reabsorption in PT
Causes weak diuresis
Used for
- glaucoma
- epilepsy
Unwanted effects
- metabolic acidosis
- enhances renal stone formation
Osmotic diuretics
Main- mannitol
- non- reabsorbable solute undergoes glomerular filtration
- excretion within 30-60 mins
- diuresis in 30-60 mins persists for 6-8 hours
Clinical uses
- cerebral oedma
- glaucoma
- cause osmotic diarrhoea
- acute renal failure
Unwanted effects
- increases plasma volume
- can’t be used in patients with hypertension
Water as a diuretic
Process controlled by ADH
Increased fluid intake leads to reduced secretion of ADH from posterior pituitary due to reduced plasma osmolality
Reduced expression of AQP2 channels on apical surface of DT and collecting duct
Potential ADH antagonists
Investigational drugs which inhibit the effects of ADH at collecting tubule
Two non- selective agents
- lithium (Li+)
- demeclocycline
Toxicity problem of ADH antagonists
Can cause diabetes insipidus
Renal failure
Li+ cause tremors, mental confusion, cardiotoxicity, thyroid dysfunction and leukocytosis
Demeclocycline shouldn’t be used in patients with liver disease
Xanthines
Caffeine, theophylline, theobromine
Produce weak diuretic effect by increasing cardiac output
Possibly also some vasodilation of glomerular afferent arteriole
Increased renal and glomerular blood flow, increase GFR and urine output
