Potassium Sparing Diuretics. ADH Antagonists, Osmotic Diuretics Flashcards
Name the osmotic diuretics
Mannitol
Glycerol
Isosorbide
Urea
How are glycerin and isosorbide administered?
IV or PO
When are osmotic diuretics contraindicated?
Heart failure
What are the adverse effects of osmotic diuretics?
Overload of circulation Dehydration Hyponatremia Pulmonary Edema Hyperkalemia secondary to DM or impaired renal function Headache, nausea, vomiting Cardiac failure
When do we use osmotic diuretics?
Brain Edema
Acute kidney failure (e.g.., shock kidney)
Refractory Edema (when it is induced by kidney or liver disorders)
Oliguric states (e,g,m rhabdomyolysis)
CF
How are mannitol and urea administered?
IV
Which osmotic diuretic can be used in CF?
Mannitol in the form of a spray
What are the K+ sparing diuretics?
Spirinolactone
Eplerenone
Amiloride
Triamterene
Name the ADH antagonists
Lithium salts
Demeclocycline
Conivaptan
Tolvaptan
What are the clinical indications for Eplerenone?
CHF
Hypertension
What are the side effects of Eplerenone?
Hyperkalemia Metabolic acidosis Gynecomastia Hirsutism Dysmenorrhea
What are the adverse effects of Spirinolactone?
Hyperkalemia Metabolic acidosis Gynecomastia Hirsutism Dysmenorrhea
What are the side effects of Amiloride and Triamterene?
Hyperuricemia
Renal stones
Hyperkalemia
Metabolic acidosis
What are the clinical indications of Amiloride and Triamterene?
Hypertension
Liddle syndrome
Li-induced nephrogenic diabetes insipidus
Cystic fibrosis
What is Liddle syndrome?
It is a genetic disorder causing increased activity of ENaC
What are the clinical indications of Spirinolactone?
Primary hyperaldosteronism
Secondary hyperaldosteronism in CHF, liver cirrhosis and nephrosis
(Hypertension - not really used)
What drugs do spironolactone interact with?
Drugs reducing RAAS activity
NSAIDs
Digoxin
What are the pharmacokinetic properties of spirinolactone?
It binds to other steroid receptors as well
It has a high 1st pass effect
It’s active metabolite is canrenoate
What sort of drugs are Spirinolactone and Eplerenone?
Aldosterone receptor antagonists
What is the receptor for Amiloride and Triamterene?
ENaC
Inhibition of ENaC
What is the effect of inhibiting the ENaC channel?
Decreased Na/K exchange - Na excretion - diuresis with no K+ loss
What are the adverse effects of Li salts, Demeclocycline, Conivaptan, Tolvaptan?
Nausea Thirst Polyuria Dehydration Hypoglycaemia
What are the clinical indications of Li salts, Demeclocycline, Conivaptan, Tolvaptan?
SIADH
Hyponatremia
Where are Li salts, Demeclocycline, Conivaptan, Tolvaptan metabolised?
In the liver
What is the mechanism of action of Li salts and Demeclocycline?
Inhibition of cAMP-mediated processes
What is the mechanism of action of Conivaptan and Tolvaptan?
ADH (V2) antagonists
Name the diuretics which act on the Enac
Amiloride
Triamterene
Name the drugs which are aldosterone antagonists
Spirinolactone
Eplerenone
What is the receptor for vasopressin?
V2
Where is the V2 receptor found?
on the basolateral membrane
What is V2 receptor coupled to?
Gs
What is the result of ADH release on the kidney?
Gs - cAMP increase - increase expression of AQP2 on the luminal membrane - increase reabsorption of solute free fluid.
Name the V2 antagonists?
Conivaptan
Tolvaptan
Name the drugs that inhibit the ADH induced cAMP mediated process
Li+ salts
Demeclocycline
What is the mechanism of action of osmotic diuretics?
They increase osmolarity in the tubular fluid and prevent water reabsorption - leading to osmotic diuresis
Hyperosmosis in the blood leads to increased EC volume leading to increased GFR and reduced ADH secretion
How are osmotic diuretics administered?
IV
