Diuretics Flashcards
What is absorbed in the PCT?
Sodium and Bicarbonate
Absorption of bicarbonate in the PCT occurs how and through what enzyme?
carbonic anhydrase dissociates bicarbonate into CO2 and H2O
where else can we find carbonic anhydrase?
Choroid plexus
eye (ciliary ?)
what gets absorbed in the Thick limb of Henle? how much of this? by using what enzyme?
What is also absorbed as well?
what gets pumped out?
Na+ 20-30% by using Na+/2Cl-/K+ co-transporter
Mg and Ca2+
pumps out sodium, potassium and Chloride into the interstitium
what gets reabsorbed in the Distal Convoluted Tubule? when?
what gets secreted? how?
Ca2+ in presence of Parathyroid hormone
Na+ Cl- cotransporter
the cortical collecting duct is highly responsive to what hormone? what will it do?
this is the primary site of what process?
In the medullary collecting duct, what gets absorbed? in the presence of what hormone?
aldosterone, reabsorb Na+
acidification of urine and excretion of K+
water in presence of ADH
what drug is used in the PCT?
what drug is used in the Ascending Loop of Henle?
what drug is used in the DCT?
what drug is used in the collecting tube?
carbonic anhydrase inhibitor
Loop diuretics
Thiazides
2 types: spironolactone and amiloride/trimterene
what are the 2 carbonic anhydrase inhibitors?
acetazolamide
Dorzolamide
how does acetazolamide work?
what will we develop in terms of acidosis or alkalosis?
What will we lose as well as bicarbonate?
Carbonic Anhydrase inhibition in the ciliary epithelium leads to what? what is the clinical application for this?
carbonic anhydrase inhibition will act in the choroid plexus involving the CSF, what is the effect of this?
what is the clinical application for this?
- inhibits carbonic anhydrase in brush border and intracellularly so we will excrete bicarbonate in urine
- we will develop metabolic acidosis
- we will lose potassium
- it leads to reduced secretion of aqueous humor
- it can be used for glaucoma
- acidosis of the CSF will lead to hyperventilation
- can be used in high altitude sickness
what are the uses of carbonic anhydrase inhibitors?
- Glaucoma
- Urinary Alkalanization for acidic drug toxicity
- Acute of mountain sickness
- Significant metabolic alkalosis
what are the adverse reactions related with carbonic anhydrase inhibitors?
- Cross alergenicity with other sulfonamides
- Hyperchloremic metabolic acidosis
- Renal stones: Alkalinization of urine may cause Ca2+ precipitation
- Hypokalemia
what is an example of a loop diuretics?
what do loop diuretics do?
furosemide
inhibit Na+/K+/2Cl- cotransporter
what is the effect of using loop diuretics?
- produce massive sodium chloride diuresis
- it will reduce blood volume
- it will reduce edema rapidly
- will reduce the dilution of urine
- will reduce lumen positive potential (because you lose Ca2+ and Mg)
- will see loss of K+ and H+ ==> hypokalemic acidosis
what are the uses of loop diuretics?
- Treatment of edematous states including heart failure, ascites
- Acute Pulmonary edema or left ventricular failure
- mild to moderate heart failure
- severe hypercalemia
what are the adverse reactions of loop diuretics?
- Hypokalemia
- Ototoxicity
- cross hypersensitivity with sulfa drugs
Give an example of a Thiazide
what do thiazides do?
Hydrochlorothiazide
inhibiting sodium chloride transporter; results in increased reabsorption of Ca from urine
for what are thiazides used for?
- Hypertension - by lowering BP
- Chronic renal calcium stone (because they reduce urine Ca concentration)
what are the adverse effects of thiazides?
- Severe hyponatremia
- Hypokalemia
- Cross hypersensitivity with sulfonamides
- Hypercalcemia
- Hyperuricemia
- Hyperlipidemia
- Hyperglycemia
what are the 2 potassium channels in the distal convoluted duct?
epithelium Na channels
aldosterone
what potassium sparing diuretic acts on aldosterone?
what potassium sparing diuretic acts on ENaC?
spironolactone = aldosterone antagonist
amiloride and triamterene = directly blocks the Na channels
how does spironolactone work?
what is its effect?
Acts as an antagonist of aldosterone in collecting tubule
By binding and blocking the aldosterone receptor, these drugs reduce expression of genes controlling synthesis of epithelial sodium ion channels and Na+K+ATPase
how do amiloride and triamterene work?
they are Competitive inhibitors of epithelial Na channels
what are the Effects of K sparing diuretics?
- Increases sodium excretion
- Decreases potassium and hydrogen ion excretion
- May cause hyperkalemic metabolic acidosis
what are the uses of potassium sparing diuretics?
- Hypokalemia caused by loop diuretics and thiazides
- Amiloride used in Lithium induced diabetes insipidus
- Spironolactone is used in hyperAldosteronism and congestive heart failure (CHF)
what are the adverse effects of giving Spironolactone or amiloride/triamterene?
Spironolactone alone causes what?
- Hyperkalemia
- Extreme caution needed when given with ACE-I
gynecomastia = Anti-androgenic effects
What is an example of an osmotic diuretic?
what makes it an osmotic diuretic?
where does it mainly work?
mannitol
the fact that it is freely filtered in the glomerulus but poorly reabsorbed; it holds water by vitue of its osmotic effect
in the proximal convoluted tubule
what are the Effects of Mannitol?
- Urine volume is increased
- Mannitol also can reduce Intracranial Pressure by osmotically extracting water from tissue into blood.
- Similar effect is eye (reduces intraocular pressure)
what are the uses of Mannitol?
- Cerebral edema
- Acute glaucoma
what are the adverse effects of mannitol?
- Aminoglycosides increases the ototoxicity of furosemide
- K+ sparing diuretics reduces digoxin action where as loop and thiazide diuretics increases digoxin toxicity
- Probenecid reduces the efficacy of diuretics by inhibiting their secretion into renal tubule
what are 2 Antidiuretic Hormone agonists?
what is their mechanism of action?
in what condition is it used?
what is the effect of these?
- Vasopressin and desmopressin
- facilitates water reabsorption from collecting tubule by activation of V2receptors – increases Gs and therefore cAMP and recruits more aquaporins
- neurogenic (pituitary) Diabetes insipidus
- reduce urine volume and increase its conc.
what are 2 ADH antagonists?
What drug has the capability to be an ADH antagonist but is never used for that purpose?
What is the mechanism of action of ADH antagonist?
What conditions merit the use of these ADH antagonists?
What can induce diabetes insipidus? how do you treat it?
Demeclocycline, Conivaptan
Lithium
oppose the actions of ADH & other peptides, which act on V2 receptors
syndrome of inapropriate ADH and small cell carcinoma
Lithium, Amiloride
