A-27. Potassium excreting (wasting) diuretics Flashcards
Which solutes are reabsorbed in the Proximal Convoluted Tubules?
66% of sodium and potassium; 85% bicarbonate; almost all glucose and Amino Acids are reabsorbed
In the Tall Ascending Limb how much sodium is reabsorbed?
20% sodium reabsorbed
Which are the other two sites of Sodium reabsorption in the renal tubules
Distal Convoluted Tubule (10% Na reabs) and Collecting Tubules (3% Na reabsor)
Classification of Diuretic Medication
3 K+ wasting diuretics
2 others
K+ wasting diuretics
1.) Carbonic Anhydrase inhibitors- work in PCT
2.) Loop diuretics- TAL
3.)Thiazide- DCT (main idication: hypertension, mild edemas)
Other diuretics
4.) K+-Sparing Diuretics- collecting tubules, in combo with K-wasting diuretics
5.) Osmotic Diuretics
Carbonic anhydrase inhibitors cause
Bicarbonate, Na+, and H2O to be excreted causing lose of fluid and alkaline urine.
Later Na+ exchanged for K+ in collecting tubules causing hypokalemia
Also leads to more Cl- reabsorption and retention of H+ causing hypercholemic metabolic acidosis
Carbonic anhydrase inhibitor drugs
Dorzolamide and Acetazolamide
Dorzolamide used for?
Used topically to treat glaucoma since ciliary body normally secretes HCO3 from blood into aqueous humor
Acetazolamide indications
1.) broad spectrum anti-epileptics
Slight acidosis inhibits neurons
Commonly used for women with seizures during mentruation
2.)Acute mountain sickness
-with dizziness, weakness, insomnia, HA, nausea +/- pulmonary and cerebral edema
-CA inhibition decrease CSF production and pH which increases ventilation and decreases hypoxia and symptoms
3.) Chronic metabolic alkalosis
4.)glaucoma
(idiopathic intracranial hypertension and cystine/urate stone prevention with increased urine pH)
Side effects of Acetazolamide
1.) Hypercholermic metabolic acidosis with normal anion gap
2.)Hypokalemia
3.) Renal stones (Ca3(PO3)2 due to alkaline urine
(Type 2 Renal Tubular Acidosis and Hypersensitivity)
Most effective diuretic
Loop Diuretics
Where and how does loop diuretics act?
On the TAL (where 25% Na is reabs) by inhibiting the Na/K/2Cl cotransporter
(Does not cause an acidosis)
What are the consequences of blocking the Na/K/2Cl cotransportor
- loss of water (diuresis)
- Na+ exchanged for K+ in the distal collecting tubule (hypokalemia)
- No electrochemical gradient made by K+ so Ca2+/Mg is not reabsorbed
- COX expression increases prostaglandins leading to direct vasodilation of vena cava to diminish pulmonary edema
- RBF and renin increased
- metabolic alkalosis in patient
How is the loss of calcium later compensated by the body? Magnesium?
PTH allows for active reabsorption of Ca2+
Magnesium needs to be given orally
Loop Diuretic Drugs (3)
Furosemide, Torsemide, and Ethacrynic Acid (not a sulfa drug)
Indications of Loop diuretics
1.) Edema
2.) Hypertension
3.) Acute Renal Failure-except anuric patients
4.) Chronic Renal Failure
5.) Hypercalcemia-
6.)Intoxications (halogen/alkali metal poisoning except Li)
(Ascites?)
Dosage of loop diuretics for Interstitial/pulmonary edema via chronic heart failure? Dosage for pulmonary edema from acute LV failure?
- ) 20 mg furosemide oral daily
- ) IV furosemide 40 mg, repeatable after half an hour acts first by dilating large veins such as vena cava, then by diuretic action)
Drug and dosage for loop diuretic use in hypertension?
Torsemide 2-3 mg
Drug and dosage for loop diuretic use in chronic renal failure?
Furosemide 200-2000 mg oral (binds protein so need high dosage to have effective dose)
Contraindications for loop diuretics?
Cirrhosis since there is a risk of hepatic encephalopathy.
Ammonia level increases due to metabolic alkalosis in the body that inhibits ammonia transformation into ammonium.
Ammonia crosses the BBB leading to encephalopathy
Side effects of loop diuretics
- )Hypokalemia
- ) Hypomagnesium
- ) Metabolic alkalosis
- ) Ototoxicity (transient deafness)
- ) Hyperuricemia
- ) Impaired glucose tolerance
- ) Hyperlipidemia (increased LDL)
- ) Interstitial Nephritis
Metabolic alkalosis mechanism
Hypovolemia increases renin and aldosterone. Aldosterone causes K+ and H+ excretion; increases angiotensin II also which directly increases Na/H exchange in PCT
Is the loop diuretic ototoxicity reversible?
Yes to a point, then can cause definite ototoxicity. Don’t combine with other ototoxic drugs like aminoglycosides
How is hyperuricemia caused by loop diuretics?
hypovolemia associated increase of uric acid reabsorption in PCT. May cause gouty arthritis. Avoidable by starting lower doses then increasing dosage
Impaired glucose intolerance in loop diuretics can be explained by?
Hypokalemia causes decreased insulin secretion and peripheral glucose uptake
