Renal 2- Johnson- Diuretics

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Carbonic Anhydrase Inhibitors SE

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Hypokalemia
Metabolic Acidosis
Reduced calcium reabsorption.
Promotion of calcium oxalate stones.*****
Numbness and tingling.
Alterations in taste.
Blurred vision.

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Contraindications:
Carbonic Anhydrase Inhibitors

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allergies to sulfa drugs
Sickle cell anemia

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Carbonic anhydrase is located in

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located in the proximal tubule, key player in metabolic regulation of whole body pH.

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Carbonic Anhydrase Inhibitors make what kinde of urine?

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Will generate alkaline urine.

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Examples:
Loop Diuretics

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Examples:
Bumetanide (Bumex®)
Ethacrynic Acid (Edecrin®)
Furosemide (Lasix®)
Torsemide (Demadex®)

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LOOP diuretics work by

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Tend to have sulfonamide moiety
Inhibit the Na+/K+/2Cl- symporter in the ascending limb of the loop of Henle
“Poisons” the Na gradient in the loop.
Cause less transport of water out of the ascending tubule.
Causes a “whoppin’ diuresis” (high ceiling).

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Loop Diuretics Side Effects

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hypokalemia
metabolic alkalosis
Hypomagnesemia and calcium loss (from decreased luminal K+ charge gradient)
hyperuricemia (secondary to hypovolemia)
dehydration (hypovolemia), leading to hypotension
dose-related hearing loss (rare but more common w/ furosomide)

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Loop Diuretics Drug Interactions

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hypokalemia potentiates digitalis toxicity
non-steroidal anti-inflammatory drugs: reduced diuretic efficacy.
corticosteroids: enhance hypokalemia
aminoglycosides: enhanced ototoxicity, nephrotoxicity.

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Thiazides and Similar Drugs
examples

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Examples:
Hydrochlorothiazide (HydroDIURIL®)
Indapamide (Lozol®)
Metolazone (Mykrox®)

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Thiazide and Related Diuretics

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Commonly used for treating hypertension (excretes sodium)
Moderately effective diuretics
Few adverse effects
Block Na+/Cl- symporter

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Thiazide and Related Diuretics
Adverse effects

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Potassium wasting (excreted)
Potassium wasting thought to contribute to elevated cholesterol, elevate glucose, electrolyte imbalances, gout
Magnesium wasting
Calcium retaining

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Thiazide-Like Diuretics
examples

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Examples:
Indapamide (Lozal®)
Metolazone (Zytanix®)
Structurally different from “classic” thiazides
Actions are similar to thiazides.
May be used if patient shows “diuretic resistance”

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Thiazide and Related Diuretics Drug Interactions

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hypokalemia potentiates digitalis toxicity
non-steroidal anti-inflammatory drugs: reduced diuretic efficacy
beta-blockers: potentiate hyperglycemia, hyperlipidemias
corticosteroids: enhance hypokalemia

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Potassium-Sparing Diuretics
examples

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Amiloride (Midamor®), Spironolactone (Aldactone®), Triamterene (Dyrenium®)

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Actions:
Potassium-Sparing Diuretics

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Actions: Block sodium entry into the late distal tubule and collecting ducts.
Allows sodium and water excretion but RETAINS POTASSIUM.

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Adverse effect:
Potassium-Sparing Diuretics

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May promote hyperkalemia if patient uses potassium supplements (salt substitute)

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Potassium Sparing Drugs
SE

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hyperkalemia
gynecomastia (aldosterone antagonists)

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Potassium Sparing Drugs
Drug Interactions

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ACE inhibitors: potentiate hyperkalemia
non-steroidal anti-inflammatory drugs: reduced diuretic efficacy

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Osmotic Diuretics
drugs

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Mannitol (Osmitrol®)

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Mannitol (Osmitrol®)

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Osmotic Diuretics

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Carbonic Anhydrase Inhibitors
drugs

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Acetazolamide (Diamox®)
Dorzolamide (Trusopt®)

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Acetazolamide (Diamox®)
Dorzolamide (Trusopt®)

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Carbonic Anhydrase Inhibitors

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Loop Diuretics
drugs

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Ethacrynic Acid (Edecrin®)
Furosemide (Lasix®)
Torsemide (Demadex®)

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Ethacrynic Acid (Edecrin®)
Furosemide (Lasix®)
Torsemide (Demadex®)

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Loop Diuretics

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Thiazide and Related Diuretics
drugs

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Hydrochlorothiazide (HydroDIURIL®)
Indapamide (Lozol®)
Metolazone (Mykrox®)

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Hydrochlorothiazide (HydroDIURIL®)
Indapamide (Lozol®)
Metolazone (Mykrox®)

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Thiazide and Related Diuretics

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Amiloride (Midamor®)
Spironolactone (Aldactone®)
Triamterene (Dyrenium®)

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Potassium-Sparing Diuretics

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Potassium-Sparing Diuretics
drugs

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Amiloride (Midamor®)
Spironolactone (Aldactone®)
Triamterene (Dyrenium®)

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Antidiuretic Hormone Antagonist
drugs

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Conivaptan (Vaprisol®)

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Conivaptan (Vaprisol®)

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Antidiuretic Hormone Antagonist

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Draw summary table on diuretics

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diuretics ppt 55-slide

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Glomerulus

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Filters plasma minus albumin into the tubule.
Structure also permits nitrogen based waste (in the plasma) to be filtered into nephron.
The rate at which plasma is filtered is termed as “glomerular filtration rate” or “GFR”.
Can be affected by renal perfusion pressure and/or renal blood flow.

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Proximal Tubule

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Absorbs amino acids, glucose, ions very early in tubule.
Some sodium absorption (66%).
Contains carbonic anhydrase
Region for adjusting urinary pH

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Loop of Henle

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Descending limb reabsorbs water
Ascending limb absorbs 30% of sodium.
Primary player in volume regulation.
Concentrates the tubular filtrate.
Ion absorption also plays CRITICAL role in establishing cortical interstitium that is VITAL for water absorption

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Length and function VITAL for concentrating urine.

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Loop of Henle

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Distal Tubule

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3-10% sodium is reabsorbed.
Some water is reabsorbed.

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Distal Tubule

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3-10% sodium is reabsorbed.
Some water is reabsorbed.

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Cortical Collecting Duct

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Final adjustments for sodium and water reabsorption.
Site for aldosterone, antidiuretic hormone, and atrial natriuretic peptide receptors.

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Cortical Collecting Duct

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Final adjustments for sodium and water reabsorption.
Site for aldosterone, antidiuretic hormone, and atrial natriuretic peptide receptors.

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Classes of Diuretic Agents

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Osmotic Diuretics
Carbonic Anhydrase Inhibitors
Loop Diuretics
Thiazide and Related Diuretics
Potassium-Sparing Diuretics
Antidiuretic Hormone Antagonist (second hour)

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Classes of Diuretic Agents

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Osmotic Diuretics
Carbonic Anhydrase Inhibitors
Loop Diuretics
Thiazide and Related Diuretics
Potassium-Sparing Diuretics
Antidiuretic Hormone Antagonist (second hour)

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Osmotic Diuretics general

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Glycerol is pretty outdated.
Increase osmotic pressure (sucking pressure) of the plasma.
Drugs filtered through the glomerulus, but not absorbed by the renal nephrons.
Draws (or retains) water in the tubules throughout the length of the nephron.
Primarily a water diuresis with some sodium.

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Osmotic Diuretics general

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Glycerol is pretty outdated.
Increase osmotic pressure (sucking pressure) of the plasma.
Drugs filtered through the glomerulus, but not absorbed by the renal nephrons.
Draws (or retains) water in the tubules throughout the length of the nephron.
Primarily a water diuresis with some sodium.

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Adverse Effect
Osmotic Diuretics general

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IV loading (mannitol) can promote volume expansion, so avoid in heart failure.
Used for emergency reduction of volume (water).

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Adverse Effect
Osmotic Diuretics general

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IV loading (mannitol) can promote volume expansion, so avoid in heart failure.
Used for emergency reduction of volume (water).

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Carbonic Anhydrase is required for reabsorption of _____ from ____.

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bicarbonate from the nephron.

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Carbonic Anhydrase Inhibitors general

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Carbonic anhydrase is located in the proximal tubule, key player in metabolic regulation of whole body pH.
Blockade causes bicarbonate to be retained in the fluid.
Will generate alkaline urine.
Changes in tubular water and sodium are corrected by remaining portions of the tubules.
Negligible diuretic.
Carbonic anhydrase inhibitors mostly to alkalize urine, reduce intraocular pressure, elevate seizure thresholds in CNS.
Off label use to reduce systemic pH, drive respiration to treat sleep apnea.

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**Structure also permits nitrogen based waste (in the plasma) to be filtered into nephron. where?

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glomerolus

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**Region for adjusting urinary pH

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PT

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**Concentrates the tubular filtrate.
Ion absorption also plays CRITICAL role in establishing cortical interstitium that is VITAL for water absorption

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Loop of Henle

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**Length and function VITAL for concentrating urine.

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Loop of Henle

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***Site for aldosterone, antidiuretic hormone, and atrial natriuretic peptide receptors.

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Cortical collecting duct

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**Will generate alkaline urine.

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CAi

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***Off label use to reduce systemic pH, drive respiration to treat sleep apnea.

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CAi

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***Promotion of calcium oxalate stones.

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CAI SE

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**“Poisons” the Na gradient in the loop.

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Loop diuretics

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**Causes a “whoppin’ diuresis” (high ceiling).

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Loop diuretics

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**hypokalemia potentiates digitalis toxicity

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Loop Diuretics drug interactions

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**Commonly used for treating hypertension (excretes sodium)

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Thiazide and Related Diuretics

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**Few adverse effects

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Thiazide and Related Diuretics

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**Calcium retaining
Potassium wasting (excreted)

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Thiazide and Related Diuretics