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    Diuretics: Diuretics Are Drugs That Increase The Volume of Urine Flow

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    Amanuel Maru
    Diuretics are drugs that increase urine output by interfering with sodium reabsorption in the kidneys. The major classes of diuretics act at different sites along the nephron. Loop diuretics are the most potent as they block sodium reabsorption in the loop of Henle. Thiazide diuretics act in the distal convoluted tubule while carbonic anhydrase inhibitors and potassium-sparing diuretics act in the collecting duct. Diuretics are used to treat conditions like heart failure, hypertension, and edema but can cause side effects like electrolyte imbalances.

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    Diuretics: Diuretics Are Drugs That Increase The Volume of Urine Flow

    Uploaded by

    Amanuel Maru
    388 views35 pages
    Diuretics are drugs that increase urine output by interfering with sodium reabsorption in the kidneys. The major classes of diuretics act at different sites along the nephron. Loop diuretics are the most potent as they block sodium reabsorption in the loop of Henle. Thiazide diuretics act in the distal convoluted tubule while carbonic anhydrase inhibitors and potassium-sparing diuretics act in the collecting duct. Diuretics are used to treat conditions like heart failure, hypertension, and edema but can cause side effects like electrolyte imbalances.

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    Diuretics

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    Diuretics

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    Diuretics are drugs that increase urine output by interfering with sodium reabsorption in the kidneys. The major classes of diuretics act at different sites along the nephron. Loop diuretics are the most potent as they block sodium reabsorption in the loop of Henle. Thiazide diuretics act in the distal convoluted tubule while carbonic anhydrase inhibitors and potassium-sparing diuretics act in the collecting duct. Diuretics are used to treat conditions like heart failure, hypertension, and edema but can cause side effects like electrolyte imbalances.

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    © All Rights Reserved
    Download as PPTX, PDF, TXT or read online from Scribd
    Download as pptx, pdf, or txt
    388 views35 pages

    Diuretics: Diuretics Are Drugs That Increase The Volume of Urine Flow

    Uploaded by

    Amanuel Maru
    Diuretics are drugs that increase urine output by interfering with sodium reabsorption in the kidneys. The major classes of diuretics act at different sites along the nephron. Loop diuretics are the most potent as they block sodium reabsorption in the loop of Henle. Thiazide diuretics act in the distal convoluted tubule while carbonic anhydrase inhibitors and potassium-sparing diuretics act in the collecting duct. Diuretics are used to treat conditions like heart failure, hypertension, and edema but can cause side effects like electrolyte imbalances.

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    Diuretics

    Diuretics are drugs that increase the


    volume of urine flow.
    Outline
    1. Sites of drug action

    2. Osmotic diuretics

    3. Carbonic anhydrase inhibitors

    4. Thiazide diuretics

    5. Loop diuretics

    6. Potassium-sparing diuretics
    What are diuretics?
    Drugs that increase the volume of urine flow
    How do they work?
    In general, diuretics affect ion transport in the
    nephron.
    Clinically useful diuretics primarily inhibit Na+
    reabsorption.
    Water is then carried along passively in order to
    maintain an osmotic equilibrium.
    Principal sites of action
    Proximal convoluted tubule (PCT)
    Thick ascending limb of loop of Henle
    Distal convoluted tubule (DCT)
    Collecting duct
    Knowing the sites of action helps predict:
    The magnitude and pattern of diuresis
    The side effects of the medication
    The pattern of electrolyte loss
    5 major classes of diuretics?
    Structure of Classes of Diuretics
    Osmotic Diuretics
    do not interact with
    receptors or directly
    block renal transport

    activity depends on
    development of osmotic
    pressure

    Mannitol (prototype)

    Urea

    Glycerol

    Isosorbide
    Mechanism of Action
    Osmotic diuretics are freely filterable substances and
    they are not reabsorbed

    Once they become a component of the luminal fluid,


    they create an osmotic effect along the entire nephron.

    Prevents passive reabsorption of H2O

    Osmoticforce solute in lumen > osmotic force of


    reabsorbed Na+
    Therapeutic Uses
    Mannitol

    drug of choice: non-toxic, freely filtered, non-


    reabsorbable and non-metabolized

    administered prophylatically for acute renal failure


    secondary to trauma, CVS disease, surgery or
    nephrotoxic drugs

    short-term treatment of acute glaucoma

    infused to lower intracranial pressure

    Urea, glycerol and isosorbide are less efficient

    can penetrate cell membranes


    Side Effects

    increased extracellular fluid volume

    pulmonary edema

    Hypernatremia

    headache, nausea, vomiting


    Carbonic Anhydrase Inhibitors

    limited uses as diuretics

    Acetazolamide

    prototype carbonic anhydrase


    inhibitor

    developed from sulfanilamide


    (caused metabolic acidosis and
    alkaline urine)
    Mechanism of Action
    carbonic anhydrase is an enzyme that catalyzes the following reaction
    CO2 + H2O H2CO3
    How CAI produce diuresis?
    The H+ ion produced by the breakdown of H2CO3 is usually
    exchanged for Na+ and is used to combine with HCO3 in the lumen
    of the PCT.
    Without the H+ there is decreased reabsorption of Na+ and HCO3 ;
    this results in diuresis.

    less H+ for Na+/H+


    exchange
    increased lumen Na+,
    increased H2O retention
    How efficient is the diuresis produced by CAIs?
    It is relatively weak, because other sites further
    along in the nephron can compensate for the
    increased Na+ load.
    Therapeutic Uses
    used to treat glaucoma

    aqueous humor has high [HCO3-]

    acute mountain sickness

    metabolic alkalosis

    sometimes epilepsy

    mostly used in combination with other diuretics in resistant


    patients
    Adverse Effects
    metabolic acidosis caused by loss of
    bicarbonate
    Potassium depletion caused by the sodium
    load and increased flow rate past the DCT
    paresthesia (pins and needles under skin)
    nephrolithiasis (renal stones)
    Thiazide Diuretics
    Sulfonamide derivatives
    active in the early segment DCT structurally related with
    CAIs

    Chlorothiazide (prototype)

    Hydrochlorothiazide

    Chlorthalidone

    Metolazone
    Mechanism of Action
    inhibit Na+ and Cl- transporter in distal convoluted
    tubules

    increased Na+ and Cl- excretion

    weak inhibitors of carbonic anhydrase, increased


    HCO3- excretion

    increased K+ excretion

    decrease Ca2+
    excretion
    How effective are thiazides?
    They are only moderately effective because
    most of the filtered Na+ is absorbed before it
    reaches the DCT
    Therapeutic Uses

    hypertension

    congestive heart failure

    hypercalciuria: prevent excess Ca2+ excretion to


    form stones in ducts

    osteoperosis

    nephrogenic diabetes insipidus


    Pharmacokinetics
    orally administered

    poor absorption

    onset of action in ~ 1 hour

    wide range of T 1/2 amongst different thiazides,


    longer then loop diuretics

    free drug enters tubules by filtration and by organic


    acid secretion
    Side Effects

    hypokalemia
    increased Na+ exchange in CD
    hyponatremia
    hyperglycemia
    diminished insulin secretion
    elevated plasma lipids
    hyperuricemia
    hypercalcemia
    Loop Diuretics
    active in loop of Henle

    Furosemide (prototype)

    Bumetanide

    Torsemide

    Ethacrynic acid
    Mechanism of Action
    enter proximal tubule via organic acid transporter

    Works by blocking the Na-K-2Cl transporter in the thick


    ascending loop of henle
    competes with Cl- binding site

    enhances passive Mg2+


    and Ca2+ excretion
    increased K+ and H+
    excretion in CCD
    Most effective

    They are called high ceiling diuretics


    because they have the highest efficacy of all
    diuretics.
    Why are they the most efficacious diuretics?
    25% to 35% of NaCl is normally reabsorbed at the
    ascending loop of Henle.
    Sites downstream along the nephron (DCT and CD)
    cannot fully compensate if Na+ reabsorption in the
    loop of Henle is blocked.
    Comparison of loop and thiazide diuretics
    Therapeutic Uses
    edema: cardiac, pulmonary or renal

    renal failure

    hypertension

    hypercalcemia

    acute and chronic hyperkalemia


    Pharmacokinetics

    orally administered, rapid absorption

    rapid onset of action

    bound to plasma proteins: displaced by warfarin, and


    clofibrate

    additive toxicity with other ototoxic drugs

    inhibitors of organic acid ion transport decrease


    potency (i.e. probenecid, NSAIDs)
    Side Effects
    hypokalemia

    Volume depletion

    hyperuricemia

    metabolic alkalosis

    hyponatremia

    Ototoxicity- especially when used in conjunction


    with an aminoglycoside

    Mg2+ depletion, hypocalcemia


    K+ sparing diuretics
    Three groups

    steroid aldosterone antagonists

    spironolactone, eplerenone

    Pteridines

    triamterene

    Pyrazinoylguanidines

    amiloride
    Mechanism of Action
    K+ sparing diuretics function in CD
    decrease Na+ transport in collecting tubule

    Spironolactone
    competitive antagonist for mineralocorticoid receptor
    prevents aldosterone stimulated increases in Na+
    transporter expression

    Triamterene/Amiloride
    organic bases
    secreted into lumen by
    proximal tubule cells
    inhibit apical Na+ channel
    Therapeutic Uses
    primary hyperaldosteronism (adrenal adenoma,
    bilateral adrenal hyperplasia)

    congestive heart failure

    cirrhosis

    nephrotic syndrome

    in conjunction with K+ wasting diuretics


    Pharmacokinetics
    Spironolactone
    orally administered
    aldactazide: spironolactone/thiazide combo
    Amiloride
    oral administration, 50% effective
    not metabolized
    not bound to plasma proteins
    Triamterine

    oral administration, 50% effective


    60% bound to plasma proteins
    liver metabolism, active metabolites
    Side Effects
    hyperkalemia: monitor plasma [K+]

    spironolactone: gynecomastia

    triamterene: megaloblastic anemia in cirrhosis


    patients

    amiloride: increase in blood urea nitrogen,


    glucose intolerance in diabetes mellitus
    Potassium sparing diuretics

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