DIURETIC AGENTS by N7vJp41

VIEWS: 0 PAGES: 49

									DIURETIC AGENTS

   Anita Q. Sangalang, MD, FPOGS
        FACULTY OF PHARMACY
     UNIVERSITY OF SANTO TOMAS
           DIURETIC AGENTS
        DRUGS USED IN RENAL DISORDERS

      Drugs that modify                   Drugs that modify
        salt excretion                     water excretion

  PCT   TAL DCT     CCT    Osmotic diuretics     ADH       ADH
                                               agonist antagonist
                     K+-sparing
                      diuretics
              Thiazides
           Loop
         diuretics
 Carbonic
anhydrase
 inhibitors
ANATOMY OF THE KIDNEY
         DIURETIC AGENTS


NEPHRON
    Proximal Convoluted Tubules (PCT)
   Isosmotic reabsorption of amino acids,
    glucose, and numerous cations
   Major site for sodium chloride (60-70%)
    reabsorption in exchange for H+ ion
        DIURETIC AGENTS

NEPHRON
    Proximal Convoluted Tubules (PCT)
   Bicarbonate is converted to Co2 via
    carbonic acid to permit reabsorption and
    regenerated within the tubular cell
   Uric acid transport
          DIURETIC AGENTS

NEPHRON
    Proximal Convoluted Tubules (PCT)
   Weak acid transport occur in the straight
    S2 segment
   Weak bases are transported in the S1 and
    S2 segments
   Target of carbonic anhydrase inhibitor
    diuretic drugs
          DIURETIC AGENTS

NEPHRON
    Thick Ascending Limb of the Loop of Henle
    (TAL)
   Reabsorption of sodium (20-30%),
    potassium and chloride carried out by a
    single carrier (cotransporter)
   Major site of calcium and magnesium
    reabsorption
   Target of loop diuretics
       DIURETIC AGENTS

NEPHRON
Distal Convoluted Tubules (DCT)
  Responsible for the reabsorption of 5-8%
   of sodium via a contransporter
  Calcium is reabsorbed under the control
   of parathyroid hormone (PTH)
  Target of thiazide diuretics
          DIURETIC AGENTS

NEPHRON
    Cortical Collecting Tubules (CCT)
   Final segment of the nephron
   Last tubular site for sodium reabsorption
    (2-5%) via channels (not a transporter)
   Accompanied by equivalent loss of K+ or
    H+ ion
   Controlled by aldosterone
          DIURETIC AGENTS

NEPHRON
    Cortical Collecting Tubules (CCT)
   Primary site of acidification of urine and
    potassium excretion
   Target for potassium-sparing diuretics
   Reabsorption of water occurs in the
    medullary collecting tubule under the
    influence of antidiuretic hormone (ADH)
         DIURETIC AGENTS

    CARBONIC ANHYDRASE INHIBITORS
   Acetozolamide
   Sulfonamide derivatives
   Inhibition of carbonic anhydrase in the
    brush border and intracellular carbonic
    anhydrase in the PCT
         DIURETIC AGENTS

    CARBONIC ANHYDRASE INHIBITORS
   Major renal effect is bicarbonate diuresis
    and results to metabolic acidosis
   Bicarbonate depletion results to slowing
    of its excretion
   Self-limiting diuresis in 2-3 days
         DIURETIC AGENTS


    CARBONIC ANHYDRASE INHIBITORS
   Inhibitory effect occurs thru out the body
   Useful reduction in IOP in the eye which
    is not self-limiting
   Used for the treatment of glaucoma
          DIURETIC AGENTS

    CARBONIC ANHYDRASE INHIBITORS
   In the CNS, acidosis can result to
    hyperventilation which can protect against
    high altitude sickness (acute mountain
    sickness)
    Administered orally
         DIURETIC AGENTS

    CARBONIC ANHYDRASE INHIBITORS
   Dorzolamide, brinzolamide
     • Topicals for the eye
   Used as diuretic if the edema is
    accompanied by metabolic alkalosis
   Drowsiness and paresthesias occur after
    oral intake
         DIURETIC AGENTS

    CARBONIC ANHYDRASE INHIBITORS
   Alkalinization of the urine may cause
    precipitation of calcium salts and
    formation of renal stones
   Renal potassium wasting
   Patients with hepatic impairment may
    develop encephalopathy due to ammonia
    reabsorption
         DIURETIC AGENTS

    LOOP DIURETICS
   Furosemide, bumetanide, and torsemide
     • Sulfonamide derivatives
   Ethacrynic acid
     • Phenoxy acid derivative
     • Acts by the same mechanism
     • Uricosuric drug
      DIURETIC AGENTS


    LOOP DIURETICS
   Inhibit the cotransport of sodium,
    potassium and chloride
   Short-acting (diuresis over a 4-hour
    period
         DIURETIC AGENTS


    LOOP DIURETICS
   Full dose produces massive sodium
    chloride diuresis
   Diluting ability of the nephron is reduced
    (site of significant dilution of urine)
         DIURETIC AGENTS


    LOOP DIURETICS
   Calcium excretion is increased due to the
    inhibition of the Na+/K+/2Cl- transporter
   Potassium wasting and proton excretion
          hypokalemic alkalosis
       DIURETIC AGENTS


    LOOP DIURETICS
   Non-steroidal anti-inflammatory drugs
    (NSAIDS) decreases the efficacy
   Pulmonary vasodilating effect
         DIURETIC AGENTS

    LOOP DIURETICS
   Treatment of edematous states (heart
    failure, acute pulmonary edema, ascites)
   Used in HPN if response to thiazides is
    inadequate
   Treatment of hypercalcemia (induced by
    malignancy) accompanied by parenteral
    volume and electrolyte supplementation
       DIURETIC AGENTS

    LOOP DIURETICS
   Can induce hypokalemic metabolic
    alkalosis
   Potassium wasting maybe severe
   Can cause hypovolemia and
    cardiovascular complications
   Ototoxicity and sulfonamide allergy
    DIURETIC AGENTS

    THIAZIDE DIURETICS
   Hydrochlorothiazide
   Sulfonamide derivative
   Active by the oral route
   6-12 hours duration of action
   Inhibit sodium chloride transport
    in the early segment of the DCT
        DIURETIC AGENTS


    THIAZIDE DIURETICS
   Produces moderate sodium and chloride
    diuresis
   Hypokalemic metabolic alkalosis may
    occur
         DIURETIC AGENTS

    THIAZIDE DIURETICS
   Promotes sodium-calcium exchange
    calcium reabsorption       urine calcium
    content is decreased
   Opposite of loop diuretics
         DIURETIC AGENTS

    THIAZIDE DIURETICS
   Act the diluting segment of the
    nephron
   Interfere with excretion of water
    dilutional hyponatremia
   Reduce BP at doses lower than
    maximal diuretic dose (treatment of HPN)
         DIURETIC AGENTS


    THIAZIDE DIURETICS
   Synergistic effect with loop diuretic
    producing marked diuresis
   Used for chronic therapy of mild
    edematous conditions (mild heart failure)
     DIURETIC AGENTS

    THIAZIDE DIURETICS
   Control of renal calcium stone
    formation
   Massive sodium diuresis with
    hyponatremia can be an early
    dangerous effect
       DIURETIC AGENTS

    THIAZIDE DIURETICS
   Potassium wasting
   Diabetic patients may have significant
    hyperglycemia
   Serum uric acid and lipid levels may
    increase
   Sulfonamide allergy
          DIURETIC AGENTS

    POTASSIUM-SPARING DIURETICS
   Spironolactone and eplenerone
     • Slow onsets and offsets of action
       (24-72 hours)
   Steroid derivatives
   Pharmacologic antagonists of aldosterone
    in the collecting tubules
       DIURETIC AGENTS


    POTASSIUM-SPARING DIURETICS
   Combine and block intracellular
    aldosterone receptor     reduce
    expression of genes controlling
    synthesis of sodium ion channels
    and Na+/K+ ATPase
        DIURETIC AGENTS


    POTASSIUM-SPARING DIURETICS
   Amiloride and triamterene
    • Block sodium channels in the same
      portion of the nephron
    • 12—24 hours
        DIURETIC AGENTS


    POTASSIUM-SPARING DIURETICS
   Increase sodium clearance and decrease
    potassium and hydrogen excretion
   May cause hyperkalemic metabolic
    acidosis
         DIURETIC AGENTS

    POTASSIUM-SPARING DIURETICS
   Treatment of potassium wasting caused
    by chronic therapy with loop and thiazide
    diuretics (combination in a single pill)
   Treatment of aldosteronism in cirrhosis
    and heart failure
       DIURETIC AGENTS


    POTASSIUM-SPARING DIURETICS
   Hyperkalemia is the most important
    toxicity
   Can cause endocrine abnormalities
    (gynecomastia and antiandrogenic
    effects)
        DIURETIC AGENTS

    OSMOTIC DIURETICS
   Mannitol
   Glycerin, isosorbide, urea
   Freely filtered at the glomerulus but
    poorly reabsorbed in the tubules
    remains in the lumen and “holds” water
    by virtue of osmotic effect
     DIURETIC AGENTS


OSMOTIC DIURETICS
 Given intravenously

 Sodium excretion is increased because

  the rate of urine flow is accelerated
      DIURETIC AGENTS

OSMOTIC DIURETICS
 Reduce brain volume and intracranial

  pressure (neurologic conditions) by
  osmotically extracting water from the
  tissue
 With similar effect in the eye (acute
  glaucoma)
      DIURETIC AGENTS


    OSMOTIC DIURETICS
   Used to maintain high urine flow in
    conditions of solute overload
     • Severe hemolysis
     • Rhabdomyolysis
        DIURETIC AGENTS

    OSMOTIC DIURETICS
   Removal of water from intracellular
    compartment may cause hyponatremia
    and pulmonary edema       hypernatremia
    when water is excreted
   Headache, nausea and vomiting
       DIURETIC AGENTS

    ANTIDIURETIC HORMONE AGONISTS
    AND ANTAGONISTS
   Antidiuretic hormone (ADH) and
    desmopressin
     • ADH agonists
     • Peptides
     • Given IV
         DIURETIC AGENTS

    ANTIDIURETIC HORMONE AGONISTS
    AND ANTAGONISTS
   Antidiuretic hormone (ADH) and
    desmopressin
     • Facilitates water reabsorption from
       collecting tubule by activation of V2
       receptors
         DIURETIC AGENTS

    ANTIDIURETIC HORMONE AGONISTS
    AND ANTAGONISTS
   Antidiuretic hormone (ADH) and
    desmopressin
   Increased in cAMP causes insertion of
    additional aquaporin water channels into
    the tubule
   Reduce urine volume and increase its
    concentration
         DIURETIC AGENTS

    ANTIDIURETIC HORMONE AGONISTS
    AND ANTAGONISTS
   Antidiuretic hormone (ADH) and
    desmopressin
   Useful in pituitary diabetes insipidus
   Large water load may cause hyponatremia
   May cause hypertension
          DIURETIC AGENTS

    ANTIDIURETIC HORMONE AGONISTS
    AND ANTAGONISTS
   Demeclocycline and lithium
    • ADH antagonists
    • Administered orally
    • Inhibit the action of ADH and interfere
      with the insertion of water channels
          DIURETIC AGENTS

    ANTIDIURETIC HORMONE AGONISTS
    AND ANTAGONISTS
   Demeclocycline and lithium
   Treatment of Syndrome of Inappropriate
    ADH secretion (SIADH)
     • Condition where peptides are produced
       by certain tumors
     • Can cause water retention and
       dangerous hyponatremia
         DIURETIC AGENTS


    ANTIDIURETIC HORMONE AGONISTS
    AND ANTAGONISTS
   Demeclocycline
    • Causes bone and teeth abnormalities
      in children younger than 8 years
         DIURETIC AGENTS


    ANTIDIURETIC HORMONE AGONISTS
    AND ANTAGONISTS
   Lithium
     • Causes nephrogenic diabetes insipidus
     • Never used to treat SIADH

								
To top