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Pitfalls in Diuretic Use – Metabolic Adverse Reactions

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					Pitfalls in Diuretic Use –
Metabolic Adverse Reactions


    Iwan Darmansjah, MD
 Some commonly used diuretics
• Thiazides and Thiazide analogs
   – Bendroflumethiazide, hydrochlorothiazide, indapamide
• Loop diuretics
   – Furosemide, bumetanide, torasemide (long half-life)
• Potassium-sparing diuretics
   – Amiloride, spironolactone, triamterene
• Carbonic anhydrase inhibitors
   – Acetazolamide (specific use)
• Adverse reactions to diuretics well known
  – Elderly people most affected
• Mainly prescribed for hypertension and
  cardiac insufficiency
• Thiazide as antihypertensive should not be
  called “diuretic”, because of the small doses
  used, and is not diuretic.
         URINARY ELECTROLYTE COMPOSITION DURING DIURESIS

                              Volume pH              Na+ K+        Cl+     HCO3-
                              (ml/min)                      (mM)

 Control                           1           6      50     15       60          1
 Mannitol                         10         6.5      90     15     110           4
 Acetazolamide                     3         8.2      70     60       15       120
 Benzothiadiazides                 3         7.4    150      25     150         25
 (thiazides)
 High-celling diuretics            8           6    140      10     155           1
 Potassium-sparing                 2         7.2    130       5     110         15
 diuretics
 Aminophylline                     3           6    150      15     160           1
Source : Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 8 th ed. 1999
  Loop-diuretic as Fluid-mover

• Furosemide increases urine vol 8 x Normal
• Thiazide (diuretic dose)       3xN
• Potassium-sparing diuretic     2 xN
 Main Indications of furosemide
• Removing edema fluid from:
  – Feet and legs, ascites, pulmonary interstitial and
    alveoli, whole body tissue edema
• Acute and chronic Heart Failure
• Forced diuresis
                   HCT dose
• As diuretic: 50-100 mg
• As antihypertensive dose much smaller:
   – 6.25 mg (as in Lodoz) –12.5 mg/day
   – No problem of hyponatremia, nor hypokalemia
• No need of routine K supplementation
• Most metabolic adverse reactions of thiazide was
  reported from the 70’s – late 80’s, when the doses
  used were large (50-100 mg/day or more).
                Hyponatremia
• Hyponatremia is the most frequent electrolyte
  abnormality among diuretic (all diuretics) users. It
  may be fatal.
• Furosemide has the strongest natriuretic effect,
  and therefore the most frequent adverse reaction.
• Factors: age, female, malnutrition, renal failure,
  combination with NSAID, ACE-inhib.
• When severe renal failure: hyperkalemia,
  hyperphosphatemia, hyperuricemia. .
              Hypokalemia
• Hypokalemia is the most feared among
  furosemide, and even low-dose thiazide
  users.
• This fear is unfounded and results in
  overuse of K salts as a preventive in all
  patients receiving long term furosemide,
  which may result in hyperkalemia.
   Nature of Adverse Reactions
• Hyponatremia: (when mild, asymptomatic)
      • Postural hypotension
      • Weakness, vomiting, mental confusion, coma,
        convulsion
      • Neurological complication when < 120 mmol/L

• Hypokalemia:
      • Cardiac arrhytmia (QRS widening)


• Excessive water loss (dehydration)
  Drugs that may alter K levels
• Hypokalemia
  –   Thiazide as a diuretic (not if used as antihypertensive)
  –   Loop diuretic
  –   Mineralocorticoids (fludrocortisone)
  –   Cathartics
  –   Adrenergics, theophylline (high dose)
• Hyperkalemia
  –   KCL tablets
  –   Potassium –sparing diuretics
  –   ACE-inhibitors
  –   NSAID (especially when renal impairment)
        Some Mechanisms (1)
• ACE-inhib may increase serum K by:
  – Reducing angiotensin-II mediated release of
    aldosterone, which reduces K excretion in the
    distal tubules.
• Fludrocortisone produces hypokalemia by
  – increasing K renal excretion with Na absorption
    in the distal tubule.
       Some Mechanisms (2)
• Adrenergics: stimulate K uptake by muscles
          redistribution of K (usually mild)

• Furosemide depends on renal excretion;
  Bumetanide does not, because metabolized
       Treatment of Hyponatremia

• Slow infusion of isotonic or hypertonic
  NaCl solution.

• Restriction of water intake.

• Precaution: when checking K level, one
  should include Na.
Treatment of Hypo- and Hyper-kalemia

• Severe hypo- or hyper-kalemia must be
  treated fast with cardiac monitoring.
• Hypo: Slow infusion of KCL solution.

• Hyper: Infusion of glucose and insulin
  (stimulates K uptake in the cell)
  – Also: anion exchange resin to bind K ion.
                  Conclusion
• Diuretics are beneficial for many diseases

• It may also cause fatal adverse reactions (elderly!)

• Monitoring of electrolyte levels are needed

• Judicious use is warranted
       E-mail: <puko98@indosat.net.id>
 Homepage: <http://www.iwandarmansjah.web.id>




Thank you !

				
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posted:4/18/2008
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