From the reaction above, it can be deduced that removal of or blocking the enzyme
carbonic anhydrase would result in a much slower reaction. Consequently, there would
be a greatly reduced production of hydrogen ions and bicarbonate ions. This interferes
with the ion exchange mechanism at the distal tubule, where the sodium ion that
accompanies the bicarbonate ion is reabsorbed only by exchange for hydrogen or
potassium ions secreted into the tubule. Normally the bicarbonate ion that
accompanies the sodium ion (provided by the glomerular filtrate) is reabsorbed almost
complete at the distal tubule. With reduced production of hydrogen ion due to inhibition
of the carbonic anhydrase, the bicarbonate ion, together with the sodium ion will not be
reabsorbed. Thus, the sodium will be excreted in an unusually large amount--with a
corresponding loss of water (remember, where sodium goes, water goes).
Acetazolamide (Diamox). Acetazolamide is one example of a carbonic
anhydrase inhibitor. Although rarely used today, it may be used in the treatment of
edema because of congestive heart failure; drug-induced edema; petit mal and
unlocalized seizures; and open-angle and secondary glaucoma. The usual dosage of
this drug ranges from 250 milligrams to 2 grams--depending on the type of condition
being treated. Actually, the dosage recommendations for glaucoma and epilepsy differ
considerably from those of congestive heart failure, since the first two conditions are not
dependent on carbonic anhydrase inhibition in the kidney which requires intermittent
dosage if it is to recover from the inhibitory effect of the therapeutic agent. The side
effects of this agent include loss of appetite, transient myopia (nearsightedness),
drowsiness, and acidosis. Acetazolamide is available in the injectable form.
e. Inhibition of Sodium Transport in the Ascending Limb of the Loop of
Henle, the Distal Tubule, and the Proximal Sites Diuretics. Diuretics of this type are
extremely potent and rapidly acting. In fact, they are used only after less potent--but
safer--diuretics have failed. As the category type states, this type of diuretic acts by
inhibiting sodium transport in the ascending limb of the loop of Henle, the distal tubule,
and in the proximal sites. Thus, a greater fraction of filtered sodium can escape
reabsorption. Thereby, increased sodium and water excretions occur. Diuretics of this
type are called "loop diuretics".
Furosemide (Lasix). Furosemide is used in the treatment of edema
(1)
associated with congestive heart failure, cirrhosis of the liver and renal disease,
pulmonary edema, and hypertension. It is particularly useful when an agent with a
greater diuretic potential than that of those commonly used is desired. This agent is
also a rapidly acting diuretic. When administered orally it acts within one hour. When
administered by injection it acts within 5-10 minutes. However, the agent does produce
massive changes in electrolyte and water balance in the body. The usual dosage of
furosemide is 20 to 80 milligrams given in a single dose--preferably in the morning.
Depending on the patient's response, this dose can be repeated, maintained, or
reduced. There are numerous adverse effects associated with the use of furosemide.
These adverse effects include hypokalemia, hyponatremia, hyperglycemia, electrolyte
depletion, and hypovolemia. Reservsible and irreversible hearing impairment and loss
may occur with any of the loop diuretics. It is often associated with rapid infusion and
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