Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

DIURETICS
ability to promote sodium and thus water excretion and
in mechanism of action. The loop diuretics are the most
potent and can be used in small doses in patients with
mild to moderate heart failure and in higher doses in
patients with severe heart failure. They can be administered
orally for chronic administration or can be administered
parenterally to patients with acute, severe heart
failure. Thiazide diuretics are mildly to moderately
potent agents. They are most commonly used in conjunction
with a loop diuretic in patients with severe
CHF that have become refractory to loop diuretics
over time. Historically, the use of potassium-sparing
diuretics has been reserved for those patients that
become hypokalemic secondary to the use of other
diuretics and for patients refractory to other agents
because of an elevated plasma aldosterone concentration.
In the latter situation, potassium-sparing
diuretics are administered in conjunction with another
diuretic, usually a loop diuretic. More recently, the
potassium-sparing diuretic and aldosterone antagonist
spironolactone has been used as an inhibitor of the
renin-angiotensin-aldosterone system alone or in combination
with an ACE inhibitor. If it is used in combination
with an ACE inhibitor there is a risk of clinically
significant hyperkalemia. This is minimized if furosemide
is administered concurrently.
Adverse effects
Diuretic therapy has the potential to cause undesirable
effects, primarily electrolyte disturbances, dehydration
and prerenal and renal azotemia. The relative risks of
azotemia are heightened when they are used con -
currently with ACE inhibitors and/or nonsteroidal
anti-inflammatories (NSAIDs) and other potential renal
toxins. Diuretics may also increase the risk of digoxin
toxicity.
Electrolyte abnormalities
● Electrolyte disturbances are less common in dogs and
cats than they are in humans. However, they can
occur, especially in those canine and feline patients
that are not eating and/or drinking normally, or in
patients administered acute, high-dose therapy.
● Cats appear to be more susceptible than dogs to
becoming electrolyte depleted and dehydrated with
diuretic therapy. This may be because of a species
difference in drug effect but is more probably caused
by the fact that cats tend to stop eating and drinking
more readily when they are unwell.
● Hypokalemia is one of the more common undesirable
effects. However, two studies have documented
that the incidence of hypokalemia is low in dogs
administered furosemide chronically and who are
eating and drinking normally. Hypokalemia is always
a significant risk, even in dogs that eat, when sequential
nephron blockade is initiated with a rescue
diuretic such as hydrochlorothiazide. Dogs that are
hypokalemic and hypomagnesemic may not respond
to potassium supplementation alone.
● Hyponatremia may occur in patients on high dose
diuretic therapy. Patients with severe heart failure
may also become hyponatremic through inappropriate
antidiuretic hormone secretion and resultant
water retention. It may be impossible to distinguish
between these two causes in some heart failure
patients. No primary corrective therapy is
recommended.
● Hypomagnesemia may occur but the incidence in
dogs with heart failure receiving diuretics is very low.
In one study, there was no significant difference in
serum magnesium concentration between control
dogs and dogs with heart failure treated with diuretics
± digoxin. In another study of 113 dogs with
heart failure, only four had a low serum magnesium
concentration. Hypomagnesemia may accompany
hypokalemia. Dogs that are hypokalemic and hypomagnesemic
may not respond to potassium supplementation
alone.
Note: electrolyte abnormalities can be profound when
sequential nephron blockade is employed. Potassium
supplementation may help with normalization of potassium
concentrations. Hypochloremia and hyponatremia
should not be corrected via supplementation of parenteral
fluids.
Dehydration and prerenal azotemia
Subclinical hypovolemia (dehydration) is probably
common in patients with severe heart failure that require
maximum doses of diuretics to treat their heart failure.
At times patients can become clinically dehydrated and,
in some, prerenal azotemia will be present. If the patient
is clinically affected (e.g. not eating), the diuretic dose
must be reduced or discontinued temporarily and in
some cases judicious intravenous fluid therapy must be
employed. However, in patients that are not clinically
affected by their dehydration and azotemia, the prerenal
azotemia can be safely ignored as long as it is not severe
or obviously progressive on serial analysis (e.g. urea