Pharmacology for Dentistry

206 Section 4/ Drugs Acting on Cardiovascular & Urinary System

diuretic action starts within one hour and
lasts up to 4 to 6 hours. Furosemide produces
more loss of chloride than sodium, potassium
loss also occurs, which is probably an indirect
effect due to the large Na+ load reaching to
the distal tubules. In low doses, these drugs
do not appreciably effect HCO 3 – or H+
excretion.

Pharmacokinetics

All the loop diuretics are rapidly
absorbed from the GIT, usually within 30
minutes after oral, and 5 minutes after IV
administration. The bio-availability of
furosemide is about 60% while that of
bumetanide is nearly 100%. They are
extensively bound to plasma proteins, but
they are rapidly secreted by the organic acid
transport system of the proximal tubule. They
produce a peak diuresis in about 2 hours with
a total duration of diuretic action of 6 to 8
hours.

Furosemide is mainly excreted
unchanged by glomerular filtration as well
as tubular secretion.

Adverse Reactions

Abnormalities of fluid and electolyte
imbalance are the most common forms of
clinical toxicity, overdose may result in rapid
reduction of blood volume, dizziness,
orthostatic hypotension, headache,
hypokalemia.

Gastrointestinal symptoms of nausea,
vomiting, diarrhoea are common with
ethacrynic acid.

Ototoxicity has been reported with all
the three loop diuretics, which is seen more

commonly in patients with renal

insufficiency.

Therapeutic Uses

Edema: The high ceiling diuretics are

effective for the treatment of edema of

cardiac, hepatic or renal origin. They are the

drug of choice in case of congestive heart

failure. These are preferred initially in all

cases for rapid mobilization of edema fluid.

IV administration of furosemide

produces prompt relief in acute pulmonary

edema (acute left ventricular failure,

following myocardial infarction). This is due

to the vasodilator action that precedes the

saluretic action.

In the management of refractory edema,

the high ceiling diuretics may be used in

conjunction with other types of diuretics.

They are also useful for forced diuresis in

hypnotic or other poisonings.

BUMETANIDE

Bumetanide is chemically similar to

furosemide. It induces very rapid diuresis.

The site and mechanism of action is similar

to furosemide but it is 40 times more potent

than furosemide.

It is highly effective in pulmonary

edema. Adverse effects such as

hyperuricaemia, potassium loss and

ototoxicity are less than furosemide.

ETHACRYNIC ACID

Ethacrynic acid is chemically distinct

from the thiazides and furosemide but

ceiling effect is similar. It is a phenoxyacetic

acid derivative that also contains an adjacent

ketone and methylene group.