Pharmacology for Dentistry

Antihypertensive Agents 181

enalaprilat – a highly specific, long acting,
non-sulphydryl angiotensin converting
enzyme (ACE) inhibitor.

It is indicated in all grades of essential
hypertension and renovascular hyperten-
sion where standard therapy is ineffective
or inappropriate because of adverse effects
and in congestive heart failure. It should be
used as an adjunctive therapy with digitalis
and/or diuretics.

Enalapril is well tolerated in most
patients. The most common side effects
include dizziness, headache, nausea,
diarrhoea, fatigue, muscle cramps, rash and
cough. Other side effects are angioneurotic
edema, hypotension, urticaria which are rare.

LISINOPRIL

It is lysine derivative of enalaprilat.
Mechanism of action is same as other ACE
inhibitors. After oral administration it is
absorbed incompletely and slowly.

Adverse effects include dizziness,
cough, hyperkalemia, headache, hypoten-
sion and angioedema.

RAMIPRIL

Ramipril is a long acting ACE inhibitor
and is converted to active metabolite –
ramiprilat.

Ramipril in patients with mild to mod-
erate hypertension results in a reduction of
both supine and standing blood pressure.
In patients of acute myocardial infarction
with CHF, ramipril reduced total mortality,
progression of heart failure and CHF-related
hospitalizations.

ANGIOTENSIN ANTAGONISTS

LOSARTAN

Angiotensin II is a potent vasoconstrictor,

stimulant of aldosterone secretion and an

important component in the pathophysiol-

ogy of hypertension. Both losartan and its

principal active carboxylic acid metabolite.

(10-40 times more potent than losartan)

block the vasoconstrictor and aldosterone

secreting effects of angiotensin II by selec-

tively blocking the binding of angiotensin

II to the AT 1 receptor found in many tis-

sues (e.g. vascular smooth muscle, adrenals).

Losartan does not inhibit ACE (kininase II),

the enzyme that converts angiotensin I to

angiotensin II and degrades bradykinin.

Losartan potassium is well tolerated.

Bioavailability is 33% due to hepatic first

pass metabolism. It is 98% plasma protein

bound. It is activated in liver. Both parent

compound and active compound are

excreted in urine.

Adverse effects seen most often are

dizziness or light-headedness and rash.

Angioedema (involving swelling of face, lips

and/or tongue) have been rarely reported.

There is also headache, asthenia, fatigue and

dizziness.

IRBESARTAN

It is a specific antagonist of AT 1

receptors with a much greater affinity (more

that 8,500 fold) for the AT 1 receptor than for

the AT 2 receptor and no agonist activity.

Irbesartan is an orally active agent that

does not require biotransformation into an

active form. It is rapidly absorbed from the