APO-ATENOL (atenolol) is a
beta-adrenergic receptor blocking agent with predominant blocking effect on
beta-receptors. It does not possess membrane stabilizing or intrinsic
sympathommetic (partial agonist) activities.
The mechanism of this
antihypertensive effect has not been established. Among the factors that may
be involved are
a) competitive ability to
antagonize catecholamine induced tachycardia at the beta-receptor sites in
the heart thus decreasing cardiac output :
b) inhibition of renin release by
c) inhibition of the vasomotor
The mechanism of the anti-anginal
effects is also uncertain. An important factor may be the reduction of
myocardial oxygen requirements by blocking catecholamine-induced increases
in heart rate, systolic blood pressure and the velocity and extent of
Approximately 50 percent of an
oral dose of atenolol is absorbed from the gastrointestinal tract the
remainder being excreted unchanged in the feces. 6 to 16 percent of atenolol
is bound to plasma protein. Maximum plasma concentrations are reached within
2-4 hours. The mean peak plasma concentrations of atenolol were
approximately 300 and 700 nanogram/mL following administration of 50 and 100
mg respectively. The plasma half-life is approximately 6-7 hours. Atenolol
is extensively distributed to extravascular tissues but only a small amount
is found in the central nervous system.
Approximately 10 percent of
atenolol is metabolized in man. About 3 percent of the material recovered in
the urine was the hydroxylated metabolite which has been shown in animal
studies to have 10 percent of the pharmacological activity of atenolol.
Approximately 47 and 53 percent of the oral dose is eliminated in the urine
and feces, respectively. Recovery is complete after 72 hours.
A comparative bioavailability
study was performed using normal human volunteers. The rate and extent of
absorption after a single oral 100 mg dose of Tenormin 100 mg or Apo-Atenol
100 mg was measured and compared. The results can be summarized as follows :
||Tenormin 100 mg
||Apo-Atenol 100 mg
|AUC 0.48 ( ng-hr/mL )
|Cmax ( ng/mL )
|Tmax ( hr )
½ ( hr )
Hypertension : APO-ATENOL
(atenolol) is indicted in patients with mild or moderate hypertension. It is
usually used in combination with other drugs, particularly a thiazide
diuretic. However, it may be tried alone as an initial agent in those
patients in whom, in the judgment of the physician. Treatment should be
started with diuretics and/or vasodilators to treat severe hypertension.
The combination of atenolol with
a diuretic or peripheral vasodilator has been found to be compatible. Limited
experience with other antihypertensive agents has not shown evidence of
incompatibility with atenolol. Therefore abrupt withdrawal of atenolol may
be followed by an exacerbation of the symptoms of hyperthyroidism, including
a) Because of its predominantly
beta-block effect APO-Atenol (atenolol) may be tried in patients with
diseases associated with bronchospasm who require beta-blocker therapy.
However, careful monitoring of such patients is mandatory and a
bronchodilator must be administered concomitantly. If initial bronchodilator
therapy is being contemplated a sympathomimetic brondilator might be
considered. in patients already on bronchodilator therapy, the dose may have
to be increased if necessary. Despite these precautions, the respiratory
status of some patients may worsen, and in such cases, atenolol should be
b) There may be increased
difficulty in treating an allergic type reaction in patients on
beta-blockers. In these patients, the reaction may be more severe due to
pharmacological effects of beta-blockers and problems with fluid-changes.
Epinephrine should be administered with caution since it may not have its
usual effects in the treatment of anaphylaxis. On the one hand, large
dosages of epinephrine may be needed to overcome the bronchospasm, while on
the other, these dosages can be associated with excessive alpha adrenergic
stimulation with consequent hypertension, reflex bradycardia and heart-block
and possible potentiation of bronchospsasm. Alternatives to the use of large
doses of epinephrine include vigorous supportive care such as fluids and the
use of beta agonists including parenteral salbutamol or isoproterenol to
overcome bronchospasm and norepinephrine to overcome hypotension.
c) Atenolol should be
administered with caution to patients subject to spontaneous hypoglycemia,
or to diabetic patients (especially those with labile diabetes) who are
receiving insulin or oral hypoglycemic agents. Beta-adrenergic blockers may
mask the premonitory signs and symptoms of acute hypoglycemia.
d) Animal Studies : Chronic
studies performed in animals have revealed the occurrence of vacuolation of
epithelial cells of Brunner's glands in the duodenum of both male and female
dogs at all tested dose levels of atenolol (starting at 15 mg/kg/day or 7.5
times the maximum recommended human dose) and an increased incidence of
atrial degeneration of hearts of male rats at 300 but not 150 mg/atenolol/kg/day
(150 and 75 times the maximum recommended human dose, respectively).
e) Appropriate laboratory tests
for monitoring renal, hepatic and hematoporetic function should be performed
at regular intervals during long-term treatment.
Atenolol is not recommended for
the emergency treatment of hypertensive crises.
Angina Pectoris: Atenolol
is indicated in the long-term management of patients with angina pectoris
due to ischemic heart disease.
APO-ATENOLOL (atenolol) should
not be used in the presence of
1. sinus bradycardia
2. second and third degree A-V
3. right ventricular failure
secondary to pulmonary hypertension
4. Congestive heart failure
5. Cardiogenic shock
6. Anesthesia with agents that
produce myocardial depression, e.g ether
7. Hypersensitivity to atenolol.