Atenolol in Hypertension: A Cardioselective Drug

Atenolol

in

Hypertension:

Card ioselective

A

Drug* D. Ezra,

M.D.;f

M. Moiho,

M.D.4

and

T.

M.D.

Rosenthal,

The efficacy of atenolol given once daily was assessed in 41 otherwise healthy hypertensive patients over a period of six months. Twelve patients whose blood pressure was not well-controlled on methyldopa and chiorthalidone and 11 patients who were treated previously with other beta-blockers all benefited from atenolol which appeared to be effective and well-toler-

tenolol ing

(Teriormin)

cardioselective given

is a new

(Fig

compound

fl-blocker,

once

daily.

Animal

which

rier.4

shown

that

possesses

Theoretically,

it

in the that

it is no

a specific

intrinsic

minutes

thus

seems

to

offer

certain

treatment of hypertension. some investigators gave

In light atenolol

function

during

efout of to

achieved

the nuclear

performed

Plasma

and

11

were

taking

p-blockers,

Following ingestion of placebo ment with atenolol was begun daily. The maintenance dose the

response

clinical two-week ways *

taken

From

the

Medical tlnstructor.

Head

adjusted

by

the

Chaim

upwards was

Blood

pressure

Sheba

physician Medical

School, Tel-Hashomer, professor. received

at

the

renin at

in the

the

and

beginning

function, blood

at

was

and

taking

renal

and

(PRA)

during before

white

beginning,

activity

the

at

anti-

cell

counts

three-month

measured the

end

or

twice

could be drug in the

morning

for

red

taken

This

inter-

radio-

by

blood

of

the

study.

order

to

samples

estimate

excretion

was

of

the

the

quantity

during

the

study.

Blood

of sodium

Each

examined.

period,

run-in

of urine collections. of the subjects,

samples 3 women

in

patient for and

the

body,

sodium

collected

and PRA

again, were

27 men,

24-hour towards the taken on the

were

selected

OH :H2CHCH2

NHCH(CH3)2

propranolol.

alone for three weeks, treatat an initial dose of 100 mg was determined according to

patients same

always

determinations

examination and

was

period. taking

pressure

came

Thirty

mostly

standing,

were collected at the same time of day (8 to 11 AM) after a period of one hour’s rest in the supine position, and then, after walking for three hours. No attempt was made to control their dietary salt intake, but in All

or

assessed

downwards.

The

at one-,

and

measurements at

each

Center,

visit Tel-Aviv

later,

were after

at

alleast

University

Israel.

CH2CONH2

of Laboratory.

§Associate Manuscript

662

and

status of the intervals.

blood

(ANF)

immunoassay

pressure

a 24-hour who were

patients

factor

were

Forty-one hypertensive patients were studied (35 men and 6 women), with an average age of 39 years. Informed consent was obtained from each patient, and the study was approved by the hospital’s Helsinki Committee. Eighteen subjects were new hypertensive patients with no previous treatment; 12 had been treated previously with methyldopa and chiorthalidone and were referred to our study because of poor response;

for

Routine

vals.

days

METHODS

ANI)

drug.

blood

patients

came

Other

day.

end

PATIENTS

2 minutes

and

(lying),

in

and

specimens

treatment.

rest

the

their

bar-

at

same arm. In most of the patients, even three times during from

evening

sym-

twice daily5 and the known bronchoconstrictor fect of $-blockers, the present study was carried in order to learn the effect of one daily dose atenolol on hypertension, with special attention respiratory

a

when

effects, has no membrane-stabilizdoes not cross the blood-brain

and

advantages of the fact

effective

is

five

to be

easily

have

of ni-receptors,

pathomimetic ing effect,

block-

-adrenergic

It is considered

1

studies

inhibitor

1).

ated. Ten patients complained of fatigue not necessarily related to a drop in blood pressure, and two of headache. Respiratory functions were assessed in a double blind trial on 30 patients. No significant changes in any of the expiratory flow rates were recorded after three months of continuous treatment with atenolol in either smokers or nonsmokers.

May

18; revision

EZRA, MOLHO, ROSENTHAL

accepted

July

31.

FZCURE

1. Structural

formula

of atenolol.

CHEST, 77: 5, MAY, 1980

for a comparison of the effects of atenolol and placebo on expiratory flow rates. These patients had no bronchopulmonary disease in the past and were free of respiratory symptoms at the time of the trial. They were divided into nonsmokers (NS), 19 patients, and smokers (S), 11. Patients recorded a forced expiration before and lii hours after oral administration of 100 mg of atenolol or placebo during the two

days

least

of treatment.

three

forced

tory

times,

vital

The the

(FEY),

best

50 percent

and 25 percent

After

three

months

these

factors

All saturation.

The

those those

and

t-test.

(X ±

(V5() and

administration

of the

in the

decrease

between

at

results rate

went

minute

drug,

atenolol.

for

pressure

FVC

the

and

and

VC

sure

were

for V50 and

done

are

using

expressed

and significance

the

student

as mean

paired

±

standard

dosages

RESULTS

and

was

diastolic

atenolol. 163.8

(±

blood Mean

mm

15.8)

pressure

a meaningful pressure

systolic

Hg

(SD

15.4)

atenolol down

a, I

in both

during

pressure

±

taking went

decrease

from

treatment went

taking

(Fig

down

placebo

2). Mean

102.7

systolic

mm

Hg

of

drug

was

of

was

in

two

with from

did

show

month

diastolic

mal,

and

ANF

(±

22 patients

in

7.2)

period

the

was whom

month Pulse

beats per receiving

while

blood and

of the

pres-

8 patients

drug.

These

controlled to the

by

study.

good,

and

the study. uric acid

changes of

sixth occur.

although

ten

fatigue and two of severe 44 to 46 beats per minute,

patients,

be withdrawn from for urea, creatinine,

and

5.07)

50 mg

week.

throughout between the

satisfactorily prior

Bradycardia,

not

fourth

daily,

drugs

the

not

4.02)

of other the

taking

satisfactory

on only

complained

to 144.3

(± (±

atenolol

been

headache. noted

did

exhibited

not

Tolerance

(P).

the

third,

88.92

100 mg

be managed

high

7.9)

of this reduction with a very small

and

first,

to 65.95

with had

the

from

patients

patients

There

down

levels

patients

(±

hypotension

on placebo

could

V25,

after

Orthostatic

V,5).

Hg

second

the

achieved

period.

mm

greatest part first two weeks,

no further significant change No difference was observed

Sixteen

temperature,

et aI,6

was

Values

SD)

capacity

body

values

by Morris by Bass.7 analysis

unpaired

recorded

to 86.5

3). The

occurred

as before.

to

predicted

statistical

deviation

again

corrected

recommended recommended

The

of vital

measured

were

was

(Fig

There was the study.

curve

of continuous

were

values

expiration

placebo

drug

was used to measure the (FVC), the one-second forced expiraand the maximal expiratory flow rates at

and

capacity

volume

forced

taking

one

of them

throughout study.

Blood

negative

had

to

Blood investigations and electrolyte levels

in all.

PRA was

the

entire

six-

counts

were

nor-

Eighteen

examined

out showed

of a

200

E

190

E

180

170

I a.

140 130

C 0

th

120

0

110

a.

UI >..

100

U.’

1001U

Systolic BP. on FIGURE

CHEST,

2. Systolic

77: 5, MAY, 1980

blood

pressure

levels

mm

placebo during

administration

of placebo

and

treatment

Hg period.

ATENOLOLIN HYPERTENSION 663

a,

125

I

E E

120 115 110

105

I

100 95

C 0i

E

90

85 a.: a)

80

0 a. UI 0

75

a

70 70

75

80

85

90

BR

on

pLacebo

DiastoLic FIGURE

decrease There

was

during no

3. Diastolic

treatment, correlation

blood

and 3 showed between the

effect of atenolol and the change selected group of 30 patients, the

FVC,

FEy1,

limits

in the

In

the

and

during

in PRA. In basic values

however,

was

found

Table

1-Values

a mild (Table

reduction 1).

Be/ore

No

the

of

of

V50

significant

1)5

both ences the

110

115

of placebo

administration

changes months

no change. hypotensive

V50, and V25 were within predicted NS group at the beginning of the study.

S group, V25

levels

pressure

1)0

and

(Table between

beginning

of

125

mm

Hg

treatment

in these factors of continuous groups found

120

period.

were treatment

2), nor placebo the

recorded with

were and

after three atenolol in

significant atenolol

treatment

(Table

differvalues at 3),

or

be-

tween control values after three months continuous treatment with atenolol and those obtained after additional

tablet

of the

drug

(Table

an

4).

Treatment

DIscussIoN

Nonsmokers

1,

X SD

I

Smokers

X SD

FVC

FEY,

J5O

\2b

100.4 9.8

102.8 11.9

92.5 21.7

94.9 35.1

100.8 8.8

980 11.6

75.6 19.1

83.1 20.1

The was other Table

Table and

2-Differences Values Three

Between Months

X Nonsmokers

Smokers

SD P

X SD P

Values After

Treatment,

Before

Continuous

drug

degree

in of

\T,4,

Vu

-0.9 5.9 NS

-1.9 6.6 NS

-3.4 33.0 NS

-4.6 25.0 NS

Nonsmokers

-1.7 5.5 NS

0.2 6.0

-1.0 14.5 NS

-8.4 16.5 NS

Smokers

the

hypertension

by high doses of blood pressure levels

Changes of

against

whose

controlled reduced

as Percent

Treatment

effective

Patients

3-Differences

Atenolol,

FEy,

664 EZRA, MOLHO, ROSENTHAL

to be very

not satisfactorily drugs exhibited

FVC

NS

appeared

of hypertension.

Between

Predicted

Placebo at

the

and

Onset

Treatment \T

FVC

FEy1

,Tu

P

-2.0 3.0 NS

-1.9 5.8 NS

3.0 16.2 NS

-4.4 25.2 NS

X

-1.5

-1.9 6.3 NS

-13.4 15.7 NS

-11.8 23.7 NS

X SD

SD P

3.6 NS

CHEST, 77: 5, MAY, 1980

Table

4-Differences

Between

Continuous

Months

Obtained

After

Nonsmokers

for

atenolol. these

An

9.1 11.4

-0.2 8.2

NS

NS

NS

NS

3.2 3.2

1.4 2.7

-4.6 12.4

7.7 12.3

NS

NS

NS

NS

required

large

of their

as well

blood

made

by

compliance of hypertension,

drug

maximizes

the

doses

drug

of

is that

by a single

dose, and

is a major problem a single daily dose likelihood

of

success

of

treatment. Side were

effects no

were

rarely

complaints

of

often seen with other Depression, which

encountered,

and

sleeplessness

or

fl-blockers. was observed

noted, smokers. period

was in

no of

any

This and

was after

significant the true

test both

long-term

there

results have with chronic

77: 5, MAY, 1980

use be

of even consid-

patients. The criticism

authors wish to thank of the manuscript.

Dr.

C.

in hypertension.

Postgrad

JD, et al: A new type of cardioselective adrenoceptive blocking drug. Br J Pharmacol 1973; 48:340 5 Zacharias FJ, Cowen KJ, Cuthbertson PJR, et al: Atenolol in hypertension: a study of long-term therapy. Postgrad Med J 1977; 53( suppl 3): 102-110 F, Koski A, Johnson

healthy

nonsmoking

adults.

LC: Am

Spirometric Rev

standards

Respir

Dis

for 1971;

103:57-67

prior

to the

7

study did three

bronchoconstriction subjects, in the

including early

administration

the of

been obtained bronchitis

by and

others asthma,84’

Bass

H:

The

abnormalities

Chest 8

Benson

flow in

1973; MK,

valume

chronic

loop:

normal

obstructive

standards

pulmonary

and diseases.

63:171 Berrill

and noncardioselective tive airways disease. 3) : 143-148

\VT,

Sterling

beta-blockers Postgrad Med

GM:

Cardioselective

in reverse J 1977;

obstruc53(suppl

9 Perks

treatment the in

and these, together with our observations, confirm the cardioselective character of this drug. Some patients, however, with hyperreactive airways can re-

CHEST,

in these

once and twice daily atenolol Med J 1977; 53-679-682 4 Barrett AM, Carter J, Fitzgerald

6 Morris

drug. Similar patients

as risky

the must

and

fl-blockers

AP, Cruikshank JM: Once-daily dosing with mild or moderate hypertension. Br Med J 1976; 1:990-991 2 Harris AM, Woolard Ky, Tweed JA: A study of once daily Tenormin (atenolol) in hypertension: some implications in patient compliance. Intern Med Res 1976; 4:347351 3 Castleden CM, Dathan JRE, George CF: A comparison ol

nightmares

in two patients, and cold extremities in another, not occur during treatment with atenolol. All had been previously treated with propranolol. There

manner,

cardioselective

1 Douglas-Jones

of

Douglas-Jones

Since

most

ACKNOWLEDGMENT: L. Baum, for constructive

could

smaller of the

in an unpredictable

REFERENCES

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confirming

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act the ered

1.1 3.6

additional

results

Drug

3.7 8.7

control

just

of

Vu

Patients

propranolol

Tablet

Those

V50

SD P

be controlled

Three and

FEY,

X

atenolol.

After

Atenolol

FVC

SD P

Smokers

With

Additional

X

on

Values

Treatment

WH, Chatterjee SS, Croxson RS, et al: Comparison of atenolol and oxprenolol in patients with angina or hypertension and co-existent chronic airways obstruction. Br J Clin Pharmacol 1978; 5:101-106 10 Boye NP, Vale JR: Effect in bronchial asthma of a new beta-adrenergic blocking drug-atenolol (ICI 66082). Europ J Clin Pharmacol 1977; 11:11-14 11 Vilsvilc JS, Schaanning J: Effect of atenolol on cardiac and ventilatory function in patients with chronic asthma. Br Med J 1976; 2:453

ATENOLOLIN HYPERTENSION 665