Journal of Toxicology: Clinical Toxicology

ISSN: 0731-3810 (Print) (Online) Journal homepage: http://www.tandfonline.com/loi/ictx19

Cerebral Infarction Associated with Oral Verapamil
Overdose
Nemer Samniah M.D. & Francise Schlaeffer M.D.
To cite this article: Nemer Samniah M.D. & Francise Schlaeffer M.D. (1988) Cerebral Infarction
Associated with Oral Verapamil Overdose, Journal of Toxicology: Clinical Toxicology, 26:5-6,
365-369, DOI: 10.1080/15563658809167100
To link to this article: http://dx.doi.org/10.1080/15563658809167100

Published online: 31 Jan 2011.

Submit your article to this journal

Article views: 8

View related articles

Citing articles: 1 View citing articles

Full Terms & Conditions of access and use can be found at
http://www.tandfonline.com/action/journalInformation?journalCode=ictx19
Download by: [McMaster University]

Date: 16 March 2016, At: 23:45

CLINICAL TOXICOLOGY, 2 6 ( 5 & 6 ) ,

365-369 (1988)

Downloaded by [McMaster University] at 23:45 16 March 2016

CEREBRAL INFARCTION ASSOCIATED WITH ORAL VERAPAMIL OVERDOSE

Nemer Samniah, M.D. and F r a n c i s c S c h l a e f f e r , M.D.
Department o f I n t e r n a l Medicine " A " ,
Soroka U n i v e r s i t y H o s p i t a l and F a c u l t y o f H e a l t h S c i e n c e s ,
Ben-Gurion U n i v e r s i t y o f t h e Negev,
Beer-Sheva 84101, I s r a e l

ABSTRACT

Verapamil i s a w i d e l y used c a l c i u m c h a n n e l b l o c k e r .
Side e f f e c t s
w i t h o r a l u s e a r e u s u a l l y m i l d , however, major hemodynamic c o m p l i c a t i o n s and d e a t h c a n o c c u r i f t h e d r u g i s g i v e n i n o v e r d o s e . We d e s c r i b e
a case of cerebral i n f a r c t i o n associated with attempted s u i c i d e with
v e r a p a m i l o v e r d o s e , t h e f i r s t r e p o r t e d t o o u r knowledge.

INTRODUCTION

Verapamil

is a

s y n t h e t i c d r u g r e l a t e d t o p a p a v e r i n , which h a s

c o r o n a r y d i l a t o r , a n t i a r r h y t h m i c and a n t i h y p e r t e n s i v e p r o p e r t i e s (1).
The d r u g a c t s on c e l l u l a r membrane p e r m e a b i l i t y b y b l o c k i n g c a l c i u m
i o n i n f l u x and t o some e x t e n t , sodium i o n i n f l u x ( 2 ) .
S e r i o u s s i d e e f f e c t s have been r e p o r t e d a f t e r i n t r a v e n o u s u s e

(7). S e v e r a l c a s e s o f o r a l o v e r d o s e have been d e s c r i b e d i n t h e E n g l i s h
l i t e r a t u r e (4-18).

Only two c a s e s o f n e u r o l o g i c a l s i d e e f f e c t s due t o

verapamil overdose are reported ( 5 , l l ) .
We p r e s e n t a c a s e o f permanent f o c a l b r a i n damage a f t e r a t t e m p t e d
s u i c i d e with verapamil.

365

SAMNIAH AND SCHLAEFFER

3 66
Case R e p o r t

woman was a d m i t t e d t o t h e e m e rge nc y room a f t e r a

A 39-year-old

s u i c i d e attempt.

She had i n g e s t e d 2280 mg o f v e r a p a m i l ,

1 2 0 mg o f

p r o p r a n o l o l an d 400 mg o f o p i p r a m o l .
On a d m i s s i o n , t h e p a t i e n t was i n a d e e p s t u p o r , p e r i p h e r a l p u l s e s
The h e a r t r a t e

were n o t p a l p a b l e and b l o o d p r e s s u r e was u n d e t e c t a b l e .

Downloaded by [McMaster University] at 23:45 16 March 2016

was

55-60

per

minute

on

monitor

and

electrocardiogram

showed

AV

d i s s o c i a t i o n and n o d a l r h y t h m w i t h r e t r o g r a d e P wave.
I n t r a v e n o u s a t r o p i n and n o r mal s a l i n e were s t a r t e d a nd t h e b l o o d
p r e s s u r e r a i s e d t o 8 0 / 5 0 mmHg.

The p a t i e n t was t r a n s f e r r e d t o t h e

I n t e n s i v e Coronary Care Unit.

On p h y s i c a l e x a m i n a t i o n :

w e r e c l e a r , h e a r t s o u n d s w e r e n o r m a l , w i t h o u t murmurs.
was c o n s c i o u s ,

t h e lungs
The p a t i e n t

r e s p o n d i n g t o h e r name, a nd no n e u r o l o g i c a l d e f i c i t s

were s e e n .

S e v e r a l h o u r s l a t e r , b l o o d p r e s s u r e a nd h e a r t r a t e f e l l ;

intravenous

i s o p r o t e r e n o l was i m m e d i a t e l y s t a r t e d a nd v i t a l s i g n s

r e t u r n e d t o normal.
left

hemiparesis

tempero-

parietal

angiography.

On t h e n e x t d a y , r o u t i n e e x a m i n a t i o n i d e n t i f i e d

and

48

hours

infarction.

later,
The

brain

patient

CT

scan

refused

E c h o c a r d i o g r a m showed norm a l h e a r t

showed

right

carotid

artery

contraction without

a n y s i g n o f t h r o mb u s .
L a b o r a t o r y f i n d i n g s wer e a s f o l l o w s :
b l o o d c e l l c o u n t = 13800 c m " m ;
creatinine

glucose

- 1 . 2 mgg; Na - 1 3 8 mEq/L;

K

Hemoglobin 17

- 171 mgg;

urea

8 , white

- 3.6 mgg;

- 47 mEq/L; pH - 7 . 3 6 ; Pa02 -

75 mm Hg; PaC02 - 38 mHg ; H2C02 - 22 mEq/L.
T h r e e mo n t h s l a t e r , o n r o u t i n e f o l l o w u p , m i l d r i g h t h e m i p a r e s i s
was s t i l l f o u n d .

CEREBRAL INFARCTION AND ORAL VERAPAMIL OVERDOSE

367

DISCUSSION
Verapamil h a s been used s u c c e s s f u l l y f o r o v e r 25 y e a r s a s a n
anti-anginal,

a n t i a r r h y t h m i c and a n t i h y p e r t e n s i v e a g e n t .

Oral u s e may

c a u s e o c c a s i o n a l l y moderate s i d e e f f e c t s such a s headache, d i z z i n e s s ,
c o n s t i p a t i o n , f l u s h i n g r a s h , p e r i t i b i a l edema, f i r s t and second d e g r e e
A V b l o c k and h y p o t e n s i o n

(3).

I n t r a v e n o u s u s e can b e a s s o c i a t e d w i t h

Downloaded by [McMaster University] at 23:45 16 March 2016

t r a n s i e n t s e v e r e h y p o t e n s i o n , e x a g g e r a t e d b r a d y c a r d i a o r even a s y s t o l e

(3).

Seventeen c a s e s of o r a l v e r a p a m i l overdose were r e p o r t e d i n t h e

English

literature.

Doses

ranged

from

0.8-9.6

g.

The

observed

e f f e c t s o f t h e s e i n t o x i c a t i o n s were e x t e n s i o n s of t h e d r u g ' s pharmacol o g i c a c t i v i t y i n c l u d i n g s e v e r e h y p o t e n s i o n , b r a d y c a r d i a , AV d i s s o c iation
Altered

and

complete AV-block,

mental

peripheral

status

and

s i n u s a r r e s t and a s y s t o l e ( 4 , 6 - 1 8 ) .
metabolic

acidosis

p e r f u s i o n s were a l s o noted

(5,6,9-11).

due

to

decreased

Three c a s e s were

f a t a l i n s p i t e o f t r e a t m e n t w i t h calcium and i s o p r o t e r e n o l

(8,9,12).

One p a t i e n t was l e f t w i t h s e v e r e d i f f u s e a n o x i c b r a i n damage due t o
prolonged h y p o p e r f u s i o n and m e t a b o l i c a c i d o s i s b e f o r e i n s t i t u t i o n of
t h e r a p y (11).
Our p a t i e n t i n g e s t e d 2880 mg o f v e r a p a m i l and showed hemodynamic
changes s i m i l a r t o t h o s e r e p o r t e d i n t h e l i t e r a t u r e i n such c a s e s .
I n a d d i t i o n , s h e developed c e r e b r a l i n f a r c t i o n .
t h e r e a r e no

reported

v e r a p a m i l overdose.

cases of

To o u r knowledge

such c o m p l i c a t i o n a s

a

result

of

Two c a s e s of b r a i n damage were d e s c r i b e d ,

the

f i r s t had d i f f u s e d c e r e b r a l a n o x i c damage, s e c o n d a r y t o s e v e r e prolonged

hypoperfusion

(11).

The

second

is

a

c h i l d with

s e i z u r e s (5), b u t no f o c a l b r a i n damage was d e s c r i b e d .

transient

SAMNIAH A N D SCHLAEFFER

368

I n o u r p a t i e n t , t h e c e r e b r a l i n f a r c t i o n was p r o b a b l y s e c o n d a r y t o
s e v e r e h y p o t e n s i o n caused by v e r a p a m i l o v e r d o s e . P r o p r a n o l o l i n g e s t e d
i n a low d o s e (120 mg) c o u l d n o t have s u c h e x a g g e r a t e d e f f e c t s e e n i n
t h e case under discussion.

Opipramol i s a t r i c y c l i c a n t i d e p r e s s a n t .

I t i s g i v e n i n d o s e s o f 150-300 mg d a i l y i n d i v i d e d d o s e s o r w i t h t h e
major p a r t given a t night.

Of

18 r e p o r t e d i n s t a n c e s o f overdosage

Downloaded by [McMaster University] at 23:45 16 March 2016

w i t h o p i p r a m o l , s i x had been f a t a l and f o u r o f t h e s e a t t r i b u t e d t o
sudden c a r d i a c a r r e s t . Hypotension was n o t d e s c r i b e d a s a s i d e e f f e c t
(19,20).

Our p a t i e n t

t h e r a p e u t i c regimen.

i n g e s t e d 400 mg which i s v e r y c l o s e t o t h e
We suppo s e t h a t t h i s d i d n o t p l a y any r o l e i n

t h e hypotension t h e p a t i e n t s u f f e r e d .
r e f u s e d c a r o t i d angiography.
pathology

did

not

As mentioned a b o v e , t h e p a t i e n t

We c a n n o t be s u r e t h a t any p r e e x i s t e n t

contribute

to

the

focal

damage

although

the

serious

irreversible

p a t i e n t ' s young a g e makes t h i s u n l i k e l y .
In

conclusion,

this

patient

exhibited

a

c o m p l i c a t i o n o f o r a l v e r a p a m i l overdose.

REFERENCES
1.

L. Schamroth, D.M. K r i k l e r , and C . G a r r e t , Immediate e f f e c t s o f
B r . Med. J . , 1,
i n t r a v e n o u s veraparnil i n c a r d i a c a r r h y t h m i a ,
660-662 ( 1 9 7 2 ) .

2.

B . N . S i n g h . J . T . C o l l e t , and C . Y . C . Chew, New p
- e r s -p e c t i v e s i n t h e
pharmacologic t h e r a p y o f c a r d i a c a r r h y t h m i a s ,
Prog. C a r d i o v a s c .
D i s . , 22, 247-301 ( 1 9 8 0 ) .

3.

P. Needleman, P. Corn, and
Johnson, Calcium "Channel b l o c k e r s "
i n t h e Goodman & G i l m a n ' s - The P h a r m a c o l o g i c a l b a s i s o f t h e r a p e u t i c s . S e v e n t h e d i t i o n - MacMillan 1985, p. 816.

4.

J. C a u d e l l , V. V a l l e , M.
with verapamil, Chest,

2,200-201 ( 1 9 7 9 ) .

5.

D.B. P a s s a d , and F.H.

Crespin,

-

infant,

I

Pediatrics,

S o l e r , and J. R i u s ,

Jr.,

Acute i n t o x i c a t i o n

Verapamil p o i s o n i n g i n a n

3, 543-545 (1984).

CEREBRAL INFARCTION AND ORAL VERAPAMIL OVERDOSE

6.

369

I. Moroni, P.T. M a n n a i o n i , A . D o l a r a , and M. C i a c c h o r i , Calcium
g l u c o n a t e and h y p e r t o n i c sodium c h l o r i d e i n a c a s e o f m a s s i v e
verapamil poisoning, C l i n i c a l Toxicology,
395-400 (1980).

17,

7.

O r l a n d o A n t o n i o Da S i l v a , Riamundo A n t o n i o De Melo,
Pedro Jorge F i l h a ,
Verapamil a c u t e s e l f - p o i s o n i n g ,
Toxicology,
361-367 (1979).

14,

and J o s e
Clinical

8.

H.P. G e l b k e , H.J. S c h l i c h t , and G. S c h m i d t , F a t a l p o i s o n i n g w i t h
v e r a p a m i l , Arch. T o x i c o l , 37, 89-94 (1977).

9.

G.M. Orr, H . J . Bordansky, D.S. Dymond, a n d M.
Taylor,
v e r a p a m i l o v e r d o s e . L a n c e t , 11, 1218-1219 (1982).

Fatal

Downloaded by [McMaster University] at 23:45 16 March 2016

~L

Perkins,
Serious verapamil poisoning:
10. C.M.
i n t r a v e n o u s c a l c i u m g l u c o n a t e , B r . Med. J . ,

Treatment w i t h
c,1127
(1978).

11.

B . J . Crump, D.W.
venous calcium

H o l t , a n d J . A . V a l e , Lack o f r e s p o n s e t o i n t r a i n s e v e r e verapamil poisoning,
L a n c e t , 11,
~L

979-940 (1982).
12.

J . Van d e r Meer, and E. Ver Der W a l l , F a t a l a c u t e i n t o x i c a t i o n
with verapamil,
Neth. J. Med.,
130-132 (1982).

13.

P. Immonen, A . L i n k o l a , and E. Waris,
Three c a s e s o f s e v e r e
I n t . J. C a r d i o l . , 1,101-105 (1981).
verapamil poisoning,

26,

Bharadwaj, R.K.
S h u k l a , M . Ahmad, and S.P.
- MS.C.a t h u rJ,a iSne,v eR.P.S.
r e h y p o t e n s i o n and b r a d y c a r d i a a f t e r s u i c i d a l con-

14

s u m p t i o n o f 100 t a b l e t s of v e r a p a m i l : a c a s e r e p o r t , I n d i a n H e a r t

J., 34, 175-176 (1982).
15 *

L . Woie, and L. S t o r s t e i n ,
Successful treatment of s u i c i d a l
verapamil poisoning with calcium gluconate,
Eur. H e a r t J . , 2,

239-242 (1982)*

16. U. d e J a i r e , and T. Lundman, Attempted s u i c i d e w i t h v e r a p a m i l ,
Eur. J. C a r d i o l . , 6, 195-198 (1977).

17.

J . J. E n y e a r t , W . A . P r i c e , D . A . Hoffman, and L. Woods,
Profound
h y p e r g l y c e m i a and m e t a b o l i c a c i d o s i s a f t e r v e r a p a m i l o v e r d o s e ,
J. Am. C o l l . C a r d i o l . , 2, 1228-1231 (1983).

18.

M. C h i m i e n t i , M. P r e v i t a l i , A . M e d i c i , and M . P i c c i n i n i , Acute
verapamil poisoning: successful treatment with epinephrine, Clin.
C a r d i o l . , 5, 219-222 (1982).

19. J . E . F .

R e y n o l d s , M a r t i n d a l e The e x t r a p h a r m a c o p o e i a . Twentye i g h t h e d i t i o n . The P h a r m a c e u t i c a l P r e s s , London 1982, p 128.

20.

C.A. Fuge, Treatment o f poisoning by a n t i d e p r e s s a n t drugs.
Med. J. 4, 108 (1967).

Br.