C'est une malade de 62 ans, arthrosique chez
qui une HTA s'est développée
à la suite de la prise
d'anti-inflammatoires. Ils ont été
supprimés depuis deux ans.
Une polythérapie s'est
avérée nécessaire pour
maitriser l'HTA:
Amlodipine (une dihydropyridine), un
beta-bloqueur (bisoprolol) et diurétique(
thyazide)
Lors du bilan de l' HTA, un scanner du
cerveau fut pratiquéne, ne montrant
aucune anomalie.
Après un an de traitement,
apparurent des crises de
bâillements accompagnées de
douleurs rétrosternales, chaleurs
céphaliques et lourdeur des bras à
la suite d'efforts modérés. Ces
crises pouvaient durer une dizaine d'heures,
sans horaire d'apparition particulier.
Lors d'une crise matinale plus importante,
un voisin lui donna de la trinitrine
(nitoglycérine) par voie
sublinguale.
Une bouffée fit disparaitre tous les
symtpômes en 30 secondes. Le cardiologue
consulté n'a mis en évidence
aucune lésion des artères
coronaires.
Sur suggestion du cardiologue le bisoprolol
a été cessé et l'Amlodipine
a été augmentée. Depuis 2
mois, les crises sont plus fréquentes
mais soulagées par la trinitrine. La
moitié des crises surviennent le matin au
lever lorsque la patiente bouge ses bras et sa
tête. Les autres apparissent en fin
d'après-midi ou en soirée sans
douleur rétrosternale. Y aurait-il une
"angine" du tronc cérébral qui
provoquerait ceci?
Dr M. G.
Réponse:
je pense d'abord à un effet
iatrogène de l'amlodipine. Toutes les
dihydropyridines peuvent interagir avec la
dopamine et l'oxytocine au niveau du noyau pvn
de l'hypoyhalamus.
je conseillerais l'arrêt de
l'amlodipine et son remplacement par de
l'enalapril
en quelques jours les bâillements
induits disparaitront... je pense. OW.
Le bésylate d'amlodipine est un
antagoniste du calcium à longue action
utilisé comme antihypertenseur et pour le
traitement de l'angine de poitrine. Son nom
systématique est (R.S.)
3-éthyl-5-méthyl-2-(
2-aminoéthoxyméthyl )-4-(
2-chlorophényl
)-1,4-dihydro-6-méthyl-3,5-pyridinedicarboxylate
benzènesulfonate et sa formule chimique
est C20H25ClN2O5.C6H6O3S.
Références :
1°) Argiolas,
A., M. R. Melis, et al. (1990).
"Oxytocin-induced penile erection and yawning:
role of calcium and prostaglandins." Pharmacol
Biochem Behav 35(3): 601-5.
The effect of verapamil, flunarizine,
nimodipine, nicardipine, and nifedipine, calcium
channel inhibitors, and of indomethacin and
aspirin, inhibitors of prostaglandin synthesis,
on penile erection and yawning induced by
oxytocin was studied in male rats. All calcium
channel inhibitors given intraperitoneally (IP)
60 min before the intracerebroventricular (ICV)
injection of oxytocin (30 ng) prevented in a
dose-dependent manner oxytocin effect.
Nimodipine and nicardipine were the most
effective being active at doses between 5 and 20
mg/kg, while the others were active at doses
higher than 15 mg/kg. Prevention of oxytocin
effect was also seen after ICV injection of the
above compounds. Unlike calcium channel
inhibitors, indomethacin given either IP (10 and
50 mg/kg) or ICV (50 micrograms), or aspirin
(100 mg/kg IP) were ineffective. Microinjection
of calcium, but not of prostaglandin E2 and
prostaglandin F2 alpha in the paraventricular
nucleus of the hypothalamus, the brain area most
sensitive for the induction of the above
behavioral responses by oxytocin, induced a
symptomatology similar to that induced by
oxytocin. The present results suggest that
calcium might be the second messenger which
mediates the expression of penile erection and
yawning induced by oxytocin.
2°) Bourson,
A. and P. C. Moser (1990). "Yawning induced
by apomorphine, physostigmine or pilocarpine is
potentiated by dihydropyridine calcium channel
blockers." Psychopharmacology (Berl) 100(2):
168-72.
Previous studies have shown that
dihydropyridine (DHP) calcium channel blockers
can potentiate yawning induced by apomorphine in
rats. The present study was undertaken to
examine whether or not this interaction was seen
with other compounds that induce yawning or if
it represented a specific interaction with
dopaminergic mechanisms. Yawning induced by
apomorphine (40 micrograms/kg SC), physostigmine
(50 micrograms/kg SC) or pilocarpine (1 mg/kg
SC) was dose-dependently potentiated by the DHP
calcium channel blocker nifedipine (1.25-10
mg/kg IP). Nimodipine (1.25-5 mg/kg IP) and
nitrendipine (1.25-5 mg/kg IP) also
significantly increased the yawning response.
The DHP calcium channel blockers alone induced
only a low incidence of yawning. The effects of
nifedipine on physostigmine-induced yawning were
reversed by the DHP calcium channel activator
BAY K 8644 which also inhibited yawning induced
by physostigmine (100 micrograms/kg SC) and
pilocarpine (2 mg/kg SC). In contrast to the DHP
compounds, diltiazem (2.5-10 mg/kg IP) and
verapamil (2.5-10 mg/kg IP) failed to potentiate
yawning. Sulpiride (10 mg/kg SC) antagonised the
nifedipine potentiation of apomorphine-induced
yawning but not that of physostigmine-induced
yawning; atropine (2.5 mg/kg SC) antagonised
both effects. These results support the
hypothesis that this effect of dihydropyridine
compounds is not dependent on, nor mediated
through, dopaminergic mechanisms.
3°) Bourson, A. and P. C. Moser (1989).
"The effect of pre- and postoperative procedures
on physostigmine- and apomorphine-induced
yawning in rats." Pharmacol Biochem Behav 34(4):
915-7.
Previous experiments have shown that the
potentiation of physostigmine-induced yawning by
nifedipine is abolished by sham-lesioning
procedures in rats, whereas the nifedipine
potentiation of apomorphine-induced yawning is
unaffected. The present results demonstrate that
either the presurgical drug treatment
(desmethylimipramine and pentobarbital) or 7
days isolation was alone sufficient to reduce
the yawning response to physostigmine and
abolish its potentiation by nifedipine. The
sham-lesioned rats responded normally to a
combination of apomorphine and nifedipine. These
results suggest that the stress associated with
standard operative procedures can differentially
affect drug interactions with yawning induced by
either apomorphine or physostigmine and that
caution should be exercised when interpreting
results from animals that have been similarly
stressed.
4°) Bourson, A., A. J. Gower, et al.
(1989). "The effects of dihydropyridine
compounds in behavioural tests of dopaminergic
activity." Br J Pharmacol 98(4): 1312-8.
1. The effects of the dihydropyridine
calcium channel blocker nifedipine and the
activator Bay K 8644 were investigated in
different behavioural tests involving
dopaminergic systems. These were the
discriminative stimulus induced by amphetamine,
rotational behaviour in rats with unilateral
6-hydroxydopamine (6-OHDA) lesions and
apomorphine-induced yawning in rats.
2. The yawning induced by apomorphine (40
micrograms kg-1 s.c.) was significantly
potentiated by nifedipine (5-10 mgkg-1 i.p.).
Bay K 8644 (0.05-0.5 mgkg-1 i.p.)
dose-dependently inhibited yawning induced by
apomorphine (80 micrograms kg-1 s.c.) and, at
0.4 mgkg-1, inhibited the nifedipine
potentiation of apomorphine-induced yawning. In
contrast to their effects on apomorphine-induced
yawning, nifedipine and Bay K 8644 had no effect
on apomorphine-induced penile erection. 3. Bay K
8644 (0.06-0.5 mgkg-1 i.p.) and nifedipine (5-20
mgkg-1 i.p.) had no dose-related effect on the
discrimination performance of rats trained to
discriminate amphetamine from saline. However,
nifedipine dose-dependently reduced the response
rate of amphetamine-treated rats. Bay K 8644 had
no effect on this measure except at high doses
that also caused disruption. 4. Neither
nifedipine (5-10 mgkg-1 i.p.) nor Bay K 8644
(0.06-0.5 mgkg-1 i.p.) affected the turning
behaviour induced by amphetamine (1 mgkg-1 i.p.)
in rats with unilateral 6-OHDA lesion of the
medial forebrain bundle, and did not induce
turning themselves. 5. As the dihydropyridine
compounds affected apomorphine-induced yawning
but not penile erection, and did not affect
amphetamine-induced rotation or drug
discrimination, it seems unlikely that they are
affecting dopamine release in vivo.
