This case presentation is intended to draw attention to the
possibility of drug interaction between ranitidine and
nondepolarizing neuromuscular blocker drugs. Further study is
needed to determine what effects, if any, it has at the
neuromuscular junction or on the bioavailability of other drugs.
Most of the obvious potential causes of the failure of
drug action during anesthesia were excluded. Failure of the
drug to enter the blood stream was ruled out because the
patient had functioning peripheral venous access via an 18G
angiocath and a central venous catheter. Loss of potency of the drug was excluded by the fact that the same batches of these
drugs were used successfully on other patients.
The relationship between an administered dose of a
nondepolarizing muscle relaxant and the resulting degree of
neuromuscular blockade is known to be modified by a
multiplicity of factors. These include age, acid base status,
temperature, pathologic derangements such as burns or lower
motor neurone disease 1,11 and concurrent drug therapy.
Drug interactions described to date generally have
involved the potentiation of neuromuscular blockade, most
notably antibiotics. Chen et al. reported that a patient being
treated with phenytoin therapy requires approximately 80%
more pancronium than control patients to maintain a stable
level of neuromuscular blockade. Metteo et al 6 reported that
plasma protein binding affects the free drug levels of dtubocurarine
available to exert pharmacological action.
Increased binding of this drug can reduce its effectiveness.
Duvaldestin and her co-workers 12 have demonstrated that
liver disease increases the distribution volume necessitating
more drug-pancuronium-to produce a given degree of
blockade.
Mishra and et al. 13 were investigated in the rat phrenic
nerve-hemidiaphragm preparation in-vitro study. They
suggested ranitidine augmented the indirectly-evoked muscle
response at concentrations between 30 and 160 microM but at
higher concentrations, between 300 and 1800 microM,
produced neuromuscular paralysis. These data indicate that
higher than clinically relevant concentrations of ranitidine
produce neuromuscular paralysis and may potentiate the action
of vecuronium. Low concentrations of ranitidine may
antagonize the action of vecuronium.
Cross-resistance among chemically dissimilar
neuromuscular blocking agents poses a difficult patient
management problem and supports a pharmacodynamic basis
of resistance to these agents. This would suggest that
significant extrajunctional acetylcholine receptor proliferation
is an unlikely mechanism 14.
Since none of the causes described above adequately
explains the resistance observed in our patient, we think that
this resistance can be attributed to an interaction between
ranitidine and nondepolarizing muscle relaxants resulting from
some undefined pharmacodynamic alterations. But, McCarthy
et al. 15 investigated the effects of oral administration of
ranitidine 150 mg 90 min before anaesthesia on the
neuromuscular blocking effects of atracurium or vecuronium.
There were no significant differences in any of the variables
following ranitidine pretreatment. A single dose ranitidine has
been used in this study. In contrast to this report, it is important
that the patient had prolonged treatment with ranitidine for 10
years. We want to stress that whatever a drug may existence
serious advers effects, if it uses in very long time.
The preceding only one report 16’s described to
resistance d-tubocurarine and pancuronium with ranitidine. As
far as we are aware, this is the first report decribed with
vecuronium and mivacurium resistance with ranitidine. Our
report would strengthen the paper to indicate that vecuronium
and mivacurium by same mechanism as d-tubocurarine and and
pancuronium. Thus, the observation would act as a
confirmation of the interaction between the non-depolarizing
and H2 antagonists. This is probably more important than
claming a first observation, as vecuronium and mivacurium are
used mainly so clinical practice at nowadays.
Because neuromuscular monitoring is not essential a
monitorization device, we were not planned to place
neuromuscular monitoring in this patient because he had no
history of a muscle disease or drug allergy. The evidence for
the lack of relaxation is clinical; we had no access to a
peripheral nerve stimulator to confirm this finding. Although
Parr et al 9 did not use a neuromuscular monitarization; they
suggested that neuromuscular resistance can be established as
clinically. Our clinical observation and evidence based
experience were very important and helpful in diagnosis and
problem solving in this patient as Parr experienced. There is
no doubt that neuromuscular monitorization would make richer
the patient’s findings. Both vecuronium and mivacurium did
not adequately caused muscle relaxation in the patient. We
thought, because of inadequate relaxation, spleen was lacerated
by surgeons. Only following depolarizan muscle relaxant,
abdominal muscles were effectively relaxed.
Although no clinical findings, hypothyroidism could be
the reason for the resistance. In addition to this, increased level
of endogenous testosterone and steroidal-core structure of
vecuronium may explain the increased tolerance to vecuronium
in this patient. Regarding as far as plasma cholinesterase is
concerned, ıncreased plasma cholinesterase activity might be
the clinical discovery. In the patient, all laboratory
investigations were in normal limits. That is to say, supporting
neuromuscular resistance of patient was no laboratory result.
We want to stress that some drugs may cause vital advers
effects being used in over time
In conclusion, we would like to point out that
anesthesiologists should be aware that ranitidine can cause
resistance to vecuronium and mivacurium.
