35
Otoneurología 2014:
comprendiendomejor los trastornos vestibulares
SUPLEMENTO
original
Actual.Med.
2014; 99: (791). Supl. 35-60
H
1
antagonists with antiemetic action are first-generation
antiH
1
drugs receptors that cross the blood-brain barrier with a
strong sedative and hypnotic effect. Antiemetic effect appears
mediated throughantimuscarinicanticholinergicactivitywhereas
their action as vestibular suppressants may be related with a
decreased activity in the vestibular nuclei. Diphenhydramine
and its derivative dimenhydrinate are ethanolamines that are
useful for treating milder attacks. Meclizine and cyclizine are
piperazinederivativeswithantihistaminicactionandwitha lesser
drowsiness effects that ethanolamines.
The adverse effects of H
1
antihistamines are related to
their antimuscarinic properties: somnolence, drymouth, urinary
retention, blurred vision. Agentswithantimuscarinic effects such
as antipsychotic andH
1
receptor antagonists are contraindicated
in patients with angle-closure glaucoma. They also should be
usedwith caution in elderlymenwith prostatic hyperplasia and
inpatientswithasthma, especially children.
Cinnarizine and flunarizine are also calcium channel
blockers with vasodilatation action. Flunarizine is more potent
and can be administered once a day nevertheless may induce
parkinsonism due to its antidopaminergic properties. Although
some studies have shown its effectiveness to reduce the severity
of acutemigraine attacks, flunarizine ismore commonly used in
preventive treatment ofmigraineandVM.
Benzodiazepines
Diazepam, alprazolam, clonazepam and lorazepam, can
be used for acute crisis of VM because they act as vestibular
suppressants enhancing the inhibitory action of GABA in
the vestibular nuclei. Benzodiazepines are also effective as
antiemetics and to reduce the anxiety often associated to the
episodeof vertigo.
For treating acute vertigo, a parenteral administration
of low dose of diazepam is generally effective in reducing the
intensity of the spell; once the symptoms decrease diazepam
canbe continuedorally for a fewdays. Alprazolam is particularly
useful if panicdisorder develops.
In general, benzodiazepines are safe and effective in the
short term use, although cognitive impairments and paradoxical
effectsmay appear, mainly in the elderly. Intravenous diazepam
cancause respiratorydepressionandhypotension, so it shouldbe
usedonly if resuscitationequipment is available. Adverseeffects,
tolerance, and physical and psychological dependence are
associatedwith the long-termadministrationof benzodiazepines
andarenot expected inmanagingacutevertigo.
Corticosteroids
The basis for the antiemetic action of the corticosteroids
is unknown. Dexamethasone and methylprednisolone are
the more commonly used in relieving vomiting, both by oral
route or parenteral injection. They can be combined with
other pharmacological groups such as benzamides and 5-HT
3
antagonists.
Triptans
Triptans are serotonin (5-hydroxytryptamine, or 5-HT)
subtype agonists. Their action inmigrainemay be related to the
activation of 5-HT
1D
receptors on presynaptic trigeminal nerve
endings that innervate meningeal blood vessels, preventing
the release of vasoactive neuropeptides (CGRP, substance P,
neurokinin A), as well as by a direct action on 5-HT
1B
receptors
in intracranial extracerebral arterial smooth muscle causing
vasoconstriction. In addition, a central mechanism could explain
the efficacy of triptans in controlling nausea and vomiting, and
cessationof phonophobiaandphotophobia.
Minor adverse effects such as paresthesia, flushing,
dizziness, somnolence, asthenia and transient necktightness are
common.Althoughmostcasestriptan-associatedchestpain isnot
causedbycoronaryvasoconstriction, triptansarecontraindicated
incoronarypatientsandcerebrovasculardisease.Naritriptanand
eletriptan are contraindicated in patients with severe hepatic of
renal failure, orperipheral vasculardisease; zolmitriptan inWolff-
Parkinson-White syndrome; frovatriptan is also contraindicated
inperipheral vascular disease.
In a survey conducted in migraine patients with dizziness,
sumatriptan was found to be the most effective medication
at improving headache and vertigo, with a highly significant
correlation inamelioratingboth symptoms regardlessofwhether
or not a temporal relationexistedbetween them (13).
Zolmitriptan was studied in VM in a pilot randomized
placebo-controlled trial. The authors appreciated a low response
rateof38% for zolmitriptanversus22% forplacebo. These results
were inconconclusive because of the small smaple size (14). It is
to be noted that rizatriptan has shown a decrease in vestibular-
inducedmotion sickness inmigraineurs (15).
Other drugs
Ondasetron, granisetron, dolasetron, tropisetron and
palonosetronare serotonin5-HT
3
antagonistsusedmainly for the
preventionof nausea and emesis inducedby chemotherapy. The
5-HT
3
receptors are locatedperipherallyonvagal nerve terminals
and enteric neurons in the gastrointestinal tract, and centrally
in the chemoreceptor trigger zone on the floor of the fourth
ventricle. In the last years ondasetron is being used successfully
to treat postoperative vomiting, and in patients presentingwith
vomiting associatedwith vertigo in the emergency department.
Some formulations combine a serotonin 5-HT
3
antagonist with
dexamethasone and neurokin 1 (NK
1
)-receptor antagonists. NK
1
-
receptor antagonists such as aprepitant and fosaprepitant are
used as antiemetic in the prevention of nausea and vomiting
associated to chemotherapy.
Scopolamine is a muscarinic cholinoceptor antagonist
prescribed to prevent nausea and vomiting caused by motion
sickness. Its action is related to the high density of muscarinic
receptors in vestibular nuclei. Scopolamine can be administered
byenteralorparenteralrouteaswellastransdermalretroauricular
patch,whichallows a continuous releaseof thedrugover 3days.
Adverseeffects includedrowsiness,drymouth,andblurredvision.
Aswithothermuscarinic receptor-blockingdrugs, scopolamine is
contraindicated in angle-closure glaucoma and should be used
with caution in men with prostatic hyperplasia. It is not useful
inVM.
PREVENTIVETREATMENT
The main goal of preventive treatment is to decrease
the negative impact of VM on patient´s quality of life when
considering his or her daily activities (work tasks, school
attendance,etc.). Secondarygoalsare to reduceattack frequency,
duration and severity. The wide range of duration of VM spells,
lasting from seconds to several days, hampers the definition of
a limit from which prophylaxis should be indicated. We think
that the combination of frequency, duration and severity of the
attacks in a certain subject determines the formula to consider
theneed forpreventive treatment. For example, it isevident that
prophylaxis isnecessarywhen threeormoreepisodespermonth
occur, lastingoveranhourat least,demanding reliefandaffecting
daily routines.
Preventive treatment includes dietary changes and lifestyle
modifications, pharmacotherapyand vestibular rehabilitation.
DIETARYCHANGESAND LIFESTYLEMODIFICATIONS
Experimental studies suggest a common biochemical
mechanism for caffeine, ethanol and stress asmigraine triggers.
They would act in the Purkinje cells of cerebellummediated by
Ca
v
2.1 channels (16).
Dietary manipulation has been shown effective in VM in
descriptive studies (17,18). Themost important dietary change is
caffeine decrease (19); this includes coffee, tea, chocolate, cola
and energetic drinks. It is also important a proper hydration and
avoid fasting. Certain foods andbeverages arepotentialmigraine
triggers: mature and aged cheese, yogurt, salty foods, smoked,
