34
original
SUPLEMENTO
Otoneurología 2014:
comprendiendomejor los trastornos vestibulares
Actual.Med.
2014; 99: (791). Supl. 34-60
wide analyses have revealed linkage to chromosome 5q35, 11q
and 22q12, no candidate gene has been validated. VM, like other
migraine syndromes, suggests genetic heterogeneity. Within the
same family somemembers may havemigraine and other VM or
benign paroxysmal vertigo of childhood indicating also phenotypic
heterogeneity. Mutations on CACNA1A gene, which encodes the
central pore-formingsubunitof thevoltage-gatedCa
V
2.1 (P/Q-type)
calciumchannels,causethreeneurologicalcalciumchannelopathies:
episodic ataxia type 2, familial hemiplegic migraine type 1 and
spinocerebellar ataxia type6 (10). Accumulatingevidence suggests
that Ca
V
2.1 channels could be implicated not only in migraine
pathogenesisbutalso inVM (6,11).
VM is a chameleonic disorder. Differential diagnosis includes
benign paroxysmal positional vertigo (BPPV), Meniere´s disease
(MD), labyrinthtransient ischemicattacks,superiorcanaldehiscence
syndrome and psychiatric dizziness, being the distinction between
MDandVM isthemajordiagnosticchallenge,particularly inthefirst
yearsof thedisease.MigraineandMDcanbecomorbidconditions;
equallyMD andVM can also coexist in the samepatient according
to the current diagnostic criteria. Moreover, epidemiological and
genetic information suggest that the episodic vestibular syndrome
could be a clinical multifactorial disorder where bilateral MD and
migrainewithout aurawill be theextremephenotypes. So, several
intermediate phenotypes could be considered such us unilateral
MD, VM or migraine with aura and they would be a continuum
betweenbothextremes (12).
TREATMENTOFVESTIBULARMIGRAINE
VM treatment is categorized as either acute treatment or
preventive treatment. Patients with a spell of VM often require a
symptomatic treatment during the acute episode, almost always
drug therapy. Depending on the impact on patient´s quality of
life, a prophylactic treatment may be also required. Preventive
treatment includes dietary changes and lifestyle modifications,
pharmacotherapy, andvestibular rehabilitation.
ACUTETREATMENT
Symptomatic treatment should be considered when the
episodes lastmorethan1hourbecauseusuallybloodconcentration
of themedicationdoesnot reach thepeakuntil 1-2hoursafteroral
administration. Vestibular suppressants and antiemetic agents are
themaindrugs foramelioratingsymptomsofVM;mostmedications
share antivertiginous and antiemetic effects to a greater or lesser
degree (table 1). It is remarkable that abortive therapy including
migraine-specific treatments (ergot derivatives, triptans) aswell as
nonspecificagents(acetaminophen,nonsteroidalanti-inflammatory
drugs (NSAIDs)andopioids) ispoorlyeffective inVM.
Neuroleptics
Neuroleptics are antipsychotic agents used innon-psychiatric
indications to treat vomiting for their antiemetic and sedative
properties. Some of them lack antipsychotic properties and they
are used exclusively as antiemetics. These drugs are primarily
antidopaminergic drugs. The mechanism of action is probably
producedbyblockadeofdopamineD
2
receptorsatthechemoreceptor
triggerzoneof theareapostremaat thefloorof the fourthventricle.
Athighdoses, someneurolepticssuchuschlorpromazinemayactat
thevomitingcenterwithin the lateralmedullary reticular formation.
Antipsychoticwithantiemeticproperties include:
Benzamides:metoclopramide, sulpiride.
Phenotiazines:
chlorpromazine,
prochlorperazine,
promethazine, thiethylperazine.
Butyrophenones:domperidone,droperidol.
Metoclopramide also exhibits a mixed 5-HT
3
receptor
antagonist / 5-HT
4
receptor agonist action that could explain its
peripheral effect as a prokinetic, facilitating gastric emptying and
thus it may improve absorption of oral medication. Sulpiride is a
selectivedopamineD
2,3
antagonistalsowith5-HT
7
antagonistaction.
Sulpiride isnotavailable inUnitedStates.
Table1. Vestibular suppressantsandantiemetics.
*: predominantlyantiemetic
im: intramuscular injection
iv: intravenous injection
po: peros, orally
pr: per rectum, by rectal route
Themainadverseactionsofneurolepticsareextrapyramidal
side effects due to D
2
-receptor blockade: akathisia, dystonias,
parkinsonism, amenorrhea, galactorrhea. These extrapyramidal
reactions disappear with biperiden administration. In relation
to metoclopramide, the EuropeanMedicines Agency has noted
that the risk of extrapyramidal effects and tardive dyskinesia is
increased in patients under 18 years, at high doses orwith long-
term treatment.
Among phenotiazines, thiethylperazine is the most widely
used in Spain, whereas promethazine or prochlorperazine are
used in other countries. Thiethylperazine has lesser sedative
and extrapyramidal effects than chlorpromazine. In addition
to antidopaminergic action, other adverse effects are related
to muscarinic cholinoceptor blockade: drowsiness, dry mouth,
difficulty urinating, accommodation disturbances, constipation.
PhenotiazinesexhibitalsoH
1
antihistaminicaction.Phenotiazines,
especially promethazine, and droperidol can induce orthostatic
hypotension and tachycardia caused by blockade of peripheral
alphaadrenoceptors.
Domperidone ispreferred inchildrenandteenagersbecause
it is not associated with the risk of extrapyramidalism with
metoclopramide. Droperidol produces greater extrapyramidal
effects thanphenothiazines and it is extremely sedating.
Some antipsychotics have been implicated in the
prolongationoftheQT interval,resulting inventriculartachycardia
including torsade de pointes. These include chlorpromazine,
domperidone, droperidol, promethazineand sulpiride.
H
1
receptor antagonists
Drug
Dosage
Sideeffects
Metoclopramide* 5-10mg/6-8hpo
10-20mg /8h iv
extrapyramidal
symptoms
Sulpiride
50-100mg/8h
po im
extrapyramidal
symptoms
Promethazine*
25mg/8hpo, im drymouth
extrapyramidal
symptoms,
drowsiness
Thiethylperazine* 6.5mg/8hpo, pr
extrapyramidal
symptoms
Prochlorperazine* 10mg/6hpo, im
25mg/12pr
extrapyramidal
symptoms
Domperidone
10-20mg /6-8hpo
60mg/12pr
extrapyramidal
symptoms
Diphenhydramine 25-50mgpo
drymouth
Dimenhydrinate 50mg/4-6hpo drymouth
Meclizine
25-50mgp.o.
drymouth
Diazepam
2-10mg /6hpo, iv,
im, pr
drowsiness,
withdrawal
symptoms
Lorazepam
0.5mg/8hpo,
iv, im
drowsiness,
withdrawal
symptoms
Scopolamine*
0.5mg
transdermal
drymouth,
tachycardia,
withdrawal
symptoms
