Upload
pushpak-kacholia
View
251
Download
2
Tags:
Embed Size (px)
Citation preview
PHARMACOTHERAPY OF
VERTIGODr.Anita Bhandari
Consultant Neurotologist
Vertigo and Ear clinic
Jaipur
NO COMMON TREATMENT FOR
ALL PATIENTS.Therapeutic approach requires recognition
of the pathomechanism
Detailed history
Clinical examination
Neurotological tests
Imaging
ETIOLOGY
Central
Otological
Systemic
Unknown
OTOLOGICAL CAUSES
Meniere's disease
Vestibular neuritis
Labyrinthitis
BPPV
Fistula
AUTONOMIC NERVOUS
SYSTEM
•Major role in balance control
•3 major neurotransmitters involved in 3
neuron arc between vestibular hair cells
and oculomotor nuclei - VOR
NEUROTRANSMITTERS
Acetylcholineexcitatory
GABAinhibitory
MAO Dopamine
5-HT Norepinephrine
maintain resting tone of vest nucleus
DRUGS MODIFYING ACTION
OF NEUROTRANSMITTERS
Agonists
Antagonists
TREATMENT MODALITIES OF
VERTIGO
Anticholinergics
Antihistamines
Benzodiazepines
Ca Channel blockers
GABA modulators
Neurotransmitter reuptake
inhibitors[SSRI,tricyclic antidepressants]
Nootropics
Vestibular Suppressants
Rascol O et al, Drugs 1995; 50: 777-91
Lacour M. Curr Med Res Opion 2006; 22: 1651-9
Reduction in the
symptom of vertigo
comes at a price of
reduction in
vestibular function
Vestibular Suppressants
Useful for prevention of nausea and
reduce vomiting (generally to be used for
not more that 1-3 days) post an event
Should be discontinued as soon as
possible after event subsides
They are not to be used chronically or for
prophylaxis against subsequent attacks
Lacour M. Curr Med Res Opion 2006; 22: 1651-9
Goebel J. Otolaryngol Clin N Am 2000; 33: 483-93
Brandt T, Vertigo. Its Multisensory Syndromes, 2nd Ed: Pg 49-61
Treatment with Vestibular
Suppressants
Suppressants reduce activity at intact side and thus hamper recovery by VC
Not recommended for long term use
They should be discontinued as soon as possible
Lacour M. Curr Med Res Opion 2006; 22: 1651-9
Vestibular
Nuclei
INTACT DAMAGED
ANTI-CHOLINERGIC DRUGS
Suppress spontaneous firing of
Vestibular nuclei
2ND & 3RD order neurons
Reticulo-vestibular pathway
TYPES OF
CHOLINORECEPTORS
Muscaranic
Nicotinic
Nerve terminal activated
Influx of Ca ions Release of Ach
ANTIMUSCARANIC DRUGS
Atropine and its analogues 0.4 mg orally or IM
Scopalamine
Most potent 0.6mg orally
Transdermal patch 0.05mg
S/E Dry mouth
Tachycardia
Sedation
Cause of Side Effects
Drugs which act by interfering with the
function of neurotransmitters have the
disadvantage of causing effects wherever the
neurotransmitters work in the CNS.
Anti-cholinergics- sedation, dryness of mouth,
tachycardia
Anti-dopaminergic drugs – sedation,
depression
HISTAMINERGIC
RECEPTORS
H1 receptors
• Smooth muscle
• Endothelial cells
• Brain
H2 receptors
• Gastric mucosa
• Cardiac muscle
• Brain
H3 receptor
• Brain
ROLE OF HISTAMINE
Histamine is not a major neurotransmitter in the vestibular pathway
It exerts effect by acting on H1 and H3 receptors present in the brain
Structure of H1 receptors is similar to Muscaranic receptorsDrug which blocks H1 receptors will also
have an anti-cholinergic effect
DIMENHYDRINATE
Inhibits spread of hyperactive vestibular input into vegetative regulation centers of medulla
Effective anti-vertigo and anti-emetic drug
S/E – drowsiness , dry mouth, constipation
Caution – glaucoma , urinary retention
Dosage: 50mg TID
Gravol, Dramamine
PROMETHAZINE
Useful in motion sickness
Dosage: 25-50mg TID
Avomine,Phenargan
PROCLOPERAZINE
Antimuscaranic and anti-dopaminergiceffect
Effective in acute vertigo and vomiting
S/E – CNS depressantExtrapyramidal reactionsHypotension
Dosage: 5-25mg TID Stemetil, Acuvert
MECLIZINE
1ST line of treatment for vertigo in USA
Less anticholinergic activity than other antihistamines
Safe in pregnancy
Also effective in sea sickness
Diligan,Pregnidoxin
CINNARIZINE : MODE OF ACTION
Antihistaminic effect
Ca channel blocker
• Anticholinergic effect
• Reduced irritability of labyrinth
• Reduced blood viscosity
• Antivasoconstrictive effect
• Stabilizes vascular endothelium
CINNARIZINE –Mode of
Action Anti-histaminic effect
Ca channel blocker
reduces labyrinthine irritability
reduces blood viscosity
anti-vasoconstrictive effect
stabilizes vascular endothelium
CINNARIZINE
Dosage : 25-75mg TID
Contraindications:
Hypersensitivity
Parkinsonism
Children
Hypotension
Side Effects :
Extrapyramidal effect
Drug induced Parkinsonism
BETAHISTINE
Historically seen that histamine relieved
vertigo. However had to be given IV and
had serious side effects.
Betahistine is a histamine analogue having
the advantages of histamine like action
without its side effects.
Peripheral vestibular lesion Activation of vestibulo-hypothalmic-vestibular loop
Release of endogenous histamine in vestibular nuclei
Betahistine competes with histamine for binding to histaminergic receptors in vestibular nuclei
Histamine cannot bind to receptors due to betahistine binding
Free histamine increases alertness and vestibular compensation
BETAHISTINE
Inhibits response of rotatory stimuli in
medial vestibular nucleus
Reduces firing rate in lateral vestibular
nucleus
Enhances cochlear blood flow
Important not to use generalized
vasodilators as they lead to“STEAL
EFFECT”
BETAHISTINE
Contraindications :
Bronchial asthma
Peptic ulcer
Phaeochromocytoma
Porphyria
Concurrent use with antihistaminics
Dosage : 48mg in divided doses
ANTIEMETICS
Antidopaminergic
• Metaclopromide
• Domperidon
Antiserotonergic
• Ondansterone
Antimuscaranic
• Procloperazine
• Cinnarizine
MIGRAINE RELATED VERTIGO
5-HT [Serotonin] – the mediator in the
pathogenesis of migraine.
5-HT 1B & 1D are the selective receptors
implicated in migraine.
5-HT receptors agonists form the
mainstay of treatment .
Avoidance of triggers
Abortive therapy
Preventive therapy
MIGRAINE RELATED VERTIGO
MIGRAINE ABORTIVE THERAPY
Triptans
Selective 5-HT I agonists
Useful only in acute attacks; not for prophylaxis
Contraindications: IHD , CAD, HTN
Side effects: Coronary artery spasm
Transient MI
Arrhythmias
Paraesthesia
Drug reaction with MAO inhibitors
TRIPTANS
Triptans act by binding to serotonin 5-
HT.sub.1B and 5-HT.sub.1D receptors
in cranial blood vessels (causing their
constriction) and subsequent inhibition
of pro-inflammatory neuropeptide
release.
TRIPTANS
Sumatriptan
Oral – 25- 100mg
Nasal spray – 5-25mg
Subcut. – 6mg
Zolmitriptan
Oral- 1.25-2.5mg
Nasal spray
Rizatriptan
5-10 mg
MIGRAINE ABORTIVE THERAPY
Ergot alkaloids
Should be restricted to patients with
frequent moderate headaches or
infrequent severe headaches.
Sublingual Ergotamine tartarate 2mg
[Ergomar]
Ergotamine nasal spray[Migranal]
MIGRAINE PROPHYLAXIS
Beta blockers – Propranolol Adults : 40mg BID-TID; may be increased to
160mg/day
Contraindications :
Bronchial asthma
Congestive cardiac failure
DM
Hypothyroidism
Flunarizine Antihistaminic
Ca channel blocker
5-10mg/day
Tricyclic amines –Antidepressants
Flunarizine Potential mechanism in migraine prophylaxis
Interferes with initiation and propagation of spreading
depression1
Inhibits neurogenic inflammation1
Inhibits neuronal NO-synthase activity2
1. Silberstein SD. Trends in Pharmacological Sciences 2006; 27: 410-415.
2. Frediani F. Neurol Sci 2008; 29:S127–S130.
FLUNARIZINE
Dosage : 5-10mg hs
Contrindications: Pregnancy and lactation
GI & Urinary tract obstruction
Porphyria
Special precautions : Driving
Elderly
CVS disease
BOTULINUM TOXOID
Paracelsus described the duality of a
drug as "only the dose makes a
remedy poisonous" .
Botulinum toxin therapy
Minute quantities - highly selective
and long-lasting therapeutic effect
Large quantities - Botulism
BOTULINUM TOXOID
Botulin toxin or botox -toxin produced
by the Clostridium botulinum.
Interferes with release of acetylcholine
at neuromuscular junction leading
paralysis of muscles.
BOTULINUM TOXOID
Pericranial injection of Botox.RTM. Used as the prophylactic treatment of migraine
Benefit
decreased measures of migraine frequency, maximal severity, associated vomiting and acute medication use over the three month period following the 100U injection.
Disadvantage – very expensive
STEROIDS
Uses
Vestibular neuritisInitial treatment : 60-80mg/day then taper
Auto-immune vestibulopathyPrednisolone : 80-100mg/day for 2-3 weeks then
taper & continue with maintenance dose of
10mg/day
Multiple sclerosis
GINKGO BILOBA
Extract from gingko biloba tree leaves
Contains flavanoids , terpenoids and
organic acids
Used in ischemia, dementia ,tinnitus,
VBI,
SNHL, Meniere’s disease,
Neurological diseases
GINGKO BILOBA : MODE OF
ACTION
↑blood supply to brain & peripheral vascular system
Antagonist of PAF to ↑ microvascular permeability
Thrombolytic & vasoprotective
Inhibition of MAO
↑ glucose uptake in brain
Scavenging of free radicals
ACETAZOLAMIDE
Carbonic anhydrase inhibitor
Inhibition of carbonic anhydrase in dark
cells and stria vascularis decreases the
formation of endolymph
K rich diet
Dose: 250 -500mg /day
Side effects:
Paraethesia
Tingling
Drowsiness
DIURETICS IN MENIERE’S
DISEASE
Triamterene 50mg with
hydrochlorthiazide 50mg
Frusemide – 40mg /day
Spironolactone – 100mg /day
PIRACETAM
Cyclic derivative of GABA
Decreases vertigo of central origin
Decreases frequency and severity of
exacerbations in chronic & recurrent
vertigo
PIRACETAM : MODE OF ACTION
Interaction with polar heads of phospholipidmembrane
Reoganizationof lipid molecules with formation of drug-phospholipidcomplex
Restored membrane fluidity
RESTORED MEMBRANE
FLUIDITY
• Improves
• Neurotransmission,
• Neuroplasticity
• Interhemispheric info transfer
Neuronal effects
• RBC deformability
• adhesion of RBC prevents vasospasm
Vascular effects
PIRACETAM : MODE OF ACTION
Facilitates vestibular
compensation and
adaptability
Improvedneuronal function
Improvedmicrocirculation
INTRATYMPANIC DRUG
DELIVERY
Intratympanic steroids
Indications Suspected auto-immune mediated
vestibulo/cochleopathy
Meniere’s disease
Technique: 1ml of methylprednisolone/dexamethasonewith 0.5 ml hyaluronidase injected in posteroinferior quadrant. Patient to lie with injected ear up for minimum 30 min.
INTRATYMPANIC GENTAMYCIN
Used for vestibular ablation in
Meniere’s disease which is not
controlled by oral medicines when
other ear shows normal hearing
Converts unstable labyrinth to stable
non-functioning labyrinth
GENTAMYCIN : MODE OF
ACTION
Reduces endolymphatic production
Damage to dark cells of secretory epithelium
Death of vestibular cells
Gentamycin passes RW→Perilymph to endolymph
Damage to mitochondria
GENTAMYCIN
Technique
0.7ml gentamycin + 0.3ml of soda
bicarb injected intratympanically . Pt
should lie with injected ear up for
30min.
Repeat audiometry before each
injection to rule out SNHL , check for
spontaneous nystagmus and do Head
Impulse test to look for peripheral
dysfunction
AGOROPHOBIA
SOMATISATION DISORDER
HYPOCHONDRIADEPRESSION
ANXIETY
PANIC
PSYCHOTROPIC DRUGS
ANTIDEPRESSANTS
TRICYCLIC ANTIDEPRESSANTS
SSRI
BENZODIAZAPINESALPRAZOLAM
DIAZEPAM
• Effective in anxiety, panic disorders, agorophobia
• Ineffective in depression
• Addictive, sedative
• Inhibits vestibular compensation
BENZODIAZAPINES
ANTI DEPRESSANTS
Tricyclic antidepressants
Strong anticholinergics
May precipitate orthostatic
hypotension
Imipramine : 25mg TID
Nortryptaline : 25-50mg BD
ANTI DEPRESSANTS
Selective serotonin reuptake inhibitors
Very effective in anxiety, anxiety with
depression and panic disorders
Delayed onset of action – 3-4 weeks.
Hence better to combine
benzodiazepines initially , then
withdraw after 4 weeks.
Fluvoxamine: 25-50mg/day
Sertaline : 50-100mg/day
“Only a dose can make a remedy
poisonous…” PARCELUS
An incorrectly prescribed drug can also
make a remedy poisonous.
Judicious use of medicines remains the
key in vertigo.