Pharmacotherapy of vertigo

1. PHARMACOTHERAPY OF
VERTIGO
Dr.Anita Bhandari
Consultant Neurotologist
Vertigo and Ear clinic
Jaipur

2. NO COMMON TREATMENT FOR
ALL PATIENTS.
Therapeutic approach requires recognition
of the pathomechanism
 Detailed history
 Clinical examination
 Neurotological tests
 Imaging

3. ETIOLOGY
Central
Otological
Systemic
Unknown

4. OTOLOGICAL CAUSES
Meniere's disease
Vestibular neuritis
Labyrinthitis
BPPV
Fistula

5. AUTONOMIC NERVOUS
SYSTEM
•Major role in balance control
•3 major neurotransmitters involved in 3
neuron arc between vestibular hair cells
and oculomotor nuclei - VOR

6. NEUROTRANSMITTERS
Acetylcholine
excitatory
GABA
inhibitory
MAO
Dopamine
5-HT
Norepinephrine
maintain
resting tone of
vest nucleus

7. DRUGS MODIFYING ACTION
OF NEUROTRANSMITTERS
Agonists
Antagonists

8. TREATMENT MODALITIES OF
VERTIGO
 Anticholinergics
 Antihistamines
 Benzodiazepines
 Ca Channel blockers
 GABA modulators
 Neurotransmitter reuptake
inhibitors[SSRI,tricyclic antidepressants]
 Nootropics

9. 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

10. 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

11. 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

12. ANTI-CHOLINERGIC DRUGS
Suppress spontaneous firing of
 Vestibular nuclei
 2ND & 3RD order neurons
 Reticulo-vestibular pathway

13. TYPES OF
CHOLINORECEPTORS
Muscaranic
Nicotinic

14. Nerve terminal
activated
Influx of Ca ions Release of Ach

15. 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

16. 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

17. HISTAMINERGIC
RECEPTORS
H1
receptors
• Smooth
muscle
• Endothelial
cells
• Brain
H2
receptors
• Gastric
mucosa
• Cardiac
muscle
• Brain
H3
receptor
• Brain

18. 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 receptors
Drug which blocks H1 receptors will also
have an anti-cholinergic effect

19. 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

20. PROMETHAZINE
 Useful in motion sickness
 Dosage: 25-50mg TID
 Avomine,Phenargan

21. PROCLOPERAZINE
 Antimuscaranic and anti-dopaminergic
effect
 Effective in acute vertigo and vomiting
 S/E – CNS depressant
Extrapyramidal reactions
Hypotension
 Dosage: 5-25mg TID
 Stemetil, Acuvert

22. 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

23. CINNARIZINE : MODE OF ACTION
Antihistaminic
effect
Ca channel
blocker
• Anticholinergic effect
• Reduced irritability of
labyrinth
• Reduced blood
viscosity
• Antivasoconstrictive
effect
• Stabilizes vascular
endothelium

24. CINNARIZINE –Mode of
Action
 Anti-histaminic effect
 Ca channel blocker
reduces labyrinthine irritability
reduces blood viscosity
anti-vasoconstrictive effect
stabilizes vascular endothelium

25. CINNARIZINE
Dosage : 25-75mg TID
Contraindications:
 Hypersensitivity
 Parkinsonism
 Children
 Hypotension
Side Effects :
 Extrapyramidal effect
 Drug induced Parkinsonism

26. 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.

28. 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

32. 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”

33. BETAHISTINE
Contraindications :
 Bronchial asthma
 Peptic ulcer
 Phaeochromocytoma
 Porphyria
 Concurrent use with antihistaminics
Dosage : 48mg in divided doses

35. ANTIEMETICS
Antidopaminergic
• Metaclopromide
• Domperidon
Antiserotonergic
• Ondansterone
Antimuscaranic
• Procloperazine
• Cinnarizine

36. 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 .

37. Avoidance of
triggers
Abortive therapy
Preventive
therapy
MIGRAINE RELATED VERTIGO

38. 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

39. 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.

40. TRIPTANS
 Sumatriptan
 Oral – 25- 100mg
 Nasal spray – 5-25mg
 Subcut. – 6mg
 Zolmitriptan
 Oral- 1.25-2.5mg
 Nasal spray
 Rizatriptan
 5-10 mg

41. 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]

42. 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

43. 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.

44. FLUNARIZINE
 Dosage : 5-10mg hs
 Contrindications:
Pregnancy and lactation
GI & Urinary tract obstruction
 Porphyria
 Special precautions :
Driving
Elderly
CVS disease

45. 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

46. BOTULINUM TOXOID
 Botulin toxin or botox -toxin produced
by the Clostridium botulinum.
 Interferes with release of acetylcholine
at neuromuscular junction leading
paralysis of muscles.

47. 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

48. STEROIDS
Uses
 Vestibular neuritis
Initial treatment : 60-80mg/day then taper
 Auto-immune vestibulopathy
Prednisolone : 80-100mg/day for 2-3 weeks then
taper & continue with maintenance dose of
10mg/day
 Multiple sclerosis

49. 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

50. 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

51. 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

52. DIURETICS IN MENIERE’S
DISEASE
 Triamterene 50mg with
hydrochlorthiazide 50mg
 Frusemide – 40mg /day
 Spironolactone – 100mg /day

53. PIRACETAM
 Cyclic derivative of GABA
 Decreases vertigo of central origin
 Decreases frequency and severity of
exacerbations in chronic & recurrent
vertigo

54. PIRACETAM : MODE OF ACTION
Interaction with
polar heads of
phospholipid
membrane
Reoganization
of lipid
molecules with
formation of
drug-
phospholipid
complex
Restored
membrane
fluidity

55. RESTORED MEMBRANE
FLUIDITY
• Improves
• Neurotransmission,
• Neuroplasticity
• Interhemispheric info
transfer
Neuronal
effects
• RBC deformability
• adhesion of RBC
prevents vasospasm
Vascular
effects

56. PIRACETAM : MODE OF ACTION
Facilitates
vestibular
compensation
and
adaptability
Improved
neuronal function
Improved
microcirculation

57. INTRATYMPANIC DRUG
DELIVERY
 Intratympanic steroids
 Indications
 Suspected auto-immune mediated
vestibulo/cochleopathy
 Meniere’s disease
Technique:
1ml of methylprednisolone/dexamethasone
with 0.5 ml hyaluronidase injected in
posteroinferior quadrant. Patient to lie with
injected ear up for minimum 30 min.

58. 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

59. 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

60. 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

62. AGOROPHOBIA
SOMATISATION
DISORDER
HYPOCHONDRIADEPRESSION
ANXIETY
PANIC

63. PSYCHOTROPIC
DRUGS
ANTIDEPRESSANTS
TRICYCLIC
ANTIDEPRESSANTS
SSRI
BENZODIAZAPINES
ALPRAZOLAM
DIAZEPAM

64. • Effective in anxiety, panic
disorders, agorophobia
• Ineffective in depression
• Addictive, sedative
• Inhibits vestibular compensation
BENZODIAZAPINES

65. ANTI DEPRESSANTS
Tricyclic antidepressants
 Strong anticholinergics
 May precipitate orthostatic
hypotension
 Imipramine : 25mg TID
 Nortryptaline : 25-50mg BD

66. 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

67. “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.