1. PHARMACOTHERAPY OF
VERTIGO
Dr. Anita Bhandari

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
MAO
Dopamine
5-HT
Acetylcholine GABA
Norepinephrine
excitatory inhibitory
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
Reduction in the
symptom of vertigo
comes at a price of
reduction in
vestibular function
Rascol O et al, Drugs 1995; 50: 777-91
Lacour M. Curr Med Res Opion 2006; 22: 1651-9

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 INTACT DAMAGED
recommended Vestibular
Nuclei
for long term use
 They should be
discontinued as 22: 1651-9
Lacour M. Curr Med Res Opion 2006;

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
Influx of Ca ions Release of Ach
activated

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 H2 H3 receptor
receptors receptors • Brain
• Smooth • Gastric
muscle mucosa
• Endothelial • Cardiac
cells muscle
• Brain • 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

22. MECLIZINE
 1ST line of treatment for vertigo in USA
 Less anticholinergic activity than other
antihistamines
 Also effective in sea sickness
 Diligan,Pregnidoxin

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

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

25. 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.

27. 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

31. 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”

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

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

35. 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 .

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

37. 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

38. 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.

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

40. 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]

41. 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

42. 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.

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

44. 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

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

46. 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

47. 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

48. 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

49. GINGKO BILOBA : MODE OF
ACTION
↑blood supply to brain & peripheral vascular system
Scavenging of free radicals Antagonist of PAF to ↑
microvascular permeability
↑ glucose uptake in brain Thrombolytic &
vasoprotective
Inhibition of MAO

50. 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

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

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

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

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

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

56. 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.

57. 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

58. Gentamycin passes RW→Perilymph to endolymph
GENTAMYCIN : MODE OF ACTION
Damage to mitochondria
Death of vestibular cells
Damage to dark cells of secretory epithelium
Reduces endolymphatic production

59. GENTAMYCIN
 Technique
0.7ml gentamycinin 0.3ml of soda bicarb injected
intratympanically every week for upto 3 weeks.Pt
should lie with injected ear up for 30min.
 Repeat audiometry before each inj. To rule out
SNHL and check for spontaneous nystagmus.

61. AGOROPHOBIA
ANXIETY SOMATISATION
PANIC DISORDER
DEPRESSION HYPOCHONDRIA

62. TRICYCLIC
ANTIDEPRESSANTS
ANTIDEPRESSANTS
SSRI
PSYCHOTROPIC
DRUGS
ALPRAZOLAM
BENZODIAZAPINES
DIAZEPAM

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

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

65. 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

66. “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.