Pharmacotherapy of vertigo


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Pharmacotherapy of vertigo

  2. 2. NO COMMON TREATMENT FOR ALL PATIENTS.Therapeutic approach requires recognition of the pathomechanism Detailed history Clinical examination Neurotological tests Imaging
  3. 3. ETIOLOGY Central Otological Systemic Unknown
  4. 4. OTOLOGICAL CAUSES Menieres disease Vestibular neuritis Labyrinthitis BPPV Fistula
  5. 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. 6. NEUROTRANSMITTERS MAO Dopamine 5-HTAcetylcholine GABA Norepinephrine excitatory inhibitory maintain resting tone of vest nucleus
  8. 8. TREATMENT MODALITIES OF VERTIGO Anticholinergics Antihistamines Benzodiazepines Ca Channel blockers GABA modulators Neurotransmitter reuptake inhibitors[SSRI,tricyclic antidepressants] Nootropics
  9. 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. 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. 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. 12. ANTI-CHOLINERGIC DRUGSSuppress spontaneous firing of Vestibular nuclei 2ND & 3RD order neurons Reticulo-vestibular pathway
  13. 13. TYPES OFCHOLINORECEPTORS Muscaranic Nicotinic
  14. 14. Nerve terminal Influx of Ca ions Release of Ach activated
  15. 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. 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. 17. HISTAMINERGIC RECEPTORSH1 H2 H3 receptorreceptors receptors • Brain• Smooth • Gastric muscle mucosa• Endothelial • Cardiac cells muscle• Brain • Brain
  18. 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. 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. 20. PROMETHAZINE Useful in motion sickness Dosage: 25-50mg TID Avomine,Phenargan
  21. 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. 22. MECLIZINE 1ST line of treatment for vertigo in USA Less anticholinergic activity than other antihistamines Also effective in sea sickness Diligan,Pregnidoxin
  23. 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. 24. CINNARIZINEDosage : 25-75mg TIDContraindications: Hypersensitivity Parkinsonism Children HypotensionSide Effects : Extrapyramidal effect Drug induced Parkinsonism
  25. 25. BETAHISTINEHistorically 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.
  26. 26. Peripheral vestibular lesionActivation 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
  27. 27. 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”
  28. 28. BETAHISTINEContraindications : Bronchial asthma Peptic ulcer Phaeochromocytoma Porphyria Concurrent use with antihistaminicsDosage : 48mg in divided doses
  29. 29. ANTIEMETICSAntidopaminergic Antiserotonergic Antimuscaranic• Metaclopromide • Ondansterone • Procloperazine• Domperidon • Cinnarizine
  30. 30. 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 .
  31. 31. MIGRAINE RELATED VERTIGO Avoidance of triggers Abortive therapy Preventive therapy
  32. 32. MIGRAINE ABORTIVE THERAPYTriptans 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
  33. 33. TRIPTANSTriptans act by binding to serotonin 5-HT.sub.1Band 5-HT.sub.1D receptors in cranial bloodvessels (causing their constriction) andsubsequent inhibition of pro-inflammatoryneuropeptide release.
  34. 34. TRIPTANS Sumatriptan  Oral – 25- 100mg  Nasal spray – 5-25mg  Subcut. – 6mg Zolmitriptan  Oral- 1.25-2.5mg  Nasal spray Rizatriptan  5-10 mg
  35. 35. 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]
  36. 36. 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
  37. 37. 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.
  38. 38. FLUNARIZINE Dosage : 5-10mg hs Contrindications:  Pregnancy and lactation  GI & Urinary tract obstruction  Porphyria Special precautions :  Driving  Elderly  CVS disease
  39. 39. 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
  40. 40. BOTULINUM TOXOID Botulin toxin or botox -toxin produced by the Clostridium botulinum. Interferes with release of acetylcholine at neuromuscular junction leading paralysis of muscles.
  41. 41. 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
  42. 42. STEROIDSUses 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
  43. 43. 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
  44. 44. GINGKO BILOBA : MODE OF ACTION ↑blood supply to brain & peripheral vascular systemScavenging of free radicals Antagonist of PAF to ↑ microvascular permeability↑ glucose uptake in brain Thrombolytic & vasoprotective Inhibition of MAO
  45. 45. 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
  46. 46. DIURETICS IN MENIERE’S DISEASE Triamterene 50mg with hydrochlorthiazide 50mg Frusemide – 40mg /day Spironolactone – 100mg /day
  47. 47. PIRACETAM Cyclic derivative of GABA Decreases vertigo of central origin Decreases frequency and severity of exacerbations in chronic & recurrent vertigo
  48. 48. PIRACETAM : MODE OF ACTION Restored membrane fluidity Reoganization of lipid molecules with formation of drug- Interaction with phospholipid polar headsof complex phospholipid membrane
  49. 49. RESTORED MEMBRANE FLUIDITY • Improves • Neurotransmission, Neuronal • Neuroplasticity effects • Interhemispheric info transfer • RBC deformability Vascular • adhesion of RBC prevents vasospasm effects
  50. 50. PIRACETAM : MODE OF ACTIONImproved neuronal Improved function microcirculation Facilitates vestibular compensation and adaptability
  51. 51. 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.
  52. 52. 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
  53. 53. Gentamycin passes RW→Perilymph to endolymphGENTAMYCIN : MODE OF ACTION Damage to mitochondria Death of vestibular cells Damage to dark cells of secretory epithelium Reduces endolymphatic production
  54. 54. 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.
  57. 57. BENZODIAZAPINES• Effective in anxiety, panic disorders, agorophobia• Ineffective in depression• Addictive, sedative• Inhibits vestibular compensation
  58. 58. ANTI DEPRESSANTSTricyclic antidepressants Strong anticholinergics May precipitate orthostatic hypotension Imipramine : 25mg TID Nortryptaline : 25-50mg BD
  59. 59. 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
  60. 60. “Only a dose can make a remedypoisonous…” PARCELUSAn incorrectly prescribed drug can alsomake a remedy poisonous.Judicious use of medicines remains thekey in vertigo.