TREATMENT MODALITIES OF VERTIGO Anticholinergics Antihistamines Benzodiazepines Ca Channel blockers GABA modulators Neurotransmitter reuptake inhibitors[SSRI,tricyclic antidepressants] Nootropics
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
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 INTACT DAMAGED recommended Vestibular Nuclei for long term use They should be discontinued as 22: 1651-9 Lacour M. Curr Med Res Opion 2006;
Nerve terminal Influx of Ca ions Release of Ach activated
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
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
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-dopaminergic effect Effective in acute vertigo and vomiting S/E – CNS depressant Extrapyramidal reactions Hypotension Dosage: 5-25mg TID Stemetil
MECLIZINE 1ST line of treatment for vertigo in USA Less anticholinergic activity than other antihistamines Also effective in sea sickness Diligan,Pregnidoxin
CINNARIZINE : MODE OF ACTION Antihistaminic • Anticholinergic effect effect • Reduced irritability Ca channel of labyrinth blocker • Reduced blood viscosity • Antivasoconstrictive effect • Stabilizes vascular endothelium
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.
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
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”
BETAHISTINEContraindications : Bronchial asthma Peptic ulcer Phaeochromocytoma Porphyria Concurrent use with antihistaminicsDosage : 48mg in divided doses
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 .
MIGRAINE RELATED VERTIGO Avoidance of triggers Abortive therapy Preventive therapy
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
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.
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
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
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 systemScavenging of free radicals Antagonist of PAF to ↑ microvascular permeability↑ glucose uptake in brain Thrombolytic & vasoprotective Inhibition of MAO
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 Restored membrane fluidity Reoganization of lipid molecules with formation of drug- Interaction with phospholipid polar headsof complex phospholipid membrane
RESTORED MEMBRANE FLUIDITY • Improves • Neurotransmission, Neuronal • Neuroplasticity effects • Interhemispheric info transfer • RBC deformability Vascular • adhesion of RBC prevents vasospasm effects
PIRACETAM : MODE OF ACTIONImproved neuronal Improved function microcirculation Facilitates vestibular compensation and adaptability
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.
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 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
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.
BENZODIAZAPINES• Effective in anxiety, panic disorders, agorophobia• Ineffective in depression• Addictive, sedative• Inhibits vestibular compensation
ANTI DEPRESSANTSTricyclic 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 remedypoisonous…” PARCELUSAn incorrectly prescribed drug can alsomake a remedy poisonous.Judicious use of medicines remains thekey in vertigo.