vertigo - alexorlalexorl.edu.eg/alexorlfiles/pptorl2007/156003.pdf · serotenergic pathway....
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Fatthi Abdel Baki MDAlexandia Medical School
VertigoPharmacotherapy
Neurotransmitters
Neurotransmitters
Post synaptic neuron
Post synaptic receptor
Pre synaptic neuron
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Excitatory or Inhibitory
Glutamate:Excitatory
GABA (2):
Inhibitory
Main Neurotransmitters
Excitatory or Inhibitory
• Depends on type of receptors:
– Acetyl choline Nicotinic & Muscarinic (5)– Dopamine (5) D1 to D5– Histamine (3) H1; H2;H3– Serotonin 5 HT (7)– Nitric oxide
Other Neurotransmitters
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Vestibular Lesion
Vestibular suppressants
Vestibular Stimulants
Management Plan
Acute Episode Speed recovery Target treatment
VertigoVomitingNystagmus
VasodilatorsRheologyOxygenationVestibular activity
MeniereVestibular neuritisVBIMigraineVascular loop
Vertigo
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Vestibular suppressants
Vestibularactivity
GABA
HistamineGlutamateCalcium ion
GABA (A) agonist:Benzodiazepines
GABA (B) agonist: Baclofen
Antihistamine:MeclizineCalcium channel
blockerCinnarazine
VomitingCentre
GIT
CTZVestibular
NucleiDopaminergic
pathway
hist
amin
ergi
c
path
way
SerotoninSerotoninblockersblockers(5HT3)(5HT3)
antihistamines antihistamines (H1)(H1)
DopamineDopamineantagonist antagonist
(D2)(D2)
Metoclopramide(Primperan)
Ondansetron(Zofran)
Meclizine
Antiemetics
Sero
ten
erg
icp
ath
way
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RheologyRBC …
Poor tissuePerfusion &oxygenation
Inner ear vessel
Poor vestibular activity
Vasodilators
Vasoactive
Oxygenator
Vestibularstimulants
Histamine agonistsCalcium blockersPentoxyphyllineOxybralGinko
Buflomedil Calcium blockersPentoxyphylline
almitrine + raubasineBuflomedilVincaminevinpoctineHistamine agonists
PiribidilPiracetamGinko
Speed Recovery
vestibularSuppressant
Antiemetic
VasoDilator
Vasoactive
O 2 vestibularStimulant
Antihistamine + +
Benzodiazepam +
Cinnarazine + + +
Betahistine + +
Vicamine + +
almitrine + raubasine
+
Buflomidil + +
Pirebidil + +
Pentoxyphilline + +
Ginko + +
Drugs: mechanism of Action
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Side Effects / Precautions
Antihistamine Sedation; anticholinergic; extrapyramidal
Benzodiazepam Sedation; habituation
Betahistine Bronchial asthma
Cinnarizine Sedation
Vincamine Hypotension
Almitrine + Raubasine
Drowsiness
Buflomedil GIT
Pirebidil GIT
Pentoxyphylline Flushing/headache
Drugs: Side effects
BetahistineBetaserc
• Widely used for the management of vertigo.• UK (Meniere’s): 94% betahistine; 63%
diuretics• Not approved by the FDA • Randomized controlled trial: controversial
– No EBM– Recent large study (144) showed
statistically significant improvement• Dose 16-32 mg three times/day for 2 to 40 w• Do not use with antihistamine
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Beta-Histine
Action
Post-synaptic
Microcirculation ofinner ear and brain
Central activity vestibular nuclei
Vestibularcompensation
Pre
synaptic
H
H
H3
H
BH
HistaminergicNerve ending
Buflomedil HClLoftyl
RBC’s deformability
RBC’s aggregation
Platelet aggregation
Leukocytic adherence to vessel wall
Tissue Perfusion
Tissue Oxygenation
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Alimintrine bismesylate / rabusineDuxil
Increases Oxygen availabilityIncreases Oxygen availability Increases Oxygen utilizationIncreases Oxygen utilization
VincamimeOxybral
• Increase cerebral flow
• Increase oxygen capture and utilization by the hypoxic neurons.
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Dopamine agonistsPiribedil
•• Compensate deficient Dopaminergic Compensate deficient Dopaminergic neurotransmission (aging)neurotransmission (aging)
•• Reducing the sympathetic vasoReducing the sympathetic vaso--constrictingconstrictingtone.tone.
Ginko
• Reduces the viscosity of the blood
• Anti-oxidant.
• Enhance vestibular compensation in animals
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Target treatment
• Meniere
• Vestibular neuritis
• VBI
• Migraine
Vertigo
Prophylaxis
• Vasodilators
• Diuretics and dietary salt restriction – in salt sensitive persons
• Glucocorticoids– in salt insensitive persons
• Chemical labyrinthectomy
Meniere
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Vasodilators
• Betahistine (an oral histamine analogue)
• Role of Betahistine in Meniere disease:– No EBM
Meniere
Ions Homeostasis
VasopressinAldosterone
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Ions HomeostasisMeniere
IncreaseVasopressinAldosterone
DiureticSteroids
Diuretics
• Potassium loosing diuretics (Thiazide) – Multiple undesirable side effects
• Potassium sparing diuretic (Spironolactone)– Homeostasis theory
• Combined (Thiazide+ Amiloride)• Role of diuretics in Meniere:
– No EBM
Meniere
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Intra- tympanic steroids
Methyl prednisolone: solumederol
• Advantage:– Higher concentration in endolymph and perilymph
after administration
• Disadvantage:– Slow absorption from endolymph into stria. It remain
in endolymph longer than dexa by 6hs– Painful
Meniere
Intra- tympanic steroidsDexamethasone: (fortacorten)
• Advantage:– Faster absorption and diffusion from endolymph into
stria and surrounding tissue (steroid act intracellular)
• Disadvantage:– Need high concentration; 24mg /ml not available in
market
• Dose:– 24mg (compounding) /cc / week (2
treatment) most effective in early stage
Meniere
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Intratympanic gentamycinProtocol
• Base line caloric before injection to determine degree of vestibular function in the other ear
• Standard protocol– 0.3-0.6 ml of gentamycin 40mg /ml (12-24 mg)– Repeated weekly till end points
• Low dose protocol– Single dose protocol– Injection of low concentration (10mg/ml)– Repeated after 2-4 weeks if vertigo remains
Meniere
Intratympanic injectionsEnd Point
• Hearing worsened– PTA increase > 15db
in 3 consecutive freq. – SDS fell > 20 %
• Nystagmus– Spontaneous paralytic– Head shaking– Head thrust
• 4 scheduled treatment
Head shaking
Head thrust
Meniere
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Intractable vertigoProtocol
• Early stage: Mild / fluctuant hearing loss:– Intra-tympanic steroids if failed– Vestibular neurectomy
• Advanced stage: Moderate/ severe HL with poor discrimination:– Intra- tympanic gentamycin
Meniere
Management
• Vestibularsuppressant(3 days)
• Steroids
• Antiviral
• Vestibular Rehab.
Vestibular neuritis
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Management
• Treatment of risk factors:– Hyperlipidemia; hypertension; diabetes;
smoking
• Drugs– Antiplatelet: Aspirin; plavix; persantin
• Neck care– Collars; Physiotherapy Cautions neck
movements
VBI
Management
• Trigger factors: avoidance• Drugs:
– Beta blockers: • Propanolol
– Calcium channel blockers:• Cinnarazine
– TCA antidepressant:• Amitryptiline (tryptizol)
– Novel antiepileptic: • Topamax
Migraine
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Other conditions• Motion sickness • Orthostatic hypotension • Psychogenic Vertigo (hyperventilation)• Juvenile vertigo• Senile vertigo "presbyastasis" • Microvascular compression• Bilateral vestibular loss• Treatment of undetermined or ill defined
cause of vertigo
Management
• Prevention:– Anticholinergic (scopolamine) pure anticholinergics
are ineffective if administered after symptoms have already appeared
• Treatment:– Calcium channel blockers: Cinnarizine– Antihistamine: Dramamine
Motion Sickness
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Nonpharmacologic treatment
• Slow, careful changes in position, especially on arising in the morning
• Avoidance of hot environments and hot showers or baths
• Multiple small meals
• Increased salt ;fluid and caffeine intake
Orthostatic Hypotension
Pharmacologic treatment
• Removal of medications that exacerbate hypotension when possible
• Fludrocortisone (Florinef)
• Midodrine (ProAmatine)
• Sympathomimetics
• Erythropoietin
Orthostatic Hypotension
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Management
• Drugs:– Benzodiazepines– SSRI (selective serotonin reuptake inhibitors eg
cipralex ) less effectiveness but less habituation
• Breath into a bag in the event of an attack
• Psychiatric consultation is suggested.
Psychogenic vertigo
Management
• Antiepiletics– low dose– where the frequency
of the attacks is more than once a week..
BPV of childhood
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Management
• Anti-convulsants:– Carbamazepine (Tegretol)– Gabapentin (Neuronton)
Microvascular compression
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Thank you
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