PHARMACOTERAPY IN NEUROLOGY

Wiwik Kusumawati

CONTENS

1. Drug used in Nausea and Vertigo (anti-emetics)

2. Anti-epileptic drugs3. Drug used in Parkinson

1. Drug used in Nausea and Vertigo (anti-emetics)

• Nausea and Vomiting• Drugs• Vestibular disease• Provocative movement• Migraine• Pregnancy

Nausea and Vomiting

• CTZ (Chemoreceptor Triger Zone)• D2 receptor• 5HT3 receptor• - BBB• Vomiting centre (lateral reticular formation of the

Medulla)• The vagus nerve• The spinal motor neurones-the abdominal muscles

Classification

• Dopamine antagonist : prochlorperazine, metoclopramide, domperidon

• 5HT3 antagonist : ondansetron, granisetron• Anticholinergic drugs : hyoscine• Antihistamines : cinnarizine, promethazine,

cyclizine

Drugs

• Cytotoxic drugs – CTZ• Metoclopramide - Dexamethazone• Ondansetron – Dexamethazone• Motion sickness – hyoscine, cinnarizine• Vestibular disease – antihistamine,

phenothiazines• Pregnancy - promethazine

Drugs

• Prochlorperazine • Phenothiazines derivate• Widely used• Less sedative• Severe distonic reaction

Drugs• Metoclopramide • Prokinetic action in the gut – increase absorbtion

many drugs• Effective in migraine• Distonic reaction – young and females• Domperidon • Does not pass BBB• Rarely causes sedation or extrapyramidal effect• Ondansetron – lack side effect but constipation or

headache

2. Anti-epileptic drugs

• Epilepsy• A chronic disease in which seizures result

from the abnormal discharge of cerebral neurones

• Partial (focal) seizures• Generalized seizures : tonic clonic (grand

mal), absences (petit mal)

Anti-epileptic drugs

• Etiology • Unknown 60 – 70 %• Heredity • Trauma, infection, tumors, etc.• Precipitating factors

Anti-epileptic drugs

• Tonic clonic and partial seizures• Carbamazepine, phenytoine and valproate• Phenoberbitone, primidone and

clonazepam

Status epilepticus

• A state in which fits follow each other without consciousness being regained

• Clonazepam or diazepam • Chlormethiazole

Mechanism of action

• GABA• Reduction Na+ fluxes• Inhibition spike-generating Ca+ current

Drugs used in partial and grand mal seizures

• Single drugs is preferred• Carbamazepine and valproate are the first

line drugs • Phenytoine, phenobarbitone : liver enzyme

inducer

Carbamazepine

• Is metabolized in liver• Has active metabolite – anti convulsant

effect and neurotoxic (nausea, drowsiness, headache, diplopia and ataxia)

• Agranulocytosis – idiosyncratic reaction• There is a linier increase in serum

concentration with dosage

Phenytoine

• Is hydroxylated in the liver by saturated enzyme system

• More 20 days – changing the dose ( steady state)

• The dose may be increase gradually – fits are prevented or nystagmus, ataxia, dysarthria

• A small increase in dose may produce toxic blood levels of drug

Phenobarbitone

• Is the one of metabolite active if primidone• As effective as carbamazepine or pheny

toine for tonic clonic and partial seizures • More sedative• Sudden withdrawal precipitate status

epilepticus • Side effect : cerebellar symptoms,

drowsiness and hiperkinesia

Ethosuximide

• Only effective in the treatment of absences and myoclonic seizures

Valproate

• Effective in grand mal and petit mal epilepsy

• Relative lack of sedative effect• Side effect : severe or fatal hepatic toxicity

(idiosyncratic)

Benzodiazepinesclonazepame

• Potent anticonvulsant, very sedative• Effective in absences, tonic clonic and

myoclonic seizures• Tolerance with prolonged oral

administration

3. Drug used in Parkinson

• Parkinson• Poverty of movement, rigidity and tremor • Decreased levels of dopamine in the basal

ganglia• 1/3 develop dementia • Dopamine replacement tx – NO• LEVODOPA

• A 58 years old woman who presents to the neurology clinic because of stiffness on her right side over the last 6 months. It takes her longer to do things because it take more effort to get movement started and her muscles feel stiff. For the last year she feels that she does not think as quickly and it takes her longer to remember thinks. She also complains of constipation and decreased libido for over a year. Recently it has become difficult to read because the word occasionally look blurry. These symptoms have affected her jobs performance as a high school gym teacher resulting in her contemplating early retirement.

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• Untuk kasus di atas manakah di antara kombinasi obat berikut yang merupakan best therapy ?

A.levodopa + carbidopa.B.levodopa + bromocriptin.C.levodopa + apomorphin.D.amantadin + carbidopa.E.amantadin + selegilin.

Parkinson

• Etiology• Drugs addict – pethidine – MAO• Degeneration of the nigrostriatal tract –

damage mitochondria and cell membrane• Neuroleptic drugs

Classification

• MAO Inhibitor : selegiline• Anticholinergic drugs : benzhexol,

benztropine, orphenadrine • Dopaminergic drugs : levodopa,

amantadine, bromocriptine, lysuride, apomorphine

Levodopa

• Immediate precursor of dopamine• Able penetrate the brain• Side effects : nausea-vomiting, psychiatric

disorder, postural hypotension

Bromocriptine

• A selective D2 agonist• Combination with levodopa – later stages• Side effects : similar to levodopa, inhibits

release prolactine & growth hormon

Apomorphine

• D1 and D2 agonist• SC injections• Advanced stages of parkinsonism

Amantadine

• Has muscarinic blocking agents• Dopamine release• Modest antiparkinson effect - tolerance

MAO Inhibitor

• Selegiline • Reduces metabolism of dopamine in the

brain• Potentiation with levodopa