FarmakologiFarmakologi ObatObat GangguanGangguan

SarafSaraf

M. M. BakhriansyahBakhriansyah, H., dr., , H., dr., M.KesM.Kes, , M.Med.EdM.Med.Ed

BagianBagian FarmakologiFarmakologi FK UNLAM FK UNLAM BanjarbaruBanjarbaru

Status Status EpilepticusEpilepticus

•• SE : SE : –– Continues seizures Continues seizures occuringoccuring 30 minutes 30 minutes ((epilepsiepilepsi foundation)foundation)

–– More than 30 minutes More than 30 minutes of continues seizures of continues seizures activity or 2 or more activity or 2 or more sequential seizures sequential seizures without full recovery of without full recovery of consciousness consciousness between seizures between seizures (Dodson, 1993)(Dodson, 1993)..

•• Systemic and primary brain changes Systemic and primary brain changes �� related related

to morbidity and mortality ratesto morbidity and mortality rates

–– Decreasing GABA inhibition. Decreasing GABA inhibition.

–– Increasing blood pressure (early stage) Increasing blood pressure (early stage) �� decreasingdecreasing

–– Acidosis (+)Acidosis (+)

–– Pulmonary edemaPulmonary edema

–– HyperthermiaHyperthermia

–– Mild Mild leukocytosisleukocytosis

–– GABAergicGABAergic mechanism failsmechanism fails

•• Goal of therapy: to treat the epilepsy and to Goal of therapy: to treat the epilepsy and to minimaliseminimalise the side effectsthe side effects

Principal therapy:Principal therapy:

•• MonotherapyMonotherapy is better than is better than polypharmacypolypharmacy

•• Dosage is increased until the therapeutic effect Dosage is increased until the therapeutic effect or toxicity effect are met. or toxicity effect are met.

•• PolypharmacyPolypharmacy is introduced when is introduced when monotherapymonotherapydoes not workdoes not work

•• Avoiding the sudden withdrawal Avoiding the sudden withdrawal

Treatment flowchart for status Treatment flowchart for status

epilepticusepilepticus

Medications Medications

BarbituratBenzodiazepinAsam valproatGabapentin

Lamotrigin

FenitoinKarbamazepinAsam valproatEtosuksimid

FenitoinKarbamazepin

GABA

Glutamate

Ca

Na

STATUS EPILEPTICUS

Klonazepam

Felbamat

Primidon

Asam valproat

Lamotrigin

KlonazepamGabapentin*

Lamotrigin

Primidon

Fenobarbital

Alternative

Asam valproatKarbamazepin

Fenitoin

Fenobarbital

Etosuksimid

Asam valproat

Karbamazepin

Fenitoin

Asam valproat

First line

Atonik,

MioklonikGrand malPetit malParsial

Parkinson diseaseParkinson disease

•• A progressive A progressive neurodegenerative neurodegenerative disorder associated disorder associated with loss of with loss of dopaminergicdopaminergicnigrostriatalnigrostriatal neurons.neurons.

•• Distinctive features:Distinctive features:–– Resting tremor, Resting tremor, rigidity, rigidity, bradikinetiabradikinetia, , and postural instability and postural instability

Principle therapyPrinciple therapy

•• Increasing the Increasing the synthesis and release of synthesis and release of dopamine (Ldopamine (L--dopa+karbidopadopa+karbidopa, , amantadinamantadin))

•• Inhibiting Inhibiting dopamindopaminmetabolism metabolism ((selegilin/deprenilselegilin/deprenil))

•• Activating dopamine Activating dopamine receptor receptor ((bromocriptinebromocriptine, , pergolidepergolide))

•• Blocking Blocking muscarinicmuscarinic/ /

cholinergic receptor cholinergic receptor

((trihexiphenidiletrihexiphenidile, ,

benzathropinebenzathropine, ,

diphenhidraminediphenhidramine))

To facilitate action of dopaminergic To suppress action of cholinergic

Anti cholinergicAmantadine

L-dopa+karbidopa

Dopamine agonists drugsMAO B inhibitors

Protocol of therapyProtocol of therapy

LL--dovadova ((levodopalevodopa))

•• Dopamine precursor Dopamine precursor �� inactive forminactive form

•• Activated by Activated by decarboxilasedecarboxilaseenzyme;enzyme;–– Brain Brain

–– Lever & kidneys Lever & kidneys �� can can not pass through BBB not pass through BBB �� bioavailability bioavailability countered by countered by karbidopa/benserazidekarbidopa/benserazide..

•• On/off phenomenon On/off phenomenon

(+) after 3(+) after 3--5 years 5 years

application application ��

mechanism ??? mechanism ???

Desensitization of Desensitization of

dopamine receptordopamine receptor

•• Not a first line Not a first line

therapy therapy

Headache/Headache/CephalgiaCephalgia

•• MigraineMigraine

•• Tension headacheTension headache

•• Cluster headacheCluster headache

MigraineMigraine

•• Mechanism: Mechanism:

–– GeneticGenetic

–– VascularVascular

–– Neural Neural

–– Neurotransmitter serotoninNeurotransmitter serotonin

–– Neurotransmitter dopamineNeurotransmitter dopamine

–– Activation of Activation of symphaticsymphatic

nervous systemnervous system

•• NSAIDsNSAIDs + caffeine + caffeine ((asetaminophenasetaminophen, acetic , acetic salicilicsalicilic acid, etc)acid, etc)

•• Serotonin receptor Serotonin receptor agonists (ergotamine, agonists (ergotamine, dihidroergotaminedihidroergotamine, , sumatriptanesumatriptane, , naratriptanenaratriptane, , rizatriptanerizatriptane, , zolmatriptanezolmatriptane))

•• Dopamine antagonist Dopamine antagonist ((metochlopramidemetochlopramide, CPZ, , CPZ, proCPZproCPZ) )

Protocol of therapyProtocol of therapy

Serotonin receptor agonists (SC/IM/IV), orDopamine receptor antagonist (IM/IV)

Serotonin receptor agonists (oral/nasal/SC), orDopamine receptor antagonist (oral)

NSAIDs, orSerotonin receptor agonist (oral)

Severe migraine

Moderate migraine

Mild migraine

NSAIDsNSAIDs

•• SE: SE: dispepsiadispepsia

Stimulator of serotonin (5Stimulator of serotonin (5--HTHT11) receptors: ) receptors:

1.1. ergotamine, ergotamine, dihidroergotaminedihidroergotamine

•• Non selective 5Non selective 5--HTHT1 1 receptor agonistreceptor agonist

•• Contra indication: CHD, pregnancy, Contra indication: CHD, pregnancy,

peripheral blood vessel constriction, level peripheral blood vessel constriction, level

and kidney disorders.and kidney disorders.

Dopamine antagonistsDopamine antagonists

•• Adjuvant therapyAdjuvant therapy

•• Increasing gut Increasing gut

motilitymotility

•• Also could treat: Also could treat:

Nausea & vomit Nausea & vomit

PreventionPrevention

•• 3 times per month3 times per month

•• Beta blockers Beta blockers ((propanololpropanolol, , timololtimolol))

•• Anti convulsive agents Anti convulsive agents ((valproicvalproic acid)acid)

•• MAO inhibitors MAO inhibitors ((phenelzinephenelzine, , isokarbosazideisokarbosazide))

•• SerotonergicSerotonergic agents agents ((metisergidemetisergide, , siproheptadinesiproheptadine))

•• Ca antagonist (Ca antagonist (verapamilverapamil))

TensionTension headacheheadache

•• Usually bilateralUsually bilateral

•• Usually following anxiety or depressionUsually following anxiety or depression

•• Therapy:Therapy:

–– NSAIDsNSAIDs + + coffeinecoffeine

–– Muscle relaxant agentsMuscle relaxant agents

•• Prevention: Prevention: amitriptilineamitriptiline a.na.n

Cluster headacheCluster headache

•• PeriorbitalPeriorbital pain pain

(temporal bone pain)(temporal bone pain)

•• Some signs and Some signs and

symptoms related to symptoms related to

eyeseyes

•• Mechanism: ??? May Mechanism: ??? May

be be serotonergicserotonergic

transmission disordertransmission disorder

•• Therapy:Therapy:

–– PrednisonPrednison

–– LithiumLithium

–– MetisergidMetisergid

–– ErgotamineErgotamine

–– Na Na valproicvalproic

–– VerapamilVerapamil