FarmakologiFarmakologi ObatObatGangguanGangguan 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 between consciousness between seizures (Dodson, seizures (Dodson, 1993)1993)..

►► Systemic and primary brain changes Systemic and primary brain changes related to related to morbidity and mortality ratesmorbidity and mortality rates

Decreasing GABA inhibition. Decreasing GABA inhibition. Increasing blood pressure (early stage) Increasing blood pressure (early stage) decreasingdecreasingAcidosis (+)Acidosis (+)Pulmonary edemaPulmonary edemaHyperthermiaHyperthermiaMild Mild leukocytosisleukocytosisGABAergicGABAergic 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 or Dosage is increased until the therapeutic effect or

toxicity effect are met. toxicity effect are met. ►► PolypharmacyPolypharmacy is introduced when is introduced when monotherapymonotherapy

does not workdoes not work►► Avoiding the sudden withdrawal Avoiding the sudden withdrawal

Treatment flowchart for status Treatment flowchart for status epilepticusepilepticus

Medications Medications

BarbituratBenzodiazepinAsam valproat

Gabapentin

Lamotrigin

FenitoinKarbamazepinAsam valproatEtosuksimid

FenitoinKarbamazepin

GABA

Glutamate

Ca

Na

STATUS EPILEPTICUS

Parsial Petit mal Grand mal Atonik, Mioklonik

First line KarbamazepinFenitoinAsam valproat

EtosuksimidAsam valproat

KarbamazepinFenitoinFenobarbital

Asam valproat

Alternative Gabapentin*LamotriginPrimidonFenobarbital

Klonazepam PrimidonAsam valproatLamotrigin

KlonazepamFelbamat

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, rigidity, Resting tremor, rigidity, bradikinetiabradikinetia, and , and postural instability postural instability

Principle therapyPrinciple therapy

►► Increasing the synthesis Increasing the synthesis and release of dopamine and release of dopamine (L(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

decarboxilasedecarboxilase enzyme;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 therapy Not a first line therapy

Headache/Headache/CephalgiaCephalgia

►► MigraineMigraine►► Tension headacheTension headache►► Cluster headacheCluster headache

MigraineMigraine►► Mechanism: Mechanism:

GeneticGeneticVascularVascularNeural Neural Neurotransmitter serotoninNeurotransmitter serotoninNeurotransmitter dopamineNeurotransmitter dopamineActivation of Activation of symphaticsymphaticnervous 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, peripheral Contra indication: CHD, pregnancy, peripheral

blood vessel constriction, level and kidney blood vessel constriction, level and kidney disorders.disorders.

Dopamine antagonistsDopamine antagonists►► Adjuvant therapyAdjuvant therapy►► Increasing gut motilityIncreasing gut motility►► Also could treat: Nausea & Also could treat: Nausea &

vomit 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 + + coffeinecoffeineMuscle 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 serotonergicserotonergictransmission disordertransmission disorder

►► Therapy:Therapy:PrednisonPrednisonLithiumLithiumMetisergidMetisergidErgotamineErgotamineNa Na valproicvalproicVerapamilVerapamil