Obat Neurologi dan Neuromuskular PSIK R - Drug Addicts · PDF fileOBAT NEUROLOGI dan...
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OBAT NEUROLOGI OBAT NEUROLOGI dandan
NEUROMUSKULARNEUROMUSKULAR
M. M. BakhriansyahBakhriansyah, H., dr., , H., dr., M.KesM.Kes, , M.Med.EdM.Med.Ed
BagianBagian FarmakologiFarmakologi
BanjarbaruBanjarbaru
SasaranSasaran BelajarBelajar
DiDi akhirakhir pembelajaranpembelajaran, , mahasiswamahasiswa mampumampu
memahamimemahami mekanismemekanisme kerjakerja, , indikasiindikasi dandan efekefek
sampingsamping obatobat::
1.1.AntikonvulasiAntikonvulasi
2.2.HipnotikHipnotik sedatifsedatif
3.3.ParkinsonParkinson
4.4.PelemasPelemas OtotOtot
5.5.AnestesiAnestesi UmumUmum
6.6.AnestesiAnestesi LokalLokal
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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) �� decreasingdecreasing
�� Acidosis (+)Acidosis (+)
�� Pulmonary edemaPulmonary edema
�� HyperthermiaHyperthermia
�� Mild Mild leukocytosisleukocytosis
�� GABAergicGABAergic mechanism failsmechanism fails
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►► 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 monotherapymonotherapydoes not workdoes not work
►► Avoiding the sudden withdrawal Avoiding the sudden withdrawal
Treatment flowchart for status Treatment flowchart for status
epilepticusepilepticus
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Medications Medications
BarbituratBenzodiazepinAsam valproatGabapentin
Lamotrigin
FenitoinKarbamazepinAsam valproatEtosuksimid
FenitoinKarbamazepin
GABA
Glutamate
Ca
Na
STATUS EPILEPTICUS
KarbamazepinKarbamazepin
►► Stabilize neural Stabilize neural
membrane by membrane by
decreasing Na, Ca and decreasing Na, Ca and
K flows through it.K flows through it.
►► avoid to be given with avoid to be given with
MAO inhibitor MAO inhibitor
consecutivelyconsecutively
FenitoinFenitoin
►► DifenilhidantoinDifenilhidantoin
derivatederivate
►►Mechanism of actions Mechanism of actions
are similar to are similar to
KarbamazepinKarbamazepin
►► Could be given orally, Could be given orally,
intra venous and intra intra venous and intra
muscularmuscular
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ValproicValproic AcidAcid
►► Increasing GABA Increasing GABA
transmission transmission
►► Sedation effect is Sedation effect is
minimalminimal
EtosuksimidEtosuksimid
►►Mechanism of action Mechanism of action is is
unknownunknown
►► Probably by inhibiting Probably by inhibiting
Ca channelCa channel
PhenobarbitalPhenobarbital
►► Stimulating GABA Stimulating GABA
receptorreceptor
►► SE: sedation, SE: sedation,
nistagmusnistagmus, ataxia and , ataxia and
allergyallergy
►► Inducing Inducing enzymenzym P450 P450
PrimidonPrimidon
►►Mechanism of actions Mechanism of actions
are unknownare unknown
►► Its active Its active metabolitmetabolit
has long half lifehas long half life
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GabapentinGabapentin
►► GABA agonist GABA agonist
►► Adjuvant therapyAdjuvant therapy
LamotriginLamotrigin
►► Stabilizing neuron and Stabilizing neuron and
affecting glutamate affecting glutamate
releaserelease
►► Adjuvant therapyAdjuvant therapy
►► SE: rash (prominent)SE: rash (prominent)
KlonazepamKlonazepam
►► Stimulating GABA Stimulating GABA
receptor receptor
FelbamatFelbamat
►► Stimulating GABA Stimulating GABA
receptor and inhibiting receptor and inhibiting
NMDA receptorNMDA receptor
►► Used unUsed un--frequentlyfrequently
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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
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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..
►► Interaction: Interaction: piridoxinepiridoxineincreases increases decarboxilateddecarboxilatedreaction. reaction.
►► 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
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SelegilineSelegiline ((deprenildeprenil))
►► Instead of inhibiting Instead of inhibiting
metabolism of dopamine:metabolism of dopamine:
�� Stimulating dopamine Stimulating dopamine
release.release.
�� NeuroNeuro--protective effect protective effect
►► + MOA inhibitors + MOA inhibitors �� crisis crisis
of hypertension. of hypertension.
BromociptineBromociptine & & PergolidePergolide
►► Dopamine receptor Dopamine receptor
agonists agonists
►► Action: Lesser than LAction: Lesser than L--dopadopa
►► As a single therapy at the As a single therapy at the
early stageearly stage
►► Combination with LCombination with L--dopa dopa
at the moderate and late at the moderate and late
stage. stage.
►► Tapering dose Tapering dose
TrihexiphenidileTrihexiphenidile & &
benzotropinebenzotropine
►► Action: less than LAction: less than L--
dopadopa
►► Adjuvant therapyAdjuvant therapy
►► Tapering doseTapering dose
DiphenhidramineDiphenhidramine
►► Anti cholinergic effect Anti cholinergic effect
at central level at central level
►► Anti histamineAnti histamine
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AmantadineAmantadine
►► Anti virusAnti virus
►► Mechanism: ??? May be by Mechanism: ??? May be by
facilitating dopamine facilitating dopamine
releaserelease
►► Action:Action:
�� Less than LLess than L--dopadopa
�� Better than anti cholinergicBetter than anti cholinergic
►► Early stage:Early stage:
�� Anti cholinergic orAnti cholinergic or
�� AmantadineAmantadine
►► When early stage therapy When early stage therapy
is not effective, Lis not effective, L--
dopa+karbidopadopa+karbidopa are are
started.started.
►► Final stage: dopamine Final stage: dopamine
agonists medications and agonists medications and
MAO inhibitors. MAO inhibitors.
Headache/Headache/CephalgiaCephalgia
►►MigraineMigraine
►► Tension headacheTension headache
►► Cluster headacheCluster headache
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MigraineMigraine
►► Mechanism: Mechanism: �� GeneticGenetic
�� VascularVascular
�� Neural Neural
�� Neurotransmitter serotoninNeurotransmitter serotonin
�� Neurotransmitter dopamineNeurotransmitter dopamine
�� Activation 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)
Heavy migraine
Moderate migraine
Mild migraine
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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.
2. 2. triptantriptan
►► Selective 5Selective 5--HTHT11 receptor agonistreceptor agonist
►► RizatriptanRizatriptan: quickest onset, highest : quickest onset, highest
efficacyefficacy
►► NaratriptanNaratriptan: in contrast: in contrast
►► MonotherapyMonotherapy is unadvisableis unadvisable
►► Contra indication: cardiovascular diseasesContra indication: cardiovascular diseases
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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 + + coffeinecoffeine
�� Muscle relaxant agentsMuscle relaxant agents
►►Prevention: Prevention: amitriptilineamitriptiline a.na.n
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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