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OBAT NEUROLOGI dan NEUROMUSKULAR M. Bakhriansyah, Bakhriansyah, H., dr., M.Kes, M.Kes, M.Med.Ed Bagian Farmakologi Banjarbaru
Sasaran Belajar Di akhir pembelajaran, pembelajaran, mahasiswa mampu memahami mekanisme kerja, kerja, indikasi dan efek samping obat: obat: 1.Antikonvulasi 2.Hipnotik sedatif 3.Parkinson 4.Pelemas Otot 5.Anestesi Umum 6.Anestesi Lokal
Status Epilepticus ► SE
:
Continues seizures occuring 30 minutes (epilepsi foundation) More than 30 minutes of continues seizures activity or 2 or more sequential seizures without full recovery of consciousness between seizures (Dodson, 1993). 1993).
► Systemic
and primary brain changes related to morbidity and mortality rates
Decreasing GABA inhibition. Increasing blood pressure (early stage) decreasing Acidosis (+) Pulmonary edema Hyperthermia Mild leukocytosis GABAergic mechanism fails
► Goal
of therapy: to treat the epilepsy and to minimalise the side effects
Principal therapy: ► Monotherapy is better than polypharmacy ► Dosage is increased until the therapeutic effect or toxicity effect are met. ► Polypharmacy is introduced when monotherapy does not work ► Avoiding the sudden withdrawal
Treatment flowchart for status epilepticus
Medications Fenitoin Karbamazepin
Lamotrigin
Na
Glutamate
STATUS EPILEPTICUS
GABA
Barbiturat Benzodiazepin Asam valproat Gabapentin
Karbamazepin ► Stabilize neural membrane by decreasing Na, Ca and K flows through it. ► avoid to be given with MAO inhibitor consecutively
Ca Fenitoin Karbamazepin Asam valproat Etosuksimid
Fenitoin ► Difenilhidantoin derivate ► Mechanism of actions are similar to Karbamazepin ► Could be given orally, intra venous and intra muscular
Valproic Acid ► Increasing GABA transmission ► Sedation effect is minimal
Etosuksimid ► Mechanism of action is unknown ► Probably by inhibiting Ca channel
Phenobarbital ► Stimulating GABA receptor ► SE: sedation, nistagmus, nistagmus, ataxia and allergy ► Inducing enzym P450
Primidon ► Mechanism of actions are unknown ► Its active metabolit has long half life
Gabapentin ► GABA agonist ► Adjuvant therapy
Lamotrigin ► Stabilizing neuron and affecting glutamate release ► Adjuvant therapy ► SE: rash (prominent)
Klonazepam ► Stimulating GABA receptor
Felbamat ► Stimulating GABA receptor and inhibiting NMDA receptor ► Used unun-frequently
Parkinson disease ►A
progressive neurodegenerative disorder associated with loss of dopaminergic nigrostriatal neurons.
► Distinctive
features:
Resting tremor, rigidity, bradikinetia, bradikinetia, and postural instability
Principle therapy To facilitate action of dopaminergic
►
►
►
Increasing the synthesis and release of dopamine (L(L-dopa+karbidopa, dopa+karbidopa, amantadin) amantadin) Inhibiting dopamin metabolism (selegilin/deprenil) selegilin/deprenil) Activating dopamine receptor (bromocriptine (bromocriptine,, pergolide) pergolide)
To suppress action of cholinergic
►
Blocking muscarinic/ muscarinic/ cholinergic receptor (trihexiphenidile, trihexiphenidile, benzathropine, benzathropine, diphenhidramine) diphenhidramine)
Protocol of therapy Anti cholinergic Amantadine
L-dopa+karbidopa
Dopamine agonists drugs MAO B inhibitors
L-dova (levodopa) levodopa) ► Dopamine precursor inactive form ► Activated by decarboxilase enzyme; Brain Lever & kidneys can not pass through BBB bioavailability countered by karbidopa/benserazide. karbidopa/benserazide.
► Interaction:
piridoxine
increases decarboxilated reaction. ► On/off phenomenon (+) after 33-5 years application mechanism ??? Desensitization of dopamine receptor ► Not a first line therapy
Selegiline (deprenil) deprenil) ► Instead of inhibiting metabolism of dopamine: Stimulating dopamine release. NeuroNeuro-protective effect ►
+ MOA inhibitors crisis of hypertension.
Trihexiphenidile & benzotropine ► Action: less than LLdopa ► Adjuvant therapy ► Tapering dose
Bromociptine & Pergolide ► Dopamine receptor agonists ► Action: Lesser than LL-dopa ► As a single therapy at the early stage ► Combination with LL-dopa at the moderate and late stage. ► Tapering dose
Diphenhidramine ► Anti cholinergic effect at central level ► Anti histamine
Amantadine ► Anti virus ► Mechanism: ??? May be by facilitating dopamine release ► Action: Less than LL-dopa Better than anti cholinergic
►
Early stage: Anti cholinergic or Amantadine
►
►
When early stage therapy is not effective, LLdopa+karbidopa are started. Final stage: dopamine agonists medications and MAO inhibitors.
Headache/Cephalgia ► Migraine ► Tension
headache ► Cluster headache
Migraine ►
Mechanism:
►
Genetic Vascular Neural Neurotransmitter serotonin Neurotransmitter dopamine Activation of symphatic nervous system
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►
NSAIDs + caffeine (asetaminophen, asetaminophen, acetic salicilic acid, etc) Serotonin receptor agonists (ergotamine, dihidroergotamine, dihidroergotamine, sumatriptane, sumatriptane, naratriptane, naratriptane, rizatriptane, rizatriptane, zolmatriptane) zolmatriptane) Dopamine antagonist (metochlopramide, metochlopramide, CPZ, proCPZ) proCPZ)
Protocol of therapy Mild migraine
NSAIDs, or Serotonin receptor agonist (oral)
Moderate migraine
Serotonin receptor agonists (oral/nasal/SC), or Dopamine receptor antagonist (oral)
Heavy migraine
Serotonin receptor agonists (SC/IM/IV), or Dopamine receptor antagonist (IM/IV)
NSAIDs ► SE: dispepsia Stimulator of serotonin (5(5-HT1) receptors: 1. ergotamine, dihidroergotamine ► Non selective 55-HT1 receptor agonist ► Contra indication: CHD, pregnancy, peripheral blood vessel constriction, level and kidney disorders.
2. triptan ► Selective 5-HT1 receptor agonist ► Rizatriptan: quickest onset, highest efficacy ► Naratriptan: in contrast ► Monotherapy is unadvisable ► Contra indication: cardiovascular diseases
Dopamine antagonists ► Adjuvant therapy ► Increasing gut motility ► Also could treat: Nausea & vomit
Prevention ► 3 times per month ► Beta blockers (propanolol (propanolol,, timolol) timolol) ► Anti convulsive agents (valproic acid) ► MAO inhibitors (phenelzine, phenelzine, isokarbosazide) isokarbosazide) ► Serotonergic agents (metisergide, metisergide, siproheptadine) siproheptadine) ► Ca antagonist (verapamil (verapamil))
Tension headache ► Usually
bilateral ► Usually following anxiety or depression ► Therapy: NSAIDs + coffeine Muscle relaxant agents ► Prevention:
amitriptiline a.n
Cluster headache ► Periorbital
pain (temporal bone pain) ► Some signs and symptoms related to eyes ► Mechanism: ??? May be serotonergic transmission disorder
► Therapy:
Prednison Lithium Metisergid Ergotamine Na valproic Verapamil
