PHARMACOLOGY
ELLY NURUS SAKINAH
NEUROTRANSMITTER
Neurotransmitter Kelebihan Kekurangan
Asetilkolin Delirium, psikosis Penyakit alzeimer
Dopamine Psikosis, sindrom Parkinson, depresi
Tourette, chorea
GABA Depresi CNS, Sedasi Kejang, gangguan
gerak
Glutamat Kejangn degenerasi Skizofren, depresi,
neuron gangguan kognitif
Norepinefrin Ansietas, panic, Depresi
anoreksia, insomnia
Serotonin Tidur, halusinasi, Depresi, sensitive
penurunan nafsu nyeri,ansietas
makan, ansietas
TARGET MOLEKULAR FARMAKOLOGI
SISTEM SARAF PUSAT
SEDATIF HIPNOTIK
Benzodia zepin
Teori neurobiologi terjadinya gangguan
anxietas
Kelebihan serotonin (5-HT) dan kekurangan NT
noradrenergic
Kekurangan GABA
Kelebihan Glutamat
Penurunan BDNF (Brain-derived neurotropic factor)
OBAT SEDATIF-HIPNOTIK
BENZODIAZEPINE (BZD)
BARBITURAT
“Z” DRUG
RAMELTEON
BUSPIRON
BENZODIAZEPINE
FARMAKOKINETIK
Rates of oral absorption : lipophilicity major role drug
enters the CNS
Triazolam, barbiturat, newer hypnotics more rapid
Clorazepate prodrug, active desmethyldiazepam
(nordiazepam)
Cross the placental barrier depression of neonatus
Also detectable in breast milk depressant effect of nursing
infant
Biotransformation
Phase 1 (CYP3A4), phase II (eventually excreted as glucuronide
conjugates in the urine)
Understanding of the importance of drug half life
in determining appropriate drug therapy and
minimizing adverse effects
Obat penenang ideal:
Menenangkan, day time sedation -, ketergantungan
fisik/psikis -, TI lebar
Obat tidur yg ideal:
Onset of sleep cepat, mempertahankan kualitas dan
lamanya tidur, hang over -, ketergantungan
fisik/psikis -
Drug Tmax(hr) T1/2 (hr) Comments
BZD
Generalized seizure
Tonic clonic Carbamazepine Phenobarbital / primidone
Valproate Vigabatrine
Lamotrigine Phenytoin
Phenytoin
Myoclonic Valproate
Ethosuximide
Clonazepam
absence Ethosuximide Clonazepam
Valproat lamotrigine
Adverse effect antiseizure drug
Drug Adverse effect
BZD Sedasi, toleransi, dependence
Carbamazepine Diplopia, g3 kognitif, pusing, ataxia, SJS, teratogenik, blood
dyscrasia
Ethosuximide GI distress, letargi, headache, gangguan perilaku
Gabapentin Dizzines, sedasi, ataxia, nistagmus
Lamotrigine Dizzines, ataxia, nausea, rash, SJS
Phenobarbital Sedasi, g3 kognitif, toleransi, dependence, induksi enzim
metabolisme di hepar
Phenytoin Nistagmus, diplopia, sedasi, hiperplasi gingiva, hirsutism,
anemia, neuropati, osteoporosis, induksi enzim di hepar
Tiagabine Abdominal pain, nausea, dizzines, tremor, astenia
Topiramate Drowsiness, dizzines, ataxia, kelemahan psikomotor,
gangguan memori, parestesi, weight loss, miopia
Valproate Drowsiness, nausea, tremor, hair loss, weight gain,
hepatotoksik (infant), menghambat enzim di hepar
Drug interactions among
anticonvulsant
Carbamazepine (inducer p450)
Can lower plasma concentration of : clobazam, clonazepam,
lamotrigine, tiagabine, topiramat, valproate
Phenobarbital dan primidone (inducer p450)
Can lower plasma concentration of carbamazepine, clonazepam,
lamotrigine, tiagabine, phenytoin, valproate
Phenytoin (inucer p450)
Can lower plasma concentration of carbamazepine, clonazepam,
lamotrigine, tiagabine, valproate
Valproate (inhibition p450)
Increase plasma concentration of : phenobarbital, lamotrigine,
phenytoin
Anti Parkinson
Pathophysiology: degeneration of substantia
nigra neurons, which results in loss of dopamine
(DA) to striatum
Cardinal symptoms: bradykinesia (slowed movement),
rigidity, resting tremor, postural instability
Imbalance between dopamine and acetylcholine
in striatum
www.nwabr.org/.../pictures/whthppns.jpg
treatment strategies: can ↑
DA or Ach
Drugs for Parkinson’s disease
Amantadine
1. Levodopa
Mechanism:
(1) Because dopamine does not cross the blood-brain barrier,
levodopa the precursor of dopamine, is given instead.
(2) Levodopa itself has minimal pharmacologic activity, in
contrast to its decarboxylated product, dopamine.
ATYPICAL • CLOZAPINE
• LOXAPINE
Haloperidol +++ _ + - - -
Clozapine - ++ ++ ++ ++ +
Molindone ++ - + - + +
Olanzapine + - + ++ + +
Risperidone ++ - + ++ + +
ADVERSE EFFECT
• Gejala Parkinson • gerakan berulang involunter
• Acute dystonia pada lidah, wajah,
mulut/rahang dan anggota
• akathisia gerak.
EPS TD
• depression is related
to a deficiency in the
amount or function
of cortical and limbic
serotonin (5-HT),
norepinephrine (NE),
and dopamine (DA)
SSRI (selective
serotonin • Fluvoxamin, fluoxetine, paroxetin, sertralin
inhibitor)
• Tremors
• Tachycardia
Serotonin reuptake blockade
Possible clinical consequences
• Gastrointestinal disturbances
• Anxiety (dose – dependent)
• Sexual dysfunction
Dopaminergic uptake blockade
Possible clinical consequences
• Psychomotor activation
• Antiparkinsonian effects
• Psychoses
• Increased attention/concentration
Histamine H1 blockade
Possible clinical consequences
• Sedation, drowsiness
• Weight gain
• hypotension
Muscarinic receptor blockade
possible clinical consequences
• Blurred vision
• Dry mouth
• Sinus tachycardia
• Constipation
• Urinary retention
• Memory dysfunction
alpha – 1 receptor blockade
possible clinical consequences
• Postural hypotension
• Reflex tachycardia
• Dizziness
Interaction with food
• The most serious problem of this class of drugs (MAO-I)
• Much less important in novel RIMA (Reversible Inhibitors
of MAO-A) drugs like moclobemide
• Tyramine „cheese and wine“ reaction
– tyramine
• a natural indirect sympathomimetic produced by fermentation
• some food contain high amounts
• normally metabolized by MAO in the gut and liver.
– After MAOI treatment bioavailability of tyramine is significantly
higher
– hypertensive crisis, severe headache and potentially fatal
intracranial hemorrhage or other organ damage.
– Dietary restrictions: maturing cheeses, wine, beer, yogurts,
bananas etc.
• This risk is minimal with modern RIMA drugs.
Interaction with drugs
• Hypertension & hypertensive crisis
– TCA wash-out period (2 weeks) when switching these
antidepressants! Lower risk in RIMA.
– levodopa (catecholamine precursor), sympathomimetics