Agonis artinya kerja obat menyerupai sifat neurotransmitter sasaran, berikatan dg reseptor dan memperkuat kerja neurotransmiter tsb di neuron Antagonis artinya kerja obat mem-blok reseptor neurotransmitter sasaran sehingga neurotransmitter tsb tdk dapat berikatan dg neuron.
Golongan Psikofarmaka
Antipsikotik
Antidepresan Anxiolitik/Antianxietas
Hipnotik /Sedatif
Cognitive Enhancer Psikostimulan
Antipsikotik (Neuroleptik)
Golongan Tipikal (FGA) Golongan Atipikal (SGA / SDA)
Indikasi: Gangguan Psikotik (Termasuk Psikosis organik) Skizofrenia Depresi berat disertai gejala psikotik Agitasi (Gaduh-gelisah) Delirium Tic vokal (Sindrom Gilles de la tourrete)
Haloperidol Decanoat
Perphenazine Trifluoperazine
25-50mgIM/bln
4-8 mg/h 5 mg/h
50-200mg/bln
16-64 mg/h 5-40 mg/h
200 mg
64mg/h 40 mg/h
Phenothiazines
Antipsikotik pertama yg ditemukan & digunakan
Chlorpromazine (Largactil, 1952) Thioridazine (Melleril)
Pharmacokinetics:
Waktu paruh 24-48 jam Metabolisme di hepar
Pharmacodynamics:
Memblok reseptor D2 Jg mem-blok ACh, 5-HT, NE & Histamin
Butyrophenones
Haloperidol (Haldol, 1967) Longer half-life Specific D2 blocker Less sedation Parkinsonian effects like those of high-potency phenothiazines (Perphenazine, Fluphenazine Trifluoperazine) Acute extrapyrimidal effects:
Akathisia: anxious pacing Acute Dystonia: spasm and posturing Parkinsonism
Starting Dose
1 2 mg/day 5 10 mg 25 mg bid 12.5 mg Day Day Day Day Day Day Day Day
Titration Range
1 mg/2-3 days 5 mg/week 50 mg/day
Max. Dose
4 6 mg/day 10 20 mg/day 300 800 mg/day
Dose increased every 3 days 2: 25 mg 3: 25 mg bid 6: 50 mg bid 9: 75 mg bid 12: 100 mg bid 15: 125 mg bid 18: 150 mg bid 21: 200 mg bid 300 900 mg/day
No response
SGA #2
4 -12 WEEKS
No response
Conventional #1
4 12 WEEKS
No response
Clozapine
3 - 9 MONTHS
No response
Two Antipsychotics
(not 2 conventionals)
Acute dystonia
Spasm of muscles of tongue, face, neck, back; may mimic seizures; not hysteria
Many treatments can alter, but effects of antimuscarinic agents are diagnostic and curative.*
Akathisia
5 to 60 days
unknown
Reduce dose or change drug; antimuscarinic agents, dephenhydramine, benzodiazepines, or propranolol ++ may help
Parkinsonism
antagonism of dopamine
antagonism of stop antipsychotic dopamine may immediately; dantrolene contribute or bromocriptine may help; antimuscarinic agents not effective
perioral tremor (may after months be a late variant of or years of parkinsonism) treatment oral-facial dyskinesia; widespread choreoathetosis or dystonia after months or years of treatment (worse on withdrawal)
unknown
Adverse Reactions
Neurologic seizures with clozapine Cardiovascular and cerbrovascular effects hypotension peripheral a blockade Orthostatic
QT prolongation (thioridazine, ziprasidone, others) Increased risk of stroke in elderly (risperidone, olanzapine)
Weight gain and metabolic effects Prominent with clozapine and olanzapine. Uncommon with ziprasidone and aripiprazole, others. Can increase risk of Type 2 diabetes.
Sedation
Extrapyramidal
+++ +
Anticholinergic
+ +++
Hypotension
+++ +++
+++ +++
fluphenazine (Prolixin)
haloperidol (Haldol)
+++
+++
+
+
+++
+++
+
+/-
++
+
loxapine (Loxitane)
molindone (Moban) clozapine (Clozaril) risperidone (Risperdal)
++
++ ++ +++
+
++ +++ +
++
+ +/+
+/+ +++ +
+
+ +++ ++
+/++++ ++++ ++ ++
+ +/+ +/+++
+/+/+/+/+++
+/+ + +/+
Ziprasidone
+/-
++
+/-
*Clozapine is also associated with myocarditis and agranulocytosis; the other secondgeneration antipsychotics are not.
Antidepresan
Relapse Recurrence
Symptoms
Disorder
Antidepressan
Yang bersifat sedatif: Amitriptyline Imipramine Clomipramine Maproptiline Trazodone Mirtazapine Yang bersifat aktivasi/non-sedatif: Tianeptine Moclobemide SSRI (Fluoxetine,Sertraline,Citalopram,Fluvoxamine)
Pharmacodynamics of TCAs
Other antidepressants
Maprotiline (Ludiomil) is based on the TCA molecule. May cause seizures, and accumulates to toxic levels. More lethal than TCAs. Blocks reuptake of NE. Reversible MAOIs or RIMA: moclebemide (Aurorix)
SSRI antidepressants
SSRIs: Selective Serotonine (5-HT) Re-uptake Inhibitors Method of Action: They act within the brain to increase the amount of serotonin in the synaptic gap by inhibiting reuptake. In contrast to other drugs, SSRIs are more potent inhibitors of serotonin reuptake, and they have less of an effect on 1, 2, histaminic, and muscarinic receptors
SPECT tracer
Post-synaptic cell
Fluoxetine
Positive effects in one study on adults caused them to be much improved on the CGI scale (J Intellect Disabil Res 1998; 42: 3016)
Children have negative effects that cause discontinuation of the drug such as hyperactivity and agitation (Dev Med Child Neurol
1998; 40: 551-62)
Sertraline
Similar in effects to fluoxetine (Prozac) Improvement in some adults in aggression and selfinjurious behavior (J Clin Psychiarty 1996;57:333-6) Caused hyperactivity in children and agitation despite improvement in anxiety and irritability (J Child
Adolesc Psychopharmacol 1997;7:9-15)
Sexual dysfunction
Decreased libido Anorgasmia
Nervousness, tremor
Myoclonus
Serotonin syndrome
May occur if SSRIs are taken in high doses, especially combined with other serotonin-enhancing drugs, including herbs (valerian) Disorientation, agitation, shivering, diarrhea, increased reflexes, and more May be life-threatening Recover within 48 hours of abstinence
Mood Stabilizer
Used for Bipolar or Manic-Depressive to regulate mood
Mood Stabilizer
Lithium carbonate Lithium is the classic mood stabilizer. Monitoring blood lithium levels (therapeutic range: 0.8 1.2 mEq/L) and look for signs and symptoms of toxicity (such as nausea, vomiting, diarrhea, ataxia) Valproic Acid (Depakene) & Divalproex Sodium (Depakote) Can be very irritating to the stomach. Liver function and CBC should be monitored
Carbamazepine (Tegretol) Can lower white blood cell count. Therapeutic drug monitoring is required. Monitor for signs and symptoms of StevensJohnson syndrome. FDA approved for bipolar disorder
Lamotrigine (Lamictal) Particularly effective for Bipolar depression. Monitor for signs and symptoms of Stevens-Johnson syndrome. Oxcarbazepine (Trileptal) Not FDA approved for bipolar disorder.
Acute depression:
1st line: lithium or lamotrigine 1st line severe: lithium + antidepressant
Maintenance
lithium or valproate: Alternatives: lamotrigine, carbamazepine, oxycarbazepine Atypical antipsychotics may be considered
Slow titration necessary Interaction with other AEDs (especially valproic acid
and carbamazepine)
ANXIOLITIK
Types of anxiolytics
Anxiolytics are generally divided into two groups of medication: Benzodiazepines and Non-benzodiazepines
Anxiolytics
Benzodiazepines (BZDs) Barbiturates (BARBs) 5-HT1A receptor agonists: Azaspirodecanedione -Blockers
Buspirone Propranolol Clonidine
Antihistaminic drugs
Diphenhydramine
Mechanisms of Action
1) Enhance GABAergic Transmission
frequency of openings of GABAergic channels. Benzodiazepines opening time of GABAergic channels. Barbiturates receptor affinity for GABA. BDZs and BARBS
Pharmacokinetics of Benzodiazepines
BUSPIRONE
Buspirone is an antianxiety agent that acts as a partial agonist at the 5-HT1A receptor presynaptically inhibiting serotonin release and it has an affinity for brain D2 dopamine receptors, where it acts as an antagonist and agonist. Short-term symptomatic relief of excessive anxiety in patients with generalized anxiety disorder.
BUSPIRONE
Buspirone does not have sedative effects and does not potentiate CNS depressants. Has a relatively high margin of safety, few side effects and does not appear to be associated with drug dependence. No rebound anxiety or signs of withdrawal when discontinued
BUSPIRONE
Side effects:
Tachycardia, palpitations, nervousness, GI distress and paresthesias may occur. Causes a dose-dependent pupillary constriction.