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ANTI-DEPRESANANTI-DEPRESAN
KonsepKonsep
Depresi gej psikologis & fisik
Ada 3 jenis depresi reactive depression bipolar affective (manic-depressive)
disorder major depresive disorder a/
endogenous depression
Hipotesis amine mood norepinephrine (NE) dan
serotonin (5-HT) ekspresi mood aktifitas amine depresi
Tricyclic (TCAs) struktur & efek farmakologis mirip struktur & efek farmakologis mirip
antipsikotik phenothiazine antipsikotik phenothiazine oral absorpsinya baikoral absorpsinya baik metabolisme lintas pertamametabolisme lintas pertama VD tinggi VD tinggi tak dapat didialisatak dapat didialisa metabolisme hepatikmetabolisme hepatik t ½ plasma 8-36 jam, 1 x seharit ½ plasma 8-36 jam, 1 x sehari
Antidepresan tricyclic
hambat reuptake NE dan 5-HThambat reuptake NE dan 5-HT
Efek FarmakologisEfek Farmakologis
Blokade uptake amin Sedasi Blokade reseptor muskarinik Efek kardiovaskuler Kejang
Sedasi
k/ tricyclic & heterocyclic
SSRI & buproprion stimulasi SSP
blok res muskarinik
antagonis res muskarinik : TCAantagonis res muskarinik : TCA amitriptyline & doxepin : >>amitriptyline & doxepin : >> SSRI, buproprion & trazodone : SSRI, buproprion & trazodone :
<<
Efek kardiovaskulerTCA hipotensi (blok res hipotensi (blok res adrenoseptor alfa & depresi adrenoseptor alfa & depresi konduksi jantung) konduksi jantung) aritmia aritmia
KejangOverdosis maprotiline, SSRIs, Overdosis maprotiline, SSRIs, TCA & MAOI TCA & MAOI nilai ambang nilai ambang kejang kejang kejang kejang
Penggunaan KlinisPenggunaan Klinis
Depresi
Pengunaan lain
depresidepresi
indikasi utama depresi endogen respons pasien berbeda-beda
tricyclic :
px retardasi psikomotor gg tidur kurang nafsu makan penurunan berat badan
penggunaan lain
gangguan afektif bipolar serangan panik akut fobia (setara dengan
alprazolam) enuresis nyeri kronis
toksisitastoksisitas
sedasi, lesu, fatigue & confusionsedasi, lesu, fatigue & confusion efek simpatomimetik : takikardi, efek simpatomimetik : takikardi,
agitasi, berkeringat & insomniaagitasi, berkeringat & insomnia atropine-like effectatropine-like effect hipotensi ortostatik, ECG abnormal hipotensi ortostatik, ECG abnormal
& cardiomopati& cardiomopati tremor & parestesitremor & parestesi peningkatan berat badanpeningkatan berat badan
OverdosisOverdosis
sangat berbahayasangat berbahaya agitasi, delirium, iritabilitas agitasi, delirium, iritabilitas
neuromuskuler, konvulsi & neuromuskuler, konvulsi & komakoma
gejala : ‘tiga C’ : coma, colvulsi gejala : ‘tiga C’ : coma, colvulsi & cardiotoxicity& cardiotoxicity
depresan sentral (ethanol, barbiturat, benzodiazepin & opioid) depresi SSP aditif
antihipertensi (–) bila diberikan bersama :– Guanethidine – Methyldopa– Clonidine
Selektive serotonin reuptake inhibitor (SSRIs)
Fluoxetine metabolisme hepatik t ½ 18-24 jam metabolit aktif t ½ bbrp hari sertraline, citalopram & paroxetine
SSRIs :
panik social phobia bulimia premenstrual syndrome (PMS) ketergantungan alkohol
Interaksi SSRI
SSRIs : inhibitor isoenzim SSRIs : inhibitor isoenzim cytochorome P-450 hepatik cytochorome P-450 hepatik aktifitas obat lain : antidepresan aktifitas obat lain : antidepresan tricyclic & warfarintricyclic & warfarin
Fluvoxamine : hambat metab Fluvoxamine : hambat metab cisapride, astemizole & terfenadine cisapride, astemizole & terfenadine Citalopam : interaksi <<Citalopam : interaksi <<
SSRIs + obat lain fungsi serotonergik interaksi berbahaya
Sindroma serotonin interaksi fluoxetine & MAOI gawat darurat Gej : rigiditas otot, myoclonus, hipertermi,
instabilitas kardiovaskuler & stimulasi SSP kejang
MAOI, TCA, meperidine & MDMA (‘ecstasy’) Tx : antiepilepsi, relaksan otot & bloker res
5-HT (mis, cyproheptadine)
• A 28-year-old woman presents with symptoms of major depression that are unrelated to a general medical condition, bereavement, or substance abuse. She is not currently taking any prescription or over-the-counter medications. Drug treatment is to be initiated with an SSRI. In your information to the patient, you would NOT tell her that
A. Divided doses may help to reduce nausea and gastrointestinal distress
B. Muscle cramps and twitches sometimes occur
C. She must inform you if she anticipates using other medications
D. Taking the drug in the evening will ensure a good night's sleep
E. The drug may require 2 weeks or more to become effective
• Concerning the proposed mechanisms of action of antidepressant drugs, which of the following statements is accurate?
A. Bupropion inhibits NE and 5-HT transporters
B. Chronic treatment with a TCA leads to the up-regulation of adrenoceptors
C. Elevation in amine metabolites in cerebrospinal fluid is characteristic of depressed patients before drug therapy
D. MAOIs selectively decrease the metabolism of NE
E. The acute effect of venlafaxine is to block the neuronal reuptake of both NE and 5-HT in the CNS