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