OBAT PERANGSANG SSPOBAT PERANGSANG SSP( CNS STIMULANTS DRUGS)( CNS STIMULANTS DRUGS)

Dharma Permana, Apt, PhDDharma Permana, Apt, PhD

OBAT PERANGSANG SSPOBAT PERANGSANG SSP = ANALEPTIK= ANALEPTIK- dulu : stimulan SSP dulu : stimulan SSP utk depresi utk depresi * E.S >> ( batas keamanan sempit )* E.S >> ( batas keamanan sempit ) Tidak dipakai lagiTidak dipakai lagi perawatan memberikan hasil yg lebih baikperawatan memberikan hasil yg lebih baik

- Obat a.l.Obat a.l. - pikrotoksin- pikrotoksin - striknin- striknin - metrazol- metrazol - etamiven- etamiven - metilfenidat- metilfenidat - Derivat Xantin…..- Derivat Xantin….. Masih dipakai Masih dipakai - dll- dll

Derivat XantinDerivat Xantin• 3 golongan:3 golongan: - Kafein (1,3,7-trimetil xantin )- Kafein (1,3,7-trimetil xantin )

- Teofilin ( 1,3-dimetil xantin )- Teofilin ( 1,3-dimetil xantin )

- Teobromin (3,7-dimetil xantin- Teobromin (3,7-dimetil xantin ) )

Sumber:Sumber:

-Sintetis-Sintetis industri farmasi ( obat & minuman ) industri farmasi ( obat & minuman )

- Alami- Alami

Kopi Kopi Kafein Kafein

TehTeh mengandung kafein, teofilin& mengandung kafein, teofilin&

teobromin ( kafein >> ) teobromin ( kafein >> )

Coklat Coklat teobromin dan kafein teobromin dan kafein

XantinXantin StimulStimulanan

SSPSSP

Relaksasi Relaksasi otot Polosotot Polos(Bronkus)(Bronkus)

DiuresisDiuresis StimulasiStimulasiJantungJantung

Stimulasi Stimulasi otot Skeletotot Skelet

Dilatasi Dilatasi koronerkoroner

KafeinKafein 11 33 33 33 11 33

TeofilinTeofilin 22 11 11 11 22 11

TeobrominTeobromin 33 22 22 22 33 22

Farmakologi gol Xantin

Kekuatan: 1>2>3

SSP stimulasi

Ginjal Diuresis

Jantung stimulasi

Otot polos relaksasi

Xanthine Mechanisms of Xanthine Mechanisms of actionaction• inhibit cellular calcium reuptake, which increases inhibit cellular calcium reuptake, which increases

the free calcium concentration and enhances the free calcium concentration and enhances cardiac and skeletal muscle contractilitycardiac and skeletal muscle contractility

• competing for benzodiazepine receptors within competing for benzodiazepine receptors within the central nervous systemthe central nervous system

• inhibiting phosphodiesterase, resulting in inhibiting phosphodiesterase, resulting in increased intracellularcyclic adenosine increased intracellularcyclic adenosine monophosphate (cAMP)monophosphate (cAMP)

• Adenosine receptor antagonists, which inhibit Adenosine receptor antagonists, which inhibit sleepiness-inducing adenosine also sleepiness-inducing adenosine also leads to vasoconstriction.

• induce acid and pepsin secretions in the GI tractinduce acid and pepsin secretions in the GI tract

Pharmacokinetics of XanthineXanthine derivatives are well absorbed orally,

reaching peak distribution within two hours T1/2 : -TeofilinT1/2 : -Teofilin dws 8-9 jam, anak2 3 ½ jam dws 8-9 jam, anak2 3 ½ jam

- Kafein- Kafein 3 ½ jam 3 ½ jam

The compounds are metabolized by the liver (the cytochrome P-450 enzyme system).

Excreted mostly in urine ( 10% unchanged ),small amounts excreted in feces, sweat, breast

milk However, in neonates approximately 85 % of a

dose is excreted unchanged in the urine. Decreased elimination and a prolonged half-life may increase caffeine toxicity in neonates and premature infants

1. SSP1. SSP

• Kafein: - ngantuk ( - )Kafein: - ngantuk ( - )

- berpikir: lbh terang, cepat & - berpikir: lbh terang, cepat & jernihjernih

- lelah - lelah ↓↓

- panca indra- panca indrafgs baikfgs baik

↓ ↓

HasilHasil kerja efisien ( 1-2 gelas kopi ) kerja efisien ( 1-2 gelas kopi )

Dosis >> : gelisah, gugup, insomnia, tremor, Dosis >> : gelisah, gugup, insomnia, tremor,

Dosis>>>: konvulsi ( terutama teofilin )Dosis>>>: konvulsi ( terutama teofilin )

2. Kardiovaskular2. Kardiovaskular* * JantungJantung freq freq ↑, kontr ↑↑, kontr ↑ takikarditakikardi aritmia aritmia Teofilin : pernah dipakai utk terapi daruratTeofilin : pernah dipakai utk terapi darurat payah jantungpayah jantung tetapi Toksis tetapi Toksis

* Pembuluh darah * Pembuluh darah kafein & teofilin kafein & teofilin dilatasi - pembuluh darah koroner & pulmonaldilatasi - pembuluh darah koroner & pulmonal - perifer ( tdk stabil)- perifer ( tdk stabil)

• Sirkulasi Otak : - peningkatan aliran darah & OSirkulasi Otak : - peningkatan aliran darah & O22

- vasokontriksi ( vascular - vasokontriksi ( vascular cerebral )cerebral )

KafeinKafein utk migren ( Cafergot ) utk migren ( Cafergot )

3. Otot Polos

Relaksasi Otot Polos Bronkus (utk Asma Bronkial)

Teofilin > Teobromin > Kafein

4. Otot Rangka

Kapasitas otot↑ olah raga ( Kafein )

5. Diuresis

meninggikan produksi urin ( terutm teofilin )

6. Sekresi asam lambung

Kafein meningkatkan sekresi as lambung

IntoksikasiIntoksikasi

• KafeinKafein

- kejang, insomnia, takikardia- kejang, insomnia, takikardiaJarang tjd keracunanJarang tjd keracunan

• Teofilin ; seringTeofilin ; sering

- IV cepat- IV cepat

gjl: kejanggjl: kejang terapi dgn diazepam terapi dgn diazepam

Xanthine intoxicationXanthine intoxicationCaffeineCaffeine

• Acute Toxicity In adults, ingestion of 500–1000 mg of caffeine may result in

nausea, vomiting, diarrhea, tremors, and agitation. Most patients have sinus tachycardia and a mild hypertension. The estimated lethal dose of caffeine in an untreated adult is 5–10 g

• Treatment:Treatment in all cases is supportive with attention to airway,

breathing, and circulation. Oral activated charcoal, 1–2 g/kg of body weight is the primary mode of gastrointestinal decontamination. Caffeine may produce hypokalemia so Potassium and other electrolytes should be monitored and replaced as needed. An antiemetic such as metoclopromide or ondansetron may be considered if protracted vomiting occurs. Benzodiazepines such as diazepam and lorazepam should be given to patients who are agitated, hypertensive, or tachycardic.

PreparatPreparat• TeofilinTeofilin Asma Bronkial Asma Bronkial

-tab 125-500 mg-tab 125-500 mg

- tab sustaine release- tab sustaine release

- suppositoria- suppositoriarektumrektum

Aminophylin (garam teofilin) Aminophylin (garam teofilin) IV IV administrationadministration

• KafeinKafein -campuran obat Flu ( 50 mg ) -campuran obat Flu ( 50 mg )

- minuman energi (50 mg)- minuman energi (50 mg)

IndikasiIndikasi

• KafeinKafein1.1. Campuran analgetik/antipiretikCampuran analgetik/antipiretik

nyamannyaman

2.2. MigrenMigren

3.3. Meng (-) lelahMeng (-) lelah

*Teofilin*Teofilin- Asma bronkialAsma bronkial

- Apnea pada bayi prematur Apnea pada bayi prematur

Xantin pada MinumanXantin pada Minuman

• 1 gelas Kopi1 gelas Kopi 85 mg kafein 85 mg kafein

• 1 gelas Teh 1 gelas Teh 50 mg kafein 50 mg kafein

• 1 gelas coklat1 gelas coklat 250 mg teobromin & 250 mg teobromin &

5 mg kafein5 mg kafein

* 1 kaleng Coca cola* 1 kaleng Coca cola 50 mg kafein 50 mg kafein

ReferencesReferences- - Pharmacology And Pharmacotherapeutics (NewPharmacology And Pharmacotherapeutics (New Revised 21 St Ed. 2009) Revised 21 St Ed. 2009)  By R. S. Satoskar, S. D. Bhandarkar &nirmala N. Rege  By R. S. Satoskar, S. D. Bhandarkar &nirmala N. Rege--Modern Pharmacology with Clinical Applications, 6Modern Pharmacology with Clinical Applications, 6thth ed, ed, 20032003 By Charles R. Craig, Robert E. Stitzel By Charles R. Craig, Robert E. Stitzel-Farmakologi dan Terapi-Farmakologi dan Terapi, ed IV, 2007, ed IV, 2007

•Thank youThank you