Rizky Yulion P. M.Farm.

,Apt
Farmakologi Kemoterapi
UNV. M. Natsir
 MALARIA:
PENYAKIT INFEKSI
DENGAN DEMAM PERIODIK
DITULARKAN OLEH NYAMUK ANOPHELES BETINA
DISEBABKAN OLEH PARASIT
PLASMODIUM

•Falcifarum Malaria
•Malariae
•Vivax
•Ovale
1. Malaria
Malaria is the most important of
the transmissible parasitic diseases.
Over 90 million cases occur each year.
DRUG-RESISTANT MALARIA
Plasmodium falciparum is now resistant to chloroquine
in many parts of the world. Areas of high risk for
resistant parasites include Sub-Saharan Africa, Latin
America, Oceania, and some parts of South-East Asia.
Chloroquine-resistant Plasmodium vivax is also
reported.
Life cycle
of malaria
parasites
•Pl. falciparum
•Pl. malariae
•Pl. ovale
•Pl. vivax
Quinine as cinchona bark was introduced into
Europe from South America in 1633. It was
used for all fevers, amongst them malaria.

Further advance in the chemotherapy

of malaria was delayed until 1880, when
Charles Louis Alphonse Laveran, Prof. of Military
Medicine in Paris (Nobel prize winner 1907) finally
identified the parasites in the blood.
 Sporozoit dalam kel.ludah nyamuk
………………………………………………..
Fase Pre-Eritrosit : ( sel parenchim hati)

Skizon jaringan

Merozoit ( ke sirk.darah)

Fase Eritrosit: Eri + skizon matang pecah

Merozoit ke-sirkulasi
mikro/makro gametosis

…………………………………………………………..
Gamet zygot sporozoit (kel.ludah nyamuk)
Bentuk serangan
demamnya:
 Fase menggigil :
 berlangsung 30
menit–1 jam
 suhu menjadi 41 °
 Fase panas :
 berlangsung 2 – 6 jam
 mengigau (delirium)
 Fase berkeringat :
 badan terasa letih
 ingin tidur
 KELOMPOK OBAT ANTIMALARIA
Gol Antibakteri:
Gol Kuinolin:
Sulfonamid,tetrasiklin,
Kuinine,kuinidin,primakuin Spiramisin,azitromisin,
Klorokuin,amodiakuin, Klindamisin,rifampisin,
Meflokuine,halofantrin

Gol Antifolat:
Gol Artemisin:
Pirimetamin,
Artemisin,Artemer,
Trimetropim, Proguanil,
Artesunat
Klorprokuanil
 •Spesies plasmodium
•Tingkat siklus hidup
EFEKTIVITAS •Resistensi
OBAT

SCHIZONTICIDE DARAH
membunuh parasit eritrositik
CHLOROQUINE, MEFLOQUINE, QUININE

SCHIZONTICIDE JARINGAN
membunuh skizon di hepar  vivax & ovale
PRIMAQUINE  Relaps
 GAMETOSIT
membunuh gamet
CHLOROQUINE, QUININE, PRIMAKUIN

SPORONTOSID
membunuh spora
PROGUANIL, PYRIMETHAMINE
 Schizontisid Darah: Obat obat yang bekerja pada parasit
darah
 Cholroquine
 Amodiaquine
 Quinine
 Mefloquine

 Schizonticid jaringan: mengeliminasi bentuk yg sedang

berkembang dan juga dormant dalam sel hati.
 Primaquine
 Gametocid: membunuh tahap tahap
seksual dan mencegah transmisi ke
nyamuk.
- Klorokuin & kuinin  vivax & ovale
- Primaquine  falciparum

 Sporonticid:
 Proguanil, Pyrimethamine (anti folate agents)

 Obat obat kemoterapi ini diharapkan efektif

membunuh parasit eritrositik sebelum
parasit2 ini tumbuh dlm jumlah yg banyak
 G.klinis/ penyakit
 Serangan klinis :
 Dengan skizontosid fase eritrosit  tidak
terbentuk skizon baru  tidak terjadi
penghancuran eritrosit tidak muncul
gejala klinis
 Pengobatan supresi
 Membunuh semua parasit dari tubuh
dengan memberikan skintosid darah dlm
waktu lama
 Pengobatan radikal
 Untuk memusnahkan parasit fase eritrosit
dan eksoeritrosit  skiontosid darah dan
jaringan (kombinasi)
 Pencegahan
 Digunakan skizontosid jaringan
 Adanya parasit yang masih tetap hidup ataupun
mengadakan multiplikasi walaupun penderita mendapat
pengobatan dengan obat anti malaria

 Semua jenis Plasmodium

 Sering: Plasmodium falciparum

 CHLOROQUINE
 Obat utama antimalaria sampai munculnya resisten P. Falcifarum
 < Toksik dibanding turunannya
 sebagai antiinflamasi: artritis rematoid & SLE
 24-48 jam: gejala (-)
48-72 jam: parasit (-)
 IV: hindari
 Absorbsi: baik; ↑  makanan
↓  antasid, antidiare
 Mekanisme Kerja
Mencegah polimerisasi heme menjadi
hemozoin. Akumulasi heme intrasel adalah
toksik bagi parasit

Efek Samping

 Sakit kepala, g3 GIT, gatal2, g3 penglihatan (distribusi

di melanin >>  periksa rutin!)
 Jarang: gangguan EKG, rambut memutih
 KI: penyakit hepar; psoriasis/porfiria (serangan akut!!!)
 Aman untuk bumil dan anak-anak
 QUININE (KULIT POHON KINA)
 Infeksi berat (P.Falsiparum)
 Quinidine: D-rotatory stereoisomer Quinine
 Efek samping: (lebih toksik)profilaksis(-)
- Sinkonisme  reversibel
(N/V, tinitus, vertigo, visus↓, flushing)
- hipoglikemi, hipotensi (bila IV cepat)
PRIMAQUINE
 Mula kerja lambat, t ½ singkat
 Efek samping:
1. Anemia hemolitik akut  px def. G6PD
2. Methemogobinemia, Agranulositosis
3. G3 GIT  durante coenam

 KI: px granulositopenia (artritis rematoid, SLE)

px tx obat  hemolisis, depresi sutul
bumil
 AGEN ANTI FOLAT
 Menghambat enzim dihidrofolat reduktase plasmodia 
sintesis purin terhambat  skizon di hati gagal membelah.
Sulfonamid: ≠ dihidropteroat sintetase
 ES: Anemia makrositik  stop/ tx:leukovorin
 Fansidar: Pyrimethamine + Sulfadoxine tx falciparum yg
resisten klorokuin (tdk berat)
 Kemoprofilaksis dgn antifolat tunggal tdk dianjurkan  sering
resisten
 P. Falciparum P. Vivax/
P. Ovale

Chloroquine
Resistens Primaquine
Multi Obat
Resisten

Doxycycline/
Mefloquine
Chloroquine + Proguanil

Profilaksis
Antimalaria
 P. Falciparum P. Vivax/
P. Ovale

Chloroquine
Resistensi Chloroquine
Resisten, Komplikasi (+)
G6PD N
Komplikasi (-)
IV monitor
Quinine + jantung Primaquine
Fansidar/
Doxycycline/ Pengobatan
Clindamycin Antimalaria
 Pada awalnya pengobatan aritmia hanya dengan
menggunakan “electrotherapy” sebelum obat ini ditemukan
dan kembangkan oleh peneliti obat-obatan (Farmasi)
 Jean-Baptiste de Sénac, pada tahun 1749 melakukan
pengobatan malatria pada seorang pasien, dengan
menggunakan cinchona/kina, namun pasien ini juga
menderita aritmia type atrial fibrosis, dan pada saat itu juga
penyakit artimia dari pasien tersebut juga ikut sembuh
secara tidak sengaja.
 Pengobatan dengan menggunakan “electrotherapy” mulai
ditinggalkan setelah Wenckebach’s memperkenalkan
“quinidine” sebagai obat untuk terapi ARITMIA. Hingga
perkembangannya sampai sekarang menuju
Dronedarone(obat aritmia terbaru)
 Bretyliu
Lignocaine
used as a m was
LA was approved
introduced as for resist.
Procainamid antiarrhythmi VT/VF in
e c in 1962 for
discovered in emergency 1978 (US)
1951 search Rx of VT/VF
for other Dronedarone
drugs with (June 2005)
quinidine-like Flecainide Amiodaron Sanofi-aventis
activity was e submitted a New
Moricizin
Disopyra introduced was Drug Application
Wenckeback mide in 1986
(1914) reported
e
introduced
approved (NDA) for
(US), &
on effects of Phenytoin has
develope
in 1978 but for resistant dronedarone
d in later
quinine been used since (MULTAQ®)
1938 for seizures, USSR in
had Encainide VT or
alkaloids significant was
& was found to be 1960's
antimuscar
recurrent July 2, 2009
effective in VT in introduced
expt. AMI in dogs inic & -ve VF in 1986 The US Food and
in 1950, & has inotropy (US); sotalol Drug Administration
since been used
introduced approved
in man esp. for dronedarone for
VT/VF assoc. with for Mx of AF
digoxin & tricyclic atrial fibrillation
toxicity
 Tanpa Komplikasi: Kloroquine  Fansidar  Quinine/
Mefloquinine  Quinine/ Artesunat
 Relaps : 1 tablet/hari selama 14 hari
 Malaria berat
1. Kloroquinine / Artemisin supp
2. Quinine / Quinidine / Artemisin
 Bumil: Chloroquine & Proguanil
 Kemoprofilaksis tinggal >3 minggu: Fansidar 1 tablet/hari
s/ 4 minggu sesudah keluar
 PROGUANID ATAU KLOROGUANID
 Skintosid melalui mekanisme antifolat (sama
dengan pirimetamin)
 Mudah ressten (sekarang kurang digunakan)

 MEFLOKUIN
 Belum tersedia di Indonesia

 TETRASIKLIN / DOKSISIKLIN
 Digunakan untuk P. falsifarum yang resisten
terhadap klorouin atau kombinasi
pirimetamin+sulfadoksin
 Dosis : 4x250 mg selama 7-10 hr (tetrasiklin)
2x100 mg selama 7-10 hr (doksisiklin)
 ARTEMISININ
 Skintosid yang cepat  untuk malaria berat
 Use for
Drug Use in eredicati Use for prophylaxis?
acute on of
attack? Liver
Stage?
Chloroquine Yes No Yes, exept in region where
P.falciparum is resistant.
Quinine, Yes, in No Yes, Mefloquine is used in region
Mefloquine resistant with Chloroquine-resistant
P.falc P.falciparum.
Primaquine No Yes Yes, but only if exposed to P.vivax
(P.vivax, or P.ovale.
P.ovale)
Antifols Yes, but No Not usually advised.
only in
resistant
P.falc
 Obat Penggunaan Dosis dewasa
Chloroquine Daerah tanpa P.falc 500 mg setiap minggu
resisten

Mefloquine Daerah dgn P.falc 250 mg setiap minggu

resisten-Chloroquine

Doxycycline Daerah dgn P.falc 100 mg setiap hari

resisten-multi obat.

Chloroquine Regimen alternatif 500 mg Chloroquine setiap

+ Proguanil menggantikan minggu + 200 mg Proguanil
mefloquine setiap hari.

Primaquine Profilaksis terminal 26,3 mg setiap hari selama

infeksi P.vivax dan 14 hari setelah perjalanan.
P.ovale.
2. Amoebiasis
Infection occurs when mature cysts of E. histolytica
are ingested and pass into the colon where they
divide into trophozoites. Amoebiasis occurs in two
forms, both of which need treatment.
• Bowel lumen amoebiasis is asymptomatic
and trophozoites (noninfective) and cysts
(infective) are passed into the faeces. Treatment
is directed at eradicating cysts with a luminal
amoebicide; diloxanide furoate is the drug of choice;
iodoquinol or paromomycin is sometimes used.
3. African trypanosomiasis (sleeping disease)

It is caused by the hemoflagellates Trypanosoma bru-

cei rhodesiense and Trypanosoma brucei gambiense.
The organisms are transmitted by bites of tsetse flies
(genus Glossina), which inhabit shaded areas along
streams and rivers. The largest number of cases is
in the Congo. Annual incidence estimates are about
100 000 cases and 48 000 deaths.
American Trypanosomiasis (Chagas’ Disease)
is caused by Trypanosoma cruzi.
4. Leishmaniasis is a zoonosis.

•Visceral leishmaniasis (kala azar) is caused mainly

by Leishmania donovani in the Indian subcontinent
and East Africa. Treatment:
Sodium stibogluconate or meglumine antimoniate;
resistant cases may benefit from combining
antimonials with allopurinol, pentamidine,
paromomycin, or amphotericin B.
5. Toxoplasmosis

T. gondii, an obligate intracellular protozoan, is found

worldwide in humans and in many species of animals
and birds. The definitive hosts are cats. Humans are
infected after ingestion of cysts in raw or under-
cooked meat, ingestion of oocysts in food or water
contaminated by cats, transplacental transmission
of trophozoites or, rarely, direct inoculation of
trophozoites via blood transfusion or organ
transplantation.
Life cycle of Toxoplasma gondii
6. Human Trichomoniasis
(Metronidazole or tinidazole
is effective)
Human trichomoniasis caused by Tr. vaginalis,
seen in both females and males. It is usually trans-
mitted by coitus and is sometimes asymptomatic.

The symptomatic condition in females may take the

form of a severe vaginitis associated with discharge,
burning, and pruritus.

In males it may produce urethritis, enlargement of

the prostate, and epididymitis.
7. Giardiasis

It is a common infection of
the human small intestine with
the protozoan Giardia lamblia, spread via
contaminated food or water, or by direct
person-to-person contact.
Treatment:
Metronidazole, mepacrine, or tinidazole
8. Pneumocystis

Pneumocystis carinii, the causative agent

of interstitial plasma cell pneumonia,
which can also cause extrapulmonary
disease in immunocompromised
patients (AIDS, etc) .
Treatment:
Co-trioxazole: i.v./p.o. in high daily doses