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 for resist.
Procainamid as
e discovered antiarrhythmi
VT/VF in
in 1951 c in 1962 for 1978
Mautz (1936) search for emergency (US)
demonstrated other drugs Rx of VT/VF Dronedarone
application of with (June 2005)
procaine incrto be quinidine-like Flecainide Amiodaron Sanofi-aventis
similar action to
quinidine activity was e was submitted a New
Disopyra introduced
Wenckeback
Moricizin approved Drug Application
mide in 1986
e for resistant (NDA) for
(1914) reported introduced (US), &
develope
on effects of Phenytoin has in 1978 but later VT or dronedarone
been used since d in
quinine had Encainide (MULTAQ®)
alkaloids 1938 for seizures, USSR in recurrent
significant was
Frey & was found to be 1960's
antimuscar introduced VF in 1986
(1918) effective in VT in July 2, 2009
1749 By Jean- expt. AMI in dogs
inic & -ve (US); The US Food and
Baptiste de who in 1950, & has
inotropy
sotalol intro
Sénac. on Drug
cinchona for quinine & since been used
duced for Administration
malaria quinidine in man esp. for
in AF & VT/VF assoc. with Mx of AF approved
digoxin & tricyclic dronedarone for
found toxicity
atrial fibrillation
quinidine
the most
effective
 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