FARMAKOLOGI ANTI-INFEKSI :

1. ANTIVIRAL – ANTIBACTERIAL;

2. IRRASIONAL USE;
ADVERSE DRUG REACTION (ADR );
RESISTANCY ANTIBIOTICs;
DISINFECTANT-ANTISEPTIC;

3. ANTIFUNGALs; ANTIPARASITICs;
ANTIHELMENTHIC.
 Sulanto Saleh-Danu R. dr., SpFK.
Depart. Farmakologi & Terapi
Fak. Kedokteran Kesehatan Masyarakt & Keperawatan – UGM;
Fak. Kedokteran – UKDW

2
OBJEKTIF PERTEMUAN INI :

1. MENGERTI DAN MEMAHAMI KLASIFIKASI;

MEKANISME dan TITIK TANGKAP KERJA;
OBAT-OBAT ANTIFUNGAL – ANTIPARASIT –
ANTIHELMENTHIC.
2. MENGERTI; MEMAHAMI dan MAMPU
MENGGUNAKAN OBAT-OBAT ANTIFUNGAL –
ANTIPARASIT–ANTIHELMENTHIC SECARA
RASIONAL.
3. MAMPU MENDETEKSI –MEWASPADAI
AKIBAT dan DAMPAK PENGGUNAAN OBAT-
OBAT ANTIFUNGAL – ANTIPARASIT – ANTIHEL-
MENTHIC.
ANTI FUNGAL

4
 ANTIFUNGAL

SYSTEMIC (infection) MUCOCUTANEUS MUCOCUTANEUS

DRUGS INFECTION INFECTION
(oral / parentral) (ORAL) (TOPICAL)

5
PROBLEMATIK INFEKSI FUNGAL / JAMUR :
- JUMLAH KASUS MENINGKAT

- MUNCULNYA JAMUR yang RESISTEN terhadap ANTIFUNGAL

- DIJUMPAI (banyak dijumpai):

 organ transplantation
 bone marrow transplantation
 endemic HIV
 PEMAKAIAN ANTIMIKROBA
SPEKTRUM LUAS pada pasiem kritis
( superinfeksi / infeksi sekunder ).

6
ANTIFUNGAL KLASIFIKASI :

1. ANTIFUNGAL ANTIBIOTICs :
 ANTIBIOTIC POLYENE : amphotericin B;
nystatin; natamycin
 LAIN-LAIN : griseofulvin
2. ANTIMETABOLIT : flucytosine
3. AZOLEs :
IMIDAZOLEs : clotrimazole; econazole; miconazole;
ketoconazole; butaconazole; sulconazole;
TRIAZOLEs : fluconazole; itraconazole; terconazole;
voriconazole; ravuconazole; posaconazole
4. MISCELLANEOUS :
TERBINAFINE; ECHINOCANDINs : caspofungin;
micafungin; amidulafungin
5. TOPIKAL LAINNYA : tolnaftate; asam undecylenat;
asam benzoat; asam salisilat; selenium sulfide;
naftifine; ciclopirox olamine
 NUCLEUS :
-griseofulvin (mitosis

ANTIFUNGAL DRUGs
- flucytosine (protein synthese
SITE OF ACTION:

CELL MEMBRANE :
- polyenens (form
pores & leak cell
content)
- azoles ( synthesis
ergosterol)

CELL WALL :
- pneumocandins
( synhesis of
cell wall )

Synthesis of lanosterol :
- naftifine
- terbinafine
9
 Merupakan amphoteric polyene macrolide
Nyaris tidak larut dalam air
AMPHOTERICIN B Preparat dalam bentuk suspensi koloidal
(pemakaian sistemik)
MEKANISME KERJA : - fungisidal selektif
- dinding membran sel fungi
mengandung ergosterol
(predeominan :cholesterol)
- terikat pada ergosterol
mempengaruhi permeabilitas
sel membran., kerusakan : gangguan
intraseluler ion dan macromolekul
berakibat kematian sel fungi.

SPEKTRUM ANTIFUNGAL : - luas

Candida albicans
Cryptococcus neoformans
Histoplasma capsulatum
Blastomyces dermatitidis
Coccidiodes immitis
Aspargillus fumigatus , dll
10
 ADVERSE DRUG REACTION / ADR
ANTIFUNGAL.

-IMMEDIATE REACTION (infusion-related toxicity)

demam; mengigil; muscle spasms; vomiting;
headache; hypotensi.
Dapat dicegah : memperlambat infus / menurunkan dosis harian
atau dengan test 1mg iv
Premedikasi : antipyretik; antihistamin; meperidine atau kortikosteroid .

-CUMULATIVE TOXICITY :► Kerusakan ginjal.

11
 AZOLES
SENYAWA SINTETIK : imidazole X=C
R triazole X =N
N
X

N Pharmacologic propertes of AZOLE drugs

Water sol. Absorp. CSF : srm t½ (hours) Elimina- Formulat-
conc.rat tion ion
Ketoconaz low variable < 0.1 7 – 10 hepatic oral
Itraconaz low variable < 0.01 24 – 42 hepatic oral; i.v.
Fluconaz high high > 0.7 22 – 31 renal oral; i.v.
Voriconaz high high -- 6 hepatic oral; i.v.
Posaconaz low high -- 25 hepatic oral
12
 MECHANISM OF ACTION

-REDUCTION OF ERGOSTEROL SYNTHESIS by INHIBITION

OF FUNGAL CYTOCHROME P-450 ENZYMES

SIFAT SELEKTIF : pada fungal affinitas CYTOCHROME-450

> manusia

IMIDAZOLE selektifitas < TRIAZOLE

INTERAKSI OBAT
Pada
METABOLISME
13
 INTERAKSI OBAT
Pada
METABOLISME

ITRACONAZOLE + RIFAMPICINS
(RIFAMPIN,RIFABUTIN,RIFAPENTINE)

► BIOAVAILABILITY ITRACONASOLE berkurang.

14
 ANTI FUNGAL
ANTIPROTOZOAL
ANTIHELMINTHICS

Reference:
KATZUNG,BG., (ed.) 2009, BASIC AND
CLINICAL PHARMACOLOGY , 11TH Ed., pg :
835-844; 899-922; 923-934
Lange-McGrawHill., Boston.

15
16
 IMMUNIZATION PREVENTIVE

MICRO-
ORGANISM / INVASIVE HOST
PARASIT, dll

“KILLED & DESTROYED” “ SAFE “

PHARMACOTHERAPY
PHARMACOTHERAPY
should be :
17
 1. UNIQUE ENZYMES

ENZYMES PARASITES INHIBITORS

-Enzymes for dihydropteroate Apicomplexa Sulfones and

Sulfonamides
syntesis

-Glycolipid synthesis African trypanosmes None

-Pyruvate:ferrodoxin oxidoreductase Anaerobic protozoa Nitroimidazole

-Pyruvate phosphate kinase Anaerobic protozoa None

-Nucleoside phosphotranferase Flagellated protozoa Allopurinol riboside

and
formycine B

-Trypanothione reductase and Kinetoplastida Nifurtimox

peroxidase
18
 2. INDISPENSABLE ENZYMES

ENZYMES PARASITES INHIBITORS

Lanosterol C-14α demethylase Leishmania & Trypanosoma cruzii Azoles

Purine phosphoribocyl transferase Protozoa Allopurinol

Purine nucleoside kinase Trichomonas vaginalis and None

Entamoeba hystolytica

Ornitine decarboxylase African Trypanosomes α-Difluoroethylornithine

(S)-Adenosylmethionine African trypanosomes Diamidines

decarboxylase

Glycolytic enzymes Kineplastida Glycerol plus salicyl-

hydroxamic acid and
suramine

19
 3. INDISPENSABLE BIOCHEMICAL FUNCTION
WITH DIFFERENT PHARMACOLOGIC PROPERTIES

ENZYMES PARASITES INHIBITORS

Dihydrofolate reductase-thymidylate Apicomplexa and Kineto- Pyrimethamine

synthase bifunctional enzyme plastida

Thiamine transporter Coccidia Amprolium

Mitochondrial electron transporter Apicomplexa 4-Hydroxyquinolines

and
2-hydroxynaphthoquinones

Microtubules Helminth Benzimidazoles

Nervous synaptic transmission Helminth and Levamisole, piperazine,

ectoparasite the milbemycins, and
the avermectine

20
 1. MALARIA
- The most important tropical disease, affecting over 2200 million, more than
2 million deaths/year.
- Cause : PLASMODIUM : - P. VIVAX
- P. OVALE
- P. MALARIAE
- P. FALCIPARUM severity  deaths
-COMPLICATION : 1. cerebral malaria
2. hyperpyrexia
3. hemolytic anemia / black water fever
4. noncardiogenic pulmonary edema
5. acute tubular necrosis & renal failure
6. acute hepatopathy
7. hypoglycaemia
8. cardiac dysrhytmias
9. gastrointestinal syndromes
10. lactic acidosis
11. water and electrolyt imbalance

21
22
PERIODE PRAPATEN & MASA INKUBASI PLASMODIUM
PERIODE
JENIS PLASMODIUM PRAPATEN MASA INKUBASI

1. PLASMODIUM VIVAX 12.2 hari 12 – 17 hari

2. PLASMODIUM FALCIPARUM 11 hari 9 – 14 hari

3. PLASMODIUM MALARIAE 32.7 hari 18 – 40 hari

4. PLASMODIUM OVALE 12 hari 16 – 18 hari

PERIODE PRAPATEN : waktu antara terjadinya infeksi sampai ditemukannya

parasit malaria didalam darah
MASA INKUBASI : waktu terjadinya infeksi pertama kali sampai timbulnya gejala
penyakit.
SIGN & SYMPTOM :
 Febris : diawali lesu-sakit kepala-nyeri
otot & tulang-nafsu makan turun-
gangguan pencernaan.
terutama : P.vivax & P. ovale
P.falcioarum dan P. malariae
tidak terlalu nyata
Ada 3 stadium : - menggigil seluruh tubuh
 15 mnt – 60 menit;
- demam tinggi ( >40º C );
- berkeringat banyak, suhu
tubuh turun.
SPLENOMEGALI : - pada malaria khronik;
- lien membesar & nyeri
tekan
- krn adanya sumbatan sel
darah merah dan parasit.

ANEMIA : - penghancuran erithrocyt yg

berlebihan oleh plasmodium dan
pembentukannya di bone marrow
terganggu.
PRINSIP PENGOBATAN MALARIA.
PENGOBATAN MALARIA =
PENGOBATAN RADIKAL : membunuh
semua stadium parasit yang ada didalam
tubuh.
TUJUAN PENGOBATAN RADIKAL :
untuk mendapatkan kesembuhan secara
KLINIS dan PARASITOLOGIK serta me-
mutus rantai PENULARAN
MALARIA

Drug classification ( by chemical based ):

4-aminoquinolines : chloroquine; hydroxychloroquine; amodiaquine

8-aminoquinolines : primaquine
diaminopyrimidines : pyrimethamine; trimethoprim
biguanides
(folate antagonist) : proguanil; chlorguanide; chlorproguanil
quinoline methanol : quinine; quinidine, mefloquine
sulfonamides : sulfadoxine; sulfadiazine; sulfamethoxazole
folate antagonist combination :
sulfadoxin – pyrimethamine (Fansidar™ ),
chloroguanil - dapsone
tetracycline : doxycycline, clindamycin
phenanthrene methanol : halofantrine; atovaquone
sesquiterpene lactone
endoperoxiodes : artemisinins (qinghaosu), artesunate, artemether
quinone-folate antagonist
combination : atovquone-proguanil (Malarone™)
amyl alcohol : lumefantrine
artemisinin
27
MALARIA

Classification based on the drug actions.

Tissues schizonticides : inhibit the growth of pre-erythrocyt
stage of parasite (liver)  proguanil; primaquine; pyrimethamine
(with or without sulfonamides)  causal prophylactics
Antirelaps drugs : kill the dormant hypnozoites  primaquine;
8-aminoquinolones  indicated P.vivax & P ovale
Blood schizonticides : kill the erythrocytic form,  chloroquine;
quinine; mefloquine  can be used as suppressive prophylactics
Gametocytocides : destroy the asexual stage of the parasite in the
blood  primaquine
Sporozonticides : inhibit formation of oocyst and sporozoites in
mosquitoes  pyrimethamine; proguanil

28
 CHLOROQUINE

MECHANISM OF ACTION : forms a toxic complex with ferriprotoporphyrine IX

(haeme), class of blood schizontocide and gametocide.
Plasmodium sensitive : P. vivax, falciparum, ovale, malariae.
Onset of drug effects : 3 hours.

PHARMACOKINETIC PROFILE : ROUTE OF ADMINSTR.:

F (%) : 90 Oral; Parenteral
t½ß (h) : 1220 (41-50 ds) DOSAGE : 600 mg initially,
Vd (L) : 57.400 6-8 h later : 300 mg
CL (L/h) : 65 and next 2 days 300 mg
Prot.bind. (%) : 55 (total : 1.500 mg)
Route of elim. : kidney (unchanged) Duration of treatment :
Metabolite activity : less active 3 days

ADVERSE EFFECTS:
pruritis, GI upset, headache, fatigue, visual disturbances, dyskinesia,
neurovascular disease

LIMITATIONS : RESISTANCE.
29
 MEFLOQUINE
MECHANISM OF ACTION : same as chloroquine, sensitive to : Plasmodium
falciparum and P. vivax. Class : blood schizontocide;
onset : 6 hours.

PHARMACOKINETICS PROFILE : ROUTE OF ADMINSTR.:

F (%) : 85 Oral.
t½ß (h) : 530
Vd (L) : 1330 DOSAGE : Initial : 750 mg.
CL (L/h) : 2.0 6-8 (h) later : 500 mg
Prot. Bind. (%): 98 and 250 mg after a
Route of elim. : faecal & renal further 6-8 6-8 hr.
unchanged and DURATION OF TREATMENT:
carboxylic acid 1 (one) day.
metabolite (inactive).

ADVERSE EFFECTS:
dizziness, GI upset, headache, pruritis, skin rashes, CNS toxicity.

LIMITATIONS.
expensive, resistance (now some area was established).
30
 PRIMAQUINE

MECHANISM OF ACTION : interferes with plasmodial mitochondria function,

binds to DNA. Effectve : exoerythrocytic forms of P.vivax and
P.ovale. Gametocides all forms of plasmodia.
Class : tissue schizonticides / gametocide. Onset : 1 – 2 hours.

PHARMACOKINETIC PROFILE: ROUTE OF ADMINISTR.

F (%) : 90 – 100 Oral.
t½ß : 4–5
Vd (L) : 322 DOSAGES: 15 mg daily
CL (L/h) : 56 for duration of 14 days.
Prot. Binding (%) : --
Route of elim. : renal and faecal
Metabolite less active.

ADVERSE EFFECTS : mild anaemia, methaemoglobinaemia, depression,

confusion, cardiac arrhythmia, granulocytopenia, agranulocytosis.

31
ARTEMISININ dan TURUNANNYA.

ARTEMISININ :
 suatu seskuiterpen lakton yg didapat dari daun :
ARTEMISIA ANNUA, sebagai penurun demam.
 Termasuk : SCHIZONTOSIDA darah dan aktif
terhadap semua spesies plasmodium (termasuk
yg resisten terhadap klorokuin).
 Pl. FALCIPARUM : membunuh bentuk gametosit.
 Tidak larut dalam air.
 Turunan : DIHIDROARTEMISININ
ARTEMETHER
ARTEMOTIL
ARTESUNATE
ARTEMISININ :
 potensi lebih kuat ; absorpsi lebih baik bila
dibanding artemisin.
 ARTEMETHER; ARTESUNAT: ARTEMOTILdalam
tubuh diubah kembali menjadi
DIHYDROARTEMESISNIN.
 Pemberian : P ORAL; PARENTERAL; SUPPOSIT.
 ABSORPSI baik; DISTRIBUSI luas; METABOLISME:
enzym CYP-P450 CYP2B6.
 t ½ : ARTEMISININ 4 JAM; ARTESUNAT 45 mnt;
ARTEMETHER 4 – 11 JAM.
ARTEMISININ :
EFEK SAMPING dan TOKSISITAS :
 GANGGUAN (ringan); PUSING; TINITUS;
RETIKULOSITOPENIA; BRADICARDI;
perpanjangan QT interval; gangguan fungsi
HEPAR; hypersensitifitas ( tipe I ).
 TIDAK MEMPUNYAI EFEK pada bentuk :
HIPNO ZOIT di HEPAR
 TIDAK BERMANFAAT UTKHEMOPROFILAKSIS.
OTHERS ANTIMALARIA.

1. Amodiaquine
2. Quinine
3. Sulfadoxine – pyrimethamine (Fansidar®)
4. Atovaquone – proquanil (Malarone®)
5. Halofantrine

6. The Artemisinin drugs :

 artesunate
 artemether
 artemisinin
7. Artemether – lumefantrine (Co-artem)

35
 CHEMOPROPHYLAXIS

FOR THIS PURPOSE DRUGS ACT IN TWO WAYS :

 AS SCHIZONTICIDES, when parasites enter the red cell

they are destroyed;

 AS CAUSAL PROPHYLACTICS, which prevent the development

of the PE schizont in the liver, and may have
schizonticidal effects.

Currently, chemoprophylaxis is routinely advise only for :

NON-IMMUNE travellers visiting endemic area

36
 CHEMOPROPHYLAXIS /
SUPPRESSIVE DOSAGES
FOR ADULTS.

MEFLOQUINE
250 mg/week PRIMAQUINE
for 4 weeks, then 45 mg(base)/week
125 mg/week for 8 weeks

PYRIMETHAMINE DOXYCYCLIN
25 mg/week in Everyday 1-2 days
combination with arrive at location.
sulfadoxine ENDEMIC AREA : 2mg/
Kg BW for 4-6 weeks
CHLOROQUINE SULFADOXINE
300 mg (base) / 500 mg/week in
week. combination with
RESISTANCE pyrimetamine
NO MORE USE 37
 2. AMEBIASIS
CAUSE : - entamoeba histolytica

CLINICAL : - asymptomatic intestinal infection

- mild – moderate intestinal infection
- severe intestinal infection
- hepatic abcess
ameboma
& other extraintestinal
MEDICINES : - Metronidazole
- Tinidazole
- Iodoquinol
- Diloxanide furoate
- Paromycin sulfate
- Emetin & dehydroemetine 38
ASYMPTOMATIC INTESTINAL :
- diloxanide furoate 3 dd 500mg (10 days )
- iodoquinolone 3 dd 650 mg (7 days)
- paromomycin 3 dd 10 mg/kg BB (7 days)

MILD – MODERATE & SEVERE INFECTION :

- metronidazole 3 dd 750 mg or
500 mg i.v./6hours (10 days )
- tinidazole 2 g daily (3 days) + diloxanide
alternative - diloxanide + tetracycline 3 dd 250 mg
(10 days)
- erythromycin 4 dd 500 mg (10 days)

for SEVERE INFECTION : - dehydroemetine / emetine :

1 mg/kg SC or I.M (3-5 days)
39
HEPATIC ABCESS-AMEBOMA-other
EXTRA INTESTINALinfection :

same to SEVERE INFECTION but

treatment more longer (21 days)
3. FILARIASIS
CAUSES : - Wuchereria bancrofti Culex
- Brugia malayi transmitted Aedes
- Brugia timori Anopheles
incubation periode :
8 – 16 mo.

Cause : high degree of disability

- hydrocele
- scrotal lymphedema
- lymphatic varices
- elephantiasis : extrimities, genitals, breasts

R - diethylcarbamasine
- ivermectin  only as a microfilaricide combine with
diethyl carbamasine
- albendazole  only as a microfilaricide
41
Diethylcarbamazine citrate (DEC)

Effective : microfilaricidal, with

dose 1-2 mg/kg BW 3 x daily for 2-3 weeks.
Adult worms require longer course of therapy and/or
multiple therapy.
Adverse effects : allergic reactions, headache, vertigo,
dizziness, malaise, fever, or myalgia.

PREVENTION :
- reduce / eradicate population of mosquito
- protect from mosquito bites

42
4. ONCHOCERCIASIS
CAUSE : O. VOLVULUS  endemic area : Africa & Latin America
 cause of BLINDNESS, Dermatitis, Lymphadenitis

Transmitter: female black flies ( simulium species )

R - diethylcarbamazine  no effect in adult worm

- ivermectin  suitable for mass treatment
dose : 400µg/kg single dose, often combined
with a single dose albendazole 400 mg.
repeated at 3-month for 2-3 years.
- albendazole 400 mg 2x daily for 3 weeks
(  have macrofilaricidal effects )

43
5. SCHISTOSOMIASIS
CAUSED : Trematodes (blood flukes)
 S. mansoni (Africa; Arabian peninsula; South America;
the Carabbean.
 S.haematobium ( Middle East and Africa )
 S.mekongi (Southeast Asia)
 S.intercalatum (West and Central Africa)
 S. japonicum (Japan; China; Philippines)
3 stages : cercariae – mature flukes – eggs
R praziquantel  ONLY IF LIVE OVA ARE IDENTIFIED.
oxamniquine  effective only S. mansoni
metrifonate -> S. hematobium

PERMASALAHAN : ketersediaan Obat cukup sulit,tersedia

pada daerah ttt (Program: Indonesia – hanya
di Sulawesi Tengah)

44
CLINICAL (3 major disease syndromes):
mature flukes : - dermatitis (swimmers’itch)
- fever & constituional complaints
(Katayama fever)
- chronic fibro-obstructive disaese

DERMATITIS : 1-3 days after penetration of cercariae

-priritis
-papular rash
(rarely occur in primary exposure)
KATAYAMA FEVER : 4 – 8 weeks after penetration of the human skin
- severe in S japonicum; some times in
S mansoni;
- rare in S haematobicum
CHRONIC FIBRO-OBSTRUCTIVE:
- damage by deposition of eggs ->
chronic granulomatoous disease and fibrosis.

45
LABORATORY : - eosinophilia, hematurie, anemia
- chronic end-stage :
abnormal liver function
elevated serum creatinine
uremia
- characteristic by : schistomia eggs
(feces/urine or rectal biopsi)

DIFF.DIAG : hepatic Sch -> hepatoslenomegaly & portal

hypertension DD: alkoholic cirrh;
Wilson’s disease; hepatitis C.
S haematobium -> DD ca bladder / ureteral;
CRF sometimes -> hematuria

46
6. LEISHMANIASIS
Syndromes :

- Visceral leishmaniasis (kala azar): L.donavani; L. infantum;

L. chagasi

- Cutaneus leishmaniasis : Old world : L. tropica; L. major;

L. aethiopica.
New world : L. mexicana.

- Mucocutaneus leishmaniasis (espundia) : Leishmania (viannia)

braziliensis; rare L(v) panamensis.

- Diffuse cutaneus leihmaniasis : L. mexicana; L. aethiopica

47
VISCERAL LEISHMANIASIS (KALA-AZAR)
ENDEMIC : -in the South-west Asia; the Indian subcontinent; China;
the Mediterranean area; east Africa; and Central and
South America

Clinic : -Chronic irregular fever, malaise, anorexia, cough, diarrhea

and secondary infections  later : progressive enlargement
of the spleen and liver; lymph-nodes with anemia and
emaciation
-Untreated  fatal
-After cure (in Indian subcontinent)  chronic granulomatous
infiltration of the skin and patchy hypopigmentation
without ulceration

48
CUTANEOUS LEISHMANIASIS.
The Old World : in the Mediterranean area; western Asia;
the Indian subcontinent (west area) and east and west Africa.

The New World : in Central and South America ( except Chile

and Uruguay )

Characterized : a cell-mediated reaction at the site of inoculation;

immunity develops and healing occurs by fibrosis and leaving
a prominent scar.

The New World more severe and slower to heal than The Old World

49
MUCOCUTANEOUS LEISHMANIASIS.
ENDEMIC : South and Central America; Ethiopia and Kenya caused by
L.aethiopica.

Primary lesions : regional lymphangitis and lymphadenitis.

Characterized : progressive ulceration and erosion of the soft tissues

of the mucosa of the nose, mouth and pharynx  espundia
This condition : appear soon after initial infection or
many year after apparent resolution of the primary lesions.

50
DIFFUSE CUTANEOUS LEISHMANIASIS
ENDEMIC : Brazil; the Dominic Republic; Mexico; and Venezuela;
and Ethiopia and Kenya ( L.aethiopica )

Primary lesion : progressive, widespread, thickening and leprosy-like

lesion. ( once established do not regress with treatment )

51
PHARMACOTHERAPEUTIC (1)
 MEGLUMINE ANTIMONATE : inject. 85 mg/ml
 SODIUM STIBOGLUCONATE : inject. 100 mg/ml
both contain antimony (Sb pentavalent) in 5 ml ampoule.

Dosage & adminstration : 20 mg Sb pentavalent / kg BW i.m.

duration of treatment :
- Visceral L., minimum 20 days
- Cutaneous L., local (intralesion) 1 – 3 ml interval 1-2 days
systemic : 10 -20 mg until clinical cure
at least 4 weeks
- Mucocutaneous L., 20 mg / kg BW i.m. until split skin
smears negative, at least 4 weeks.
In relapse should be retreated at least twice
as long.
- Diffuse cutaneous L., 20 mg / kg BW i.m. several month
until clinical improvement occurs.

52
PHARMACOTHERAPEUTIC (2)
CONTRAINDICATIONS : - severe renal disorders
- severe heart disorders
- severe liver disorders

PREGNANCY : no evidence.

ADVERSE EVENTS : dose-dependent and reversible in

ECG changes, T-wave inversion & prolongation
Q-T interval precede serious dysrhythmia.
Hepatic and renal dysfunction  impairment.
Headache, malaise, dyspnoea, skin rashes,
Abdominal pain and facial oedema.

53
PHARMACOTHERAPEUTIC (3)
Others :
Pentamidine : all type of Leishmaniasis
dosage : 3 – 4 mg / kg BW by deep i.m.or slow iv (>60’)
for duration : 5 to 25 weeks.
CI : renal impairment
hypersensitive
AE: - mild nephrotoxicity
- acute hypotension and syncope ( rapid iv )
- hypoglycaemia ( pancreatic damage ),
- hypocalcemia; GI effects; confusion, hallucinations;
cardiac dysrhythmias; local induration (  sterile
abscess);
- rare : thrombocytopenia; leucopenia;
Stevens-Johnson syndrome;
abnormal hepatic functions.

Amphotericin B also as anti fungal.

54
7. TRYPANOSOMIASIS.

 AFRICAN ( sleeping sickness )

 AMERICAN ( Chagas diseases )

AFRICAN TRYPANOSOMIASIS.
Pharmacotherapeutics :
1. PENTAMIDINE. Injection 200, 300 mg each vial.
2. SURAMINE. Injection 1 g / vial.
3. MELARSOPROL. Injection 36 mg / vial.
4. EFLORNITHINE. Injection 200 mg in 100 ml ampoule.

AMERICAN TRYPANOSOMIASIS.
Pharmacotherapeutics :
1. BENZNIDAZOLE. Tablet 100 mg
2. NIFURTIMOX. Tablet 30, 120 and 250 mg.

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 ANTIHELMINTHIC
CAUSES : WORMS :
1. ROUNDWORMS (NEMATODA)
- ascaris lumbricoides
- trichuris trichiura
- necator americanus
- strongyloides stercoralis
- enterobius vermicularis
- trichinela spiralis
- cutaneus larva migran
(creeping eruption)
- visceral larva migran etc.
2. TREMATODES (flukes) :
- schisostoma sp (haematobium; mansoni; japonicum)
- fasciola hepatica; etc.
3. CESTODA (tape worms) : - taenia saginata
- taenia solium
- diphyllobothrium latum
- echinococcus granulosus,etc

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PHARMACOTHERAPY – ANTIHELMINTHIC (1) :
ALBENDAZOLE (Ascariasis; Trichuriasis; Hookworm and Pinworms)

BITHIONOL ( Fascioliasis/sheep liver flukes;

alternative : pulmonary paragonimiasTIN is )

DIETHYLCARBAMACEPINE CITRATE (Filariasis; Loiasis; Tropical eosinophilia)

DOXYCYCLINE (Filariasis; Onchocerciasis)

IVERMECTIN (Strongyloidiasis; Onchocerciasis)

MEBENDAZOLE (Ascariasis; Trichuriasis; Hookworm and Pinworm)

METRIFONATE (TRICHLORFON) (Schisostoma hematobium)

NICLOSAMIDE (Tapeworm)

OXAMNIQUINE (Schisostoma mansoni; hematobium; japonicum)

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PHARMACOTHERAPY - ANTIHELMINTHIC (2):

PIPERAZINE (Ascariasis)

PRAZIQUANTEL ( all type Schisostoma infection; Trematoda ; Cestoda;

Cysticercosis)

PYRANTEL PAMOATE (Pinworm; Ascariasis; Trichostrongylus orientalis)

THIABENDAZOL ( alternative to IVERMECTIN or ALBENDAZOLE; Cutaneus

larva migrans/creeping eruption

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BENZIMIDAZOLE : albendazole; mebendazole; thiabendazole

MECHANISM OF ACTION : - inhibiting microtubule synthesis

- larvacid (cysticercosis; ascariasis;
ankylostomiasis; trichuriasis)
- ovicidal
ADVERSE REACTION : - mild – moderate gastrointestnal problems
(epigastric pain;diarrhea; nausea)
- headache; dizziness; lassitude; insomnia
(especially in long-term use)
- hypersensitive
- WARNING : pregnant and child < 2 year.

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 PHARMACOKINETICS;
MECHANISM OF ACTION;
DOSAGE;
CLINICAL USES;
ADVERSE REACTION;
CONTRAINDICATION
In detail, please refered to:

Reference:
KATZUNG,BG., (ed.) 2012,
BASIC AND CLINICAL
PHARMACOLOGY ,
12TH Ed.,
Lange-McGrawHill., Boston.

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  THANK YOU
&
WASSALAMU’ALAIKUM WR WB

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