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PHARMACOTHERAPY on

TROPICAL DISEASES

R sulanto saleh-danu r.,dr., SpFK.

dept.of clinical pharmacology,


R faculty of medicine, GMU.

BLOCK 22
FACTORS DRUG USE PROBLEMS
IN TROPICAL ENVIRONMENT

Cost of medicine

Per capita income Drug production & distribution

Drug consumption in tropical countries Disease pattern

Available health services:


drug distribution between Economic and
rural-urban; self-medication education level

Inter-related factors in drug consumption pattern. (Krishnaswamy,K., 1997)


IMMUNIZATION PREVENTIVE

MICRO-
ORGANISM / INVASIVE HOST
PARASIT

KILLED & DESTROYED SAFE

PHARMACOTHERAPY
PHARMACOTHERAPY
should be :
DRUG DOSAGE,
ABSORPTION,
DISTRIBUTION,
METABOLISM,
EXCRETION TROPIC- COUNTRIES
SITUATION

PHARMACOKINETIC BODYWEIGHT
NUTRIONAL STATUS &
DIETARY HABITS
TROPICAL ENVIRONMENT:
PHARMACOTHERAPY
PHARMACOTHERAPY climatic factors
infections and infestations
environment pollutants (chemicals,
PHARMACODYNAMIC mycotoxins, alcoholism,
smoking, etc)

EFFECTS,
RESPONSES,
INTERACTIONS,
ADVERSE EFFECTS,
Etc., etc.
DRUGS NUTRIONAL STATUS/ EFFECT ON DRUG % CHANGE
CONDITION CLEARENCE

-Phenazone undernutrition increased 6


nutritional oedema decreased 21
low protein diet decreased 32
high protein diet increased 46
charcoal broiled beef increased 38

Propranolol high protein diet increased 60


high karbohydrate diet decreased 37

Tetracycline undernutrition increased 60


nutritional oedema decreased 43

Sulfadiazine undernutrition Increased 41

Rifampisin undernutrition increased 63

Chloroquine undernutrition increased 60

Phenylbutazone undernutrition increased 62

Theophylline high protein diet increased 28


low protein diet decreased 22
charcoal broiled beef increased 32
PHARMACOTHERAPY OUTCOME

Respone

PHARMACODYNAMIC
Drug receptor
interaction

Drug concentration in the body


PHARMACOKINETIC:
- absorption of drug
- distribution in the body
- metabolism of the drug
- excretion / elimination
MAYOR TROPICAL OTHERS:
INFECTIONS.
Gasterointestinal.
1. MALARIA
2. VISCERAL LEISHMANIASIS 1. Amoebiasis
3. CUTANEUS LEISHMANIASIS 2. Bacillary Dysentery
4. TUBERCULOSIS 3. Cholera
5. HIV INFECTION and 4. Giardiasis and others protozoa infect.
DISESEASE IN THE TROPICS 5. Intetstinal cestoda infect. (tapeworm)
6. FILARIASIS and 6. Soil-transmitted Helminths
ONCHOCERCIASIS 7. Viral Hepatitis
7. AFRICAN TRYPANOSOMIASIS 8. Liver Flukes
8. SOUTH AMERICAN TRYPANO- 9. Hydatid disease
SOMIASIS (CHAGAS DISEASES)
9 SCHISTOSOMIASIS
10. LEPROSY Neurological
1. Pyogenic meningitis
2. Cryptococcal meningitis
Respiratory. 3. Encephalitis
1. Pneumonia 4. Acute Flaccid Paralysis
2. Lung Flukes 5. Spastic paralysis
3. Tropical Pulmonary Eosinophilia 6. Rabies
7. Tetanus
Fever.
1. Brucellosis
2. Typhoid and Paratyphoid Fever
3. Arbovirusis Miscellaneous.
4. Viral Haemorrhagic Fever
1. Tropical Ulcer
5. Dengue and Yellow Fever
2. Buruli Ulcer
6. Relapsing Fever
3. Myasis
7. Rickettsial Infections
4. Cutaneous Larva Migrans
8. Leptospirosis
5. Scabies and Lice
9. Melioidosis
6. Strongyloides stercoralis
7. Guinea Worm Infection
(Dracunculiasis)
8. Histoplasmosis
9. Other Fungal Infections
10. Haemoglobinopathies and
Red Cell Enzymopathies
11. Haematinic Defficiencies
12. Bites and Stings
13. Non-Communicable Diseases
14. Refugee Health
(Gill and Beeching, 2004)
Pharmacotherapy on Tropical Diseases

PARASITIC INFECTIONS
1. Malaria
2. Filariasis EFFICACY
3. Onchocerciasis
SAFETY
4. Schistosomiasis
5. Leishmaniasis
6. African Trypanosomiasis
(Sleeping Sickness)
ECONOMIC

AVAILABILLITY
R
7. American Trypanosomiasis
(Chagas Disease) AFFORDABILLITY
BACTERIAL INFECTIONS
8. Leprosy
9. Tuberculosis
VIRAL INFECTION.
10. Dengue
11. HIV
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
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
MALARIA

Drug classification ( by chemical based ):

4-aminoquinolines : chloroquine; hydroxychloroquine; amodiaquine


8-aminoquinolines : primaquine
diaminopyrimidines : pyrimethamine; trimethoprim
biguanides : proguanil; chlorguanide; chlorproguanil
cinchona alkaloids : quinine; quinidine
sulfonamides : sulfadoxine; sulfadiazine; sulfamethoxazole
sulfones : dapsone
4-quinoline-carbinolamine : mefloquine
antibiotics : tetracycline; doxycycline; clindamycine
others : halofantrine; artemisinin (qinghaosu); atovaquone
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

Next: 3 examples of anti-malaria drugs profiles.


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
t (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.
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.
t (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).
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.
t : 45
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.
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)
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
CHEMOPROPHYLAXIS :

1. PROGUANIL ( PALUDRINE, CHLORGUANIDE )


2. CHLOROQUINE
3. MEFLOQUINE
4. DOXYCYCLIN
5. ATOVAQUONE-PROGUANIL
6. SULFADOXINE-PYRIMETHAMINE
CHEMOPROPHYLAXIS /
SUPPRESSIVE DOSAGES
FOR ADULTS.

CHLOROQUINE PRIMAQUINE
300 mg (base) / 45 mg(base)/week
week. for 8 weeks

PYRIMETHAMINE MEFLOQUINE
25 mg/week in 250 mg/week
combination with for 4 weeks, then
sulfadoxine 125 mg/week

SULFADOXINE
500 mg/week in
combination with
pyrimetamine
WHATS
THE MAIN PROBLEM
PHARMACOTHERAPY MANAGEMENT
in MALARIA ???
2. 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
Diethylcarbamazine citrate (DEC)

Effective : microfilaricidal, with


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

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

CAUSE : O. VOLVULUS endemic area : Africa & Latin Ameri


cause of BLINDNESS, Dermatitis, Lymphadenitis

Transmitter: female black flies ( simulium species )

R - diethylcarbamazine no effect in adult worm


- ivermectin suitable for mass treatment
dose : 400g/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 )
4. SCHISTOSOMIASIS

CAUSED : Trematodes (blood flukes)


S. mansoni (Africa; Arabian peninsula; South America;
the Carabbean.
S.haematobium ( Middle East and Africa )
S. japonicum (China; Philippines)

R praziquantel ONLY IF LIVE OVA ARE IDENTIFIED.


oxamniquine effective only S. mansoni
5. 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

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