14. Anti-amoebic and Anti-malarial Drugs

List protozoal diseases.

1. Amoebiasis

2. Giardiasis

3. Trichomoniasis

4. Toxoplasmosis

5. Leishmaniasis

6. Trypanosomiasis

Define and describe amoebiasis.

• Intestinal infection caused by Entamoeba histolytica

• Asymptomatic or may present with mild to moderate colitis or as dysentery or as liver abscess

• Drug therapy needed for acutely ill patient and asymptomatic patients

List the types of amoebicides.

1. Tissue amoebicides (destroy amoeba that have invaded tissue; tissue phase is only secondary to intestinal amoebiasis; hence, in tissues, only trophozoites present not cysts)

2. Luminal amoebicides

List tissue amoebicides.

1. Metronidazole

2. Tinidazole

3. Ornidazole

4. Chloroquine

List luminal amoebicides.

1. Diloxanide furoate

2. Antibiotics - tetracycline

Tissue Amoebicides

Describe the mechanism of metronidazole.

Forms reduced cytotoxic compounds that bind to proteins and DNA, resulting in death of E. histolytica trophozoites

Tissue Amoebicides

List the adverse effects of metronidazole.

1. Nausea

2. Vomiting

3. Metallic taste

4. Epigastric distress

5. Anorexia

6. Transient neutropenia

Tissue Amoebicides

List the contraindications of metronidazole.

1. Neurological disease

2. First trimester of pregnancy (mutagenic potential)

3. Not to be taken with alcohol - disulfiram-like effects produced

Tissue Amoebicides

List the uses of metronidazole.

1. Amoebiasis: drug of choice for all forms (intestinal or extraintestinal)

2. Giardiasis: highly effective

3. Trichomonas vaginalis: drug of choice

4. Anaerobic bacterial infections

5. Pseuodomembranous enterocolitis: drug of choice

6. Ulcerative gingivitis: drug of choice for acute condition

7. H. pylori peptic ulcer: used w/amoxicillin or clarithromycin and PPI

8. Guinea worm infestation: niridazole

Tissue Amoebicides

Describe chloroquine and what it is used for.

• Kills trophozoites of E. histolytica and is highly concentrated in liver

• Used for hepatic amoebiasis

Tissue Amoebicides

List the adverse effects of chloroquine.

Toxicity is low but adverse effects are frequent and unpleasant:

1. Bitter taste

2. May cause nausea

3. Vomiting

4. Visual defects

5. Loss of hearing

Luminal Amoebicides

Describe diloxanide furoate and how it works.

• Highly effective luminal amoebicide

• Directly kills trophozoites (acute amoebiasis)

• Effective against cyst forms of amoeba

• Effective in treating asymptomatic carriers of amoebiasis

• Not active against tissue trophozoites

• Drug of choice for mild intestinal/asymptomatic amoebiasis, and is given after any tissue amoebicide to eradicate cysts

Luminal Amoebicides

List the side effects of diloxanide furoate.

Minimal side effects, well tolerated: flatulence, occasional nausea, and itching

Malarial parasite is a single cell protozoan called Plasmodium. List clinically important species of Plasmodium.

1. Plasmodium vivax

2. Plasmodium falciparum

3. Plasmodium ovale

4. Plasmodium malariae

Describe malaria and its symptoms.

• Incubation period - 7-30 days

• Brief prodromal period with symptoms of fever, headache, and myalgia

• Symptoms begin with a cold stage (a shaking chill), following by a fever stage (40–41°C) that lasts about 24 hours, and finally a wet stage

• The wet stage occurs several hours after the fever, when the body temperature drops quickly to normal and profuse sweating begins; patient is exhausted but well until the next cycle of fever begins

• Other symptoms include splenomegaly and anemia

List and describe the 3 basic types of malaria.

1. Benign tertian (P. vivax and P. ovale): fever every second day

2. Benign quartan (P. malariae): fever every third day

3. Malignant tertian (P. falciparum):

   • cold stage is less pronounced and fever stage is more prolonged and intensified

   • fever usually continuous or briefly remittent

   • no wet stage

   • this type more dangerous because of complications caused by capillary blockage

   • large no. of RBC parasitized and destroyed = dark urine

Which 2 species of Plasmodium can remain in the liver if not treated properly? What happens when they remain in liver?

• P. vivax and P. ovale

• Organisms leave liver and reinfect RBC, causing symptoms

• Relapsing malaria occurs when there are relapses many years after initial episode of malaria

Describe the life cycle of malarial parasite/Plasmodium.

• Complex life cycle

• Alternating cycle of asexual division in human beings (intermediate hosts)

• Sexual development occurs in female mosquito (anopheline, definitive host)

List the objectives of anti-malarial therapy.

1. Treat and prevent clinical attack of malaria

2. Completely eradicate the parasites from patient’s body

3. Reduce human reservoir of infection

List anti-malarial drugs.

1. Chloroquine

2. Mefloquine

3. Proguanil

4. Primaquine

List the clinical uses of anti-malarial drugs.

1. Causal prophylactics

2. Suppressive prophylaxis/chemoprophylaxis

3. Clinical cure

4. Radical cure

Causal Prophylactics

The ________________ phase (_____) which is the cause of malarial infection and clinical attacks is the target. They prevent __________ of ____________ to _________ within the infected hepatic cells target.

• pre-erythrocytic

• liver

• maturation

• sporozoites

• schizonts

List causal prophylactics.

1. Proguanil

2. Primaquine

Suppressive Prophylaxis/Chemoprophylaxis

Do not affect the _______ phase. Destroy the ___________ released from the _____, so that the development of ____________ stage is prevented. They are mainly blood _______________.

• hepatic

• merozoites

• liver

• erythrocytic

• schizonticides

When is suppressive prophylaxis employed?

During period of exposure to infected mosquitoes and for some weeks after

List drugs used for suppressive prophylaxis/chemoprophylaxis.

1. Chloroquine

2. Proguanil + chloroquine

3. Mefloquine

4. Doxycyline

Clinical Cure

The ________ ____________ __________ state of malarial parasite is responsible for clinical symptoms (fever, chills). Hence, blood _______________ can be used to terminate an acute attack of malaria.

• asexual erythrocytic schizogony

• schizonticides

List drugs used for clinical cure.

1. Fast-acting high efficacy drugs: chloroquine, mefloquine

2. Slow-acting low efficacy drugs: proguanil

Faster-acting drugs preferred for P. falciparum

Radical Cure

Eradication of both ________________ and ____________ state of malarial parasite leads to radical cure of malaria. Adequate clinical cure of P. falciparum with ____________ results in radical cure.

• exoerythrocytic

• erythrocytic

• chloroquine

Which drug is used for radical cure?

Primaquine