CHEMOTHERAPYHIGHLIGHTS

MOHAMED BAHR; MD, PHD

Antiprotozoal Drugs

Mohamed Bahr; MD, PhD

ANTIPROTOZOAL DRUGS

Mohamed Bahr; MD, PhD

ANTIAMEBIC DRUGS

Mohamed Bahr; MD, PhD

Mohamed Bahr; MD, PhD

AMEBIASISBowel lumen amebiasis: asymptomatic (carriers or cyst

passers), may become symptomatic if left untreated.

Tissue amebiasis: cysts develop into trophozoites which feed on

intestinal bacteria or invade submucosa of large intestine,

resulting in:

• Intestinal infection: mild to moderate colitis (no dysentery) or

severe (dysentery).

• Amebic granuloma (ameboma) in intestinal wall.

• Extra-intestinal amebiasis: liver abscess, pulmonary amebiasis…

Mohamed Bahr; MD, PhD

1. DILOXANIDE

1st choice luminal amebicide used for:

asymptomatic luminal infections

tissue amebiasis, in combination with tissue amebicides, to

eradicate the source of infection

Side effects: GIT flatulence - nausea - abdominal cramps.

Teratogenic.

Mohamed Bahr; MD, PhD

2. IODOQUINOL

Alternative to diloxanide.

Also used in giardiasis.

Adverse Effects

GIT upset: nausea, vomiting, diarrhea.

SMON.

Thyroid enlargement.

Mohamed Bahr; MD, PhD

3. PAROMOMYCIN (REMAINS IN GIT LUMEN)

GIT

Mohamed Bahr; MD, PhD

1. METRONIDAZOLE (FLAGYL)

It is a prodrug which is activated by reduction of

its NITRO group → disruption of DNA structure

and function → cell death.

Mohamed Bahr; MD, PhD

USESAnaerobic protozoal infections:

• Amebiasis (all forms except asymptomatic cyst passers).

• Others: Giardiasis - Trichomoniasis (urogenital).

Anaerobic bacterial infections:

• Pseudomembranous colitis due to Clostridium difficile.

• Brain abscess, ulcerative gingivitis and dental infections, leg

ulcers.

Mohamed Bahr; MD, PhD

ADVERSE EFFECTSGIT: unpleasant metallic taste, glossitis, stomatitis, nausea and

vomiting.

CNS (serious): dizziness - vertigo - ataxia - neuropathy -

convulsions.

Dark urine - dysuria.

Neutropenia.

Teratogenic

Enzyme inhibitor: ↑ warfarin level.

Mohamed Bahr; MD, PhD

2. TINIDAZOLE (FASIGYN)Similar to metronidazole but more effective, longer t ½, and

less teratogenic.

Mohamed Bahr; MD, PhD

3. CHLOROQUINE

LIVER

Mohamed Bahr; MD, PhD

4. EMETINE AND DEHYDROEMETINERemember: Amphotericin

Severe

Mohamed Bahr; MD, PhD

5. TETRACYCLINES

Mild

Mohamed Bahr; MD, PhD

Mohamed Bahr; MD, PhD

ANTIMALARIAL DRUGS

Mohamed Bahr; MD, PhD

Mohamed Bahr; MD, PhD

PROBLEMS1. Chloroquine resistance: chloroquine is the mainstay of

antimalarial therapy, but resistance to drug

(geographically distributed) is a major problem especially

with P falciparum (most dangerous → encephalopathy

and renal failure).

2. Relapse: re-activation of dormant form in hepatic cells →

relapses in P ovale and P vivax, not in P falciparum.

Mohamed Bahr; MD, PhD

Mohamed Bahr; MD, PhD

I. 4-AMINOQUINOLINES

Mohamed Bahr; MD, PhD

CHLOROQUINE

Mohamed Bahr; MD, PhD

ADVERSE EFFECTS GIT: nausea, vomiting and diarrhea.

Hypersensitivity: pruritis (most common).

CNS…

Neutropenia.

Cardiotoxic: quinidine-like action (hypotension and arrhythmias).

Eye: corneal opacity, blurred vision and retinopathy.

Ototoxicity

Hemolytic Anemia: in G6PD-deficient subjects.

Mohamed Bahr; MD, PhD

QUININE AND QUINIDINECardiotoxic: Quinidine-like action → hypotension and

arrhythmias.

Eye → blurred vision and blindness.

Cinchonism: tinnitus - headache - dizziness and visual

disturbances.

Black water fever and hemolysis.

Uterus: abortion.

Not in Prophylaxis!

Mohamed Bahr; MD, PhD

QUININE AND QUINIDINE

Alternatives

Mohamed Bahr; MD, PhD

MEFLOQUINE

Excellent Alternative

Mohamed Bahr; MD, PhD

II. HALOFANTRINE

Cardiotoxic

Alternative

Mohamed Bahr; MD, PhD

III. 8-AMINOQUINOLINES: PRIMAQUINE

Radical cure

Terminal

prophylaxis

Gametocidal

Mohamed Bahr; MD, PhD

G6PD

Teratogenic

Mohamed Bahr; MD, PhD

IV. ANTIFOLATE ANTIMALARIAL DRUGS

Blood schizonticides (mainly)

1ry tissue schizonticides

sporontocides

Mohamed Bahr; MD, PhD

Treatment of chloroquine-resistant falciparum (fansidar plus

quinine).

Prophylaxis in all types (proguanil + chloroquine).

Mohamed Bahr; MD, PhD

ADVERSE EFFECTS

GIT

G6PD

Remember: TMP

Mohamed Bahr; MD, PhD

  Treatment Prophylaxis

Chloroquine-Sensitive P falciparum

Chloroquine

P vivax and ovale

Chloroquinethen

Primaquine(radical cure and terminal prophylaxis)

Chloroquine-Resistant P falciparum

Quinine + Fansidar (or Doxycyline)

orMefloquine

orHalofantrine

Mefloquine or

Proguanil plus chloroquine Doxycyline (in multidrug

resistant cases)

Mohamed Bahr; MD, PhD

DRUGS FOR CHEMOPROPHYLAXIS ARE GIVEN:

for 2 wks (chloroquine, mefloquine) or for 2 days

(proguanil or doxycyline) before travel

AND

for 4 wks after leaving endemic area.

Mohamed Bahr; MD, PhD

Mohamed Bahr; MD, PhD

ANTITRYPANOSOMAL DRUGS

Mohamed Bahr; MD, PhD

Mohamed Bahr; MD, PhD

Mohamed Bahr; MD, PhD

REFERENCESLippincott’s Illustrated Reviews, 5th ed.

Color Atlas of Pharmacology, 2nd ed.

Goodman and Gilman's The Pharmacological Basis of

Therapeutics, 12th ed.