Drugs for Amebiasis - Chapter 52 review part2

Drugs that act on organisms in the bowel wall and the liver.

Drugs that act only in the lumen of the bowel.

• chloroquine,
• emetines,
• metronidazole

• diloxanide,
• iodoquinol,
• paromomycin

FLAGYL

Mechanism of Action

–Undergoes reductive bio-activation of its nitro group by ferredoxin to form reactive cytotoxic products that interfere with nucleic acid synthesis

• Pseudomembranous colitis,
• amebiasis,
• trichomoniasis,
• Non-specific vaginitis

• GI irritation,
• headache,
• disulfiram reaction with EtOH,
• metallic taste in mouth

potentiates Warfarin

• Reaches high liver concentrations and may
• be used for amebic abscesses that fail to respond to metronidazole

Mechanism of action

• Emetine and dehydroemetine
• inhibit protein synthesis by blocking ribosomal movement along messenger RNA

is limited to unusual circumstances of severe amebiasis in which metronidazole cannot be used

• Hypersensitivity,
• cardiac,
• renal dz

• GI distress,
• diarrhea,
• muscle weakness,
• heart failure and hypo-tension.

Additive cardiac depressant effects with beta blockers

Intestinal amebiasis

–Pregnancy

• Flatulence,
• nausea,
• abdominal cramps

–intestinal amebiasis

–use with caution in patients with optic neuropathy, thyroid or renal disease

NVD

–increases protein-bound iodine which causes a decrease in measured 131 I uptake

–Would interfere with thyroid scan

• aminoglycoside antibiotic,
• inhibits protein synthesis

–Intestinal amebiasis

–renal insufficiency

–diarrhea

Mechanism of action

–interferes with the pyruvate-ferredoxin oxidoreductase enzyme dependent electron transfer which is essential for anaerobic energy metabolism

• Giardia lamblia,
• Cryptosporidium parvum

• headache,
• bright yellow urine,
• abdominal pain,
• yellow sclerae

• Pentamidine,
• TMP-SMX (Bactrim),
• Pyrimethamine/Sulfadiazine

Mechanism of action

–interference with nucleic acid metabolism

–Treatment and prevention of pneumonia caused by Pneumocystis jiroveci in patients who fail to respond to TMP-SMX. 

–Treatment of African trypanosomiasis. 

–Treatment of visceral leishmaniasis

• hypotension,
• tachycardia,
• nephrotoxicity

• Use with aminoglycosides increases risk of nephrotoxicity,
• use with didanosine increases risk of pancreatitis

• Used as alternative to suramin for the early hemolymphatic stage of African trypanosomiasis,
• Used as alternative to sodium stibogluconate for the treatment of visceral leishmaniasis

– African sleeping sickness

• Suramin,
• Pentamidine (alternative to Suramin)

Mechanism of action

–Sequential blockade of folate production

Drug of choice for treatment and prevention of    pneumocystis pneumonia

–sulfa allergy

• GI distress,
• rash,
• fever,
• neutropenia,
• thrombocytopenia

–TMP-SMX decreases the clearance of warfarin.

- Biaxin

Mechanism of action

–Sequential blockade of folate synthesis

• DOC for prophylaxis of Toxoplasmosis,
• Alternative to TMP/SMX or pentamidine for
• prophylaxis against pneumocystis pneumonia in AIDS patients,
• Treatment of active toxoplasmosis.

• Gastric irritation,
• headache,
• insomnia,
• tremors,
• megaloblastic anemia

Hypersensitivity

First-line treatment of cutaneous and visceral leishmaniasis.

–long QT syndrome

• GI distress,
• fever,
• headache,
• myalgia,
• rash

–Cisapride also prolongs QT interval

• fatigue,
• nausea,
• seizures,
• shock,

- treats early hemolymphatic East African Trypanosomiasis (aka African sleeping sickness)

• *Does not enter the CNS so not used for
• advanced disease

- Arsenical compound

• First line therapy for advanced CNS East African Trypanosomiasis,
• Secondline therapy for advanced West African Trypanosomiasis

• Immediate Adverse effects -
• Fever, vomiting, abdominal pain, joint pain.

• –Later…Reactive encephalopathy within
• the first week of treatment.

**Extremely toxic - arsenical

Mech of action

– inhibits ornithine decarboxylase

First line therapy for advanced West African Trypanosomiasis

• diarrhea,
• vomiting,
• anemia,
• thrombocytopenia,
• leukopenia,
• and seizures

Mech of action 

interacts with parasitic nucleic acid, inhibits trypanothione reductase (a parasite specific antioxidant defense enzyme)

treatment of American trypanosomiasis (Chagas disease)

First effective oral agent for visceral leishmaniasis

• vomiting,
• diarrhea,
• transient elevation of LTFs.

Avoid in pregnancy