Page 945 - Basic _ Clinical Pharmacology ( PDFDrive )

CHAPTER 52 Antiprotozoal Drugs 931

absorbed and then conjugated to form the glucuronide, which ■ OTHER ANTIPROTOZOAL
is promptly excreted in the urine. The unabsorbed diloxanide
is the active antiamebic substance. Diloxanide furoate is not DRUGS
available commercially in the USA but can be obtained from
some compounding pharmacies. It does not produce serious The primary drugs used to treat African trypanosomiasis are listed
adverse effects. Flatulence is common, but nausea and abdomi- in Table 52–6, and those for other protozoal infections are listed
nal cramps are infrequent and rashes are rare. The drug is not in Table 52–7. Important antiprotozoal drugs that are not covered
recommended in pregnancy. elsewhere are discussed below.

PAROMOMYCIN SULFATE PENTAMIDINE

Paromomycin sulfate is an aminoglycoside antibiotic (see also Pentamidine has activity against trypanosomatid protozoans and
Chapter 45) that is not significantly absorbed from the gas- against P jiroveci, but toxicity is significant.
trointestinal tract. It is used as a luminal amebicide and has
no effect against extraintestinal organisms. The small amount Chemistry & Pharmacokinetics
absorbed is slowly excreted unchanged, mainly by glomerular Pentamidine is an aromatic diamidine (Figure 52–3) formulated
filtration. However, the drug may accumulate with renal insuf- as an isethionate salt. The drug is only administered parenter-
ficiency and contribute to renal toxicity. Paromomycin appears ally. It leaves the circulation rapidly, with an initial half-life
to have similar efficacy and less toxicity than other luminal of about 6 hours, but is bound avidly by tissues. Pentamidine
agents; in one study it was superior to diloxanide furoate in thus accumulates and is eliminated very slowly, with a terminal
clearing asymptomatic infections. As it is readily available, par- elimination half-life of about 12 days. Only trace amounts of
omomycin can be considered the antiamebic luminal agent of pentamidine appear in the central nervous system, so it is not
choice in the USA. Adverse effects include occasional abdomi- effective against CNS African trypanosomiasis. Pentamidine
nal distress and diarrhea. Parenteral paromomycin is now used can also be inhaled as a nebulized powder for the prevention of
to treat visceral leishmaniasis and is discussed separately in the pneumocystosis. Absorption into the systemic circulation after
text that follows. inhalation appears to be minimal. The mechanism of action of
pentamidine is unknown.
EMETINE & DEHYDROEMETINE
Clinical Uses
Emetine, an alkaloid derived from ipecac, and dehydroemetine, 1. Pneumocystosis—Pentamidine is a well-established alterna-
a synthetic analog, are effective against tissue trophozoites of tive therapy for pulmonary and extrapulmonary disease caused by
E histolytica, but because of major toxicity concerns their use P jiroveci. The drug has somewhat lower efficacy and greater tox-
is limited to unusual circumstances in which severe amebiasis icity than trimethoprim-sulfamethoxazole. The standard dosage is
requires effective therapy and metronidazole cannot be used. 3 mg/kg/d intravenously for 21 days. Significant adverse reactions
Dehydroemetine is preferred because of its somewhat better are common, and with multiple regimens now available to treat
toxicity profile. The drugs should be used for the minimum P jiroveci infection, pentamidine is best reserved for patients with
period needed to relieve severe symptoms (usually 3–5 days) and severe disease who cannot tolerate or fail other drugs.
administered subcutaneously (preferred) or intramuscularly in a Pentamidine is also an alternative agent for primary or sec-
supervised setting. Adverse effects, which are generally mild with ondary prophylaxis against pneumocystosis in immunocom-
use for 3–5 days but increase over time, include pain, tenderness, promised individuals, including patients with advanced AIDS.
and sterile abscesses at the injection site; diarrhea, nausea, and For this indication, pentamidine is administered as an inhaled
vomiting; muscle weakness and discomfort; and minor electrocar- aerosol (300 mg inhaled monthly). The drug is well tolerated
diographic changes. Serious toxicities include cardiac arrhythmias, in this form. Its efficacy is good but less than that of daily
heart failure, and hypotension. trimethoprim-sulfamethoxazole.

TABLE 52–6 Treatment of African trypanosomiasis.

Disease Stage First-Line Drugs Alternative Drugs
West African Early Pentamidine Suramin, eflornithine
1
CNS involvement Eflornithine Melarsoprol, eflornithine-nifurtimox 1
East African Early Suramin 1 Pentamidine
CNS involvement Melarsoprol 1
1 Available in the USA from the Drug Service, CDC, Atlanta, Georgia (phone: 404-639-3670; www.cdc.gov/laboratory/drugservice/).