DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

1446 hyperinfection. Ivermectin is the drug of choice for treatment of
strongyloidiasis. Hyperinfection may require prolonged or repeated
therapy. Although the BZ drugs show some efficacy, they are less
effective than ivermectin.
In LF, host reaction to the adult worms initially cause lymphatic
inflammation manifested by fevers, lymphangitis, and lymphadenitis.
This can progress to lymphatic obstruction and is often
exacerbated by secondary attacks of bacterial cellulitis, leading to
lymphedema manifested by hydrocele and elephantiasis. An accentuated
immune reaction to microfilariae, termed tropical pulmonary
Enterobius vermicularis. Enterobius, the pinworm, is
one of the most common helminth infections in temperate
climates, including the U.S. Although this para-
The Global Program for the Elimination of LF recommends
eosinophilia, also occurs in some persons.
site rarely causes serious complications, pruritus in the that all at-risk individuals be treated once yearly with an oral twodrug
perianal and perineal region can be severe, and scratching
may cause secondary infection. In female patients,
worms may wander into the genital tract and penetrate
combination (Molyneux and Zagaria, 2002). Today, >500 mil-
lion people are treated annually (Hotez, 2009). For most countries,
the WHO recommends diethylcarbamate (DEC) for its micro- and
macrofilaricidal effect in combination with albendazole to
into the peritoneal cavity. Salpingitis or even peritonitis
may ensue. Because the infection easily spreads
enhance macrofilaricidal activity. The exceptions are in many
parts of sub-Saharan Africa and Yemen, where either loiasis or
throughout members of a family, a school, or an institution,
the physician must decide whether to treat all stituted for DEC (Molyneux et al., 2003). DEC and ivermectin
onchocerciasis are co-endemic. In these regions, ivermectin is sub-
individuals in close contact with an infected person.
More than one course of therapy may be required.
clear circulating microfilariae from infected subjects (Molyneux
and Zagaria, 2002), thereby reducing the likelihood that mosquitoes
will transmit LF to other individuals. The number of serious
Pyrantel pamoate, mebendazole, and albendazole are highly
effective. Single oral doses of each should be repeated after 2 weeks.
When their use is combined with rigid standards of personal hygiene,
a very high proportion of cures can be obtained. Treatment is simple
and almost devoid of side effects.
adverse events from LF-control chemotherapy programs has been
remarkably low, 1 out of 4.5 million subjects treated (Molyneux
et al., 2003).
DEC is the drug of choice for specific therapy directed
against adult worms. However, the anthelmintic effect on the adult
worms is variable. Although chemotherapy decreases the incidence
of filarial lymphangitis, it is unclear whether it reverses lymphatic
damage or other chronic manifestations of LF. In longstanding elephantiasis,
surgical measures may be required to improve lymph
drainage and remove redundant tissue.
SECTION VII
CHEMOTHERAPY OF MICROBIAL DISEASES
Trichinella spiralis. T. spiralis is an ubiquitous zoonotic
nematode parasite. Trichinosis in the U.S. and the
developing world is usually caused by eating under- or
uncooked venison and wild pigs. When released by acid
stomach contents, encysted larvae mature into adult
worms in the intestine. Adults then produce infectious
larvae that invade tissues, especially skeletal muscle
and heart.
Severe infection can be fatal, but more typically causes
marked muscle pain and cardiac complications. Fortunately, infection
is readily preventable. All pork, including pork sausages, should
be thoroughly cooked before being eaten. The encysted larvae are
killed by exposure to heat of 60°C for 5 minutes.
Albendazole and mebendazole are effective against the intestinal
forms of T. spiralis that are present early in infection. The efficacy
of these agents or any anthelmintic agent on larvae that have
migrated to muscle is questionable. Glucocorticoids may be of considerable
value in controlling the acute and dangerous manifestations
of established infection, although steroids can alter the
metabolism of albendazole.
Lymphatic Filariasis: Wuchereria bancrofti, Brugia
malayi, and B. timori. Adult worms that cause
human lymphatic filariasis (LF) dwell in the lymphatic
vessels. Transmission occurs through the bite
of infected mosquitoes; ~90% of cases are due to W.
bancrofti, most of the rest are due to B. malayi. The
major endemic regions are sub-Saharan Africa, the
Indian subcontinent, Southeast Asia and the Pacific
region, and in four tropical countries of the Americas
(Haiti, Dominican Republic, Guyana, and Brazil).
Loa loa (loiasis). L. loa is a tissue-migrating filarial
parasite found in large river regions of Central and West
Africa; the parasite is transmitted by deerflies. Adult
worms reside in subcutaneous tissues, and infection
may be recognized when these migrating worms cause
episodic and transient subcutaneous “Calabar”
swellings. Adult worms may also pass across the sclera,
causing “eyeworm.” Rarely, encephalopathy, cardiopathy,
or nephropathy occurs in association with heavy
infection, particularly following chemotherapy.
DEC currently is the best single drug for the treatment of loiasis,
but it is advisable to start with a small initial dose to diminish
host reactions that result from destruction of microfilariae.
Glucocorticoids may be administered to ameliorate post-treatment
acute reactions. In rare instances, life-threatening encephalopathy
follows the treatment of loiasis, probably due to the inflammatory
reaction to dead or dying microfilariae lodged in the cerebral
microvasculature. Guidelines have been developed aimed at screening
out populations with heavy infection so that they are not administered
ivermectin, which has also been associated with fatal
encephalopathy. The potential complications of unmonitored DEC
treatment of loiasis are a major reason why this agent is not recommended
for mass chemoprophylaxis of LF in regions of sub-Saharan
Africa where L. loa is co-endemic.
Onchocerca volvulus (Onchocerciasis or River
Blindness). Transmitted by blackflies near fast-flowing