Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 10 ANTIPARASITIC DRUGS
238
Table 10.6 Clinical applications and dose rates of antiprotozoal drugs in dogs and cats (continued)
Trypan blue
Babesia canis 10 mg/kg IV (slow) as a 1% solution
Adverse effects include shock if administered quickly and periphlebitis.
AZOLE
Ergosterol is principal sterol in plasma membrane of certain protozoa. Azoles inhibit cytochrome P450-dependent C-14 demethylation of
lanosterol, depriving cells of ergosterol and impairing normal cell membrane function. See Chapter 9 Antifungal Drugs
Ketoconazole Leishmania spp, Acanthamoeba spp.
Albaconazole (experimental) Trypanosoma cruzi
BENZIMIDAZOLE/PRO-BENZIMIDAZOLE
See entry under Internal Parasiticides
Albendazole
Giardia infection in both cats and dogs 25 mg/kg q.12 h for 2–5 days
Febantel
Bioactivated enzymatically by the host to fenbendazole and oxfendazole. Active (as fenbendazole) against giardiosis.
Fenbendazole
Giardia infection in both cats and dogs 25 mg/kg PO q.12 h for 5 days
HYDROXYNAPHTHOQUINONE
Hydroxynaphthoquinones selectively block mitochondrial electron transport thereby inhibiting ATP and pyrimidine biosynthesis in susceptible
protozoa.
Atovaquone
Pneumocystis and (uniquely) Toxoplasma tissue cysts (bradyzoites) 15 mg/kg PO q.24 h for 3 weeks
Babesia gibsoni (Asian genotype) atovaquone 13.3 mg/kg PO q.8 h (with fatty meal) + azithromycin 10 mg/kg PO q.24 h, for 10 days.
Intestinal absorption increased with fatty meal. Lipid soluble. Little metabolism. Enterohepatic cycling. Can be used in combination with
azithromycin for Babesia control. Adverse effects include nausea, vomiting, diarrhea, hypoglycemia, anemia, neutropenia. Other members
of the class (parvaquone and buparvaquone) do not appear as effective in dogs and cats.
HYDROXYQUINOLINE
Potent inhibitors of mitochondrial respiration in susceptible protozoal species, acting at a site near cyctochrome b.
Decoquinate
Hepatozoon americanum 10–20 mg/kg PO q.12 h indefinitely. Used as adjunct to primary treatment with trimethoprim, sulphonamide,
clindamycin and pyrimethamine.
NITROFURAN
Nitrofurans inhibit oxidative reactions, including decarboxylation of pyruvate to acetyl coenzyme A (catalyzed by pyruvate:ferredoxin
oxidoreductase or PFOR) reducing the available energy for vital cellular functions. In addition, reductive metabolism of the nitro group
generates reactive metabolites that bind covalently with DNA, inhibiting replication and transcription.
Furazolidone
Giardia 4.4 mg/kg PO q.12 h 5–7 days
Cystoisospora 8–20 mg/kg PO q.24 h 7 days
Entamoeba 2.2 mg/kg PO q.8 h 7 days
Experimental studies have revealed no adverse effects associated with daily oral administration for two years with doses up to 2.5 mpk. Long
term dosing with higher doses led to a variety of effects including cataracts decreased sperm motility and abnormal sperm and
neurological signs. Studies of reproductive toxicity, embryotoxicity and teratogenicity revealed no adverse effects.
Nifurtimox
Trypanosoma cruzi 2–7 mg/kg PO q.6 h for 3–5 months
Nifurtimox requires one electron reductions to form nitro ion radicala that reduce molecular oxygen to form superoxide anion, regenerating
the parent nitro compound through redox cycling. Overproduction of superoxide anion overwhelms cell pathways to remove it, and other
reactive oxygen species (H 2 O 2 and OH•) are formed, resulting in lipid peroxidation and damage to membranes, proteins, and DNA. LD50
greater than 4,000 mg/kg in both cat and dog. Daily dosing of dogs for 52 weeks was without adverse effects at a dose rate of 30 mg/kg.
NITROIMIDAZOLE
Nitroimidazoles are prodrugs that require reductive activation of the nitro group by susceptible organisms. Selective toxicity toward anaerobic
and microaerophilic pathogens such as the amitochondriate protozoa (Pentatrichomonas, Entamoeba and Giardia) reflects differences in
energy metabolism, where electron transport includes ferredoxins, small Fe-S proteins that have a sufficiently negative redox potential to
donate electrons to nitroimidazoles. Single electron transfer forms highly reactive nitro radical anions that kill susceptible organisms by
radical-mediated mechanisms that target DNA and possibly other vital biomolecules. Nitroimidazoles are catalytically recycled; loss of
electrons from the active metabolite regenerates the parent nitroimidazole. Increasing levels of O 2 inhibit nitroimidazole-induced cytotoxicity
as O 2 competes for electrons generated by energy metabolism.
Metronidazole (classified as a 5-nitroimidazole)
Balantidium coli 15–30 mg/kg PO q.12–24 h 5–7 days
Entamoeba histolytica 25 mg/kg PO q.12 h 5–7 days
Giardia duodenalis 25 mg/kg PO q.12 h 5–7 days
Metronidazole is well absorbed and widely distributed, subject to hepatic metabolism with an elimination half life of 3–13 h Adverse effects
include vomiting, hepatotoxicity, neutropenia and neurological signs. Diazepam (IV bolus followed by PO q.8 h for 3 d) has been reported to
significantly accelerate recovery from neurological toxicity. Other members of the class include ipronidazole, ronidazole (more active
against Tritrichomonas fetus than metronidazole), and tinidazole.