Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

MISCELLANEOUS ANTHELMINTICS
Adverse effects
● Direct toxicity of melarsomine is unusual. However,
the margin of safety is low, with deaths observed in
heartworm-negative dogs given 7.5 mg/kg.
● Signs of pulmonary thromboembolism; as noted
above, there may be greater risk of thromboembolism
occurring compared to thioacetarsamide treatment,
especially if patients are not appropriately
clinically staged and the manufacturer’s guidelines in
relation to patient management prior to melarsomine
treatment are not followed strictly.
● Pain and swelling at injection site.
Contraindications and precautions
● Because the hazards of treatment are related to the
health status of the pulmonary and cardiovascular
systems and their ability to cope with worm emboli,
patient evaluation before treatment is vital. Patient
evaluation algorithms are detailed on product leaflets
and should be closely observed.
● Melarsomine should not be administered to dogs
with severe heartworm disease.
Special considerations
● In cases of suspected arsenic intoxication, administration
of dimercaprol (BAL, British anti-Lewisite) at
3 mg/kg IM may reverse the signs if administered
early. However, it is expected that dimercaprol will
reduce the efficacy of melarsomine.
● To minimize the impact of pulmonary thromboembolism,
dogs should be rested after treatment.
● Microfilariae are not eliminated by melarsomine and
appropriate treatment (commonly an ML) should be
instituted.
● Refer to current Guidelines for the Diagnosis, Prevention
and Management of Heartworm (Dirofilaria
immitis) Infection in Dogs (www.heartwormsociety.
org).
MISCELLANEOUS ANTHELMINTICS
Piperazine
Hexahydropyrazine.
Clinical applications
Piperazine has particular utility against ascarid
infection.
Mechanism of action
Piperazine acts as a γ-aminobutyric acid (GABA) agonist,
causing chloride channel opening, neural hyperpolarization
and flaccid paralysis of susceptible parasites.
Affected worms are then expelled from their predilection
sites by normal enteric movements. In the absence
of peristaltic waves, worms may recover from paralysis
and resume their parasitic state.
Formulations and dose rates
Piperazine is available as a number of salts:
Piperazine hexahydrate (44% piperazine base)
Piperazine adipate
(37% piperazine base)
Piperazine citrate
(35% piperazine base)
Piperazine sulfate
(46% piperazine base)
Piperazine dihydrochloride (50% piperazine base)
Usual use rates are 45 mg piperazine base (or 100 mg piperazine
hexahydrate equivalents)/kg bodyweight PO in both dogs and cats.
Pharmacokinetics
In humans piperazine is rapidly absorbed and eliminated
after oral administration, being detected in urine
within 30 min, reaching peak concentrations within 1–
8 h and being undetectable after 24 h.
Adverse effects
At recommended use rates vomiting, diarrhea, inappetence
and depression may occur.
In addition, a dose-related neurological syndrome has
been described that includes ataxia, muscular weakness,
intention tremor of the head and neck, head pressing,
epileptiform seizures, hyperesthesia, tetanic spasms,
slow pupillary light reflex and lethargy. Symptomatic
and supportive treatment is usually quickly successful.
Known drug interactions
Since they have opposing modes of action, coadministration
of pyrantel can be expected to antagonize the
anthelmintic effects of piperazine.
Diethylcarbamazine citrate
dihy-
N,N-diethyl-4-methyl-1-piperazinecarboxamide
drogen citrate.
Clinical applications and dose rates
Since the fi rst description of oral prophylaxis against D. immitis infection
in 1962, diethylcarbamazine (DEC) has been used for prevention
of heartworm establishment. At a dose rate of 6.6 mg/kg q.24 h. PO,
DEC is active against third-stage larvae and the molt from third to
fourth stage. At 22 mg/kg/day (higher than usual prophylactic dose
rates) there is useful activity against fourth-stage larvae and possibly
young adults.
DEC is also used for treatment of ascarids in dogs and cats at a
dose of 50–100 mg/kg PO and has been reported at 100 mg/kg as
suitable for control of fourth-stage and adult B. malayi in cats.
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