PIPERAZINE DERIVATIVES

Piperazine is a widely used anthelminthic agent

Toxicokinetics. These drugs are rapidly absorbed from the stomach and small intestine and exhibit significant renal elimination. Generally these agents are considered to have a wide margin of safety .

Mechanism of action:

Piperazine and diethylcarbamazine are GABA agonists. GABA is a major inhibitory neurotransmitter and the stimulation of GABA receptors causes an influx of chloride ions that hyperpolarize the neuronal membrane. This renders the neuronal membrane less excitable and decreases nerve transmission.

 The mechanism of diethylcarbamazine-induced hypotension involves antigens released from killed heartworm microfilaria. The antigens activate complement and induce immune complex formation, yielding vasoactive mediator release and causing shock. This is not thought to be a classic type I hypersensitivity mediated by histamine in that infusion of microfilarial antigens into healthy dogs can mimic the syndrome.

  Clinical Signs: Piperazine neurotoxicosis in cats and dogs is manifested by muscle tremors, ataxia, depression, incoordination, and ataxia. High doses of piperazine may cause vomiting and diarrhea in addition to neurologic signs.

 Diethylcarbamazine-induced reactions are characterized by tachycardia, hypovolemia, and hypotension.     

   Diagnostic Testing :

A Knotts test for microfilaria in the systemic circulation may aid in a diagnosis of diethylcarbamazine-induced shock.

Treatment: Piperazine-induced intoxication requires supportive and symptomatic therapy; no antidote is available.

 Aggressive fluid therapy, thermoregulation, and possibly oxygen therapy are needed for diethylcarbamazine-induced shock.

Prognosis: Piperazine-induced intoxication is generally mild and transitory. Diethylcarbamazine-induced shock has a rapid onset and death may occur in a few hours. Survival of the animal depends on a rapid diagnosis and aggressive therapy.