Page 649 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition
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614 SECTION | VIII Rodenticides




  VetBooks.ir  Mechanism of Action                               TABLE 47.1 Acute Toxicity Data for Strychnine
             Pharmacologically, because of its bitter taste, strychnine
                                                                            Route of Administration
                                                                                                    LD 50 (mg/kg)
                                                                 Species
             strongly stimulates salivary and gastric secretions. This
             increases appetite, and as a result, strychnine has been  Rat  Oral                    2.30
             used for a long time to counteract the loss of appetite
                                                                 Rat        i.p.                    2.50
             associated with illnesses.
                Strychnine is a potent convulsant. The convulsant  Rat      s.c.                    1.20
             action of strychnine is due to interference with the post-  Rat  i.v.                  0.96
             synaptic inhibition that is mediated by the amino acid gly-
                                                                 Mice       Oral                    2.00
             cine. Glycine is an inhibitory transmitter to motor neurons
                                                                 Mice       i.p.                    0.98
             and interneurons in the spinal cord. Strychnine acts as a
             selective competitive antagonist to block the inhibitory  Mice  s.c.                   0.474
             effects of glycine at the glycine receptors. Studies indicate  Mice  i.v.              0.41
             that strychnine and glycine interact with the same recep-
                                                                 Duck       Oral                    3.00
             tor, but at different sites. It increases reflex excitability in
             the spinal cord, which results in a loss of the normal inhi-  Pigeon  Oral             21.00
             bition of spread of motor cell stimulation, so that all mus-
                                                                 i.p., intraperitoneal; i.v., intravenous; s.c., subcutaneous.
             cles contract simultaneously. There is also evidence of an  Source: From NIOSH (1983 1984).
             increase in brain levels of glutamic acid, an amino acid
             that acts as a transmitter for excitatory nerve impulses
             that excite muscle contraction. The result of these effects  Although strychnine has no direct effects on skeletal
             is that skeletal muscles become hyperexcitable. With a  muscles, all voluntary muscles contract simultaneously
             little sound or touch, uncontrollable convulsions and  (as discussed earlier). The increase in muscle tone is
             seizures become eminent, followed by suffocation and  caused by the central action of strychnine. The most pow-
             death. Death occurs due to respiratory failure.    erful effects are seen on the muscles of joints. Respiratory
                                                                muscles (diaphragm, thoracic, and abdominal) contract,
                                                                respiration ceases and, eventually, death ensues due to
             Toxicity                                           respiratory failure.
                                                                  Birds poisoned by strychnine exhibit the signs of
             Strychnine has been studied for acute toxicity in many
                                                                ataxia, ruffled feathers, wing droop, salivation, tremors,
             species, and all species that have been tested have been
                                                                and convulsions. Death occurs due to respiratory failure.
             found to be sensitive. Strychnine is an extremely toxic
                                                                On postmortem, lesions are only observed in the lungs—
             substance, with an LD 50 of 2.3 mg/kg in rats, 2 mg/kg in
                                                                i.e., pinpoint hemorrhages resulting from death due to
             mice, 0.6 mg/kg in rabbits, and 0.5 mg/kg in cats and
                                                                asphyxia. Rigor mortis occurs soon after death and per-
             dogs. An approximate lethal dose for a dog is 0.75 mg/kg
                                                                sists for days. Occasionally, wildlife species are also inad-
             body weight. Thus, 5-g bait having 0.3% strychnine could
                                                                vertently poisoned by strychnine.
             be enough to kill a 20-kg dog. Toxicity data of strychnine
                                                                  There is no evidence of cumulative toxicity from
             for various animal species are given in Table 47.1.
                                                                strychnine (Gosselin et al., 1984). From animal studies,
                Among animals, poisoning occurs with greatest fre-
                                                                there is no evidence that strychnine has potential for
             quency in dogs due to accidental ingestion or malicious
                                                                reproductive and developmental toxicity or mutagenic
             intent. The onset of signs can occur within 15 30 min or,
                                                                and carcinogenic activity.
             occasionally, 60 min after oral exposure, depending on
             whether the stomach is empty or full. The clinical signs are
             associated with CNS effects. Onset of signs includes rest-  Diagnosis
             lessness, anxiety, muscle twitching, and stiffness of the
             neck. The poisoned dogs usually show the signs of mydria-  Diagnosis of strychnine poisoning is based on (1) history
             sis, tonic convulsions, contractions of striated muscles, sei-  of exposure to a strychnine bait or the presence of
             zures, opisthotonus, and death. The animal becomes  cracked corn in the digestive tract; (2) clinical signs
             sensitive to touch, sound, noise, or any other sudden change  of tetanic convulsions, seizures, hypersensitivity to
             in the environment. A minor stimulation can trigger violent  external stimuli, and muscle stiffness; and (3) chemical
             convulsions. Muscular contractions are easily triggered by  identification of strychnine in the stomach content,
             external stimuli, accompanied by hypothermia, lactic acido-  blood, urine, or visceral organs (liver and kidney).
             sis, rhabdomyolysis and, consequently, nephrosis, which  Strychnine residue can be detected and quantified using
             may result in renal failure (Gupta and Crissman, 2012).  gas chromatography (GC) flame ionization detector or
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