Toxicology Brief: Brunfelsia species: Beautiful but deadly

The genus Brunfelsia belongs to the alkaloid-rich Solanaceae family. It consists of about 40 different species and is native to South and Central America and the West Indies. Brunfelsia species are erect, compact evergreen shrubs that are about 1.5 to 6 ft in height and diameter. In the United States, they are grown as ornamentals in gardens, especially in the warmer southern coastal regions where they can better withstand the winter season. Brunfelsia species are also grown as potted plants and, thus, can be available in the colder states year-round.

Brunfelsia species flowers are showy and appear in clusters (Figure 1). The deep-purple flowers gradually change to lavender and then white over a three-day period. This change in color has given some Brunfelsia species the popular common names the morning-noon-and-night plant and the yesterday-today-and-tomorrow plant. One plant may have all three flower colors (purple, lavender, and white) at the same time. The flowers bloom in midspring, and green to blackish-brown berries develop in summer and autumn. Each seedpod contains about 20 small, hard, dark-brown seeds.1-3

1. Brunfelsia species flowers, leaves, and seeds. Note all three flower colors-purple, lavender, and white-are present on the plant on the left. On the right, note the brown seedpods. (Photos courtesy of Dr. Linnaea Stull.)

Extracts from some Brunfelsia species possess therapeutic properties, and, historically, some Brunfelsia species have been used in the West Indies and South America to treat various ailments. Some of the therapeutic properties and uses of Brunfelsia species include anti-inflammatory, cathartic, diuretic, antipyretic, antirheumatic, abortifacient, emetic, hallucinogenic, and hypertensive effects.1,2

This article describes the clinical signs and treatment of Brunfelsia species toxicosis in dogs. It also reviews Brunfelsia species exposures reported to the American Society for the Prevention of Cruelty to Animals (ASPCA) Animal Poison Control Center (APCC) from November 2001 to November 2006.

REPORTED EXPOSURES

A search of the ASPCA APCC database AnTox for Brunfelsia species exposures from November 2001 to November 2006 revealed 38 cases involving 42 dogs (three cases involved more than one dog).4 No cases were reported in any other animal species. The most commonly involved breeds were Labrador retrievers (n=5) and golden retrievers (n=4). The age range of exposed dogs was from 1 month to 8 years. Weights ranged from 6 to 75 lb (2.7 to 34 kg).

Evidence of chewed Brunfelsia species was found in 25 cases, and in six cases, someone observed the dogs' exposure to Brunfelsia species. The quantity of ingested plant was known in four cases: One dog ingested two leaves, and three dogs ingested 15, 20, and 30 seeds, respectively.4

The Brunfelsia species involved in these cases were Brunfelsia calycina var. floribunda (n=19), Brunfelsia australis (n=7), Brunfelsia pauciflora (n=7), Brunfelsia americana (n=2), nonspecific Brunfelsia species (n=2), and Brunfelsia latifolia (n=1). Although most of the reported cases were from California (n=29), there were also cases from Texas (n=4), Oregon (n=3), Connecticut (n=1), and New Jersey (n=1).

The gastrointestinal tract and central nervous system (CNS) were most commonly affected. The outcome of 19 dogs is known: Thirteen dogs recovered with supportive care, two dogs died, two dogs developed sequelae (occasional seizure episodes), one dog was euthanized, and one dog had a continuation of clinical signs (lethargy) at follow-up.

BRUNFELSIA SPECIES TOXICOSIS CASES IN THE LITERATURE

There are case reports of Brunfelsia species toxicosis in cattle, dogs, rats, and mice.1-3,5-7 Several of these cases were fatal, with nonspecific necropsy findings. Although only a few Brunfelsia species (B. calycina var. floribunda, B. pauciflora, B. australis, B. bonodora) have been implicated in animal poisoning cases, all species and all parts of the plant (flowers, leaves, berries, and seeds) should be considered toxic to animals. Dogs appear to be particularly attracted to the berries and seeds. Four reports of Brunfelsia species toxicosis in dogs have been published—two in Australia5,6 and two in the United States.2,7

In the two Australian cases, the clinical signs of toxicosis included signs of buccal and gastric irritation (salivation, vomiting, and diarrhea), muscle spasm and rigidity, opisthotonus, and coma. Nystagmus was also described in one case. In one case, the dog recovered in two days with supportive treatment.5,6

In the first U.S. case, a 6-year-old female Siberian husky was presented for evaluation with excessive salivation, coughing, gagging, dilated pupils, muscular contractions, horizontal nystagmus, and clonic-tonic convulsions after eating B. pauciflora seeds. Convulsions stopped on the fifth day, and the dog completely recovered within three weeks. The dog was treated with activated charcoal, intravenous fluids, anticonvulsants (pentobarbital or primidone), corticosteroids, and a topical ophthalmic ointment.7

In the second U.S. case, an 11-week-old puppy was presented with acute-onset anxiety, persistent sneezing, vomiting, tremors, pyrexia, disorientation, ataxia, and seizures within two hours after exposure. The puppy died despite treatment with activated charcoal, diazepam, and prednisolone. The vomitus and stool contained several seeds of B. calycina var. floribunda. Necropsy findings in this puppy were unremarkable.2

CLINICAL SIGNS

The literature and the ASPCA APCC cases indicate that the onset of clinical signs of Brunfelsia species toxicosis in dogs may occur within two to several hours after exposure. Clinical signs may start with agitation, nervousness, or excitement followed by tremors, shaking, muscular rigidity, paddling, and tonic-clonic seizures. Table 1 lists clinical signs in dogs reported to the ASPCA APCC. The tonic-clonic seizures and other clinical signs such as muscular rigidity or the sawhorse stance may resemble the signs caused by strychnine poisoning.

Table 1: Clinical Signs Reported After Brunfelsia Species Ingestion in 42 Dogs

Clinical signs may last from a few hours to several days with or without treatment. Brunfelsia species poisoning does not seem to cause marked hematologic, serum chemistry, or pathologic changes in animals.

MECHANISM OF ACTION

Several biologically active compounds have been isolated from Brunfelsia species, although the exact toxins responsible for neurotoxicosis are unknown. The compound responsible for causing the clinical signs of toxicosis appears to be similar to a compound that interferes with neurotransmission such as that seen with strychnine toxicosis.

Two compounds that cause neurotoxicosis in mice or rats are hopeanine and brunfelsamidine.1 Hopeanine causes decreased activity, paralysis, seizures, and hypersensitivity, whereas brunfelsamidine produces excitement, tonic-clonic seizures, and death. It appears that brunfelsamidine may be the toxin responsible for neurotoxicosis in animals because of its ability to cause excitement and tonic-clonic seizures.1 According to one report, the unknown toxins isolated from B. calycina var. floribunda are water-soluble and highly stable, maintaining lethality for four months.2

DIAGNOSIS

A diagnosis of Brunfelsia species toxicosis in dogs is based on a history or evidence of exposure to the plant (flowers, leaves, berries, or seeds present in the vomitus or stool), an onset of clinical signs within hours after exposure, and the characteristic CNS signs (muscular rigidity, paddling, tonic-clonic seizures) and vomiting or diarrhea. The differential diagnoses should include toxicoses with strychnine, metaldehyde, methylxanthine, organochlorine pesticides, lead, or illicit drugs (e.g. amphetamines, cocaine) and infectious diseases such as canine distemper.

TREATMENT

The main treatment objectives are decontamination, seizure control, and supportive care. If the animal has CNS signs, stabilize it (control seizures as described below) before starting decontamination or supportive care. In the case of a recent exposure (within two hours of ingestion) when no clinical signs are present, induce emesis with 3% hydrogen peroxide (1.5 ml/kg orally; repeat in 10 minutes if emesis does not occur after first dosing) or apomorphine (0.02 to 0.04 mg/kg intramuscularly or intravenously).

After emesis, administer activated charcoal (1 to 2 g/kg orally) mixed with a cathartic such as 70% sorbitol (1 to 2 ml/kg) or magnesium sulfate or sodium sulfate (250 mg/kg). Do not give a cathartic if the animal already has diarrhea. Repeated doses of charcoal (six to eight hours apart) can be useful if seeds or fruit have been ingested. If large amounts of seeds or berries have been consumed, consider gastric or enterogastric lavage followed by charcoal administration.

Control seizures with intravenous pentobarbital sodium (given to effect and repeated as needed) or with methocarbamol (100 to 200 mg/kg intravenously; maximum dose of 330 mg/kg/day). Intravenous propofol (4 to 6 mg/kg) or diazepam (1 to 2 mg/kg) may also be useful, although success varies with diazepam. If seizures are not controlled with the preceding treatment, administer isoflurane gas anesthesia. Severely affected animals may require intubation and artificial respiration.

Animals should be kept in a dark, quiet place. Monitor for hyperthermia or hypothermia, and treat as needed with cooling baths, fans, or heating pads. Monitor complete blood counts and serum chemistry profiles as needed. Intravenous fluid diuresis may be required for one or two days or longer. Complete recovery may take several days or weeks.

CONCLUSION

Although there are only a few published reports of Brunfelsia species toxicosis in dogs, the information collected by the ASPCA APCC from 2001 to 2006 indicates that the number of cases is on the rise, probably because of the increased popularity and availability of Brunfelsia species in the United States.

Clinical signs of Brunfelsia species toxicosis are usually observed within the first few hours after exposure and mainly consist of CNS and gastrointestinal effects. Some CNS signs may be similar to those caused by strychnine.

Treatment is aimed at decontamination, seizure control, and supportive care. Since Brunfelsia species toxicosis can cause potentially life-threatening effects, all exposures should be taken seriously and treated aggressively.

"Toxicology Brief" was contributed by Safdar A. Khan, DVM, MS, PhD, DABVT, ASPCA Animal Poison Control Center, 1717 S. Philo Road, Suite 36, Urbana, IL 61802. The department editor is Petra Volmer, DVM, MS, DABVT, DABT.

REFERENCES

1. Burrows GE, Tyrl RJ. Brunfelsia L. In: Toxic plants of North America. Ames: Iowa State University Press, 2001;1107-1108.

2. Spainhour CB Jr, Fiske RA, Flory W, et al. A toxicological investigation of the garden shrub Brunfelsia calcyina var. floribunda (yesterday-today-and-tomorrow) in three species. J Vet Diagn Investi 1990;2(1):3-8.

3. Mason J, Khan SA, Gwaltney-Brant S. Toxicant exposures in small animals: recently recognized animal toxicants. In: Kirk RW, Bonagura JD, eds. Current veterinary therapy small animal practice (in press).

4. AnTox Database. Urbana, Ill: ASPCA Animal Poison Control Center, 2001-2006.

5. McBarron EJ, de Sarem W. Letter: Poisoning of dogs by the fruits of the garden shrub Brunfelsia bonodora. Aust Vet J 1975;51(5):280.

6. Neilson J, Burren V. Intoxication of two dogs by fruit of Brunfelsia australis. Aust Vet J 1983;60(12):378-380.

7. Banton MI, Jowett PL, Renegar KR, et al. Brunfelsia pauciflora ("yesterday, today and tomorrow") poisoning in a dog. Vet Hum Toxicol 1989;31(5):496-497.