Some toxicity thresholds for the clinical effects of common tiger snake (Notechis scutatus) envenomation in the dog

SUMMARY Common tiger snake (Notechis scutatus) venom was administered experimentally to dogs at doses from 0.25 lethal dose (LD) to 20 LD. Haemolysis and increased creatine kinase values occurred rapidly after injection of sublethal (subparalytic) doses, but the clotting time of blood was extended and blood became incoagulable only when dogs were dosed with 10 LD or more of venom. Haemolysis, although of a low threshold of toxicity, was not severe and should not greatly affect the lethality of the venom. Coagulopathy is a sign that the dog has been lethally envenomed and will need to be given antivenom if skeletal muscle paralysis is to be overcome.     

Induction of intestinal evacuation or vomition (or both) in the dog by prostaglandin F2alpha injection: clinical potential

Different groups of dogs were given prostaglandin F2alpha IM. The dosage range was between 0.022 and 0.555 mg/kg of body weight. Defecation, including contents from the cranial portion of the large intestine, occurred in 40% to 100% of the dogs within 3.16 to 12.5 minutes after injection depending on dosage administered. Defecation (83.3% of dogs), without vomition, occurred in dogs given a dosage of 0.111 mg/kg. Emesis (87.5% of dogs) and defecation (75.0% of dogs) were observed in dogs given a dosage of greater than or equal to 0.444 mg/kg. Emesis occurred in 1.6 to 2.6 minutes after defecation in dogs given more than 0.444 mg/kg. Latency for emesis response varied between 3.2 and 11.5 minutes. The effect of the drug lasted approximately 15 minutes, with most dogs showing a single episode of defecation or vomition (or both). Besides a marked increase in respiratory rate, side effects were minor. Seemingly, prostaglandin-F2alpha may become the preferred drug for the clinical inducement of vomition and defecation in dogs.     

Effects of dermal application of 10.0% imidacloprid-0.08% ivermectin in ivermectin-sensitive Collies

OBJECTIVE: To evaluate the safety of dermal application of 10.0% imidacloprid-0.08% ivermectin in ivermectin-sensitive Collies at dose rates of 3 to 5 times the proposed maximum therapeutic dose. ANIMALS: 15 Collies (5 males and 10 females) that were confirmed as ivermectin-sensitive dogs. PROCEDURE: Dogs were assigned to 3 treatment groups (control, 3X, or 5X group) in a randomized block design on the basis of the maximal ivermectin-sensitivity score obtained during preliminary screening. Dogs in groups 3X and 5X were treated at 3 and 5 times the maximum label dose, respectively. Control dogs received an application of an equal volume of a nonmedicated solution. Observation and scoring on all days were conducted to specifically include neurologic signs typical of ivermectin toxicosis, including lethargy, ataxia, abnormal mydriasis, and abnormal salivation. RESULTS: None of the dogs had clinical abnormalities during the study period. CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of results of this study indicates that dermal application of 10.0% imidacloprid-0.08% ivermectin is safe for use in ivermectin-sensitive Collies at dose rates of 3 or 5 times the proposed maximum therapeutic dose.     

Cardiovascular changes in dogs given diazepam and diazepam-ketamine

The cardiopulmonary consequences of diazepam (0.5 mg/kg, IV) followed by ketamine (10 mg/kg, IV) were evaluated in 11 dogs. Diazepam did not exhibit a tranquilizing effect and was frequently associated with excessive excitement. It produced minimal cardiopulmonary effects, except for a significant increase in heart rate. Ketamine administration was associated with less cardiovascular stimulation when administered after diazepam than it did when administered alone; the respiratory depression was greater. Compared with ketamine alone, the diazepam-ketamine combination was associated with more vomition, less muscle hypertonus, less seizure activity, and less salivation.     

Snake envenomation in cats and its detection by rapid immunoassay

Objective To determine the usefulness of a snake venom detection kit (SVDK) in the management of envenomed cats.
Design A clinical study.  

Animals

Twenty-two cats were investigated.
Procedure Cats injected subcutaneously with approximately 0.25 or 1.0 lethal dose (LD) of tiger snake venom or 1 or 4 LD of brown snake venom were observed for clinical symptoms of envenomation at intervals over the ensuring 24 to 48 hours(h). Blood and urine samples were taken at regular intervals and assayed in a quantitative laboratory assay for snake venoms. Selected samples were assayed in parallel in a rapid, semi-quantitative SVDK.
Results The studies showed that it was important to estimate the elapsed time from envenomation to presentation. If this time was less than 8 h, blood was the most appropriate sample and a negative result should exclude serious envenomation. If the elapsed time exceeded 8 h, it was essential that urine be sampled. Venom levels in urine were high at 8 h and approached the level of test sensitivity over 24 to 48 h; however by this time clinical signs were obvious in endangered cats.  

Conclusions

Careful use of the SVDK is a valuable aid in the management of a potentially envenomed cat.     

Autonomic and Cardiovascular Effects of Neuromuscular Blockade Antagonism in the Dog

Autonomic and cardiovascular changes were studied when neuromuscular blockade was antagonized in 96 dogs with one of eight anticholinesterase-antimuscarinic drug combinations. Neostigmine (50 or 100 micrograms/kg) was administered before or after atropine (40 micrograms/kg) or glycopyrrolate (10 micrograms/kg). The high dose of neostigmine (100 micrograms/kg) caused bradyarrhythmias, salivation, and signs of bronchosecretion when used with either antimuscarinic agent and irrespective of the administration sequence. The heart rate increased, but not significantly, when atropine was injected before either dose of neostigmine. This did not occur when this administration sequence was reversed. Arrhythmias and cardiovascular and autonomic changes did not occur when glycopyrrolate was injected before or after neostigmine at 50 micrograms/kg.     

Disposition of creatine kinase activity in dog plasma following intravenous and intramuscular injection of skeletal muscle homogenates

The fate of skeletal muscle-derived creatine kinase (CK) was investigated in six dogs. After i.m. and i.v. injections of 3000 g and 105 000 g supernatants of dog muscle homogenates, plasma CK activity was measured up to 48 h. There was no significant difference in pharmacokinetic parameters dependent on the type of supernatant injected. After i.v. injection, the volume of distribution of CK was equal to the plasma volume, CK clearance was relatively low (about 0.5 mL/kg/min) and its terminal half-life of elimination was about 2.5 h. After i.m. injection, the CK terminal half-life was about 6.5 h, demonstrating a flip-flop mechanism, i.e. a limiting absorption process from the site of injection. Bioavail-ability after i.m. injection was about 65%, and the rate of absorption from muscle injection site was relatively slow: peak activity occurred at the second hour post administration, and most CK activity had been absorbed by 24 h. These pharmacokinetic parameters can be used as a basis for a minimally invasive means of quantitating muscle damage either after intramuscular drug administration or in canine sports medicine.     

Effects of thyrotropin-releasing hormone on serum concentrations of thyroxine and triiodothyronine in healthy, thyroidectomized, thyroxine-treated, and propylthiouracil-treated dogs

Effects of thyrotropin-releasing hormone (TRH) on serum concentrations of thyroid hormones were studied in 36 mixed-bred dogs. Dogs were randomly assigned to 7 groups. Significant increases (P less than 0.05) of serum thyroxine (T4) values occurred as early as 2 hours and reached a peak at 6 to 8 hours after IV injection of 300 to 1,100 micrograms of TRH. Thyroxine concentrations in response to a TRH dose greater than 500 micrograms were similar to those observed with the 300-micrograms dose. Transient coughing, vomiting, salivation, and defecation after large doses (900 and 1,100 micrograms) were observed. Mean serum T4 concentration decreased from 2.1 micrograms/dl to 0.9 micrograms/dl within 1 day of thyroidectomy. Clinical signs of hypothyroidism, including lethargy, dry coats, and diffuse alopecia, were present in 2 dogs at a month after surgical operation. Thyroxine concentrations were detectable for greater than 2 months. Injection (IV) of 700 micrograms of TRH 6 weeks after surgical operation had no effect on serum concentration of T4 in thyroidectomized dogs. In 5 T4-treated dogs, TRH (700 micrograms, IV) significantly increased the serum T4 value, indicating that pituitary thyrotropes were responsive to TRH, in spite of daily medication of 0.8 mg of T4. Four dogs were treated orally with 200 mg of propylthiouracil/day for 5 weeks. Intravenous injection of 700 micrograms of TRH in propylthiouracil-treated dogs had no effect on the serum T4 concentration, indicating that TRH had no effect on serum T4 values in these dogs during the experimental period. These results indicate that TRH can replace bovine thyrotropin for the canine thyroid function test.(ABSTRACT TRUNCATED AT 250 WORDS)     

Myotoxicity and nephrotoxicity of common tiger snake (Notechis scutatus) venom in the dog

SUMMARY The myotoxicity and neurotoxicity of common tiger snake (Notechis scutatus) venom are major factors in the pathogenesis of envenomation in the dog. Histological examination of the tissues of experimentally envenomed dogs has demonstrated the importance of muscle damage in affecting the clinical syndrome of tiger snake envenomation. Within one hour of injection of the venom into dogs, there was selective involvement of some muscles. Cardiac and smooth muscles were not significantly affected. The severity of myofibre damage was influenced by the amount of venom injected. Immobilisation under general anaesthesia resulted in significant protection against the myotoxic effects of high doses of venom. Lesions in the kidneys of experimentally envenomed dogs were acute tubular necrosis and the variable presence of a small amount of proteinaceous material in tubules. These lesions, which were similar to those in cases of natural snake bite, were indicative of a direct nephrotoxic effect, which could be complicated by the effects of myoglobinuria. These findings emphasise the need for supportive treatment aimed at maintenance of renal function in the treatment of dogs suffering from tiger snake envenomation.     

Comparative toxicology of monensin sodium in laboratory animals

The toxicology of monensin has been studied in several laboratory animal species. There was considerable species variation in acute oral LD50 values. The consistent signs of acute toxicity were: anorexia, hypoactivity, skeletal muscle weakness, ataxia, diarrhea, decreased weight gain and delayed deaths. The 3-mo study in rats fed diets containing 0, 50, 150 or 500 ppm monensin resulted in no effects at the lowest dose level, slight reduction of body weight gain in the middle-dose group and severe depression in body weight gain, skeletal and cardiac lesions, and deaths in the highest dose group. The 3-mo study in dogs given daily oral doses of 0, 5, 15 or 50 mg/kg monensin resulted in no effects at the lowest dose level. Dogs in the 15 and 50 mg/kg groups developed, during test wk 1 to 4, anorexia, weakness, ataxia, labored respiration, body weight loss, increased serum muscle enzyme values, severe skeletal muscle degeneration and necrosis with less severe heart lesions and deaths. Mice fed diets containing 0, 37.5, 75, 150 or 300 ppm monensin for 3 mo had reduced body weight gain in all test groups but no other physical signs. Serum creatine phosphokinase (CPK) values were increased in mice in the two highest dose groups and minimal heart lesions were found in the highest dose group. Dogs given daily oral doses of 0, 1.25, 2.5, 5 or 7.5 mg/kg monensin for 1 yr survived with no evidence of toxicity in the two lowest dose groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical signs and studies of the site of action of purified larkspur alkaloid, methyllycaconitine, administered parenterally to calves

The purified diterpenoid alkaloid, methyllycaconitine was isolated from Delphinium brownii and injected intravenously into beef calves in order to observe the clinical signs. Following injection and depending upon dosage, calves showed a variety of signs; agitation, respiratory difficulty and loss of muscle control. Collapse occurred at higher doses of methyllycaconitine. Onset of clinical signs after injection occurred within two to three minutes, and recovery was rapid, clinical signs disappearing within five to ten minutes postinjection.

The clinical signs observed are consistent with a skeletal neuromuscular site of action. Methyllycaconitine may have a curare-like action of postsynaptic blockage of nicotinic cholinergic receptors in cattle as has been demonstrated by in vitro experiments in other species. Physostigmine appears to be an effective antidote to methyllycaconitine.

     

Reversal of medetomidine sedation by atipamezole in dogs

Atipamezole reversed the sedative effect of medetomidine in twelve laboratory beagles. The dogs were sedated with medetomidine doses of 20, 40 and 80 micrograms/kg body wt i.m. Atipamezole was injected (i.m.) 20 min later at dose rates two, four, six and ten times higher (in micrograms/kg) than the preceding medetomidine dose. Placebo treatment was included in the study. The deeply sedated dogs showed signs of arousal in 3-7 min and took their first steps 4-12 min after atipamezole injection. The dose-related reversal effect of atipamezole proved to be optimal with doses which were four, six or ten times higher than the preceding medetomidine dose. Drowsiness was found 0.5-1 h after atipamezole injection in 41% of the cases. No adverse effects nor cases of over-alertness or excitement were found.     

Snake bite: pit vipers

Pit vipers are the largest group of venomous snakes in the United States and are involved in an estimated 150,000 bites annually of dogs and cats. The severity of any pit viper bite is related to the volume and toxicity of the venom injected as well as the location of the bite, which may influence the rate of venom uptake. The toxicity of rattlesnake venom varies widely. It is possible for pit vipers' venom to be strictly neurotoxic with virtually no local signs of envenomation. Venom consists of 90% water and has a minimum of 10 enzymes and 3 to 12 nonenzymatic proteins and peptides in any individual snake. The onset of clinical signs after envenomation may be delayed for several hours. The presence of fang marks does not indicate that envenomation has occurred, only that a bite has taken place. Systemic clinical manifestations encompass a wide variety of problems including pain, weakness, dizziness, nausea, severe hypotension, and thrombocytopenia. The victim's clotting abnormalities largely depend upon the species of snake involved. Venom induced thrombocytopenia occurs in approximately 30% of envenomations. Many first aid measures have been advocated for pit viper bite victims, none has been shown to prevent morbidity or mortality. Current recommendations for first aid in the field are to keep the victim calm, keep the bite site below heart level if possible, and transport the victim to a veterinary medical facility for primary medical intervention. The patient should be hospitalized and monitored closely for a minimum of 8 hours for the onset of signs of envenomation. The only proven specific therapy against pit viper envenomation is the administration of antivenin. The dosage of antivenin needed is calculated relative to the amount of venom injected, the body mass of the victim, and the bite site. The average dosage in dogs and cats is 1 to 2 vials of antivenin.     

Ivermectin and piperazine toxicoses in dogs and cats

Review of all reports involving anthelmintics in dogs and cats to the IAPIC between January 1, 1986 and August 10, 1988, revealed that ivermectin (extra-label use) and piperazine accounted for over 50% of the calls assessed as toxicoses and suspected toxicoses. Both ivermectin and piperazine are gamma-aminobutyric acid (GABA) agonists and their major effects appear to be on the central nervous system. Ivermectin toxicoses at estimated doses of greater than or equal to 100-less than 500 micrograms/kg were reported more than once only in the collies (n = 25) and Australian shepherds (n = 10); these two breeds accounted for 46% (69 of 150) of the toxicoses and suspected toxicoses calls in dogs. Ataxia, behavioral disturbances, tremors, mydriasis, weakness/recumbency, apparent blindness, hypersalivation/drooling (dogs only), and coma were the most commonly reported clinical signs in dogs and cats with suspected ivermectin toxicoses. Shock, dyspnea, vomiting, and ataxia were the most common clinical signs attributed to the microfilaricidal activity of ivermectin. Piperazine was the anthelmintic with the greatest number of reports of toxicoses and suspected toxicoses in cats. Piperazine neurotoxicity in cats and dogs usually was manifested by muscle tremors, ataxia, and/or behavioral disturbances within 24 hours after estimated daily dose(s) between 20 and 110 mg/kg.     

A Retrospective Study of Pemoline Toxicosis in Dogs: 101 Cases (1987–1997)

Pemoline is a central nervous system stimulant commonly used for Attension Deficit Disorder in humans. This study describes the clinical syndrome associated with pemoline ingestion as well as its treatment. Ten years worth (1987–1997) of records from the ASPCa National Animal Poison Control Center involving pemoline ingestion in dogs were reviewed. The data suggests that most dogs ingesting pemoline show signs of central nervous system and cardiovascular stimulation including hyperactivity, tremors, ataxia, seizure, tachycardia, hyperthermia, and mydriasis. Blood chemistry alterations included electrolyte imbalances in some dogs. The minimum dose reported to cause clinical signs was 2.8 mg/kg and the minimum dose reported to have caused death was 10 mg/kg. Dogs generally showed clinical signs within 30 minutes to 24 hours of ingestion. The duration of clinical signs ranged from 15 hours to four days. Ninety-four percent of the dogs recovered with supportive treatment. (Vet. Emerg. & Crit. Care, 9:203–207, 1999)     

Alpha-chloralose poisoning in dogs and cats: a retrospective study of 33 canine and 13 feline confirmed cases

Alpha-chloralose (AC) is an anaesthetic compound also used as a rodenticide, and has dose-dependent central nervous system mixed effects of excitation and depression. The objectives of this study were to detail the clinical and clinicopathological characteristics, as well as the treatment and prognosis, of AC toxicosis in dogs and cats. Medical records were retrospectively reviewed for AC poisoning between the years 1989 and 2004, and 33 dogs and 13 cats were included in the study. The most common clinical signs were seizures, muscle tremor, hyperaesthesia, hypothermia, salivation, myosis, stupor, coma and ataxia. Coma was more common, while salivation and ataxia were less common in cats compared to dogs. Although hypothermia was very common, especially in cats (90.9%), hyperthermia was frequently observed in dogs (21%). Treatment in all patients was supportive and symptomatic, and the most commonly used anticonvulsants were diazepam and barbiturates; however, severe unresponsive seizures in three dogs had to be controlled with inhalant gas anaesthesia. The hospitalisation period was 1-3 days, and the overall mortality rate was 6.5%. Alpha-chloralose poisoning seems to have a favourable prognosis in dogs and cats.     

Effects of Brimonidine Ingestion on Cardiovascular Responses and Renal Function in Conscious Dogs

The effects of brimonidine, an α₂-adrenoceptor agonist, on blood pressure, heart rate, respiratory rate, renal function and some blood parameters were investigated in 10 dogs. Dogs were divided into two groups, low dose (LD; 0.2 mg/kg) and high dose (HD; 0.5 mg/kg) of brimonidine given orally. The α₂-adrenergic antagonist yohimbine hydrochloride was injected to dogs at a dose of 0.1 mg/kg in both groups at the fifth hour after brimonidine administration. The results demonstrated that after administration of brimonidine, mean arterial blood pressure decreased dramatically at 2 h by 23% and 20% in LD and HD groups, respectively. Heart rate was decreased in a similar manner and both remained low at 5 h after brimonidine administration. Respiratory rate was decreased by 50%, while the electrocardiogram showed prolongation of the PR interval. Glomerular filtration rate (GFR) and effective renal blood flow were reduced when measured at 4 h after brimonidine ingestion in both groups, but the effect was more pronounced in the LD group. Brimonidine caused natriuresis and kaliuresis in both LD and HD groups. The packed cell volume was decreased and hyperglycaemia was detected. Most of the effects can be reversed completely after administration of yohimbine. However, yohombine can restore GFR only partially. These data suggest that brimonidine caused cardiovascular and respiratory depression. The adverse effects of this drug can be antagonized by yohimbine, suggesting that these effects were mediated via the α₂-adrenoceptor.     

Prostaglandin therapeutics in the bitch and queen

The use of prostaglandin F2 alpha as an abortifacient and for the treatment of certain diseases affecting the reproductive system of the bitch and queen is reviewed. Doses of 0.5 to 1.0 mg/kg PGF administered by intramuscular or subcutaneous injection at intervals of 24 or 48 h after mid-gestation appears to be a satisfactory luteolytic-- abortifacient regime for use in dogs and cats. Doses of 0.25 to 0.5 mg/kg in the bitch and 0.5 to 1.0 mg/kg PGF in the queen, at intervals of 24 or 48 h, may be used as an adjunct to the therapy of metritis, endometritis or pyometritis. A median lethal dose of 5.13 mg/kg has been derived for use of PGF in the bitch and this is thought to be similar for use of PGF in the queen. Side effects of defecation and/or vomition may be observed in the bitch and queen using routine therapeutic doses.     

SNAKE BITE IN DOGS

In 7 years snake bite was diagnosed in 80 dogs. Sporting breeds figured prominently. The average was 3.6 years. The commonest presenting signs were salivation, vomiting, dilated pupils, absence of the pupillary light reflex, depression and generalised muscle weakness, hindlimb ataxia and respiratory distress. Sixty-seven cases (84%) occurred in 6 warmer months on the year. Fifty-one dogs (64%) were seen either to be bitten or in contact with a snake. Tiger and Brown snakes were implicated on 32 and 3 occasions respectively. An overall recovery rate of 87% was obtained for patients receiving antivenene, fluid and support therapy. The period from treatment-to-full recovery was shorter for cases in which the bite-to-treatment period was one hour or less (24 hours) when compared with the recovery time for all cases (36 hours). The prognosis was poor for dogs presenting with the triad of complete flaccid paralysis, dyspnoea and a sub-normal temperature.     

Respiratory Depressant and Skeletal Muscle Relaxant Effects of Low-Dose Pancuronium Bromide in Spontaneously Breathing, Isoflurane-Anesthetized Dogs

Objective—To assess and compare the respiratory depressant and skeletal muscle relaxant effects of two low doses of a nondepolarizing neuromuscular blocker, pancuronium bromide. To determine if a “low dose” of pancuronium bromide can produce selective skeletal muscle relaxation in extraocular muscles sufficient to perform intraocular surgery while sparing or minimizing depression of muscles of ventilation. Study Design—Blinded, randomized crossover, placebo controlled study. Animals—Six healthy, adult mongrel dogs weighing 20.8 ±1.9 kg. Methods—Spontaneously breathing, isoflurane-anesthetized dogs received 0.02 mg/kg pancuronium bromide, intravenously (IV), (high dose [HD]), 0.01 mg/kg pancuronium bromide, IV, (low dose [LD]), or saline placebo IV in a blinded, randomized crossover study. Indices of patient ventilation including tidal volume (Vt), respiratory rate (RR), and minute ventilation (V_E) were recorded throughout the study period. Serial arterial blood gas analyses were performed at timed intervals. Neuromuscular blockade of skeletal muscle was assessed at timed intervals with train-of-four stimulus/response ratios. Eye position scores, based on the degree of ocular rotation from a neutral gaze axis, were assigned by an ophthalmologist who was blinded to the treatment given. Results—Vt and V_E in HD dogs decreased by 82% from baseline after administration of pancuronium bromide. Similarly, Vt and V_E in LD dogs decreased 40% and 55%, respectively. Decreased ventilation in HD dogs corresponded with significant (P< .05) neuromuscular blockade, as indicated by train-of-four ratio less than 75% between 0 and 60 minutes. Eye position scores in HD and LD dogs were suitable for intraocular surgery between 0 and 60 minutes. Eye position scores in five of six control dogs were unsuitable for intraocular surgery at any time period. Conclusions—LD dogs experienced only transient, mild to moderate respiratory depression compared with HD dogs, which experienced prolonged, moderate to severe respiratory depression. Both LD and HD dogs acquired and maintained eye position scores suitable for intraocular surgery between 0 to 60 minutes. A “low dose” of pancuronium bromide, which would provide adequate extraocular muscle relaxation while minimizing ventilatory depression, was not identified. Clinical Relevance—All patients receiving any dose of neuromuscular blocking agents should be closely monitored and receive ventilatory assistance as needed.