COMPARATIVE EFFICACY OF DIFFERENT ANTIDOTES AGAINST EXPERIMENTAL NITRATE INTOXICATION IN RABBITS

The antidotal efficacy of aqueous garlic extract, methylene blue, and velenium (Vitamin E + sodium selenite) was compared against experimental nitrate intoxication in rabbits. Forty-two, albino rabbits of identical age, gender, and body weight were randomly divided into 7 groups (A to G) and subjected to experimental treatments for a period of 40 days. Rabbits of group A were offered only normal feed and served as negative control, while, rabbits of group B constituted the positive control group and received feed supplemented with sodium nitrate at 400 mg/kg body weight. Sodium nitrate-containing feed and intraperitoneal injection of 1% methylene blue solution at 2 mg/kg body weight were administered to group C. Rabbits of group D were given sodium nitrate-supplemented feed and aqueous garlic extract at 500 mg/kg body weight through oral route. Group E was treated with sodium nitrate-added feed, intraperitoneal injection of 1% methylene blue solution at 2 mg/kg body weight, and oral administration of garlic extract at 500 mg/kg. Velenium (25 mg of Vitamin E + 2.2 mg of sodium selenite per ml) was intraperitoneally injected at 1 ml/kg body weight to rabbits of group F along with the provision of sodium nitrate-supplemented feed. In addition to being fed with sodium nitrate-containing feed, group G obtained intraperitoneal injection of velenium at 1 ml/kg body weight and oral administration of garlic extract at 500 mg/kg body weight. The efficacy of antidotes was assessed on the basis of changes in blood nitrite level, biochemical profile, and gross pathological lesions manifested by the treated rabbits. The combination of methylene blue and garlic extract was highly effective in treating nitrate toxicity followed by methylene blue, garlic extract, and velenium, respectively. Whereas, the concurrent administration of garlic extract and velenium was least efficacious in terms of antidotal efficacy. In conclusion, aqueous garlic extract can be effectively used either alone or in combination with methylene blue when treating rabbits diagnosed with nitrate toxicity.     

Methylene blue or tolonium chloride antagonism of sodium nitrite induced methemoglobinemia

Methylene blue is widely accepted as an antidote for nitrite toxicosis because of its ability to stimulate reduction of methemoglobin (ferrihemoglobin) to hemoglobin. It is usually used only in low dosage (4mg/kg) because of its purported enhancement of methemoglobin formation in high dosages. Methylene blue was evaluated as a nitrite toxicosis antidote using methemoglobin reduction and lethality protection as evaluation parameters. Tolonium chloride (toluidine blue) another structurally related dye was also evaluated using the same parameters. Both dyes were very effective antidotes. Methylene blue increased in effectiveness as the dose was increased up to 22 mg/kg. Tolonium chloride provided approximately equivalent protection at 8.8 mg/kg but may be more toxic than methylene blue. High concentrations of either dye did not result in appreciable production of methemoglobin. In cases of severe intoxication by methemoglobin formers such as nitrite, larger doses of methylene blue than generally recommended, may be of considerable therapeutic value.     

Cyanide intoxication in sheep: enhancement of efficacy of sodium nitrite, sodium thiosulfate, and cobaltous chloride.

For treatment of cyanide intoxication of ruminants, the present recommended doses of sodium nitrite (5 mg/kg of body weight) and sodium thiosulfate (25 to 50 mg/kg) are smaller than those recommended for other animals; the decrease is partially attributed to the greater susceptibility of ruminants to the toxic effects of sodium nitrite. Based on the high tissue concentration and activity rate of rhodanese in ruminants, sulfur donors such as sodium thiosulfate could be utilized more efficaciously. Doses of sodium nitrite and sodium thiosulfate (up to 22 and 660 mg/kg, respectively) were evaluated in the present studies. Adjustment of the antidotal combination provided almost three times the protection afforded by the previously recommended doses. Moreover, under the conditions tested, the newly adjusted dose levels of sodium thiosulfate alone were more effective than the previously used antidotal combination of sodium nitrite and sodium thiosulfate and this protective effect was enhanced by cobaltous chloride (10.6 mg/kg) or sodium nitrite. The present recommended therapeutic approach to cyanide intoxication in sheep should be based primarily on administration of a much higher dose of sodium thiosulfate in combination with sodium nitrite or cobaltous chloride (or both).     

Nitrite poisoning in cats and dogs fed a commercial pet food

The death of three cats, from two separate households, was linked to toxic concentrations of sodium nitrite used as a preservative in a commercial pet food. Post-mortem examination of the three cats revealed a brownish discoloration of the blood suggestive of methaemoglobinaemia. Analysis of two samples of the pet food fed to the cats revealed a mean concentration of 2850 mg of total nitrite per kg of food (as fed). In a further incident, ataxia and weakness was noticed in two of four dogs after they were fed the same brand of pet food. One dog was successfully treated for methaemoglobinaemia with intravenous methylene blue.     

LD 50 and selenium concentration in organs following intravenous administration of sodium selenite in the rabbit]

In experiments on 72 rabbits, the LD50 of sodium selenite by intravenous injection was found to be 2.24 mg/kg body weight. The clinical picture and pathological changes associated with acute selenium poisoning are described. The increase in selenium concentration was up to nine times the normal in liver and up to six times in kidney and muscle. There was no sign of a return to normal values 24 hours after administration.     

The effect of a single intravenous fluid bolus on packed cell volume and plasma total solids concentration in Red-collared Lorikeets (Trichoglossus haematodus rubritorquis)

OBJECTIVE: To determine the effect of a single intravenous (IV) fluid bolus on the hydration of an avian patient, using packed cell volume (PCV) and plasma total solids (TS) to estimate hydration. PROCEDURE: Ten birds were allocated randomly to one of three groups, and administered 30 mL/kg or 50 mL/kg intravenous fluid, or were part of a control group and did not receive IV fluid. Blood was collected before the IV fluid bolus was administered, and at 1 minute, 3 hours and 6 hours after administration of the fluid. Samples were used to determine PCV and TS and results were compared between groups and between the different time points. RESULTS: Administration of 30 mL/kg or 50 mL/kg compound sodium lactate solution caused a statistically significant decrease in PCV. Within 3 hours, the PCV was not significantly different to the initial value or to the PCV of control birds. Administration of 30 mL/kg compound sodium lactate solution did not result in a significant decrease in TS. However, administration of 50 mL/kg produced a significant decrease in TS, which was still significantly less than controls 6 hours after the fluid was administered. CONCLUSION: These findings suggest that an intravenous bolus of fluid may be safely administered to an anaemic bird, since PCV is significantly decreased for less than 3 hours. Up to 50 mL/kg of fluid may be administered as an intravenous bolus to a bird, to produce significant haemodilution that persists for up to 6 hours.     

The prophylactic effect of corn supplementation on experimental nitrate intoxication in cattle

Sodium nitrate was administered through rumen cannulae to produce NO-3 intoxication in four cows (382 to 445 kg body wt) fed prairie grass hay and a protein-mineral supplement. The cows were fed 0, 1.6 or 3.2 kg of dry rolled corn daily for 10 d prior to sodium nitrate administration. Sodium nitrate administration was followed by a marked increase in intraruminal NO-2 and NH3 and blood NO-2 and methemoglobin. Six of eight cows fed 0 and 1.6 kg of corn were given methylene blue to treat severe methemoglobinemia, while none of the cows fed 3.2 kg corn required such therapy. Feeding of 3.2 kg of corn protected against nitrate poisoning by reducing intraruminal nitrite and blood methemoglobin (P less than .05).     

Nitrite poisoning in cats and dogs fed a commercial pet food

The death of three cats, from two separate households, was linked to toxic concentrations of sodium nitriterused as a preservative, in a commercial pet food. Post-mortem examination of the three cats revealed a brownish discoloration of the blood suggestive of methaemoglobinaemia. Analysis of two samples of the pet food fed to the cats revealed a mean concentration of 2850 mg of total nitrite per kg of food (as fed). In a further incident, ataxia and weakness was noticed in two of four dogs after they were fed the same brand of pet food. One dog was successfully treated for methaemoglobinaemia with intravenous methylene blue.     

Evaluation of Nociception,Sedation, and Cardiorespiratory Effects of a Constant Rate Infusion of Xylazine Alone or in Combination with Lidocaine in Horses

This study aimed to evaluate the effects of a constant rate infusion (CRI) of xylazine or xylazine in combination with lidocaine on nociception, sedation, and physiologic values in horses. Six horses were given intravenous (IV) administration of a loading dose (LD) of 0.55 mg/kg of xylazine followed by a CRI of 1.1 mg/kg/hr. The horses were randomly assigned to receive three treatments, on different occasions, administered 10 minutes after initiation of the xylazine CRI, as follows: control, physiologic saline; lidocaine low CRI (LLCRI), lidocaine (LD: 1.3 mg/kg, CRI: 0.025 mg/kg/min); and lidocaine high CRI (LHCRI), lidocaine (LD: 1.3 mg/kg, CRI: 0.05 mg/kg/min). A blinded observer assessed objective and subjective data for 50 minutes during the CRIs. In all treatments, heart and respiratory rates decreased, end-tidal carbon dioxide concentration increased, and moderate to intense sedation was observed, but no significant treatment effect was detected in these variables. Ataxia was significantly higher in LHCRI than in the control treatment at 20 minutes of infusion. Compared with baseline values, nociceptive threshold increased to as much as 79% in the control, 190% in LLCRI, and 158% in LHCRI. Nociceptive threshold was significantly higher in LLCRI (at 10 and 50 minutes) and in LHCRI (at 30 minutes) than in the control treatment. The combination of CRIs of lidocaine with xylazine produced greater increases in nociceptive threshold compared with xylazine alone. The effects of xylazine on sedation and cardiorespiratory variables were not enhanced by the coadministration of lidocaine. The potential to increase ataxia may contraindicate the clinical use of LHCRI, in combination with xylazine, in standing horses.     

Disposition of sodium salicylate,flunixin and meloxicam after intravenous administration in broiler chickens

Three nonsteroidal anti-inflammatory drugs (NSAIDs) [sodium salicylate, flunixin (FLU) and meloxicam (MEL)] were administered intravenously to broiler chickens. Plasma concentrations were determined by high-performance liquid chromatography methods and pharmacokinetic parameters were calculated. After intravenous administration of sodium salicylate (50 mg/kg), FLU (1.1 mg/kg) and MEL (0.5 mg/kg), these drugs were eliminated from plasma with a mean half-life of 04.04, 05.45 and 03.20 h, respectively. Apparent volumes of distribution (0.39, 0.08 and 0.12 L/kg, respectively) indicated that tissue distribution was limited for the three drugs. Total body clearance was 70 mL/h.kg for sodium salicylate and 10 and 25 mL/kg.h for FLU and MEL, respectively. Based on the pharmacokinetic parameters these NSAIDs may offer possibilities for treatment of various conditions in chickens.     

Analgesic and cardiopulmonary effects of premedication with tramadol in calves anesthetized with the infusion of guaifenesin and thiamylal

This study examined the analgesic and cardiopulmonary effects of intravenous (IV) tramadol during general intravenous anesthesia in calves. Calves were premedicated with diazepam (0.2 mg/kg, IV) with tramadol (2 mg/kg, IV) (group T) or saline (group S). Anesthesia was induced by thiamylal sodium (4 mg/kg, IV) and maintained with an infusion (2 ml/kg/hr) of 5% guaifenesin containing thiamylal sodium (2 mg/ml). Additional thiamylal sodium (1–2 mg/kg, IV) was administered when interference from the calves was observed during surgery. The total counts of additional thiamylal sodium administration, analgesia score using a visual analog scale, recovery time, and cardiopulmonary function in the different groups were assessed and compared. Group T showed significantly fewer counts of additional drug administration and a significantly higher analgesia score. Tramadol may provide adequate analgesia with minimal cardiopulmonary changes in calves during general anesthesia.     

Bioavailability of oral penicillins in the horse: a comparison of pivampicillin and amoxicillin

The pharmacokinetics of ampicillin and amoxicillin following intravenous administration at a dose rate of 15 and 10 mg/kg respectively were studied in four healthy adult horses. Pharmacokinetics of pivampicillin and amoxicillin were studied after oral administration to four healthy adult horses. Pivampicillin, a prodrug of ampicillin, was administered orally to starved and fed horses at a dose rate of 19.9 mg/kg, which is equivalent on a molecular basis to 15 mg/kg ampicillin. Amoxicillin was administered orally to starved horses only, at a dose rate of 20 mg/kg. Ampicillin and amoxicillin concentrations in plasma, synovial fluid and urine were determined. Mean biological half-life of intravenously administered ampicillin and amoxicillin was 1.72 and 1.43 h respectively, whilst the distribution volume (Vss) appeared to be 0.180 and 0.192 1/kg. Orally administered pivampicillin and amoxicillin were rapidly absorbed. A maximum concentration in plasma of 3.80 micrograms/ml was reached 2 h after administration of pivampicillin to starved horses; in fed horses a maximum concentration of 5.12 micrograms/ml was reached 1 h after administration. After oral administration of amoxicillin a maximum concentration of 2.03 micrograms/ml was reached after 1 h. The (absolute) bioavailability of pivampicillin administered orally was 30.9% in starved horses and 35.9% in fed horses. The bioavailability of amoxicillin administered orally was 5.3% in starved horses.     

Clinical evaluation of clonidine added to lidocaine solution for subarachnoid analgesia in sheep

Clonidine (CL) is a alpha2-adrenergic agonist that produces analgesia in animals and humans by a non-opiate alpha2-adrenergic action in the spinal cord dorsal horn. The objective of this prospective randomized study was to investigate the clinical effects of CL/lidocaine (LD) combination administered by the subarachnoid route in sheep. Each sheep received each of three treatments, at no shorter than weekly intervals. Treatments consisted of 0.003 mg/kg CL, 1.2 mg/kg LD and a combination of CL (0.003 mg/kg) and LD (1.2 mg/kg) (CLLD). Subarachnoid injections were given in all animals between the last lumbar and first sacral vertebra. Heart rate (HR), arterial pressures, respiratory rate, rectal temperature, analgesia, sedation, and motor blockade were determined before drug administration (basal) and 5, 10, 15 and 30 min after drug administration, and at 30-min intervals until loss of analgesia occurred. The duration of analgesia after subarachnoid CLLD administration was 187 +/- 24 min (mean +/- SD), i.e. more than twice of that obtained with CL (99 +/- 19 min) or LD (55 +/- 4.4 min) alone. In all sheep, CL, administered either alone or with LD, induced moderate sedation. After subarachnoid administration of three treatments, all sheep had ataxia and subsequent sternal recumbency. The CL treatment causes decreases in blood pressure (diastolic arterial pressure and mean arterial pressure) and HR. Data suggest that the CLLD combination could be used subarachnoidally in sheep requiring prolonged surgery.     

Acyclovir (Zovirax®) pharmacokinetics in Quaker parakeets, Myiopsitta monachus

The pharmacokinetics of intravenous (i.v.) and intramuscular (i.m.) single-dose administration of acyclovir were determined in Quaker parakeets. After i.v. injection at a dose of 20 mg/kg of acyclovir, elimination half-life was estimated at 0.65 h, volume of distribution at steady state was 627.65 ml/kg, and clearance was 11.22 ml/kg/min. The estimated pharmacokinetic values after i.m. injection at a dose of 40 mg/kg of acyclovir were an elimination half-life of 0.71 h and a bioavailability of 90.1%. The peak plasma acyclovir concentration occurred at 15 min when the drug was administered i.m. Plasma concentrations of acyclovir were undetectable 4-6 h after i.v. administration and 6-8 h after i.m. administration. Oral (capsules) and intravenous (sodium salt) formulations of acyclovir were given by gavage at 80 mg/kg. Peak concentrations with the sodium salt formulation were lower and developed more slowly than with the capsules. In studies designed to detect excessive drug accumulation or adverse side effects, acyclovir was administered i.m. at 40 mg/kg every 8 h for 7 days. Plasma concentrations were determined 15 min after (peak) and just prior to drug administration (trough). In another study acyclovir was gavaged at a dose of 80 mg/kg every 8 h for 4 days. Acyclovir plasma concentrations were determined just prior to and 2 h after drug administration. In both experiments, the birds maintained normal appetite and weight and did not exhibit excessive drug accumulation. Acyclovir plasma concentrations ranging from 2.07 +/- 1.09 micrograms/ml to 3.93 +/- 1.13 micrograms/ml were maintained for 4 days when acyclovir was administered in the feed and water (sole source of food and water).(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of closure of the reticular groove on the bioavailability and disposition kinetics of meclofenamate in sheep

Sodium meclofenamate is a non-steroidal anti-inflammatory drug with anaphylactic protective activity in cattle. The objectives of this study were to describe the pharmacokinetic behaviour of sodium meclofenamate after intravenous and oral administration to sheep and to determine the influence of closure of the reticular groove on the bioavailability of the drug. Sodium meclofenamate was administered by the intravenous (2.2 mg/kg) and oral (20 mg/kg) routes to sheep (n = 6). During the oral study the reticular groove was closed by intravenous administration of lysine vasopressin (0.3 IU/kg) or left open (saline solution). The closure of the reticular groove was assessed by determination of the blood glucose curves after oral administration of a glucose solution. After intravenous administration of meclofenamate, the distribution and elimination half-lives of the drug were 7.2 min and 542 min respectively, V_ss was 1.68 L/kg and Cl_B was 2.47 mL/min kg. Two different patterns of the plasma concentration curves were observed after oral administration of sodium meclofenamate. When the reticular groove was closed, two peaks were observed ( t _max-2 12-15 min, C _max-1 3.30-24.01 μg/mL; and t _max-2', 52.50-75 min, C _max-2' 6.45-11.08 μg/mL).     

Guaifenesin alone or in combination with ketamine or sodium pentobarbital as an anesthetic in rabbits.

Guaifenesin was administered alone and in combination with ketamine or sodium pentobarbital to adult New Zealand white rabbits. A solution of 5% guaifenesin in 5% dextrose given intravenously at a dosage of 200 mg/kg, abolished the pedal, palpebral and corneal reflexes for up to 15 minutes with little influence on cardiopulmonary function. Guaifenesin (200 mg/kg, intravenously) and ketamine (50 mg/kg, intramuscularly) produced effective and safe surgical anesthesia for over 30 minutes. This combination mildly depressed respiratory rate but heart rate and arterial blood pressure were not significantly affected. Guaifenesin (200 mg/kg, intravenously) was combined with sodium pentobarbital (20 mg/kg, intravenously) to produce surgical anesthesia for a period of more than 30 minutes. This combination depressed respiratory rate, produced a tachycardia and decreased arterial blood pressure.     

Pharmacokinetics of intravenously and intramuscularly administered ticarcillin and clavulanic acid in foals

Serum concentrations of ticarcillin and clavulanic acid were measured in healthy foals (2 to 6 months old) given the drugs in combination by intravenous and intramuscular routes of administration. Five foals were administered 50 mg of ticarcillin/kg of body weight and 1.67 mg of clavulanic acid/kg, IV. Five foals were administered 100 mg of ticarcillin/kg and 3.33 mg of clavulanic acid/kg, IV, and 4 of those 5 were given the same combined dose IM. The elimination half-life of ticarcillin for intravenous administration was 0.83 hour for the low dosage and 0.96 hour for the high dosage. After intramuscular administration, the half-life of elimination was 2.9 hours, with bioavailability of 54.6%. For IV administered clavulanic acid, the elimination half-life was 0.65 hour for the low dosage and 0.74 hour for the high dosage. After intramuscular administration, the elimination half-life was 0.92 hour, and bioavailability was 68.1%. A combined dosage, 50 mg of ticarcillin/kg and 1.67 mg of clavulanic acid/kg, given every 6 hours is recommended.     

Cardiovascular and renal effects of carvedilol in dogs with heart failure

To determine the acute effects of carvedilol (beta-blocker) on cardiovascular and renal function and its pharmacokinetics in dogs. Fifteen mature mongrel dogs (7-15 kg) of both sexes were used in these experiments. Eight dogs served as controls, and seven dogs served as iatrogenic mitral regurgitation (MR) experimental animals. Carvedilol (0.2, 0.4, and 0.8 mg/kg, P.O.) was administered, and the blood carvedilol concentration was analyzed by reverse-phase high-performance liquid chromatography. The response to isoproterenol or phenylephrine was also evaluated. Isoproterenol (0.025 microg/kg/min) was infused via the saphenous vein for 5 min, and phenylephrine (5 microg/kg) was injected with carvedilol (0.2, 0.4 mg/kg) or placebo for 4 days. The heart rate and arterial blood pressure were measured, and LV fractional shortening was measured by echocardiography. Glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured by intravenous infusion of sodium thiosulfate and sodium para-aminohippurate. Carvedilol (0.2 mg/kg) decreased the heart rate, whereas renal function, arterial blood pressure, and left ventricular contractile function were not affected. Carvedilol (0.4 mg/kg) decreased heart rate, blood pressure, and renal function. The tachycardic response to isoproterenol was significantly diminished for 36 hr by 0.4 mg/kg carvedilol. Carvedilol 0.2 mg/kg inhibited this effect for 24 hr. Thus, it is necessary to titrate the dosage of carvedilol, it should be initiated at less than 0.2 mg/kg and titrated up to 0.4 mg/kg for heart failure dogs.     

国产硫酸头孢喹肟对小鼠的急性和蓄积毒性研究

为了研究国产硫酸头孢喹肟对昆明小鼠的急性毒性和蓄积毒性,采用改良寇氏法测定国产硫酸头孢喹肟的LD50;以剂量定期递增法计算蓄积系数,并于给药后第21天给予试验组和对照组小鼠1 LD50的量,观察各组小鼠对硫酸头孢喹肟的耐受性。结果表明,国产硫酸头孢喹肟原料药对小鼠口服LD50大于5 000 mg/kg,其混悬液制剂对小鼠腹腔注射LD50为844.03 mg/kg,LD50的95%可信限为802.05 mg/kg~887.56 mg/kg;蓄积试验中无小鼠死亡,蓄积系数K>5.3;耐受性试验显示,试验组死亡率(10%)显著低于对照组(40%)(P<0.05)。由此可见,国产硫酸头孢喹肟毒性低,临床使用安全,对小鼠没有蓄积毒性,小鼠对本品可产生明显耐受性。     

血根碱的急性毒性研究

为评价血根碱的安全性,采用改良寇氏法进行了血根碱的急性毒性试验。分别采用腹腔注射与灌胃两种给药方式,一次性对小鼠给予不同剂量血根碱,连续观察7 d。结果表明,小鼠腹腔注射血根碱的最大耐受量为15.0 mg/kg,其LD50为9.4 mg/kg,LD50的95%可信限为8.6-10.3 mg/kg;灌胃给药的最大耐受量为2 000 mg/kg,其LD50为1 029.7 mg/kg,LD50的95%可信限为903.7-1 173.2 mg/kg。该结果为血根碱临床剂量的选择奠定了基础。