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PubMed2003

Four-week intravenous repeated dose toxicity study of L-cysteine in male rats.

A 4-week intravenous repeated dose toxicity study of L-cysteine (L-Cys) was conducted in male Sprague-Dawley rats to investigate in detail the toxic effects of this compound and to determine the dose level at which these toxic effects are observed following repeated intravenous administration. Male rats were randomly allocated to 4 groups to receive L-Cys by intravenous administration at dosages of 0, 100, 300, and 1,000 mg/kg body weight/day. Body weight gain was significantly suppressed throughout the study period in the 1,000-mg/kg group, although food consumption was reduced only on study day 3. A decrease in spontaneous activity, salivation, stereotypy, ptosis, and tremor were observed in the 1,000-mg/kg group. Mild anemia characterized by decreases in hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin and an increase in the reticulocyte count was also noted in the 1,000-mg/kg group. Histopathological examination showed sperm granulomas in the epididymis and necrosis of the Purkinje cells and granular layer in the cerebellum in the 1,000-mg/kg group. Slight tubular basophilia with blood or hyaline casts was observed in the kidney in the 300-mg/kg and 1,000-mg/kg groups, associated with proteinuria or occult blood in urinalysis. Additional studies are needed to clarify the causes for these toxicological findings by excess of L-Cys.

Animals↗
PubMed1981

[On the chronic toxicity of labetalol (AH-5158); a combined alpha-and beta-adrenoceptor-blocking agent (author's transl)].

Chronic toxicity and recovery tests of labetalol hydrochloride, alpha-and beta-adrenoceptor blocking agent, were carried out using male and female Wistar strain rats. The drug was orally administered at 50, 100 or 200 mg/kg/day for 9 months. In all the drug-treated groups, increase in salivation was observed from immediately after to 15 minutes after dosing through treatment period. Suppression of body weight gain was observed in male rats in the 200 mg/kg/day group. Food comsumption tended to be higher in all the drug-treated groups than in the control group. Similar trend was seen also in water comsumption, and increase in urine volume was noted in the groups treated with 100 and 200 mg/kg/day. In the serum biochemical examination, dose-dependent elevation in potassium level was noted in all drug-treated groups, but the values were within the range of physiological variation. In the 100 and 200 mg/kg/day groups, an increase was observed in the absolute heart weight and in its relative weight against body weight. Major abnormalities found in histopathological findings were; swelling of parenchymatous cells in liver and kidney, swelling of fibers and swelling or proliferation of interstitial cells in cardiac and skeletal muscles, and congestion in spleen. No notable abnormality was found in any examination item in the recovery test.

Animals↗
PubMed1981

[Acute toxicological studies of captopril in rats and mice].

The acute toxicity of captopril, a potential inhibitor of angiotensin converting enzyme, was studied in Sprague-Dawley rats and ICR mice. In the oral administration, a decrease of spontaneous motor activity, lacrimation, salivation and decline of body temperature was noted in the rats and mice. In the mice, tarry stool was also noted. The LD50 was estimated as: 4249 mg/kg in male mice, 5050 mg/kg in female mice, 4336 mg/kg in male rats and 4245 mg/kg in female rats, In the dead animals, a hemorrhagic erosion or ulcer was recognized in the glandular stomach. An intravenous captopril in mice, caused immediate death by dyspnea in some animals within 3 minutes, but delayed death was also occurred within 24 hours showing a decrease of spontaneous motor activity and decline of body temperature. The LD50 was estimated as 3154 mg/kg in male mice and 3225 mg/kg in female mice. A single intravenous administration of captopril in dose of 1600 mg/kg did not cause any death in the rats of both sexes. The mice of both sexes well tolerated a single subcutaneous administration of captopril in a dose of 2400 mg/kg. No death occurred in rats of both sexes received subcutaneously captopril in a dose of 1200 mg/kg. At an injection site, a necrotic ulcer was noted in the skin of rats and mice which received subcutaneously captopril in a dose of 1600 mg/kg or more and 1200 mg/kg, respectively.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1983

[Chronic toxicity study of ranitidine hydrochloride orally administered in rats].

Chronic toxicity of ranitidine hydrochloride, a new histamine H2-receptor antagonist, was studied using Sprague Dawley rats. Ranitidine was administered orally at dose levels of 30, 100, 300 and 1000 mg/kg/day for 26 or 53 weeks. In the 1000 mg/kg/day group, ten of 31 females died showing acute toxic signs. In the survived animals of this dose group, changes were observed, such as salivation, depression of body weight gain, increase in water consumption, increase in urinary Na and K excretion, increase in serum albumin content, increase in weights of the liver, kidneys and heart. Main histopathological findings were as follows: centrolobular or midzonal fat deposition in liver, increase in s-ER in hepatocytes, increase in foamy cells in lung and some slight degenerative changes occasionally seen in renal tubules. In the 300 mg/kg/day group, the changes similar to those in the 1000 mg/kg/day group were observed, however, the degree of these changes was more moderate. All of the above-mentioned findings were demonstrated to be reversible in recovery period for 8 weeks. In the 100 and 30 mg/kg/day groups, no remarkable changes were observed in both sexes. It was concluded that the maximum nontoxic dose of ranitidine hydrochloride was 100 mg/kg/day in male and female rats.

Administration, Oral↗
PubMed1984

Involvement of adrenergic and serotonergic nervous mechanisms in allethrin-induced tremors in mice.

Oral or intravenous administration of allethrin, a synthetic derivative of the pirethrin-based insecticides, produces neurotoxic symptoms consisting of mild salivation, hyperexcitability, tremors and convulsions which result in death. Intracerebroventricular injection of allethrin to mouse at about one-nineth the dose of intravenous administration, produced qualitatively identical but less prominent symptoms, indicating that at least some of the symptoms may be originated in the central nervous system. To investigate the mechanism of action of the compound, we studied the ability of agents which alter neurotransmission to prevent or potentiate the effect of convulsive doses of technical grade (15.5% cis, 84.5% trans) allethrin. Intraperitoneal pretreatment with drugs which block noradrenergic receptors or norepinephrine synthesis, such as pentobarbital, chlorpromazine, phentolamine, phenoxybenzamine and reserpine, depressed the tremor induced by allethrin. The inhibitory effect of reserpine was reversed by phenylephrine. Both the serotonergic blocker, methysergide, and the serotonin depletor, rho-chlorphenylalanine, potentiated the effect of allethrin. The potentiating effect of methysergide was antagonized by 5-hydroxytryptamine. However, intracerebroventricular administration of methysergide was ineffective in potentiating the effect of allethrin. alpha 2- and beta-adrenoceptor blockers, muscarinic antagonists, GABA mimenergics and morphine had no effect. These results suggest that allethrin produces its neurotoxic responses in mice by acting on the brain and spinal levels. Furthermore, adrenergic excitatory and serotonergic inhibitory mechanisms may be involved in the neural pathway through which the allethrin-induced tremor is evoked.

Allethrins↗
PubMed1998

Tolterodine.

Tolterodine is a competitive muscarinic receptor antagonist which has recently been launched for the treatment of overactive bladder. Tolterodine shows functional selectivity for the bladder over the salivary glands in vivo, which is not attributable to muscarinic receptor subtype selectivity. It is as potent as oxybutynin in inhibiting bladder contraction, but is much less potent in inhibiting salivation, suggesting that it may have less propensity to cause dry mouth in clinical use. In patients with overactive bladder, toleterodine significantly reduces the frequency of micturition and number of incontinence episodes, while increasing the average volume voided. The onset of pharmacological action of tolterodine is < 1 hour and therapeutic efficacy is maintained during long term treatment. In comparative trials, tolterodine and oxybutynin are equivalent in terms of efficacy. However, tolterodine is significantly better tolerated than oxybutynin, particularly with respect to the incidence and severity of dry mouth. No clinically relevant ECG changes have been noted with tolterodine.

Animals↗
PubMed2000

[A male case of Sjögren's syndrome presenting with generalized lymphadenopathy and swelling of both lacrimal and salivary glands which responded remarkably well to an administration of corticosteroids].

A 68-year-old man noticed severe oral dryness and a submandibular swelling. Sjögren's syndrome (SS) was diagnosed based on microscopic findings of a labial salivary gland biopsy although both anti-SS-A and anti-SS-B antibodies were negative. In addition, hypergammaglobulinemia (IgG 7940 mg/dl) and hypocomplementemia were pointed out and he was admitted to our department. On admission cervical, mediastinal, and abdominal lymph nodes swelling were detected together with enlargement of lacrimal and salivary glands. Lymphoproliferative disorders associated with SS were highly suspected. Biopsied specimens of his lacrimal gland and cervical lymph node disclosed neither malignant cells nor monoclonal proliferation of lymphocytes. An administration of corticosteroids caused rapid diminution in size of lacrimal glands, salivary glands, and lymph nodes. Both lacrimation and salivation recovered, and hypergammaglobulinemia and hypocomplementemia returned to normal after treatment. The characteristics of this case were an atypical onset in an elderly man, the negativity of anti-SS-A and anti-SS-B antibodies, and reversibility of dryness by corticosteroid treatment. These findings suggest that the pathogenesis of this case may be different from typical SS.

Aged↗
PubMedDate not supplied

[Krabbe s disease - case report]

OBJECTIVE: Report a case of Krabbés disease with necropsy. METHODS: Review of medical and necropsy records. RESULTS: An 8 months-old male patient developed tremors, swallowing difficulty and excessive salivation for 4 months prior to admission, evolving with vomiting and fever. Physical examination showed microcephaly and diffuse pigmentation of the retinae. Neurological examination showed flexion of upper limbs with spastic hyperthony, symmetrical global hyperreflexia, nystagmus and spontaneous spasms. EEG showed multifocal irritative activity. There was increase in both CSF protein and gamaglobulin. The patient evolved with transitory hyperthermia, vomiting and pneumopathy, dying on the 23rd day after admission. Post mortem studies revealed microcephaly with widening of brain sulci. Histological examination revealed several globoid cells in the deep portion of the white matter, reactive gliosis and demyelination. CONCLUSIONS: These findings were similar to those in the world literature, indicating a poor prognosis due to substantial brain damage.

Journal Article↗
PubMed2004

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.

Administration, Cutaneous↗
PubMed2005

Cardiovascular and respiratory effects of ketamine infusions in isoflurane-anesthetized dogs before and during noxious stimulation.

OBJECTIVE: To characterize the effects of ketamine administration on the cardiovascular and respiratory systems and on acid-base balance and to record adverse effects of ketamine in isoflurane-anesthetized dogs. ANIMALS: 6 healthy adult mongrel dogs. PROCEDURE: Dogs were anesthetized with isoflurane (1.25 times the individual minimum alveolar concentration) in oxygen, and ketamine was administered IV to target pseudo-steady-state plasma concentrations of 0, 0.5, 1, 2, 5, 8, and 11 microg/mL. Isoflurane concentration was reduced to an equipotent concentration. Cardiovascular, respiratory, and acid-base variables; body temperature; urine production; and adverse effects were recorded before and during noxious stimulation. Cardiac index, stroke index, rate-pressure product, systemic vascular resistance index, pulmonary vascular resistance index, left ventricular stroke work index, right ventricular stroke work index, arterial oxygen concentration, mixed-venous oxygen concentration, oxygen delivery, oxygen consumption, oxygen extraction ratio, alveolar-arterial oxygen partial pressure gradient, and venous admixture were calculated. Plasma ketamine and norketamine concentrations were measured. RESULTS: Overall, ketamine administration improved ventilation, oxygenation, hemodynamics, and oxygen delivery in isoflurane-anesthetized dogs in a dosedependent manner. With the addition of ketamine, core body temperature was maintained or increased and urine production was maintained at an acceptable amount. However, at the higher plasma ketamine concentrations, adverse effects such as spontaneous movement and profuse salivation were observed. Myoclonus and dysphoria were observed during recovery in most dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Infusion of ketamine appears to be a suitable technique for balanced anesthesia with isoflurane in dogs. Plasma ketamine concentrations between 2 to 3 microg/mL elicited the most benefits with minimal adverse effects.

Anesthesia, Inhalation↗
PubMed2005

Analgesic effects of epidurally administered levogyral ketamine alone or in combination with morphine on intraoperative and postoperative pain in dogs undergoing ovariohysterectomy.

OBJECTIVE: To evaluate the analgesic and adverse effects of epidurally administered levogyral (S[+]) ketamine alone or in combination with morphine on intraoperative and postoperative pain in dogs undergoing ovariohysterectomy. ANIMALS: 30 dogs scheduled for ovariohysterectomy. PROCEDURE: Dogs were randomly allocated to 1 of 3 groups. Dogs in group 1 received S(+) ketamine (1 mg/kg), dogs in group 2 received S(+) ketamine (0.5 mg/kg) and morphine (0.05 mg/kg), and dogs in group 3 received S(+) ketamine (1 mg/kg) and morphine (0.025 mg/kg). The skin was incised 15 minutes after epidural administration of analgesics. Heart rate (HR), respiratory rate (RR), systolic blood pressure (SBP), oxygen saturation as measured by pulse oximetry, and arterial blood gases were obtained before anesthesia, 15 minutes after epidural administration of analgesics, 15 and 30 minutes after initiation of surgery, and at the end of surgery. During the intraoperative period, an increase of > or =20% in baseline values for HR, RR, and SBP was considered a sign of intraoperative pain. Signs of pain and adverse effects were assessed at 2, 4, and 8 hours postoperatively. RESULTS: There were no significant differences in intraoperative or postoperative measurements among the 3 groups. No dogs had intraoperative signs of pain. Mean postoperative pain assessment scores were <3.5 in all 3 groups. Salivation was the most frequent adverse effect in dogs in groups 1 and 3, and sedation occurred more frequently in dogs in groups 2 and 3. CONCLUSIONS AND CLINICAL RELEVANCE: All 3 analgesic regimens provided good respiratory and cardiovascular stability intraoperatively and adequate postoperative analgesia with minimal adverse effects.

Analgesia, Epidural↗
PubMed2006

Effect of intravenous administration of ketamine on the minimum alveolar concentration of isoflurane in anesthetized dogs.

OBJECTIVE: To determine the effect of 6 plasma ketamine concentrations on the minimum alveolar concentration (MAC) of isoflurane in dogs. ANIMALS: 6 dogs. PROCEDURE: In experiment 1, the MAC of isoflurane was measured in each dog and the pharmacokinetics of ketamine were determined in isoflurane-anesthetized dogs after IV administration of a bolus (3 mg/kg) of ketamine. In experiment 2, the same dogs were anesthetized with isoflurane in oxygen. A target-controlled IV infusion device was used to administer ketamine and to achieve plasma ketamine concentrations of 0.5, 1, 2, 5, 8, and 11 microg/mL by use of parameters obtained from experiment 1. The MAC of isoflurane was determined at each plasma ketamine concentration, and blood samples were collected for ketamine and norketamine concentration determination. RESULTS: Actual mean +/- SD plasma ketamine concentrations were 1.07 +/- 0.42 microg/mL, 1.62 +/- 0.98 microg/mL, 3.32 +/- 0.59 microg/mL, 4.92 +/- 2.64 microg/mL, 13.03 +/- 10.49 microg/mL, and 22.80 +/- 25.56 microg/mL for target plasma concentrations of 0.5, 1, 2, 5, 8, and 11 microg/mL, respectively. At these plasma concentrations, isoflurane MAC was reduced by 10.89% to 39.48%, 26.77% to 43.74%, 25.24% to 84.89%, 44.34% to 78.16%, 69.62% to 92.31%, and 71.97% to 95.42%, respectively. The reduction in isoflurane MAC was significant, and the response had a linear and quadratic component. Salivation, regurgitation, mydriasis, increased body temperature, and spontaneous movements were some of the adverse effects associated with the high plasma ketamine concentrations. CONCLUSIONS AND CLINICAL RELEVANCE: Ketamine appears to have a potential role for balanced anesthesia in dogs.

Analysis of Variance↗
PubMed2006

Results of a phase II clinical trial on the use of ifosfamide for treatment of cats with vaccine-associated sarcomas.

OBJECTIVE: To determine clinical activity and toxic effects of ifosfamide when used to treat cats with vaccine-associated sarcoma (VAS). ANIMALS: 27 cats with a nonresectable, recurrent, or metastatic VAS. PROCEDURE: Each cat received ifosfamide (900 mg/m(2) of body surface area) as an IV infusion during a 30-minute period. Diuresis by infusion of saline (0.9% NaCl) solution and administration of mesna were used to prevent urothelial toxicosis. Treatments were administered every 3 weeks, and tumor response was assessed after the second treatment. All ifosfamide-associated toxic effects were graded in accordance with predetermined criteria. RESULTS: 61 treatments were administered to 27 cats (median, 2 treatments/cat; range, 1 to 4 treatments/cat). After ifosfamide treatment, 1 cat had a complete response and 10 had partial responses for an overall response rate of 11 of 27 (41%; 95% confidence interval [CI], 25% to 59%). Responses lasted from 21 to 133 days (median, 70 days; 95% CI, 60 to 113 days). The acute dose-limiting toxicosis was neutropenia, which was detected 5 to 28 days (median, 7 days) after treatment. Median nadir neutrophil count was 1,600 cells/muL (range, 200 to 5,382 cells/microL). Nine (33%) cats had adverse gastrointestinal effects (primarily salivation during the ifosfamide infusion and inappetence after treatment). Two cats were euthanatized because of severe nephrotoxicosis, and 1 cat developed pulmonary edema during diuresis. CONCLUSIONS AND CLINICAL RELEVANCE: Ifosfamide has antitumor activity against VAS in cats and is tolerated well by most cats. Ifosfamide should be evaluated as an adjuvant treatment for cats with VAS.

Animals↗
PubMed2000

Sedative and physiologic effects of orally administered alpha 2-adrenoceptor agonists and ketamine in cats.

OBJECTIVE: To compare efficacy of 3 regimens of orally administered sedatives and determine physiologic effects of 1 of these regimens in healthy cats. DESIGN: Prospective randomized study. ANIMALS: 34 cats. PROCEDURE: Cats were assigned to 1 of 3 groups that were treated by oral administration of detomidine and ketamine, xylazine and ketamine, or medetomidine and ketamine. Cats were monitored for degree of sedation at 5-minute intervals for 60 minutes. Physiologic effects in cats treated with detomidine and ketamine were measured at 5-minute intervals for 30 minutes and compared with effects in cats treated i.m. with detomidine and ketamine or xylazine and ketamine. RESULTS: All cats treated orally with detomidine and ketamine became laterally recumbent; sedation was more variable in the other 2 groups treated orally. Vomiting and excessive salivation were the only adverse effects. Bradycardia (heart rate < 145 beats/min) was detected at each evaluation time in cats treated orally with detomidine and ketamine and in all cats treated i.m. Minimal differences among groups were detected for heart and respiratory rates, rectal temperature, and hemoglobin oxygen saturation. CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration of detomidine and ketamine is an effective method of sedating healthy cats and induces minimal physiologic effects that are similar to those resulting from i.m. administration of sedatives.

Administration, Oral↗
PubMed2000

Suspected tolazoline toxicosis in a llama.

Clinical signs of tolazoline toxicosis developed in a 4-year-old llama that received 2 doses of tolazoline hydrochloride to reverse xylazine-induced sedation. The full first dose (4.3 mg/kg [2.0 mg/lb] of body weight) was erroneously injected i.v., and the second dose was administered half i.v., half i.m. 45 minutes later, because the llama became weak and recumbent. Signs of anxiety, hyperesthesia, profuse salivation, and tachypnea were the first detectable clinical signs of tolazoline toxicosis. Convulsions, hypotension, gastrointestinal tract hypermotility, and diarrhea also developed. The llama was treated successfully with i.v. administration of diazepam, phenylephrine, and lactated Ringer's solution supplemented with potassium chloride and oxygen administered via nasal insufflation. We suggest that the maximum dose of tolazoline administered at any one time to llamas not exceed 2 mg/kg (0.91 mg/lb). Furthermore, tolazoline should be administered slowly i.v. or i.m. to reduce the risk of adverse reactions.

Adrenergic alpha-Agonists↗
PubMed2001

Xerostomia, xerophthalmia, and plasmacytic infiltrates of the salivary glands (Sjögren's-like syndrome) in a cat.

A 2.5-year-old domestic shorthair cat was evaluated because of dysphagia and weight loss of 4 weeks' duration. MIld blepharospasm and conjunctival hyperemia were evident in both eyes, oral mucous membranes were tacky on palpation, and salivary glands were enlarged. Results of a Schirmer tear test were 0 mm/min for both eyes. Administration of atropine did not cause salivation or caused secretion fo thick rope-like saliva. Examination of biopsy specimens of salivary glands revealed a plasmacytic infiltrate. Sjögren's syndrome (SS) was diagnosed. Oral administration of prednisone was instituted but was discontinued after a minimal positive response was evident 6 weeks after initiation of treatment. Palliative treatment with a 6% solution of pilocarpine 4 to 5 times/d, cyclosporine, hylan A, and neomycin-polymyxin-bacitracin ophthalmic ointment resulted in clinical improvement in the cat. Although reported rarely in animals, SS may be more common than currently is recognized. Most treatment regimens for SS are aimed at alleviating clinical signs.

Animals↗
PubMed2001

Frequency of nonspecific clinical signs in dogs with separation anxiety, thunderstorm phobia, and noise phobia, alone or in combination.

OBJECTIVE: To determine the frequency of nonspecific clinical signs in dogs with separation anxiety, thunderstorm phobia, noise phobia, or any combination of these conditions and determine whether these conditions are associated in dogs. DESIGN: Case series. ANIMALS: 141 dogs. PROCEDURE: Diagnoses were established using specific criteria. Owners of dogs completed a questionnaire on how frequently their dogs exhibited destructive behavior, urination, defecation, vocalization, and salivation when the owners were absent and the types and frequency of reactions to thunderstorms, fireworks, and other noises. RESULTS: Associations of the 3 conditions and of various nonspecific clinical signs within and between diagnoses were nonrandom. The probability that a dog would have separation anxiety given that it had noise phobia was high (0.88) and approximately the same as the probability it would have separation anxiety given that it had thunderstorm phobia (0.86). However, the probability that a dog would have noise phobia given that it had separation anxiety (0.63) was higher than the probability that it would have thunderstorm phobia given that it had separation anxiety (0.52). The probability that a dog would have noise phobia given that it had thunderstorm phobia (0.90) was not equivalent to the converse (0.76). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that dogs with any of these conditions should be screened for the others. Interactions among these conditions are important in the assessment and treatment of dogs with > 1 of these conditions. Responses to noise were different from those to thunderstorms, possibly because of the unpredictability and uncertainty of thunderstorms.

Animals↗
PubMed2003

Use of clomipramine, alprazolam, and behavior modification for treatment of storm phobia in dogs.

OBJECTIVE: To evaluate use of clomipramine, alprazolam, and behavior modification for treatment of storm phobia in dogs. DESIGN: Prospective open clinical trial. ANIMALS: 40 dogs with storm phobia. PROCEDURE: Dogs received clomipramine at a dosage of 2 mg/kg (0.9 mg/lb), PO, every 12 hours for 3 months; then 1 mg/kg (0.45 mg/lb), PO, every 12 hours for 2 weeks; then 0.5 mg/kg (0.23 mg/lb), PO, every 12 hours for 2 weeks. Alprazolam was given at a dosage of 0.02 mg/kg (0.009 mg/lb), PO, as needed 1 hour before anticipated storms and every 4 hours as needed. Desensitization and counter-conditioning were conducted at home by the caregiver with an audio simulation of storm sounds that had induced a fear response during evaluation. RESULTS: 30 of the 32 dogs that completed the study had a degree of improvement, as measured by caregivers' global assessment. Two caregivers considered the storm phobia to be resolved. Panting, pacing, trembling, remaining near the caregiver, hiding, excessive salivation, destructiveness, excessive vocalization, self-trauma, and inappropriate elimination all decreased significantly during treatment. Improvement was greater during true storms (rain, thunder, and lightning) than during rain only. Response to audio simulation did not change during treatment. Four months after the study, improvement was maintained. CONCLUSIONS AND CLINICAL RELEVANCE: The combination of clomipramine, alprazolam, and behavior modification can be effective in decreasing or eliminating storm phobia. Improvement could not be evaluated by use of audio simulation of a storm.

Alprazolam↗