What Are the Side Effects of a Benadryl Overdose in Dogs?
Even at the appropriate dose, some cats and dogs may have what is known as paradoxical excitement. This can lead to excessive excitement, anxiety, and/or aggression, rather than the more common side effect of sedation. This is certainly not the desired outcome, especially if you are hoping Benadryl will keep your dog calmer during a road trip!
Aggression and agitation can also be a symptom of Benadryl overdose. Other potential side effects include:
Some dogs may also have difficulty urinating. These symptoms will usually show up within the first hour of dosing.
In rare cases, Benadryl toxicity can result in death.
Symptoms of Benadryl Poisoning in Dogs
Although Benadryl is generally safe for dogs, some side effects can occur. Side effects usually occur within an hour of administration. They are typically mild and can include:
Overdoses of Benadryl are more often caused by your animal getting a box of the medication from the garbage or medicine cabinet than by being given too much. If you see these signs of an overdose, contact your veterinarian immediately.
Types
Along with a version of diphenhydramine by the name of Vetadryl developed specifically for cats and dogs, there are a few other first generation antihistamines that can be used for dogs. These can include:
Chlorpheniramine – This antihistamine is frequently used in small animal veterinary practice and is less likely to cause drowsiness than some of the others
Clemastine – Clemastine is classified as an antipruritic (anti-itch), as well as a sedating antihistamine, and is tends to exhibit fewer side effects
Hydroxyzine – This drug is a more aggressive antihistamine, but also has more potent side effects
Meclizine – Commonly used to reduce nausea, particularly nausea caused by motion sickness
What if I don’t have Benadryl? Are there alternatives?
If your dog has allergies and you don’t have any Benadryl at home, you can also use cetirizine (Zyrtec) or loratadine (Claritin). As usual, always check with a vet first before administering any human medications to your dog. Especially if your dog has preexisting conditions or is on other medication.
Natural allergy relief can be gained by using quercetin which is a natural ingredient derived from the peels of fruits and vegetables. Not only does quercetin contain antihistamine properties, but it contains anti-inflammatory and antioxidant properties. Chat to your vet about quercetin as an allergy reliever in dogs.
CBD (cannabidiol) is another natural alternative to Benadryl. It’s derived from hemp plants and contains absolutely no psychoactive properties so there’s no chance of getting your dog high. The benefits of CBD include the relief of skin conditions, as well as itching and hives related to allergies. Dogs that experience motion sickness will also benefit from CBD, as will those suffering from anxiety, pain, or nausea.
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Most human medication should never be given to dogs, with the exception of a small number of medications, including Benadryl.
Always make sure to consult with your vet before giving your dog Benadryl to ensure it’s the right solution for your pet and to ensure you’re giving the correct and appropriate dose.
While Benadryl makes a handy fallback plan in an emergency, if your dog suffers from frequent allergies or regularly experiences anxiety, it’s better to get to the source of the problem instead of relying on Benadryl to deal only with the symptoms. Share this Article
Benadryl For Dogs? Dr. Dan Explains
We report a fatal diphenhydramine poisoning of a 10-year-old, male poodle-cross dog with pre-existing conditions and suspected co-ingestion of ethanol. This case illustrates that diphenhydramine overdose can be fatal in certain circumstances and that analytical toxicology may play an important role in animal death investigations.
Empoisonnement mortel à la diphenhydramine chez un chien. Nous signalons un empoisonnement mortel à la diphenhydramine chez un caniche croisé mâle âgé de 10 ans ayant des conditions préexistantes et une co-ingestion soupçonnée d’éthanol. Ce cas illustre qu’une surdose de diphenhydramine peut être mortelle dans certaines circonstances et qu’une toxicologie analytique peut jouer un rôle important dans les enquêtes sur la mort d’animaux.
Poisoning of animals with chemical agents is commonplace. Establishing whether the poisoning event was malicious, however, is difficult. In part, this is because of the vast number and types of chemical agents that may be employed. In addition, there is difficulty in discerning between ease of accessibility to the offending agent (i.e., in accidental poisonings) and intentional introduction of those agents to the animal’s environment (i.e., intentional poisoning). Most poisonings occur within a narrow range of chemical agents, including anticoagulant rodenticides, ethylene glycol, organophosphate and carbamate insecticides, strychnine, and caffeine and other methylxanthines (1). Accidental exposure to these agents results from unbridled roaming, indiscriminate oral evaluation of the environment, and access to human food and supplements. Intentional poisonings differ in that the poison is purposefully introduced into the animal’s environment, out of the normal context in which the substance resides. Examples include food bowls tainted with ethylene glycol and hot dogs or meat patties contaminated with restricted use pesticides or drugs.
Companion animal poisonings have also been reported to involve household products and drugs for veterinary and human use (2). Medications, whether over-the-counter (OTC) or prescribed, contribute to companion animal fatalities; however, these poisoning events often result from accidental exposure due to ease of accessibility and lack of adequate supervision (3). There may be instances, though, whereby an owner symptomatically treats a pet with their own medication if they think the animal is unwell or in pain (e.g., paracetamol, ibuprofen, or naproxen), thus leading to an unintended consequence. Drugs, or other chemical agents, that are intentionally introduced to animals are commonly supplied in the context of a meal, treat, or drink to reduce texture and palatability inhibitions. Intentional intoxication has also been reported with secondhand cannabis smoke blown into the face of small animals as an adolescent prank (4,5). We report a multi-disciplinary, multi-institutional forensic approach to the intoxication of a dog of advanced age with diphenhydramine, with examination of the underlying question of malicious intent.
The body of a 10-year-old, male poodle-cross dog, weighing approximately 18 kg was submitted to the Animal Health Centre in Abbottsford, British Columbia, for necropsy. The animal was found by police in its residence lying dead adjacent to its deceased owner. The owner had died from blunt force trauma; however, there was no outward evidence of trauma to the dog. Instead, there were 3 empty bottles of sleep aid discovered at the scene. Two bottles were over-the-counter sleep aids containing the active ingredient diphenhydramine. The third bottle was prescription-based, containing the active ingredient Ran-Zopiclone.
The dog was presented dead and frozen. There was moderate decomposition. The animal was well-muscled and there were abundant subcutaneous and visceral fat stores. Along the dorsolateral aspect of the torso and within the inguinal regions, fat lobules featured superficial hemorrhage. The heart was markedly enlarged with circumferential thickening of the left ventricular free wall and at the base, there was a prominent indentation. The right ventricular free wall was moderately dilated and turgid. The lungs were collapsed (atelectatic) and mottled dark red to black. Moderate amounts of dark red frothy fluid filled the tracheobronchial tree. The stomach was markedly distended with partially digested dog food pellets and fetid gas, and there was a moderate amount of partially digested food within the small and large intestines. Throughout the stomach and intestines, the serosa was variegated pale to dark red. There were no other significant gross internal or external lesions. Postmortem X-rays did not reveal any indication of trauma.
There was no indication of infection or inflammation in the examined tissues. Aerobic culture of select internal viscera yielded light to heavy mixed growth of Streptococcus spp. and Enterobacter cloacae, which were likely due to postmortem invasion and bacterial overgrowth rather than representing primary pathogens. Polymerase chain reaction of pooled tissues also proved negative for canine distemper virus (6) and canine parvovirus (7).
Consequently, stomach contents were submitted for toxicology screening. A general organic compound screen by gas chromatography coupled with mass spectral analysis (8,9) was positive for diphenhydramine, but not Ran-Zopiclone. Diphenhydramine was semi-quantitatively estimated at 250 ppm. Additionally, fatty acid ethyl esters (FAEE) were observed suggesting the concomitant ingestion of ethanol and, presumptively, an intentional introduction of the medication to the dog in the context of feed mixed with alcohol. Blood samples to assess circulating concentrations of diphenhydramine, ethanol, and fatty acid ethyl esters were unavailable since the dog was presented in rigor mortis. No other tissue samples were made available for analysis.
Initially, the cause of death for this dog was presumptively attributed to dilated cardiomyopathy. Moreover, periglomerular fibrosis in the kidney, bridging fibrosis in the liver, coronary arteriosclerosis, and parathyroid hyperplasia were sufficiently severe to have contributed to ante-mortem morbidity. Both OTC sleep aids discovered near the body of the dog contained 50 mg of active ingredient diphenhydramine per tablet with 20 tablets dispensed per bottle. All 40 tablets were missing, suggesting the potential for consumption of a maximum dose equivalent to 111 mg/kg body weight (BW). Based on this observation, analytical toxicology was performed and confirmed the presence of diphenhydramine in the stomach contents ( ) in sufficient quantity to substantiate the suspicion of poisoning as an immediate cause of death for the dog. No tablets or drug residue were visually evident in the stomach content.
Antihistamines are H1-receptor antagonists that provide symptomatic relief from allergies and may also be used as sedatives (first-generation). First-generation antihistamines may cause adverse effects because of their cholinergic activity and ability to cross the blood-brain barrier (10). Diphenhydramine is a first-generation ethanolamine-derivative antihistamine widely used in human and veterinary medicine. It is the primary active ingredient in several brand-name OTC cold and sleep aid products such as Benadryl, Nytol, and Tylenol PM.
In humans, diphenhydramine is well-absorbed orally, but undergoes first-pass metabolism in the liver with only 40% to 60% of the drug reaching the systemic circulation. The pharmacokinetics of diphenhydramine have not been studied in canines (11); however, these parameters have been evaluated in humans with peak plasma concentrations occurring within 1 to 5 h and elimination half-lives varying from 2.4 to 10 h (10). A recommended therapeutic dose for diphenhydramine in dogs is 2 to 4 mg/kg BW for the treatment of allergies or mild sedation prior to stressful situations. For an 18-kg dog, this would equate to 36 to 72 mg diphenhydramine or 1 to 1.5 tablets. The margin of safety is relatively narrow within this group of antihistamines, with adverse effects occurring at or less than 1 mg/kg above therapeutic doses (12). Therefore, 2 or more tablets may have been sufficient to initiate a cascade of potentially adverse effects for this dog. However, oral doses of 1, 3, or 10 mg/kg BW have been reported to have no effect on heart rate, mean blood pressure, or electorcardiogram in otherwise healthy dogs (13). Conversely, dogs given 10 mg/kg BW of diphenhydramine in a sleep study had significantly increased drowsiness and non-REM (rapid eye movement) sleep (14).
In living animals, hyperactivity, depression, hypersalivation, tachypnea, and tachycardia are the most common signs reported with ethanolamine-based antihistamines, usually occurring within 1 h of exposure (10). With overdose, dogs may also exhibit mydriasis, dry mucous membranes, disorientation, and fever (10). For animals exposed to an overdose of antihistamines, treatment with guaifenesin and supportive fluid therapy generally results in an excellent prognosis for recovery (15).
The lethal dose (LD50) for diphenhydramine in dogs ranges between 24 to 30 mg/kg BW by IV administration, and death has been attributed to neuromotor excitement and convulsions, followed by respiratory failure and myocardial depression (16). The LD50 for oral diphenhydramine in dogs has not been studied; however, the range may be gleaned from extrapolated values in other species. In humans the minimum lethal dose (LDmin) is 10.1 mg/kg BW and the LD50 in rodents ranges between 114 (mice) and 500 (rats) mg/kg BW (17). Based on this information, the LDmin in this case could have been reached with as few as 4 tablets and the LD50 achieved with approximately 40 tablets. However, with pre-existing multi-systemic pathologies, a lower dose of diphenhydramine may have been sufficient to cause death. For comparison, Lagutchik et al (15) reported a male Labrador retriever dog that ingested an estimated dose of 67 mg/kg BW of diphenhydramine with no concomitant drug exposures. On admission, the serum diphenhydramine concentration was reported at 537 ng/mL and although the concentration associated with toxicity in dogs is unknown, in humans it is > 60 ng/mL (15). With treatment this dog recovered and was discharged 24 h after admission (15).
The additional finding of fatty acid ethyl esters (FAEEs) provides speculative insight into the delivery of the OTC pills, and may be significant to discerning between unintentional and intentional poisoning. These esters are produced by the reaction of fatty acids with ethanol in the presence of the enzyme fatty acid ethyl ester synthase (18), which is present in almost all tissues including the gastric mucosa (19,20). In the described case, the presence of FAEEs indirectly serves as a marker for alcohol consumption. Since the stomach was markedly distended with partially digested food, it stands to reason that alcohol may have been added to the feed and medication mixture to enhance palatability and, hence, ingestion of multiple OTC pills.
Alcohol interacts with a variety of medications (21,22). These interactions may be either pharmacokinetic (affecting metabolism) or pharmacodynamic (enhancing effects) (22). When combined with other medications capable of producing sedation (e.g., antihistamines), alcohol may enhance the sedative effect of those medicines (21). Hence, it could be speculated further that the consumption of alcohol with an overdose of diphenhydramine may have produced an additive, if not lethal, combination.
Interpretation of toxicology results should be in the context of the forensic, crime scene, pathologic, and ancillary diagnostic studies. Simple exposure to a toxicant does not necessarily indicate that a toxicosis has occurred. With all toxic agents, a threshold generally exists below which acute signs will not develop. Technical advancements and the improving ability to measure the presence of toxins at minute levels means we will at times detect agents at levels consistent with casual sublethal exposure but not toxicosis (1). In the current case, the stomach contents were semi-quantitatively estimated to contain 250 ppm diphenhydramine. Based on the size of the dog and degree of gastric distention at the time of necropsy, the stomach volume was estimated to be 500 mL and the amount of diphenhydramine approximated at 125 mg present at the time of sampling. This would have been consistent with an overdose, and did not take into account the quantity of diphenhydramine already absorbed, circulated, and distributed to other body compartments prior to the dog’s death and discovery. For comparison, fatal cases in humans have recorded concentrations of 8.7, 12.3, 15, 554, and 705 mg diphenhydramine in the stomach content (23,24). Aside from differences established in gender, age, and weight, variations in the stomach concentration likely reflect the quantity consumed and the temporal relationship between consumption and presentation of the decedent to the medical examiner.
In the case presented, gross pathology did not provide any indication of foul play, rather necropsy and histopathology revealed degenerative conditions that may have left this dog more susceptible to the adverse effects of a drug overdose. In the absence of forensic investigations to evaluate the criminal environment and surrounding motives, malicious poisonings resulting from drug overdose in animals are difficult to prove beyond a reasonable doubt. In summary, thorough pathologic analysis and concomitant analytical toxicology provide invaluable support to a criminal investigation. The analytical evidence described herein suggests the intentional poisoning of this animal with diphenhydramine presented to it in a mixture of feed, drug, and presumably alcohol.
We thank Constable D.M. Reddy from the Integrated Homicide Investigation Team of the Royal Canadian Mounted Police for his review and valuable information regarding the case history. CVJ
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