Chlorphenamine Maleate
Chlorphenamine maleate is a first-generation antihistamine used in both human and veterinary medicine. It belongs to the chemical group of alkylamines and acts as a competitive antagonist at H1 receptors. In human medicine, it is found in numerous cold and allergy preparations (e.g., Grippostad), while in veterinary medicine it is primarily used to treat allergic reactions and itching. The substance is characterized by its antiallergic, antiemetic, and sedative effects. Unlike newer antihistamines, chlorphenamine maleate crosses the blood-brain barrier, which explains its central nervous system effects. Improper use or overdose can lead to severe poisoning symptoms in dogs and cats, with cats being particularly sensitive due to their specific metabolic pathways.
The most important facts at a glance
Chlorphenamine maleate poisonings in dogs and cats usually result from accidental overdose or accidental ingestion of human or veterinary medicines. The substance acts as an antihistamine and also has anticholinergic and sedative properties. The toxic dose in dogs is about 9 mg/kg, while cats can develop severe symptoms at lower doses. Clinically, poisoning manifests through a wide range of symptoms, including neurological disorders (sedation to seizures), gastrointestinal complaints (vomiting, diarrhea), and kidney dysfunction. Diagnosis is based on anamnesis, clinical picture, and laboratory tests. Therapy is symptomatic and includes decontamination, fluid therapy, forced diuresis, and supportive measures depending on the clinical presentation. With adequate treatment, the prognosis is favorable, with follow-up care focusing on kidney function being recommended. Preventively, pet owners should be educated about the safe storage of medications and the risks of self-medication for their pets.
Causes, development and progression
Chlorphenamine interferes with the body’s immune responses. It reduces the increased permeability of small blood vessels that occurs during infections and relieves muscle spasms in the lungs. The result is a decongestant effect on the mucous membranes of the respiratory tract. Furthermore, chlorphenamine has sedative properties.
Chlorphenamine maleate is also approved for veterinary use. It is used in both dogs and cats to treat itching (allergic dermatitis).
Poisoning with chlorphenamine maleate in pets primarily arises from three scenarios:
- accidental overdose during veterinary treatment,
- unintentional administration of human medications by the pet owner, and
- unintended ingestion of such medications by the animal itself.
The toxic dose for dogs is approximately 9 mg of chlorphenamine maleate per kilogram of body weight when taken orally. For cats, the toxic threshold is lower, with doses as low as 4–6 mg/kg potentially leading to severe intoxications. This increased sensitivity in cats is due to their limited ability to metabolize certain medications, which is related to a deficiency in specific glucuronidation enzymes in the liver. Young, old, or pre-diseased animals, as well as breeds with known drug sensitivity such as Collies or Australian Shepherds, who are often carriers of the MDR1 gene defect, are particularly at risk.
Mechanism of action
In small animals, symptoms of chlorphenamine maleate intoxication appear after approximately 10 hours.
The primary concern is kidney damage with corresponding effects on the internal environment. Chlorphenamine maleate has a depressive effect on the nervous system and can lead to changes in blood count.
Supplements
The pathophysiological mechanism of poisoning by chlorphenamine maleate in dogs and cats is based on an overdose of the active substance, which, as a first-generation antihistamine, has both peripheral and central effects.
1. Blockade of H1-histamine Receptors
Chlorphenamine primarily acts as a competitive antagonist at H1 receptors. In overdose, excessive blockade of these receptors leads to:
- CNS depression (sedation, somnolence)
- At higher doses, or especially in cats, also CNS stimulation (restlessness, tremor, seizures)
2. Central Effects Due to Blood-Brain Barrier
Since chlorphenamine is lipophilic, it easily crosses the blood-brain barrier. This explains the central nervous effects such as:
- Ataxia
- altered consciousness
- agitation or seizures in case of overstimulation
3. Anticholinergic Effects
Chlorphenamine also possesses anticholinergic properties by inhibiting muscarinic receptors, which can cause the following symptoms:
- dry mouth (xerostomia)
- tachycardia
- urinary retention
- mydriasis (pupil dilation)
- hyperthermia due to reduced sweating and heat regulation (especially relevant in dogs)
4. Gastrointestinal Effects
Irritation of the gastrointestinal tract or central effect on the vomiting center can lead to:
- Vomiting
- Diarrhea
- anorexia
Symptoms of intoxication
Dogs are particularly sensitive to chlorphenamine maleate.
The toxic dose for dogs is an oral intake of 9 mg maleic acid/kg body weight.
Initial symptoms include:
- Sedation
- Loss of appetite
- Vomiting
- Diarrhea
- Thirst
- Acidosis
- Increase in nitrogenous waste products in the blood (urea, creatinine)
- Lethargy
- Blutarmut (Anämie)
- Decrease in white blood cells (agranulocytosis) Decrease in platelets (thrombocytopenia).
Severe intoxications are characterized by
- Excitation
- Gait disturbances (ataxia)
- Tremor
- Seizures.
In the final stage, there is
- Cardiovascular collapse
- Coma
- Respiratory paralysis.
The clinical signs of chlorphenamine maleate poisoning typically manifest within 10 hours of ingestion and affect multiple organ systems. Initially, central nervous symptoms such as sedation, which can paradoxically turn into states of excitation, as well as coordination disorders (ataxia) and tremor, are prominent. In severe poisonings, seizures may occur. Gastrointestinal disturbances manifest as loss of appetite, vomiting, and diarrhea. Kidney dysfunction is also characteristic, recognizable by increased thirst (polydipsia) and increased urination (polyuria), followed by an increase in nitrogenous substances in the blood (azotemia). Hematological changes include anemia, leukopenia, and thrombocytopenia. In advanced stages, cardiovascular complications such as tachycardia, arrhythmias, and hypotension may occur. Untreated, circulatory collapse with coma and respiratory paralysis threatens. In cats, hyperthermia and pronounced mydriasis can also be observed, while dogs more frequently react with hypersalivation and bradycardia.
Diagnosis
The diagnosis of chlorphenamine maleate poisoning is based on anamnesis, clinical symptoms, and laboratory findings. Crucial is a thorough history, especially regarding possible medication exposures. The clinical examination focuses on neurological, cardiovascular, and renal parameters. Laboratory diagnostics include a complete blood count, clinical-chemical examinations with particular attention to kidney values (urea, creatinine), as well as electrolytes and acid-base status. A urinalysis can provide indications of renal involvement. Direct toxicological detection of chlorphenamine maleate in blood or urine using high-performance liquid chromatography (HPLC) or mass spectrometry is possible, but rarely available in practice and usually not timely enough for acute therapeutic decisions. Differential diagnoses must consider other intoxications (mainly with anticholinergics, amphetamines, or metaldehyde), metabolic disorders, and primary neurological diseases.
Therapeutic principles
For decontamination, accelerated excretion via urine (forced diuresis) is aimed for.
There is no antidote.
The therapy is symptomatic.
Treatment is carried out according to the predominant symptoms and disorders.
Fluid loss due to vomiting is compensated by infusions. At the same time, acidosis can be compensated by administering sodium bicarbonate.
Medications that suppress the vomiting center (antiemetics) and antispasmodic drugs (anticonvulsants) are used as needed.
Furthermore, stabilization of vital functions such as circulation and respiration is necessary.
For seizures, appropriate medications are used to control them.
Supplements
Treatment for chlorphenamine maleate poisoning is symptomatic, as no specific antidote exists. If ingestion occurred recently (< 2 hours), decontamination by inducing vomiting with apomorphine (dog: 0.02-0.04 mg/kg i.v.) or xylazine (cat: 0.44 mg/kg i.m.) may be considered, provided there are no contraindications. Alternatively, gastric lavage under general anesthesia can be considered. Administration of activated charcoal (1–4 g/kg p.o.) binds toxins still present in the gastrointestinal tract. Intensive care is central, including fluid therapy to correct dehydration and electrolyte imbalances, and forced diuresis to accelerate renal elimination of the toxin. In metabolic acidosis, sodium bicarbonate administration is indicated. Seizures are treated with diazepam (0.5-2.0 mg/kg i.v.) or phenobarbital (2–4 mg/kg i.v.). Antiemetics such as maropitant (1 mg/kg s.c.) can be used for persistent vomiting. In cardiovascular instability, infusions with colloidal solutions and, if necessary, catecholamines may be required. Close monitoring of vital parameters, hydration status, and laboratory values is essential. In severe renal insufficiency, hemodialysis may be considered.
Prognosis & follow-up care
The prognosis is very good.
The prognosis for chlorphenamine maleate poisoning is generally favorable with early detection and adequate therapy. Crucial prognostic factors are the ingested dose, the time until therapy begins, and the presence of pre-existing conditions. Animals with pre-existing kidney or liver diseases have an increased risk of complications. Most patients recover completely within 24–48 hours, with neurological symptoms often being the last to subside. In follow-up care, regular checks of kidney function over several weeks are recommended, as subclinical kidney damage may persist. For this purpose, blood tests with determination of urea and creatinine, as well as urine tests, should be performed. In severe cases of poisoning, neurological deficits may remain, requiring longer-term rehabilitation. Pet owners should be offered detailed advice on preventing future medication exposures, including tips on safe storage of human medications.
Research outlook
Current research in chlorphenamine maleate poisoning in small animals focuses on several aspects: Firstly, species-specific differences in pharmacodynamics and pharmacokinetics are being investigated more closely to better understand the varying sensitivity of dogs and cats. Molecular biological studies analyze the genetic basis of drug intolerances, with a focus on further potential genetic predispositions in addition to the known MDR1 gene defect. In diagnostics, new rapid test methods are being developed to enable quick identification of antihistamine poisonings in practice. Therapeutically, improved detoxification protocols are being worked on, including novel adsorbents with higher binding capacity and selectivity than conventional activated charcoal. In addition, innovative hemodialysis procedures are being evaluated that allow for more efficient elimination of toxins. Last but not least, research is concerned with the development of safe antihistamines for veterinary use that have a lower toxicity potential even in the event of accidental overdose.
Frequently asked questions (FAQs)
- Which human medications contain chlorphenamine maleate and are dangerous for my pet?
Chlorphenamine maleate is found in many over-the-counter cold and allergy medications, including Grippostad, Wick MediNait, and various antihistamine preparations. All these products can lead to poisoning in pets and should not be administered without veterinary instruction. - How quickly do poisoning symptoms appear after ingesting chlorphenamine maleate?
The first symptoms can appear as early as 1–2 hours, typically the full poisoning picture develops within 10 hours of ingestion. - Is my cat more sensitive to chlorphenamine maleate than my dog?
Yes, cats are generally more sensitive to many medications, including chlorphenamine maleate, due to their limited ability to glucuronidate in the liver. - Can I help my pet at home if I suspect poisoning?
If you suspect poisoning, you should seek veterinary help immediately. Do not try to induce vomiting yourself or use home remedies, as this can worsen the situation. - Are there long-term damages after recovering from chlorphenamine maleate poisoning?
With timely treatment, most animals recover completely. However, in severe cases, permanent kidney damage or neurological deficits may remain. - Which dog breeds are particularly at risk for drug poisoning?
Dogs with the MDR1 gene defect, such as Collies, Australian Shepherds, Shelties, and related breeds, are particularly sensitive to many medications, including potentially antihistamines. - Can chlorphenamine maleate be safely administered to my pet at the correct dosage?
Yes, at the correct dosage prescribed by a veterinarian, chlorphenamine maleate can be safely used to treat allergic reactions. - How can I prevent my pet from being poisoned by medication?
Store all medications in locked cabinets, do not administer human medications without veterinary instruction, and pay attention to the exact dosage of prescribed medications.
Literature
- https://www.vetpharm.uzh.ch/clinitox/toxdb/KLT_026.htm
- Wismer T. Toxicology of Antihistamines. Veterinary Clinics of North America: Small Animal Practice. 2018;48(6):1087-1096.
- Fitzgerald KT, Bronstein AC. Antihistamine Toxicosis. In: Small Animal Toxicology. 3rd ed. St. Louis: Elsevier; 2020:563-577.
- Gwaltney-Brant SM. Antihistamines. In: Peterson ME, Talcott PA, editors. Small Animal Toxicology. 4th ed. Philadelphia: Elsevier; 2022:489-498.
- Court MH. Feline drug metabolism and disposition: pharmacokinetic evidence for species differences and molecular mechanisms. Veterinary Clinics of North America: Small Animal Practice. 2021;51(6):1185-1206.
- Mealey KL, Fidel J. P-glycoprotein mediated drug interactions in animals and humans with cancer. Journal of Veterinary Internal Medicine. 2019;33(6):2-10.
- Löwe G, Löwe O. Poisoning in Dogs and Cats – A Veterinary Guide. 2nd edition. Kreuztal: Kynos-Verlag. 2021; 208 p.