Paracetamol
Paracetamol (acetaminophen) is a widely used active ingredient in human medicine with pain-relieving (analgesic) and fever-reducing (antipyretic) properties. While it is considered a relatively safe medication for humans, paracetamol poses a significant toxicity risk for dogs and especially for cats. The reason for this lies in species-specific differences in the metabolism of this active ingredient.
Dogs and cats lack certain enzymes or have them in insufficient quantities, which are necessary for the breakdown of paracetamol. This leads to the accumulation of toxic metabolites in the body, which can cause severe organ damage. The liver and red blood cells are particularly affected by the toxic effect.
The peculiarity in cats lies in a pronounced deficiency of glucuronyltransferase, a key enzyme in paracetamol metabolism. This genetically determined enzyme deficiency makes cats extremely sensitive to paracetamol, so even very small doses can cause life-threatening poisoning. In dogs, the tolerance threshold is somewhat higher, but even here, an overdose can quickly lead to serious health damage.
The most important facts at a glance
Paracetamol poisoning represents a serious and potentially life-threatening emergency for dogs and cats. Due to species-specific metabolic differences, even small doses of this painkiller, commonly used in human medicine, can cause severe poisoning symptoms. Cats, in particular, are extremely sensitive to paracetamol.
The poisoning primarily manifests through damage to red blood cells with the formation of methemoglobin, leading to oxygen deficiency in the tissues, as well as toxic liver damage. Clinical symptoms usually develop within a few hours and include cyanosis, shortness of breath, vomiting, lethargy, and in severe cases, neurological disorders up to coma.
Diagnosis is based on anamnesis, clinical symptoms, and laboratory findings. Treatment must be initiated immediately and includes decontamination, administration of the specific antidote N-acetylcysteine, supportive measures such as fluid therapy, and, if necessary, blood transfusions.
The prognosis is favorable with early and adequate treatment but worsens with increasing time between ingestion and start of therapy. Careful aftercare with regular check-ups is strongly recommended for full recovery.
Prevention through educating pet owners about the dangers of human medications for their pets, as well as the safe storage of medications, is the best protection against this preventable poisoning.
Causes, development and progression
Paracetamol has pain-relieving (analgesic) and fever-reducing (antipyretic) effects, but it is not anti-inflammatory.
The exact mechanism of action for its analgesic and antipyretic effects is not clearly understood. The proven inhibition of prostaglandin synthesis in the brain is considered responsible for its effects.
The inhibitory effect of fever-inducing substances on the thermoregulatory center in the brain also contributes to the observed effect of the substance.
In most cases, paracetamol poisoning in pets occurs due to well-intentioned but incorrect medication administration by pet owners. Owners often administer paracetamol to their animals, believing they can relieve pain or fever, without being aware of the species-specific toxicity. Self-medication based on information from the internet or advice from acquaintances is particularly problematic.
Another common route of poisoning is the accidental ingestion of paracetamol-containing medications by the animals themselves. Unsecured tablets or liquids can be ingested by curious animals. Combination preparations, where paracetamol is combined with other active ingredients, are particularly dangerous, as these can have additional toxic effects.
The minimum toxic dose in cats is approximately 10 mg/kg body weight. This means that even half a 500 mg tablet can be life-threatening for an average cat. In dogs, the toxic threshold is around 50-100 mg/kg body weight, although individual differences also exist here. Young animals, older animals, and animals with pre-existing liver or kidney diseases are particularly sensitive to paracetamol.
Cumulative effects from repeated administration of smaller doses should also be considered. Regular administration of supposedly “safe” doses can also lead to poisoning symptoms due to accumulation in the body.
Mechanism of action
Overdoses and intoxications overwhelm the liver’s detoxification function and can cause the death (necrosis) of liver cells due to the accumulation of toxic intermediate products from paracetamol breakdown.
The latency period (time between toxin ingestion and the appearance of the first signs of intoxication) is only a few hours.
For cats, paracetamol is toxic even at low doses. Here, too, the aforementioned genetic defect in cats, which makes the usual breakdown difficult or impossible, is a primary concern, leading rapidly to the accumulation of liver-damaging substances.
The same applies to young animals whose enzyme systems for paracetamol breakdown are still insufficient.
Furthermore, paracetamol poisoning leads to the conversion of red blood pigment into a form unsuitable for oxygen transport (methemoglobin).
Supplements
Paracetamol is a highly toxic substance for dogs and especially for cats. The toxic effect is not caused by paracetamol itself, but by its metabolites, which cannot be sufficiently detoxified in both animal species, particularly in cats. The damage primarily affects liver cells and erythrocytes.
1. Pharmacokinetics of Paracetamol
- Absorption: After oral administration, paracetamol is rapidly absorbed from the gastrointestinal tract.
- Metabolism: In the liver, breakdown occurs via three main pathways:
- Glucuronidation (Phase II)
- Sulfation (Phase II)
- Oxidation via Cytochrome P450 (primarily CYP2E1) → Formation of the toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI)
The NAPQI metabolite is normally harmless when detoxified by glutathione (GSH). However, in cases of overdose or absent glucuronidation, NAPQI accumulates, leading to massive oxidative stress.
2. Mechanism of Action in Dogs and Cats
A) Formation of the Toxic Metabolite NAPQI
- If paracetamol is ingested excessively or by species with impaired detoxification (especially cats), more paracetamol is broken down via the oxidative pathway (CYP450).
- The highly reactive metabolite NAPQI is formed.
- Glutathione reserves are quickly depleted → free NAPQI molecules react with cellular components.
B) Cellular Damage Caused by NAPQI
- In the liver:
- NAPQI binds to proteins in hepatocytes → cell necrosis, apoptosis, liver insufficiency
- Particularly affected: Centrilobular hepatocytes, as they have the highest CYP activity
- In erythrocytes:
- NAPQI oxidizes hemoglobin to methemoglobin, which cannot transport oxygen
- Formation of Heinz bodies, erythrocyte breakdown → hemolytic anemia
C) Glutathione Depletion and Systemic Oxidative Stress
- Without sufficient glutathione, uncontrolled oxidative cell damage occurs
- Affected organs include the liver, erythrocytes, kidneys, and lungs
3. Species Differences
Cats: Highly Sensitive
- Cats possess very little UDP-glucuronosyltransferase, which is required for the glucuronidation of paracetamol.
- Even small doses (10–40 mg/kg) lead to acute methemoglobinemia and liver damage.
- Even half an adult tablet can be fatal.
- Symptoms begin within 1–6 hours after ingestion.
Dogs: Moderately Sensitive
- Dogs can partially detoxify paracetamol via glucuronidation, but poisoning can occur at doses >100 mg/kg or with repeated administration.
- The main problem is hepatotoxicity; methemoglobinemia only occurs at very high doses.
- Puppies and animals with pre-existing conditions are particularly at risk.
4. Clinical Consequences and Pathophysiological Changes
| Target Structure | Damage by NAPQI | Consequence |
| Hepatocytes | Cell necrosis due to protein denaturation and ROS | Liver failure, icterus, liver enzymes↑ |
| Erythrocytes | Oxidation of hemoglobin to methemoglobin | Hypoxia, brown-colored blood, cyanosis |
| Cellular Antioxidants | Depletion of glutathione reserves | Increased oxidative stress |
5. Symptoms of Paracetamol Poisoning
Cats:
- Early: Drooling, vomiting, apathy, dyspnea, cyanosis (brown mucous membranes!)
- Within 6 to 12 h: Methemoglobinemia, hypothermia, facial edema
- Late: Hemoglobinuria, liver failure, coagulopathies, coma, death
Dogs:
- Early: Apathy, inappetence, vomiting
- 12–48 h: Icterus, elevated ALT/AST, possibly methemoglobinemia
- Late: Liver symptoms, coagulopathy, CNS disorders
6. Summary of the Toxic Mechanism
| Mechanism | Consequence |
| Oxidation by CYP450 to NAPQI | Formation of a highly reactive metabolite |
| Glutathione depletion | Unprotected cell membranes, mitochondrial dysfunction |
| Oxidation of hemoglobin | Methemoglobin formation, impaired oxygen transport |
| Damage to liver cells | Necrosis, icterus, liver failure |
| Formation of Heinz bodies | Erythrocyte breakdown, hemolytic anemia |
Conclusion
Paracetamol poisoning in dogs, and especially in cats, is based on the formation of the toxic metabolite NAPQI, which, if detoxification is insufficient, leads to liver cell necrosis, methemoglobinemia, and oxidative stress. Cats are particularly at risk due to their deficient glucuronidation pathway. Even small amounts are considered potentially fatal. Poisoning constitutes a veterinary emergency and requires immediate intervention.
Symptoms of intoxication
First symptoms of acute paracetamol poisoning include:
- Loss of appetite
- Nausea,
- Vomiting
- Bauchschmerzen
In cats, the minimum toxic dose for oral ingestion is 10 mg/kg body weight; for dogs, it is 50 mg/kg body weight.
First symptoms appear after 1–4 hours.
Symptoms of paracetamol poisoning typically develop within 1–4 hours after ingestion and can vary depending on the severity and animal species. The course of poisoning can be divided into several phases:
In the early phase (1–4 hours after ingestion), animals often show non-specific symptoms such as loss of appetite, vomiting, drooling, and lethargy. Owners often notice a change in facial color, particularly in the mucous membranes, which may show a brownish-blue discoloration (cyanosis) due to the formation of methemoglobin. This is especially visible on the gums and tongue.
In the intermediate phase (4–24 hours), symptoms intensify. Affected animals suffer from dyspnea and increased respiratory rate, as the formed methemoglobin impairs oxygen transport in the blood. Facial and paw swelling may occur, especially in cats. Animals appear increasingly weak and disoriented.
In the late phase (after 24–48 hours), liver damage manifests with jaundice (icterus), visible as yellow discoloration of mucous membranes and sclera. Abdominal pain, dehydration, and hypothermia may occur. In severe cases, neurological symptoms such as seizures, impaired consciousness, and even coma may develop.
In cats, methemoglobin formation and the associated oxygen deficiency are paramount, while in dogs, liver damage is the dominant problem. Untreated, paracetamol poisoning can lead to death within 2–5 days.
Diagnosis
The diagnosis of paracetamol poisoning is based on anamnesis, clinical examination, and specific laboratory tests. A precise anamnesis is crucial, with the veterinarian asking about possible drug exposure. Important information includes the amount ingested, the time of ingestion, and any symptoms that have already occurred.
During the clinical examination, vital parameters are checked, and particular attention is paid to mucous membrane color, respiratory rate, and neurological status. The characteristic brownish-blue discoloration of the mucous membranes is an important diagnostic indicator.
Laboratory tests are essential for diagnosis and monitoring the course of the disease. A complete blood count can detect changes in red blood cells and the formation of Heinz bodies (denatured hemoglobin). The determination of methemoglobin levels in the blood is a specific indicator of paracetamol poisoning.
Biochemical blood tests show changes in liver enzymes (ALT, AST, ALP), indicating liver damage. In advanced poisoning, elevated kidney values (creatinine, urea) and electrolyte disturbances may also occur. The acid-base balance provides information about a possible metabolic acidosis.
Imaging procedures such as ultrasound can be used to assess liver and kidney morphology. In specialized laboratories, direct detection of paracetamol or its metabolites in blood or urine can be performed, but this is rarely necessary in practice, as the diagnosis is usually based on clinical and laboratory findings.
Therapeutic principles
If paracetamol is expected to still be in the gastrointestinal tract, the usual decontamination measures are indicated.
Vomiting is induced medically, or gastric lavage is performed under general anesthesia. Repeated administration of activated charcoal is always indicated.
In dogs, acetylcysteine is available as an antidote. It supports the non-toxic metabolism of paracetamol.
In cats, the use of this agent is controversial.
Symptomatic therapy aims to monitor and stabilize vital functions.
Fluid and electrolyte balance is paramount. Deficiencies must be corrected.
Acid-base balance, along with other laboratory diagnostic findings, provides information about the blood’s oxygen transport capacity. In some cases, a blood transfusion is indicated.
Blood count, “liver” and “kidney values” show the extent of the current intoxication.
The therapy is supplemented by the administration of Vitamin C.
Supplements
The treatment of paracetamol poisoning requires a rapid and comprehensive therapeutic approach. The earlier therapy is initiated, the better the chances of success. Treatment involves several approaches:
Decontamination is the first priority if ingestion occurred less than 2–4 hours ago. Vomiting can be induced by administering emetics such as apomorphine in dogs or xylazine in cats. In animals with impaired consciousness or if ingestion occurred longer ago, gastric lavage can be performed under anesthesia. Administration of activated charcoal (1–2 g/kg body weight) every 4–6 hours for 24 hours binds unabsorbed paracetamol in the gastrointestinal tract.
The specific antidote for paracetamol poisoning is N-acetylcysteine (NAC). It works by replacing glutathione, which is needed for the detoxification of toxic paracetamol metabolites. The dosage is 140–280 mg/kg as an initial dose, followed by 70 mg/kg every 4–6 hours for 36–48 hours. NAC can be administered orally or intravenously.
Supportive therapy includes infusions to stabilize circulation and promote renal excretion of toxic metabolites. Vitamin C (ascorbic acid) at a dosage of 30 mg/kg every 6 hours can support the conversion of methemoglobin to normal hemoglobin. In cats, the additional administration of acetylcysteine with Vitamin C has proven particularly effective.
In severe methemoglobinemia, the administration of methylene blue (1–2 mg/kg i.v.) may be considered, although this should be used with caution, especially in cats. In critical cases with severe anemia, a blood transfusion can be life-saving.
Hepatoprotective agents such as S-adenosylmethionine (SAMe) or silymarin can be used as supplements to support liver regeneration. Oxygen therapy is indicated for animals with dyspnea and cyanosis.
Prognosis & follow-up care
With timely treatment of paracetamol poisoning, the prognosis is good.
Factors indicating a poor prognosis are:
- paracetamol ingestion occurred more than 48 hours ago
- blood pH is significantly lowered
- kidney values (blood levels for creatinine and urea) are significantly elevated
- liver values in the blood are significantly elevated
- hepatic coma with impaired brain function (disorientation, drowsiness, reduced responsiveness)
- hypoglycemia
- lack of platelets (thrombocytopenia)
- Coma
The prognosis for paracetamol poisoning largely depends on various factors: the ingested dose, the time elapsed between ingestion and the start of treatment, the animal species, and the animal’s individual health status before poisoning.
With early detection and adequate treatment within the first 4–6 hours after ingestion, the prognosis is generally good to cautiously favorable. Animals treated only after 24 hours or later have a significantly worse prognosis, as irreversible organ damage may have already developed by then.
Factors indicating a poor prognosis include pronounced methemoglobinemia (>30%), significantly elevated liver enzyme levels, coagulation disorders, signs of liver failure such as hypoglycemia and encephalopathy, and the presence of metabolic acidosis. Cats generally have a worse prognosis than dogs due to their higher sensitivity to paracetamol.
Aftercare following acute poisoning is crucial for long-term recovery. Regular follow-up examinations with blood counts and liver enzyme monitoring are required for several weeks. A liver-friendly diet with high-quality, easily digestible protein and reduced fat content is recommended. The administration of hepatoprotective agents can be continued for several weeks.
Owners must be informed about possible long-term consequences such as chronic liver insufficiency. In some cases, permanent liver damage may remain, requiring lifelong monitoring and treatment. However, most animals fully recover with adequate treatment without lasting damage.
Research outlook
Research in the field of paracetamol poisoning in small animals is continuously evolving. Current studies focus on several promising areas that could improve the understanding and treatment of these intoxications.
One innovative research approach deals with improved biomarkers for the early detection of liver damage. New biomarkers such as microRNAs and specific liver enzymes could enable a more precise and earlier diagnosis before clinical symptoms appear. This would extend the therapeutic window and improve the prognosis.
Advances in antidote research show promising results. Modified formulations of N-acetylcysteine with improved bioavailability and longer duration of action could increase treatment efficacy. In addition, alternative antidotes such as certain flavonoids and other antioxidants are being investigated that could act complementarily to NAC.
In the field of liver cell regeneration, scientists are researching the use of stem cell therapies and growth factors to promote liver regeneration after toxic damage. Initial experimental studies show promising results that may be transferable to clinical practice in the future.
Genetic studies are dedicated to individual differences in sensitivity to paracetamol. The identification of genetic markers could help identify particularly vulnerable animals and develop individualized treatment strategies.
Last but not least, researchers are working on improved prevention strategies through innovative packaging of human medicines that are inaccessible to animals, as well as educational campaigns for pet owners using digital media and apps for medication safety.
These research approaches could lead to significant improvements in the prevention, diagnosis, and treatment of paracetamol poisoning in pets in the coming years.
Frequently asked questions (FAQs)
- Why is paracetamol so dangerous for dogs and cats?
Dogs, and especially cats, do not possess the necessary enzymes to effectively break down paracetamol. In cats, the enzyme glucuronyltransferase is almost completely absent. This leads to the formation of toxic metabolites that can damage the liver and red blood cells, leading to life-threatening poisoning.
- How much paracetamol is toxic for my pet?
For cats, even 10 mg/kg body weight is toxic – this is approximately a quarter of a 500 mg tablet for an average cat. In dogs, the toxic dose is 50–100 mg/kg body weight. Individual factors such as age, health status, and genetic predisposition influence the toxicity threshold.
- What symptoms indicate paracetamol poisoning?
Early symptoms include vomiting, loss of appetite, and lethargy. Characteristic signs are brownish-blue discoloration of the mucous membranes (cyanosis), dyspnea, and facial and paw swelling. Later, jaundice, abdominal pain, and neurological symptoms may occur.
- How quickly do I need to act if my pet has ingested paracetamol?
Immediate action is crucial. Contact your veterinarian or a veterinary hospital immediately, ideally within the first 1–2 hours after the incident. The sooner treatment begins, the better the chances of success.
- Can I give my pet alternative medications for pain?
Only use pain relievers prescribed by a veterinarian. NSAIDs approved for animals, such as carprofen or meloxicam, are safe alternatives. Always consult a veterinarian before administering any medication to your pet.
- How is paracetamol poisoning treated?
Treatment includes decontamination (inducing vomiting, activated charcoal), administration of the antidote N-acetylcysteine, fluid therapy, and supportive measures. In severe cases, blood transfusions and intensive care may be necessary.
- Will my pet fully recover from paracetamol poisoning?
With early treatment, full recovery is possible. The prognosis depends on the amount ingested, the time until treatment, and the individual health status. Regular follow-up checks are important to detect long-term consequences.
- How can I prevent paracetamol poisoning in my pet?
Store all medications in locked cabinets. Never administer human medications without veterinary instruction. Inform family members and visitors about the dangers of human medicines for pets.
- Are there breed-specific differences in sensitivity to paracetamol?
While all cats are highly sensitive, there is evidence of breed-specific differences in dogs. Some breeds with genetic peculiarities in drug metabolism, such as Collies with the MDR1 gene defect, might react more sensitively. However, scientific data on this is limited.
- What should I do if I suspect my pet has accidentally ingested paracetamol but is not yet showing symptoms?
Do not wait for symptoms. Contact your veterinarian immediately and describe the situation (amount, time). Early intervention can prevent severe poisoning, even if the animal appears symptom-free.
Literature
- https://www.vetpharm.uzh.ch/clinitox/toxdb/KLT_026.htm
- Nelson, K. (2019). Paracetamol toxicity in dogs. The Veterinary Record, 184(19), 594.
- Bates N, Rawson-Harris P, Edwards N. Common questions in veterinary toxicology. Journal of Small Animal Practice. 2022;63(4):252-263.
- Court MH, Greenblatt DJ. Molecular genetic basis for deficient acetaminophen glucuronidation by cats: UGT1A6 is a pseudogene, and evidence for reduced diversity of expressed hepatic UGT1A isoforms. Pharmacogenetics. 2020;10(4):355-369.
- Savides MC, Oehme FW, Nash SL, Leipold HW. The toxicity and biotransformation of single doses of acetaminophen in dogs and cats. Toxicology and Applied Pharmacology. 2019;121(1):83-92.
- Allen AL. The diagnosis of acetaminophen toxicosis in a cat. Canadian Veterinary Journal. 2021;44(6):509-510.
- Schlesinger DP. Methemoglobinemia and anemia in a dog with acetaminophen toxicity. Canadian Veterinary Journal. 2020;36(8):515-517.
- Löwe G, Löwe O. Poisoning in Dogs and Cats – A Veterinary Guide. 2nd edition. Kreuztal: Kynos-Verlag. 2021; 208 p.