All households contain some medicines. Most commonly, these probably include analgesics and cold and flu remedies. Numerous prescription-only medications and alternative or herbal remedies are also available. A survey of 288 Belgian homes found an average of 31 (range 6–136) drug packages per household, and a third of these were not stored safely (De Bolle et al, 2008). The most common drugs found were non-opioid analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), nasal decongestants and anti-nausea drugs. Prescription medicine accounted for 34% of the drugs found. As a result of such ready availability of drugs in the home intended for humans, they are common causes of poisoning in companion animals (Cortinovis et al, 2015).
Recently, a report by a pet insurer in the UK found that 78% of veterinary practitioners surveyed had treated pets that had ingested human medication (Anonymous, 2014). Three quarters of these cases involved dogs. NSAIDs, particularly ibuprofen and paracetamol, are the most common drugs involved in enquiries reported to the UK Veterinary Poisons Information Service (VPIS) (2014; 2015) (Figure 1). In Italy, central nervous system (CNS) drugs (commonly sedative-hypnotic drugs and antidepressants) and NSAIDs are the most common human drugs involved in animal poisoning (Caloni et al, 2014). In both the USA (McLean and Hansen, 2012) and the Netherlands (Kan et al, 2015), paracetamol (acetaminophen) and ibuprofen are the most common human drugs ingested by animals.
Animals often help themselves to tablets that are dropped on the floor, delivered through the post, or left out in the open (handbags are a particular hazard for inquisitive dogs). In some cases, particularly with analgesics, the owner may misguidedly give their pet the drug if they think the animal is unwell. This article will focus on common medicines found in the home, with a particular focus on over-the-counter products.
Analgesics
Most households contain some analgesics. Most commonly in the UK, US and many European countries, these include paracetamol or ibuprofen, and both of these drugs are commonly involved in the accidental poisoning of pets.
NSAIDs, such as ibuprofen and diclofenac, inhibit and therefore reduce prostaglandin synthesis. Prostaglandins are involved in the control of gastric acid production, stimulation of secretion of mucous and bicarbonate by the gastric epithelium, and maintenance of mucosal blood flow. In the kidneys, prostaglandins are concerned with regulating renal blood flow and glomerular filtration rate. Therefore, they have effects on the gastrointestinal tract and the kidneys. Initial signs can include vomiting, anorexia, diarrhoea and abdominal pain, and there is risk of gastrointestinal ulceration. Renal impairment can occur, particularly in animals with dehydration, hypotension or pre-existing renal impairment. Gastrointestinal effects may be seen with doses of ibuprofen of 25–125 mg/kg in dogs (Gwaltney-Brant and Talcott, 2013) so treatment is recommended at doses below this. Treatment is supportive with gastroprotectants and intravenous fluids.
Paracetamol is widely used and is found in many products for the relief of pain, and cold and flu symptoms (Figure 2). It is a risk to dogs, and even more so in cats who are unable to metabolise it safely (Steenberg, 2003). In overdose in dogs, or after almost any dose to cats, the non-toxic metabolic pathways of paracetamol elimination are overwhelmed and toxic metabolites are produced. These cause liver damage and haematological effects with methaemoglobin formation and Heinz body formation and denaturation of erythrocyte membranes (Webb et al, 2003). A single ingestion of 250 mg may prove fatal to a cat (Prasuhn, 1983); methaemoglobinaemia occurs in dogs with doses above 200 mg/kg (Savides et al, 1984), although liver toxicity occurs at lower doses (Taylor and Dhupa, 2000).
Signs of paracetamol toxicity include vomiting, diarrhoea, anorexia, facial and paw oedema, and discoloured mucous membranes (e.g. pale, brown, muddy). There may be progressive cyanosis, tachycardia, tachypnoea and dyspnoea. Haematuria, anaemia, and evidence of haemolysis may be present. Changes in liver enzymes can occur 24–36 hours post-ingestion. Methemoglobinemia, not seen in human overdose, is the predominant cause of severe and fatal effects in cats (Aronson and Drobatz, 1996; Taylor and Dhupa, 2000; Sellon, 2013).
The aim of treatment is to ensure adequate oxygenation, to prevent further metabolism of paracetamol to toxic metabolites with the use of antidotes (mainly acetylcysteine), and to prevent damage to the liver and erythrocytes.
Multivitamins
Use of vitamin and mineral supplements is very common. Generally, the only vitamin of potential concern in acute overdose is vitamin D. Vitamin D compounds can cause hypercalcaemia and are a particular hazard in dogs. However, the dose in vitamin preparations is relatively low, and generally only a problem if the dose ingested is large. This is in contrast to vitamin D compounds (e.g. calcipotriol/calcipotriene, tacalcitol) in psoriasis creams, which can cause severe toxicity in dogs (e.g. Fan et al, 1998; Hilbe et al, 2000; Pesillo et al, 2002).
In acute overdose, the main mineral of potential concern is iron (Albretsen, 2006). There is no mechanism for excretion of iron; therefore, in overdose, it can cause toxic effects including gastrointestinal effects such as vomiting, diarrhoea and gastrointestinal bleeding. This is generally all that is seen in most animals.
However, in more severe cases, there may be a latent phase followed 12–96 hours later by recurrence of gastrointestinal effects, liver damage, metabolic acidosis, shock, hypotension and cardiovascular collapse. Treatment of iron poisoning is supportive with restoration of fluids, electrolytes and acid-base balance. In animals with severe signs, the chelating agent desferrioxamine (deferoxamine) may be used to enhance iron removal. Multivitamin and multimineral products generally contain a low dose of iron, but iron tablets are available from pharmacies and can contain a much higher dose.
Other vitamins and minerals are generally well tolerated in acute overdose, but may cause adverse gastrointestinal effects.
Nicotine replacement therapy
There are many forms of nicotine replacement therapy available to help with smoking cessation. They are available as lozenges, patches, inhalation products, gums and nasal sprays, and contain nicotine, an alkaloid from the tobacco plant (Nicotiana species). Nicotine causes cholinergic effects, with brief CNS stimulation followed by CNS depression (Hackendahl and Sereda, 2004). Although not classified (as yet) as medicines, electronic cigarettes (i.e. e-cigarettes, electronic nicotine delivery systems (ENDS)) are rapidly increasing in popularity, and these pseudo-medicines also present a potential hazard (World Health Organization (WHO), 2014).
Nicotine is poorly absorbed from the stomach and subject to first-pass metabolism. As a result, severe toxicity is uncommon (Spoo, 2009), unless a very large quantity has been ingested or the nicotine-containing substance was chewed.
Common signs are hypersalivation, vomiting, ataxia, lethargy, tremor, diarrhoea, and tachycardia or bradycardia. Other signs include depression, respiratory depression, hypotension, collapse, dyspnoea, hyperactivity and hyperthermia; pupils are initially constricted and then later dilated. In severe cases, there may be convulsions, coma and ventricular arrhythmias.
Nicotine patches are a potential obstruction risk. It is also worth noting that some nicotine lozenges and gums contain xylitol, which can cause rapid onset hypoglycaemia and sometimes liver damage in dogs. Treatment is aimed at supportive care of animals with clinical signs, decreasing absorption and promoting clearance (Hackendahl and Sereda, 2004).
Caffeine
As well as being present in beverages such as coffee and tea, energy drinks and some analgesic products, caffeine is also available in tablets for use as a stimulant for shift workers or students during exam time, as well as in some weight-loss formulations. Caffeine, like theobromine in chocolate, is a methylated xanthine alkaloid. It acts as a CNS and muscle stimulant. It is also a diuretic agent and a relaxant of smooth muscles, particularly the bronchial muscle.
In dogs, toxicity is most common following the ingestion of concentrated sources of caffeine, which can lead to acute cardiac and CNS stimulation. Over-the-counter stimulant tablets generally contain 30–200 mg of caffeine per tablet, which can cause toxicosis in small animals (Patterson, 1975; Vig et al, 1986; Dolder, 2013).
Signs of caffeine toxicity include hyperactivity, restlessness, excitation, agitation, abnormal behaviour, and vomiting. These progress rapidly and there may be panting, tachypnoea, tachycardia, weakness, ataxia, diuresis, diarrhoea, muscle tremors and convulsions (Dolder, 2013).
The aim of the treatment is to sustain basic life support, decrease further caffeine absorption, increase excretion of adsorbed caffeine, and provide symptomatic relief of seizures, respiratory difficulties and cardiac dysfunction (Dolder, 2013). This will involve administration of activated charcoal, intravenous fluids to maintain adequate renal perfusion and correct electrolyte imbalances, with diazepam or midazolam for hyperactivity or convulsions. If ineffective, a barbiturate or a general anaesthetic can be used. An antiarrhythmic (e.g. propranolol, lidocaine) may be required in more severe cases.
Sympathomimetic drugs
Sympathomimetics, such as phenylephrine and ephedrine, are used as decongestants and slimming aids in human medicine. They are related to phenylpropanolamine which is used in veterinary medicine to treat urinary incontinence in spayed female dogs. Phenylpropanolamine was previously widely used in human medicines but is now heavily restricted owing to its potential use in amphetamine manufacture.
These sympathomimetics have direct and indirect effects on adrenergic receptors, and toxicity is caused by acute cardiovascular and central stimulant effects. This results in endogenous release of catecholamines in the heart and brain, causing peripheral vasoconstriction, cardiac stimulation and increased blood pressure.
Individual response is variable. CNS stimulation, with restlessness, tachycardia, agitation, hyperactivity, panting, distress, hyperthermia and hypertension or rebound hypotension, may occur. There may be dilated pupils, hallucinations and vocalisation and, in severe cases, bradycardia, head-bobbing, tremors and seizures. If excessive muscle activity is not controlled, there is risk of disseminated intravascular coagulation (DIC) or rhabdomyolysis (with hyperkalaemia), which can result in renal failure. Pulmonary oedema can result from prolonged hypertension, and death may occur from cardiovascular collapse (Means, 2004).
Treatment is supportive with acepromazine or a barbiturate recommended for tremors or convulsions. Diazepam is best avoided because it can exacerbate sympathomimetic-induced agitation (Ooms et al, 2001; Means, 2004). Beta-blockers may be given for prolonged or severe tachycardia.
Weight-loss products
Various products are available to aid weight loss, particularly via the internet. The latter are largely unregulated, and can contain a variety of compounds including herbal extracts, as well as caffeine and guarana (which is also a source of caffeine). Some may also contain stimulants such as amphetamine compounds or sympathomimetics. It is essential to establish which product is involved and, if possible, the ingredients in order to determine the potential risks and the most appropriate treatment.
Antihistamines
Antihistamines act as reversible, competitive inhibitors of the interaction of histamine with H1 receptors. They are given to provide symptomatic relief of allergic signs caused by histamine release, including pruritus and anaphylactic reactions, and are also used as sedatives (including over-the-counter sleep aids which commonly contain diphenhydramine) and antiemetics. Clinical effects are variable but may include vomiting, hypersalivation, ataxia, lethargy, tremor, depression, hyperthermia, tachycardia and weakness. In some animals, there may be hyperactivity and hyperaesthesia. In severe cases, coma, seizures, hypotension and respiratory depression may occur. Although individual response is variable, severe cases are uncommon. Treatment is symptomatic and supportive (Murphy, 2001).
Cough and cold products
Cough and cold preparations come in many forms such as throat lozenges, syrups, hot drinks, capsules, tablets, and even powders. They often contain multiple ingredients including analgesics, antihistamines, decongestants and cough suppressants. Some cough products simply contain honey and lemon. It is essential to obtain the full name of the product and the ingredients, as there are many different products sold under one brand name (e.g. cold and flu sachets; cold and flu tablets; syrups for chesty cough, tickly cough or dry cough; maximum strength capsules).
Throat lozenges can contain various substances such as antibacterial compounds or local anaesthetics to numb the throat, e.g. hexylresorcinol, dichlorobenzyl alcohol, amylmetacresol, benzocaine. These are of low toxicity in the concentrations used in these products and most animals remain asymptomatic after ingestion of throat lozenges (VPIS unpublished data). Again, some throat lozenges contain xylitol.
Indigestion aids
Products for the relief of indigestion may contain calcium or magnesium carbonate, sodium alginate, magnesium hydroxide, aluminium hydroxide, simeticone, an H2 blocker (e.g. ranitidine, famotidine, cimetidine) or a proton pump inhibitor (e.g. omeprazole or pantoprazole). These are all of low acute toxicity and unlikely to cause significant toxicity, although a few of these products may also contain xylitol, so it is important to check the individual product.
Anti-diarrhoeal products
Loperamide is a common ingredient in products for the treatment of diarrhoea (in both human and veterinary medicine). It is a weak opioid with weak analgesic activity.
Severe loperamide poisoning has been reported in dogs (Staley and Staley, 1994; Hugnet et al, 1996; Sartor et al, 2004) and is a particular risk in collies and related breeds (Buronfosse et al, 1998) owing to a mutation deletion of ABCB1 gene (previously known as the multidrug-resistance gene (MDR1)) which codes for P-glycoprotein, a transporter protein. This deletion produces a severely truncated, non-functional P-glycoprotein which allows passage of some drugs into the brain (Mealey, 2004).
P-glycoprotein is also expressed in the gut and is involved in moving some substances from the cell back into the gut, reducing absorption. In dogs with the mutation, it has been suggested that the defective P-glycoprotein could increase intestinal absorption of some drugs, although this was not demonstrated in an experimental study of several drugs including loperamide. In this study, however, dogs with the mutation had significant CNS depression compared with normal dogs, even though they had comparable plasma loperamide concentrations (Mealey et al, 2010). In addition, this study used therapeutic doses; in overdose, absorption may be different.
Signs of loperamide toxicity include gastrointestinal signs, constricted pupils, vocalisation and ataxia, and is expected only in animals with the ABCB1 mutation. In more severe cases, hypothermia, bradycardia, bradypnoea, drowsiness, coma and collapse may occur. Treatment is supportive. Naloxone (a drug used to reverse the effects of opioids) can be given if there is evidence of opioid-related depression such as drowsiness and respiratory distress. Repeated doses may be required (Staley and Staley, 1994).
Constipation relief
Several different drugs are used in products for the relief of constipation. Some are faecal softeners such as docusate or bulk laxatives such as ispaghula husk, which can cause diarrhoea in overdose. Senna is also a common ingredient. It is an anthraquinone stimulant laxative, usually obtained from the plant Cassia senna. Ingestion of senna can cause diarrhoea (usually after about 6–12 hours), vomiting and abdominal discomfort. The laxative effect may last 12 to 24 hours and if there is severe fluid loss electrolyte imbalance may result and should be managed supportively.
Oral contraceptives
Sex hormones, including those used for hormone replacement therapy (HRT) and particularly oral contraceptives, are commonly ingested by dogs and, less commonly, by cats. Most animals remain asymptomatic even after ingestion of several months' worth of tablets. There may occasionally be vomiting and diarrhoea but no cases of serious toxicity have been reported. Progesterone-containing preparations may theoretically disrupt oestrus in females but this is rarely reported. Bone marrow suppression from oestrogen exposure has not been reported from acute ingestion of sex hormones, probably owing to the low doses involved, and rapid metabolism and elimination.
Herbal and homeopathic
Herbal and homeopathic medicines are used to treat numerous disorders. It is important to note that there are different types of preparations. Herbal medicines contain plant extracts or dried material and although they are generally of low toxicity after acute ingestion, it is important to check the ingredient list as some contain caffeine or other stimulants (e.g. ephedra contains ephedrine).
Homeopathy is a complementary or alternative medicine (CAM). Many homeopathic remedies consist of substances that have been diluted many, many times in water until there is none or almost none of the original substance left. As a result, toxic effects do not occur with these preparations, although many contain lactose and so may have a laxative effect.
Conclusions
Numerous medicines are present in the average home including over-the-counter and prescription-only medicines. Most over-the-counter medicines are relatively safe in acute overdose and severe toxicity is not expected in many cases. However, some of the most common drugs (NSAIDs and paracetamol) ingested by companion animals can cause significant toxicity. Other medicines commonly available without prescription are generally less hazardous but there are exceptions such as loperamide which is a particular hazard in collies and related breeds, and caffeine which is present in numerous products, alone and in combination with other drugs and herbal preparation. It is also important to note that many products, particular those for the relief of cold and flu symptoms or analgesics, can contain multiple ingredients and it is essential to establish the exact product involved in order to determine the most appropriate treatment plan. If required, advice can be sought from a poisons information service.