How common is acetaminophen poisoning?

Hydrocodone/paracetamol, also known as hydrocodone/acetaminophen, is the combination of the pain medications hydrocodone and paracetamol (acetaminophen). It is used to treat moderate to severe pain. It is taken by mouth. Recreational use is common in the United States.
Common side effects include dizziness, sleepiness, constipation, and vomiting. Serious side effects include addiction, respiratory depression (a decreased effort to breathe), low blood pressure, serotonin syndrome, severe allergic reactions, and liver failure. Use during pregnancy may harm the baby. Use with alcohol is not recommended. Hydrocodone works by binding to the mu-opioid receptor. How acetaminophen works is unclear.
Hydrocodone/paracetamol was approved for medical use in the United States in 1982. In the United States it is a schedule II controlled substance. In 2016 it was the 13th most prescribed medication in the United States with more than 43 million prescriptions. It is not available in the United Kingdom. It is sold under the trade name Vicodin among others.

Hydrocodone/paracetamol

Hydrocodone/acetaminophen is a two-ingredient combination formula consisting of the opioid hydrocodone and the non-opioid analgesic acetaminophen. It is indicated for relief of moderate to severe pain of acute, chronic, or postoperative types. Hydrocodone/acetaminophen comes in oral solution and tablet formulations; however strength of each component may vary. In October 2014, the Drug Enforcement Administration rescheduled hydrocodone combination drugs from schedule III to schedule II due to its risk for misuse, abuse, and diversions.

Hydrocodone diversion and recreational use has escalated in recent years due to its opioid effects. In 2009 and 2010, hydrocodone was the second-most frequently encountered opioid pharmaceutical in drug evidence submitted to U.S. federal, state, and local forensic laboratories as reported by DEA's National Forensic Laboratory Information System (NFLIS) and System to Retrieve Information from Drug Evidence (STRIDE).

Pregnancy category C: Risk in pregnancy cannot be ruled out. Animal controlled studies have not been conducted with this medication.

Low concentrations of acetaminophen is excreted through breast milk, however, hydrocodone's excretion is unknown.

Use with caution due to possible risk of toxicity.* Exact prevalence (%) is unknown

"Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed 4000 milligrams per day, and often involve more than one acetaminophen-containing product."

"Do not take hydrocodone bitartrate and acetaminophen tablets if you are allergic to any of its ingredients. If you develop signs of allergy such as a rash or difficulty breathing stop taking hydrocodone bitartrate and acetaminophen tablets and contact your healthcare provider immediately."

Hydrocodone: Respiratory depression, extreme somnolence progressing towards coma, muscle limpness, cold and clammy skin, slow heart rate, low blood pressure, abrupt loss of heart function, and death may occur.

Acetaminophen: Liver and kidney failure, low blood sugar coma may occur.

Hydrocodone/acetaminophen may demonstrate an enhanced respiratory depressant effect when combined with other sedatives such as other opioids, benzodiazepines, nonbenzodiazepine sedatives, psychotropics, and anticonvulsants.

Concurrent use with alcohol products may increase the risk of acute liver failure.

Laboratory function tests should be used to monitor therapy in people with severe liver or renal disease.
In May 2017, professional golfer Tiger Woods was arrested by the police for driving under influence. Woods said that this was due to four prescription drugs that he was taking for a back operation, one of which was Vicodin.

On June 30, 2009, a U.S. Food and Drug Administration (FDA) advisory panel voted by a narrow margin to advise the FDA to remove Vicodin and another opioid, Percocet, from the market because of "a high likelihood of overdose from prescription narcotics and acetaminophen products". The panel also cited concerns of liver damage from their acetaminophen component, which is also the main ingredient in commonly used nonprescription drugs such as Tylenol. Each year, acetaminophen overdose is linked to about 400 deaths and 42,000 hospitalizations.

In January 2011, the FDA asked manufacturers of prescription combination products that contain acetaminophen to limit the amount of acetaminophen to no more than 325 mg in each tablet or capsule within 3 years. The FDA also required manufacturers on all acetaminophen containing products to issue a black box warning indicating the potential risk for severe liver injury and a warning highlighting potential for allergic reactions.

On August 22, 2014, the Drug Enforcement Administration (DEA) announced that all hydrocodone combination products (HCPs) will be rescheduled from Schedule III to Schedule II of the Controlled Substances Act (CSA), effective on October 6, 2014. In 2010, more than 16,000 deaths were attributed to abuse of opioid drugs. Even though there are legitimate medical uses for HCPs, data suggest that a significant number of individuals misuse HCPs.

Vicodin is mentioned in songs such as Eminem's "Kill You", Blackbear's "Sniffing Vicodin in Paris", Kendrick Lamar's "A.D.H.D", Future's "Lay Up", Lupe Fiasco's "Mural", Queens of the Stone Age's "Feel Good Hit of the Summer", A Winged Victory for the Sullen's "Steep Hills of Vicodin Tears" and The Wombats' "Give Me a Try". Vicodin use is a central theme in the 2004–2012 medical TV drama "House", in which the lead character Dr. Gregory House is addicted to it.

Brand names include "Adol" among others.

Paracetamol poisoning, also known as acetaminophen poisoning, is caused by excessive use of the medication paracetamol (acetaminophen). Most people have few or non-specific symptoms in the first 24 hours following overdose. This may include feeling tired, abdominal pain, or nausea. This is typically followed by a couple of days without any symptoms after which yellowish skin, blood clotting problems, and confusion occurs as a result of liver failure. Additional complications may include kidney failure, pancreatitis, low blood sugar, and lactic acidosis. If death does not occur, people tend to recover fully over a couple of weeks. Without treatment some cases will resolve while others will result in death.
Paracetamol poisoning can occur accidentally or as an attempt to end one's life. Risk factors for toxicity include alcoholism, malnutrition, and the taking of certain other medications. Liver damage results not from paracetamol itself, but from one of its metabolites, "N"-acetyl-"p"-benzoquinone imine (NAPQI). NAPQI decreases the liver's glutathione and directly damages cells in the liver. Diagnosis is based on the blood level of paracetamol at specific times after the medication was taken. These values are often plotted on the Rumack-Matthew nomogram to determine level of concern.
Treatment may include activated charcoal if the person presents soon after the overdose. Attempting to force the person to vomit is not recommended. If there is a potential for toxicity, the antidote acetylcysteine is recommended. The medication is generally given for at least 24 hours. Psychiatric care may be required following recovery. A liver transplant may be required if damage to the liver becomes severe. The need for transplant is often based on low blood pH, high blood lactate, poor blood clotting, or significant hepatic encephalopathy. With early treatment liver failure is rare. Death occurs in about 0.1% of cases.
Paracetamol poisoning was first described in the 1960s. Rates of poisoning vary significantly between regions of the world. In the United States more than 100,000 cases occur a year. In the United Kingdom it is the medication responsible for the greatest number of overdoses. Young children are most commonly affected. In the United States and the United Kingdom paracetamol is the most common cause of acute liver failure.

Paracetamol poisoning

The signs and symptoms of paracetamol toxicity occur in three phases. The first phase begins within hours of overdose, and consists of nausea, vomiting, a pale appearance, and sweating. However, patients often have no specific symptoms or only mild symptoms in the first 24 hours of poisoning. Rarely, after massive overdoses, patients may develop symptoms of metabolic acidosis and coma early in the course of poisoning.

The second phase occurs between 24 h and 72 h following overdose and consists of signs of increasing liver damage. In general, damage occurs in liver cells as they metabolize the paracetamol. The individual may experience right upper quadrant abdominal pain. The increasing liver damage also changes biochemical markers of liver function; International normalized ratio (INR) and the liver transaminases ALT and AST rise to abnormal levels. Acute kidney failure may also occur during this phase, typically caused by either hepatorenal syndrome or multiple organ dysfunction syndrome. In some cases, acute kidney failure may be the primary clinical manifestation of toxicity. In these cases, it has been suggested that the toxic metabolite is produced more in the kidneys than in the liver.

The third phase follows at 3 to 5 days, and is marked by complications of massive liver necrosis leading to fulminant liver failure with complications of coagulation defects, low blood sugar, kidney failure, hepatic encephalopathy, brain swelling, sepsis, multiple organ failure, and death. If the third phase is survived, the liver necrosis runs its course, and liver and kidney function typically return to normal in a few weeks. The severity of paracetamol toxicity varies depending on the dose and whether appropriate treatment is received.

The toxic dose of paracetamol is highly variable. In general the recommended maximum daily dose for healthy adults is 4 grams. Higher doses lead to increasing risk of toxicity. In adults, single doses above 10 grams or 200 mg/kg of bodyweight, whichever is lower, have a reasonable likelihood of causing toxicity. Toxicity can also occur when multiple smaller doses within 24 hours exceed these levels. Following a dose of 1 gram of paracetamol four times a day for two weeks, patients can expect an increase in alanine transaminase in their liver to typically about three times the normal value. It is unlikely that this dose would lead to liver failure. Studies have shown significant hepatotoxicity is uncommon in patients who have taken greater than normal doses over 3 to 4 days. In adults, a dose of 6 grams a day over the preceding 48 hours could potentially lead to toxicity, while in children acute doses above 200 mg/kg could potentially cause toxicity. Acute paracetamol overdose in children rarely causes illness or death, and it is very uncommon for children to have levels that require treatment, with chronic larger-than-normal doses being the major cause of toxicity in children.

Intentional overdosing (self-poisoning, with suicidal intent) is frequently implicated in paracetamol toxicity. In a 2006 review, paracetamol was the most frequently ingested compound in intentional overdosing.

In rare individuals, paracetamol toxicity can result from normal use. This may be due to individual ("idiosyncratic") differences in the expression and activity of certain enzymes in one of the metabolic pathways that handle paracetamol (see paracetamol's metabolism).

A number of factors can potentially increase the risk of developing paracetamol toxicity. Chronic excessive alcohol consumption can induce CYP2E1, thus increasing the potential toxicity of paracetamol. In one study of patients with liver injury, 64% reported alcohol intakes of greater than 80 grams a day, while 35% took 60 grams a day or less. Whether chronic alcoholism should be considered a risk factor has been debated by some clinical toxicologists. For chronic alcohol users, acute alcohol ingestion at the time of a paracetamol overdose may have a protective effect. For non-chronic alcohol users, acute alcohol consumption had no protective effect.

Fasting is a risk factor, possibly because of depletion of liver glutathione reserves. The concomitant use of the CYP2E1 inhibitor isoniazid increases the risk of hepatotoxicity, though whether 2E1 induction is related to the hepatotoxicity in this case is unclear. Concomitant use of other drugs that induce CYP enzymes, such as antiepileptics including carbamazepine, phenytoin, and barbiturates, have also been reported as risk factors.

When taken in normal therapeutic doses, paracetamol has been shown to be safe. Following a therapeutic dose, it is mostly converted to nontoxic metabolites via Phase II metabolism by conjugation with sulfate and glucuronide, with a small portion being oxidized via the cytochrome P450 enzyme system. Cytochromes and 3A4 convert approximately 5% of paracetamol to a highly reactive intermediary metabolite, "N"-acetyl-"p"-benzoquinone imine (NAPQI). Under normal conditions, NAPQI is detoxified by conjugation with glutathione to form cysteine and mercapturic acid conjugates.

In cases of paracetamol overdose, the sulfate and glucuronide pathways become saturated, and more paracetamol is shunted to the cytochrome P450 system to produce NAPQI. As a result, hepatocellular supplies of glutathione become depleted, as the demand for glutathione is higher than its regeneration. NAPQI therefore remains in its toxic form in the liver and reacts with cellular membrane molecules, resulting in widespread hepatocyte damage and death, leading to acute liver necrosis. In animal studies, the liver's stores of glutathione must be depleted to less than 70% of normal levels before liver toxicity occurs.

A person's history of taking paracetamol is somewhat accurate for the diagnosis. The most effective way to diagnose poisoning is by obtaining a blood paracetamol level. A drug nomogram developed in 1975, called the Rumack-Matthew nomogram, estimates the risk of toxicity based on the serum concentration of paracetamol at a given number of hours after ingestion. To determine the risk of potential hepatotoxicity, the paracetamol level is traced along the nomogram. Use of a timed serum paracetamol level plotted on the nomogram appears to be the best marker indicating the potential for liver injury. A paracetamol level drawn in the first four hours after ingestion may underestimate the amount in the system because paracetamol may still be in the process of being absorbed from the gastrointestinal tract. Therefore, a serum level taken before 4 hours is not recommended.

Clinical or biochemical evidence of liver toxicity may develop in one to four days, although, in severe cases, it may be evident in 12 hours. Right-upper-quadrant tenderness may be present and can aid in diagnosis. Laboratory studies may show evidence of liver necrosis with elevated AST, ALT, bilirubin, and prolonged coagulation times, particularly an elevated prothrombin time. After paracetamol overdose, when AST and ALT exceed 1000 IU/L, paracetamol-induced hepatotoxicity can be diagnosed. In some cases, the AST and ALT levels can exceed 10,000 IU/L.

Paracetamol may be quantified in blood, plasma, or urine as a diagnostic tool in clinical poisoning situations or to aid in the medicolegal investigation of suspicious deaths. The concentration in serum after a typical dose of paracetamol usually peaks below 30 mg/l, which equals 200 µmol/L. Levels of 30–300 mg/L (200–2000 µmol/L) are often observed in overdose patients. Postmortem blood levels have ranged from 50–400 mg/L in persons dying due to acute overdosage. Automated colorimetric techniques, gas chromatography and liquid chromatography are currently in use for the laboratory analysis of the drug in physiological specimens.

Limiting the availability of paracetamol tablets has been attempted in some countries. In the UK, sales of over-the-counter paracetamol are restricted to packs of 32 x 500 mg tablets in pharmacies, and 16 x 500 mg tablets in non-pharmacy outlets. Pharmacists may provide up to 100 tablets for those with chronic conditions at the pharmacist's discretion. In Ireland, the limits are 24 and 12 tablets, respectively. Subsequent study suggests that the reduced availability in large numbers had a significant effect in reducing poisoning deaths from paracetamol overdose.

One suggested method of prevention is to make paracetamol a prescription-only medicine, or to remove it entirely from the market. However, overdose is a relatively minor problem; for example, 0.08% of the UK population (over 50 thousand people) present with paracetamol overdose each year. In contrast, paracetamol is a safe and effective medication that is taken without complications by millions of people. In addition, alternative pain relief medications such as aspirin are more toxic in overdose, whereas non-steroidal anti-inflammatory drugs are associated with more adverse effects following normal use.

One strategy for reducing harm done by acetaminophen overdoses is selling paracetamol pre-combined in tablets either with an emetic or an antidote. Paradote was a tablet sold in the UK which combined 500 mg paracetamol with 100 mg methionine, an amino acid formerly used in the treatment of paracetamol overdose.

There have been no studies so far on the effectiveness of paracetamol when given in combination with its most commonly used antidote, acetylcysteine.

Calcitriol, the active metabolite of vitamin D, appears to be a catalyst for glutathione production. Calcitriol was found to increase glutathione levels in rat astrocyte primary cultures on average by 42%, increasing glutathione protein concentrations from 29 nmol/mg to 41 nmol/mg, 24 and 48 hours after administration; it continued to have an influence on glutathione levels 96 hours after administration. It has been proposed that co-administration of calcitriol, via injection, may improve treatment outcomes.

Paracetamol ester prodrug with L-pyroglutamic acid (PCA), a biosynthetic precursor of glutathione, has been synthesized to reduce paracetamol hepatotoxicity and improve bioavailability. The toxicological studies of different paracetamol esters show that L-5-oxo-pyrrolidine-2-paracetamol carboxylate reduces toxicity after administration of an overdose of paracetamol to mice. The liver glutathione values in mice induced by intraperitoneal injection of the ester are superimposable with the GSH levels recorded in untreated mice control group. The mice group treated with an equivalent dose of paracetamol showed a significative decrease of glutathione of 35% (p<0.01 vs untreated control group). The oral LD50 was found to be greater than 2000 mg kg-1, whereas the intraperitoneal LD50 was 1900 mg kg-1. These results taken together with the good hydrolysis and bioavailability data show that this ester is a potential candidate as a prodrug of paracetamol.

In adults, the initial treatment for paracetamol overdose is gastrointestinal decontamination. Paracetamol absorption from the gastrointestinal tract is complete within two hours under normal circumstances, so decontamination is most helpful if performed within this timeframe. Gastric lavage, better known as stomach pumping, may be considered if the amount ingested is potentially life-threatening and the procedure can be performed within 60 minutes of ingestion. Activated charcoal is the most common gastrointestinal decontamination procedure as it adsorbs paracetamol, reducing its gastrointestinal absorption. Administering activated charcoal also poses less risk of aspiration than gastric lavage.

It appears that the most benefit from activated charcoal is gained if it is given within 30 minutes to two hours of ingestion. Administering activated charcoal later than 2 hours can be considered in patients that may have delayed gastric emptying due to co-ingested drugs or following ingestion of sustained- or delayed-release paracetamol preparations. Activated charcoal should also be administered if co-ingested drugs warrant decontamination. There was reluctance to give activated charcoal in paracetamol overdose, because of the concern that it may also absorb the oral antidote acetylcysteine. Studies have shown that 39% less acetylcysteine is absorbed into the body when they are administered together. There are conflicting recommendations regarding whether to change the dosing of oral acetylcysteine after the administration of activated charcoal, and even whether the dosing of acetylcysteine needs to be altered at all. Intravenous acetylcystine has no interaction with activated charcoal.

Inducing vomiting with syrup of ipecac has no role in paracetamol overdose because the vomiting it induces delays the effective administration of activated charcoal and oral acetylcysteine. Liver injury is extremely rare after acute accidental ingestion in children under 6 years of age. Children with accidental exposures do not require gastrointestinal decontamination with either gastric lavage, activated charcoal, or syrup of ipecac.

Acetylcysteine, also called "N"-acetylcysteine or NAC, works to reduce paracetamol toxicity by replenishing body stores of the antioxidant glutathione. Glutathione reacts with the toxic NAPQI metabolite so that it does not damage cells and can be safely excreted. NAC was usually given following a treatment nomogram (one for patients with risk factors, and one for those without) but the use of the nomogram is no longer recommended as the evidence base to support the use of risk factors was poor and inconsistent and many of the risk factors are imprecise and difficult to determine with sufficient certainty in clinical practice. Cysteamine and methionine have also been used to prevent hepatotoxicity, although studies show that both are associated with more adverse effects than acetylcysteine. Additionally, acetylcysteine has been shown to be a more effective antidote, particularly in patients presenting greater than 8 hours post-ingestion and for those who present with liver failure symptoms.

If the person presents less than eight hours after paracetamol overdose, then acetylcysteine significantly reduces the risk of serious hepatotoxicity and guarantees survival. If acetylcysteine is started more than 8 hours after ingestion, there is a sharp decline in its effectiveness because the cascade of toxic events in the liver has already begun, and the risk of acute liver necrosis and death increases dramatically. Although acetylcysteine is most effective if given early, it still has beneficial effects if given as late as 48 hours after ingestion. If the person presents more than eight hours after the paracetamol overdose, then activated charcoal is not useful, and acetylcysteine is started immediately. In earlier presentations, charcoal can be given when the patient arrives and acetylcysteine is initiated while waiting for the paracetamol level results to return from the laboratory.

In United States practice, intravenous (IV) and oral administration are considered to be equally effective and safe if given within 8 hours of ingestion. However, IV is the only recommended route in Australasian and British practice. Oral acetylcysteine is given as a 140 mg/kg loading dose followed by 70 mg/kg every four hours for 17 more doses, and if the patient vomits within 1 hour of dose, the dose must be repeated. Oral acetylcysteine may be poorly tolerated due to its unpleasant taste, odor, and its tendency to cause nausea and vomiting. If repeated doses of charcoal are indicated because of another ingested drug, then subsequent doses of charcoal and acetylcysteine should be staggered.

Intravenous acetylcysteine is given as a continuous infusion over 20 hours for a total dose 300 mg/kg. Recommended administration involves infusion of a 150 mg/kg loading dose over 15 to 60 minutes, followed by a 50 mg/kg infusion over four hours; the last 100 mg/kg are infused over the remaining 16 hours of the protocol. Intravenous acetylcysteine has the advantage of shortening hospital stay, increasing both doctor and patient convenience, and allowing administration of activated charcoal to reduce absorption of both the paracetamol and any co-ingested drugs without concerns about interference with oral acetylcysteine. Intravenous dosing varies with weight, specifically in children. For patients less than 20 kg, the loading dose is 150 mg/kg in 3 mL/kg diluent, administered over 60 minutes; the second dose is 50 mg/kg in 7 mL/kg diluent over 4 hours; and the third and final dose is 100 mg/kg in 14 mL/kg diluent over 16 hours.

The most common adverse effect to acetylcysteine treatment is an anaphylactoid reaction, usually manifested by rash, wheeze, or mild hypotension. Adverse reactions are more common in people treated with IV acetylcysteine, occurring in up to 20% of patients. Anaphylactoid reactions are more likely to occur with the first infusion (the loading dose). Rarely, severe life-threatening reactions may occur in predisposed individuals, such as patients with asthma or atopic dermatitis, and may be characterized by respiratory distress, facial swelling, and even death.

If an anaphylactoid reaction occurs the acetylcysteine is temporarily halted or slowed and antihistamines and other supportive care is administered. For example, a nebulised beta-agonist like salbutamol may be indicated in the event of significant bronchospasm (or prophylactically in patients with a history of bronchospasm secondary to acetylcysteine). It is also important to closely monitor fluids and electrolytes.

In people who develop acute liver failure or who are otherwise expected to die from liver failure, the mainstay of management is liver transplantation. Liver transplants are performed in specialist centers. The most commonly used criteria for liver transplant were developed by physicians at King's College Hospital in London. Patients are recommended for transplant if they have an arterial blood pH less than 7.3 after fluid resuscitation or if a patient has Grade III or IV encephalopathy, a prothrombin time greater than 100 seconds, and a serum creatinine greater than 300 mmol/L In a 24-hour period. Other forms of liver support have been used including partial liver transplants. These techniques have the advantage of supporting the patient while their own liver regenerates. Once liver function returns immunosuppressive drugs are commenced and they have to take immunosuppressive medication for the rest of their lives.

The mortality rate from paracetamol overdose increases two days after the ingestion, reaches a maximum on day four, and then gradually decreases. Acidosis is the most important single indicator of probable mortality and the need for transplantation. A mortality rate of 95% without transplant was reported in patients who had a documented pH less than 7.30. Other indicators of poor prognosis include renal insufficiency (stage 3 or worse), hepatic encephalopathy, a markedly elevated prothrombin time, or an elevated blood lactic acid level (lactic acidosis). One study has shown that a factor V level less than 10% of normal indicated a poor prognosis (91% mortality), whereas a ratio of factor VIII to factor V of less than 30 indicated a good prognosis (100% survival). Patients with a poor prognosis are usually identified for likely liver transplantation. Patients that do not die are expected to fully recover and have a normal life expectancy and quality of life.

Many over-the-counter and prescription-only medications contain paracetamol. Because of its wide availability paired with comparably high toxicity, (compared to ibuprofen and aspirin) there is a much higher potential for overdose. Paracetamol toxicity is one of the most common causes of poisoning worldwide. In the United States, the United Kingdom, Australia, and New Zealand, paracetamol is the most common cause of drug overdoses. Additionally, in both the United States and the United Kingdom it is the most common cause of acute liver failure.

In England and Wales an estimated 41,200 cases of paracetamol poisoning occurred in 1989 to 1990, with a mortality of 0.40%. It is estimated that 150 to 200 deaths and 15 to 20 liver transplants occur as a result of poisoning each year in England and Wales. Paracetamol overdose results in more calls to poison control centers in the US than overdose of any other pharmacological substance, accounting for more than 100,000 calls, as well as 56,000 emergency room visits, 2,600 hospitalizations, and 458 deaths due to acute liver failure per year. A study of cases of acute liver failure between November 2000 and October 2004 by the Centers for Disease Control and Prevention in the USA found that paracetamol was the cause of 41% of all cases in adults, and 25% of cases in children.

Paracetamol poisoning

The signs and symptoms of paracetamol toxicity occur in three phases. The first phase begins within hours of overdose, and consists of nausea, vomiting, a pale appearance, and sweating. However, patients often have no specific symptoms or only mild symptoms in the first 24 hours of poisoning. Rarely, after massive overdoses, patients may develop symptoms of metabolic acidosis and coma early in the course of poisoning.

The third phase follows at 3 to 5 days, and is marked by complications of massive liver necrosis leading to fulminant liver failure with complications of coagulation defects, low blood sugar, kidney failure, hepatic encephalopathy, brain swelling, sepsis, multiple organ failure, and death. If the third phase is survived, the liver necrosis runs its course, and liver and kidney function typically return to normal in a few weeks. The severity of paracetamol toxicity varies depending on the dose and whether appropriate treatment is received.

Intentional overdosing (self-poisoning, with suicidal intent) is frequently implicated in paracetamol toxicity. In a 2006 review, paracetamol was the most frequently ingested compound in intentional overdosing.

In rare individuals, paracetamol toxicity can result from normal use. This may be due to individual ("idiosyncratic") differences in the expression and activity of certain enzymes in one of the metabolic pathways that handle paracetamol (see paracetamol's metabolism).

Fasting is a risk factor, possibly because of depletion of liver glutathione reserves. The concomitant use of the CYP2E1 inhibitor isoniazid increases the risk of hepatotoxicity, though whether 2E1 induction is related to the hepatotoxicity in this case is unclear. Concomitant use of other drugs that induce CYP enzymes, such as antiepileptics including carbamazepine, phenytoin, and barbiturates, have also been reported as risk factors.

When taken in normal therapeutic doses, paracetamol has been shown to be safe. Following a therapeutic dose, it is mostly converted to nontoxic metabolites via Phase II metabolism by conjugation with sulfate and glucuronide, with a small portion being oxidized via the cytochrome P450 enzyme system. Cytochromes and 3A4 convert approximately 5% of paracetamol to a highly reactive intermediary metabolite, "N"-acetyl-"p"-benzoquinone imine (NAPQI). Under normal conditions, NAPQI is detoxified by conjugation with glutathione to form cysteine and mercapturic acid conjugates.

In cases of paracetamol overdose, the sulfate and glucuronide pathways become saturated, and more paracetamol is shunted to the cytochrome P450 system to produce NAPQI. As a result, hepatocellular supplies of glutathione become depleted, as the demand for glutathione is higher than its regeneration. NAPQI therefore remains in its toxic form in the liver and reacts with cellular membrane molecules, resulting in widespread hepatocyte damage and death, leading to acute liver necrosis. In animal studies, the liver's stores of glutathione must be depleted to less than 70% of normal levels before liver toxicity occurs.

Clinical or biochemical evidence of liver toxicity may develop in one to four days, although, in severe cases, it may be evident in 12 hours. Right-upper-quadrant tenderness may be present and can aid in diagnosis. Laboratory studies may show evidence of liver necrosis with elevated AST, ALT, bilirubin, and prolonged coagulation times, particularly an elevated prothrombin time. After paracetamol overdose, when AST and ALT exceed 1000 IU/L, paracetamol-induced hepatotoxicity can be diagnosed. In some cases, the AST and ALT levels can exceed 10,000 IU/L.

Paracetamol may be quantified in blood, plasma, or urine as a diagnostic tool in clinical poisoning situations or to aid in the medicolegal investigation of suspicious deaths. The concentration in serum after a typical dose of paracetamol usually peaks below 30 mg/l, which equals 200 µmol/L. Levels of 30–300 mg/L (200–2000 µmol/L) are often observed in overdose patients. Postmortem blood levels have ranged from 50–400 mg/L in persons dying due to acute overdosage. Automated colorimetric techniques, gas chromatography and liquid chromatography are currently in use for the laboratory analysis of the drug in physiological specimens.

Limiting the availability of paracetamol tablets has been attempted in some countries. In the UK, sales of over-the-counter paracetamol are restricted to packs of 32 x 500 mg tablets in pharmacies, and 16 x 500 mg tablets in non-pharmacy outlets. Pharmacists may provide up to 100 tablets for those with chronic conditions at the pharmacist's discretion. In Ireland, the limits are 24 and 12 tablets, respectively. Subsequent study suggests that the reduced availability in large numbers had a significant effect in reducing poisoning deaths from paracetamol overdose.

One suggested method of prevention is to make paracetamol a prescription-only medicine, or to remove it entirely from the market. However, overdose is a relatively minor problem; for example, 0.08% of the UK population (over 50 thousand people) present with paracetamol overdose each year. In contrast, paracetamol is a safe and effective medication that is taken without complications by millions of people. In addition, alternative pain relief medications such as aspirin are more toxic in overdose, whereas non-steroidal anti-inflammatory drugs are associated with more adverse effects following normal use.

One strategy for reducing harm done by acetaminophen overdoses is selling paracetamol pre-combined in tablets either with an emetic or an antidote. Paradote was a tablet sold in the UK which combined 500 mg paracetamol with 100 mg methionine, an amino acid formerly used in the treatment of paracetamol overdose.

There have been no studies so far on the effectiveness of paracetamol when given in combination with its most commonly used antidote, acetylcysteine.

Calcitriol, the active metabolite of vitamin D, appears to be a catalyst for glutathione production. Calcitriol was found to increase glutathione levels in rat astrocyte primary cultures on average by 42%, increasing glutathione protein concentrations from 29 nmol/mg to 41 nmol/mg, 24 and 48 hours after administration; it continued to have an influence on glutathione levels 96 hours after administration. It has been proposed that co-administration of calcitriol, via injection, may improve treatment outcomes.

Inducing vomiting with syrup of ipecac has no role in paracetamol overdose because the vomiting it induces delays the effective administration of activated charcoal and oral acetylcysteine. Liver injury is extremely rare after acute accidental ingestion in children under 6 years of age. Children with accidental exposures do not require gastrointestinal decontamination with either gastric lavage, activated charcoal, or syrup of ipecac.

The most common adverse effect to acetylcysteine treatment is an anaphylactoid reaction, usually manifested by rash, wheeze, or mild hypotension. Adverse reactions are more common in people treated with IV acetylcysteine, occurring in up to 20% of patients. Anaphylactoid reactions are more likely to occur with the first infusion (the loading dose). Rarely, severe life-threatening reactions may occur in predisposed individuals, such as patients with asthma or atopic dermatitis, and may be characterized by respiratory distress, facial swelling, and even death.

If an anaphylactoid reaction occurs the acetylcysteine is temporarily halted or slowed and antihistamines and other supportive care is administered. For example, a nebulised beta-agonist like salbutamol may be indicated in the event of significant bronchospasm (or prophylactically in patients with a history of bronchospasm secondary to acetylcysteine). It is also important to closely monitor fluids and electrolytes.

Many over-the-counter and prescription-only medications contain paracetamol. Because of its wide availability paired with comparably high toxicity, (compared to ibuprofen and aspirin) there is a much higher potential for overdose. Paracetamol toxicity is one of the most common causes of poisoning worldwide. In the United States, the United Kingdom, Australia, and New Zealand, paracetamol is the most common cause of drug overdoses. Additionally, in both the United States and the United Kingdom it is the most common cause of acute liver failure.

Paracetamol poisoning

The signs and symptoms of paracetamol toxicity occur in three phases. The first phase begins within hours of overdose, and consists of nausea, vomiting, a pale appearance, and sweating. However, patients often have no specific symptoms or only mild symptoms in the first 24 hours of poisoning. Rarely, after massive overdoses, patients may develop symptoms of metabolic acidosis and coma early in the course of poisoning.

The third phase follows at 3 to 5 days, and is marked by complications of massive liver necrosis leading to fulminant liver failure with complications of coagulation defects, low blood sugar, kidney failure, hepatic encephalopathy, brain swelling, sepsis, multiple organ failure, and death. If the third phase is survived, the liver necrosis runs its course, and liver and kidney function typically return to normal in a few weeks. The severity of paracetamol toxicity varies depending on the dose and whether appropriate treatment is received.

Intentional overdosing (self-poisoning, with suicidal intent) is frequently implicated in paracetamol toxicity. In a 2006 review, paracetamol was the most frequently ingested compound in intentional overdosing.

In rare individuals, paracetamol toxicity can result from normal use. This may be due to individual ("idiosyncratic") differences in the expression and activity of certain enzymes in one of the metabolic pathways that handle paracetamol (see paracetamol's metabolism).

A number of factors can potentially increase the risk of developing paracetamol toxicity. Chronic excessive alcohol consumption can induce CYP2E1, thus increasing the potential toxicity of paracetamol. In one study of patients with liver injury, 64% reported alcohol intakes of greater than 80 grams a day, while 35% took 60 grams a day or less. Whether chronic alcoholism should be considered a risk factor has been debated by some clinical toxicologists. For chronic alcohol users, acute alcohol ingestion at the time of a paracetamol overdose may have a protective effect. For non-chronic alcohol users, acute alcohol consumption had no protective effect.

Fasting is a risk factor, possibly because of depletion of liver glutathione reserves. The concomitant use of the CYP2E1 inhibitor isoniazid increases the risk of hepatotoxicity, though whether 2E1 induction is related to the hepatotoxicity in this case is unclear. Concomitant use of other drugs that induce CYP enzymes, such as antiepileptics including carbamazepine, phenytoin, and barbiturates, have also been reported as risk factors.

When taken in normal therapeutic doses, paracetamol has been shown to be safe. Following a therapeutic dose, it is mostly converted to nontoxic metabolites via Phase II metabolism by conjugation with sulfate and glucuronide, with a small portion being oxidized via the cytochrome P450 enzyme system. Cytochromes and 3A4 convert approximately 5% of paracetamol to a highly reactive intermediary metabolite, "N"-acetyl-"p"-benzoquinone imine (NAPQI). Under normal conditions, NAPQI is detoxified by conjugation with glutathione to form cysteine and mercapturic acid conjugates.

In cases of paracetamol overdose, the sulfate and glucuronide pathways become saturated, and more paracetamol is shunted to the cytochrome P450 system to produce NAPQI. As a result, hepatocellular supplies of glutathione become depleted, as the demand for glutathione is higher than its regeneration. NAPQI therefore remains in its toxic form in the liver and reacts with cellular membrane molecules, resulting in widespread hepatocyte damage and death, leading to acute liver necrosis. In animal studies, the liver's stores of glutathione must be depleted to less than 70% of normal levels before liver toxicity occurs.

Clinical or biochemical evidence of liver toxicity may develop in one to four days, although, in severe cases, it may be evident in 12 hours. Right-upper-quadrant tenderness may be present and can aid in diagnosis. Laboratory studies may show evidence of liver necrosis with elevated AST, ALT, bilirubin, and prolonged coagulation times, particularly an elevated prothrombin time. After paracetamol overdose, when AST and ALT exceed 1000 IU/L, paracetamol-induced hepatotoxicity can be diagnosed. In some cases, the AST and ALT levels can exceed 10,000 IU/L.

Paracetamol may be quantified in blood, plasma, or urine as a diagnostic tool in clinical poisoning situations or to aid in the medicolegal investigation of suspicious deaths. The concentration in serum after a typical dose of paracetamol usually peaks below 30 mg/l, which equals 200 µmol/L. Levels of 30–300 mg/L (200–2000 µmol/L) are often observed in overdose patients. Postmortem blood levels have ranged from 50–400 mg/L in persons dying due to acute overdosage. Automated colorimetric techniques, gas chromatography and liquid chromatography are currently in use for the laboratory analysis of the drug in physiological specimens.

Limiting the availability of paracetamol tablets has been attempted in some countries. In the UK, sales of over-the-counter paracetamol are restricted to packs of 32 x 500 mg tablets in pharmacies, and 16 x 500 mg tablets in non-pharmacy outlets. Pharmacists may provide up to 100 tablets for those with chronic conditions at the pharmacist's discretion. In Ireland, the limits are 24 and 12 tablets, respectively. Subsequent study suggests that the reduced availability in large numbers had a significant effect in reducing poisoning deaths from paracetamol overdose.

One suggested method of prevention is to make paracetamol a prescription-only medicine, or to remove it entirely from the market. However, overdose is a relatively minor problem; for example, 0.08% of the UK population (over 50 thousand people) present with paracetamol overdose each year. In contrast, paracetamol is a safe and effective medication that is taken without complications by millions of people. In addition, alternative pain relief medications such as aspirin are more toxic in overdose, whereas non-steroidal anti-inflammatory drugs are associated with more adverse effects following normal use.

One strategy for reducing harm done by acetaminophen overdoses is selling paracetamol pre-combined in tablets either with an emetic or an antidote. Paradote was a tablet sold in the UK which combined 500 mg paracetamol with 100 mg methionine, an amino acid formerly used in the treatment of paracetamol overdose.

There have been no studies so far on the effectiveness of paracetamol when given in combination with its most commonly used antidote, acetylcysteine.

Calcitriol, the active metabolite of vitamin D, appears to be a catalyst for glutathione production. Calcitriol was found to increase glutathione levels in rat astrocyte primary cultures on average by 42%, increasing glutathione protein concentrations from 29 nmol/mg to 41 nmol/mg, 24 and 48 hours after administration; it continued to have an influence on glutathione levels 96 hours after administration. It has been proposed that co-administration of calcitriol, via injection, may improve treatment outcomes.

Inducing vomiting with syrup of ipecac has no role in paracetamol overdose because the vomiting it induces delays the effective administration of activated charcoal and oral acetylcysteine. Liver injury is extremely rare after acute accidental ingestion in children under 6 years of age. Children with accidental exposures do not require gastrointestinal decontamination with either gastric lavage, activated charcoal, or syrup of ipecac.

The most common adverse effect to acetylcysteine treatment is an anaphylactoid reaction, usually manifested by rash, wheeze, or mild hypotension. Adverse reactions are more common in people treated with IV acetylcysteine, occurring in up to 20% of patients. Anaphylactoid reactions are more likely to occur with the first infusion (the loading dose). Rarely, severe life-threatening reactions may occur in predisposed individuals, such as patients with asthma or atopic dermatitis, and may be characterized by respiratory distress, facial swelling, and even death.

If an anaphylactoid reaction occurs the acetylcysteine is temporarily halted or slowed and antihistamines and other supportive care is administered. For example, a nebulised beta-agonist like salbutamol may be indicated in the event of significant bronchospasm (or prophylactically in patients with a history of bronchospasm secondary to acetylcysteine). It is also important to closely monitor fluids and electrolytes.

Many over-the-counter and prescription-only medications contain paracetamol. Because of its wide availability paired with comparably high toxicity, (compared to ibuprofen and aspirin) there is a much higher potential for overdose. Paracetamol toxicity is one of the most common causes of poisoning worldwide. In the United States, the United Kingdom, Australia, and New Zealand, paracetamol is the most common cause of drug overdoses. Additionally, in both the United States and the United Kingdom it is the most common cause of acute liver failure.

Some common household chemicals are particularly dangerous to dogs:Poisoning with pain medications is common. Aspirin, paracetamol (acetaminophen, Tylenol), ibuprofen (Advil), and naproxen (Aleve) can all cause severe clinical signs in dogs, including vomiting blood, diarrhea, and abdominal pain. Specifically, aspirin can cause metabolic acidosis and bleeding disorders, acetaminophen can cause liver disease, ibuprofen can cause kidney disease, and naproxen can cause ulcers in the stomach, which can perforate. Treatment depends on the clinical signs.

Dog health

The health of dogs is a well studied area in veterinary medicine.

Infectious diseases that affect dogs are important not only from a veterinary standpoint, but also because of the risk to public health; an example of this is rabies. Genetic disorders also affect dogs, often due to selective breeding to produce individual dog breeds. Due to the popularity of both commercial and homemade dog foods, nutrition is also a heavily studied subject.

Some diseases and other health problems are common to both humans and dogs; others are unique to dogs and other animals. Dogs are susceptible to various diseases; similarly to humans, they can have diabetes, epilepsy, cancer, or arthritis.

Dogs are prone to a number of diseases which affect them and at the same time their owners. A pet in pain is one of the most painful images to see. There are certain ways, through which these diseases can be minimized and the pain that the breed goes through reduced. One of the best ways to do this is to get an early knowledge of the disease, recognize its symptoms early on so that treatment can begin early which may save the breed from a lot of trouble. Effective weight management and a balanced diet also go a long way in preventing diseases. Some of the diseases to watch out for are listed below-

1- Canine Distemper – Canine distemper is a kind of virus infection which doesn't carry with it, a cure. It is contagious in nature and can be very harmful for the specie. This virus attacks puppies who are young and haven't got the vaccination yet. Older dogs who weren't vaccinated are also susceptible to this illness. This virus is contagious and can spread through air or infected utensils in the breed. Generally contact with an infected animal also leads to the spread of the disease. The infection starts from the lymph nodes and spreads to the respiratory organs of the breed. The initial symptoms of this disease would be high temperature, coughing, and wheezing, red eyes. The dog will appear extremely tired and exhausted. In the later stages the nervous system of the dog gets affected, there can be fits, seizures etc. This disease can lead to demise also, generally in a period between 2–5 weeks of the virus's infection. A vaccinated breed is generally prevented from this outbreak. A combination of Biochemical tests and Urine tests are done to diagnose this disease.

2- Kennel Cough – The early symptoms of Kennel cough is endless coughing and the sound that the dog might be choking on something. Kennel cough is not a life-threatening disease but it can be extremely painful for the breed. It is treatable and a number of times the pet recovers without medication. There are several reasons why your breed may develop kennel cough, but the most reoccurring reason is the presence of this bacterium called Bordetella bronchiseptica. Generally, the inhalation of this bacteria leads to an infection in the windpipe of the breed which leads to inflation. There are some causes which are predominant in making a breed susceptible to Kennel cough they are cold temperatures, stress which happens due to travelling too much, crowded places and inhalation of cigarette and other kind of smoke. Generally dogs who suffer from Kennel cough have coughing fits and likes but will not have decreased energy levels or anything like that. This condition is contagious and can spread from one breed to the other, It is important to keep other pets away from the one suffering from Kennel cough. This one doesn't treatment but pneumonia can happen after kennel cough so regular monitoring should be done of the breed suffering from Kennel cough.

3- Canine Corona Virus – Corona Virus is a kind of intestinal infection that affects breeds across the world. This disease when stands alone is not that harmful to the pet but in case it occurs with other intestinal issues, it can prove to be fatal for the specie if not treated properly. In case of adult dogs, the symptoms might appear to be nonexistent. In case of other younger puppies there are some apparent symptoms like vomiting, diarrhea and in later stages anorexia and depression are also there. There is a lot of dehydration also when this virus hits. In small puppies if there is severe infection in the intestine, it may also result in death. The causing agent of this is called Canine Corona virus which may come from the infected specie. Other causes of this infection can be dogs present in overcrowded places, un sanitary conditions and stress because of too intense training. Generally a couple of tests are done to determine the cause of this infection and treated thereof. There is a vaccine available which may help prevent the specie from contracting this disease but other than that the owner should check regularly for fleeces in the specie.

4- Canine Parvo Virus – Parvo is one the diseases which dog owners need to be most careful about especially in young puppies. This is a gastro intestinal illness which if not treated properly can prove fatal for the dog. This virus spreads very fast in dog population, it is contagious and spreads through fleeces or through contact with someone who is carrying this disease. Young puppies who are between six and eight weeks are most prone to this disease especially if they haven't got vaccination yet. It is very important to get a vaccination against this virus as they can prove to be very dangerous. There are certain symptoms which show in dogs suggesting of Parvo Virus – these are diarrhea, lethargy, anorexia, fever, weight loss, vomiting etc. if the dog suffers from any of these, a Vet should be consulted immediately and steps should be taken towards the treatment of the dog. If the dog is diagnosed with Canine Parvo Virus, the breed will require intensive care with hospitalization of the breed. It is important that the breed gets diagnosed with this in the early stages before the infection has the capacity to get worse.

5- Hip Dysplasia – This is a condition in which there is deformity in the hip joint of the specie, it generally affects larger breeds. In this the body of the femur may not fit properly into the hip socket. It is a genetic condition mostly and is very common in Golden Retrievers, German Shepherds, Labs, Rottweilers etc. This can also occur due to excessive weight gain, poor diet and lack of exercise. There are certain symptoms of this condition including uneven gait, difficulty in standing and running etc.

An infectious disease is caused by the presence of organisms such as viruses, bacteria, fungi, or parasites (either animalian or protozoan). Most of these diseases are spread directly from dog to dog, while others require a vector such as a tick or mosquito. Certain infectious diseases are a concern from a public health standpoint because they are zoonoses (transmittable to humans).

Viral diseases in dogs can be serious, especially in kennels. Timely vaccination can reduce the risk and severity of an infection. The most commonly recommended viruses to vaccinate dogs against are:Kennel cough is a respiratory infection that can be easily transmitted from one dog to another. Symptoms include runny nose and loss of appetite. This disease can be prevented by vaccination.

Other canine viral diseases of note include herpesvirus and influenza.

Bacterial diseases in dogs are usually not contagious from dog to dog; instead they are usually the result of wound colonization, opportunistic infections secondary to decreased resistance (often the result of viral infections), or secondary to other conditions (pyoderma secondary to skin allergies or pyometra secondary to cystic endometrial hyperplasia). These examples are not considered infectious diseases because they do not satisfy Koch's postulates - for example "Staphylococcus intermedius", a commonly isolated bacteria from skin infections in dogs, would not cause pyoderma when introduced to a healthy dog. In all likelihood that type of bacteria is already present on the skin of a healthy dog.

There are some bacteria that are contagious from dog to dog. The most notable of these are "Bordetella bronchiseptica", one of the causes of kennel cough, "Leptospira" sp, which cause leptospirosis, and "Brucella canis", cause of brucellosis in dogs. There are also common tick-borne bacterial diseases, including Lyme disease, ehrlichiosis, and Rocky Mountain spotted fever.

Leptospirosis is a zoonotic disease caused by bacteria of the genus "Leptospira". Humans and dogs become infected through contact with water, food, or soil containing urine from infected animals. This may happen by swallowing contaminated food or water or through skin contact, especially with mucosal surfaces, such as the eyes or nose, or with broken skin. In dogs, transmission most commonly occurs by drinking puddle, pond, or ditch water contaminated by urine from infected wildlife such as squirrels or raccoons. The liver and kidney are most commonly damaged by leptospirosis. Vasculitis can occur, causing edema and potentially disseminated intravascular coagulation (DIC). Myocarditis, pericarditis, meningitis, and uveitis are also possible sequelae.
Brucellosis in dogs is caused by "Brucella canis". It is a sexually transmitted disease, but can also be spread through contact with aborted fetuses. The most common sign is abortion during the last trimester or stillbirth. Other symptoms include inflammation of the intervertebral disc and eye (uveitis), and inflammation of the testicle (orchitis) and prostate (prostatitis) in males.

Tick-borne diseases are common in dogs. Lyme disease, or borreliosis, is caused by "Borrelia burgdorferi" and spread by "Ixodes pacificus" on the West coast of the United States and by "I. scapularis" (deer tick) in the rest of the U.S. Signs and symptoms include fever, joint swelling and pain, lameness, and swelling of the lymph nodes. It has been diagnosed in dogs in all 48 states of the continental U.S. "Ehrlichia canis", which causes canine ehrlichiosis, and "Rickettsia rickettsii", which causes Rocky Mountain spotted fever, are both spread by the American dog tick, "Dermacentor variabilis", and the brown dog tick, "Rhipicephalus sanguineous".

One of the most common fungal diseases in dogs is ringworm, or dermatophytosis, an infection of the skin, hair, or nails. There are three fungal species that cause ringworm in dogs. About 70 percent of infections are caused by "Microsporum canis", 20 percent by "M. gypseum", and 10 percent by "Trichophyton mentagrophytes". Signs include hair loss and scaling of the skin. Treatment for localized ringworm is not always necessary as the disease is self-limiting, but the cliinical course can be shortened by using topical miconazole or clotrimazole. Generalized infections, most commonly seen in immunocompromised dogs, can be treated with oral antifungal drugs such as griseofulvin or itraconazole. Infection can spread to humans.
There are several fungal diseases that are systemic in nature, meaning they are affecting multiple body systems. Blastomycosis, caused by "Blastomyces dermatitidis", is a fungal disease that affects both dogs and humans, although it is only rarely zoonotic. It is found mainly in the United States in the Mississippi River and Great Lakes areas. It has also been reported in four Canadian provinces; Saskatchewan, Manitoba, Ontario and Quebec. Signs include weight loss, cough, fever, enlarged lymph nodes, draining skin lesions, eye inflammation with discharge, blindness, and lameness. Because dogs are ten times more likely to become infected from the environment than humans, they are considered to be sentinels for the disease. Treatment requires a minimum 60-90 day course of oral antifungal medication or in severe cases intravenous antifungal injections.

Histoplasmosis, caused by "Histoplasma capsulatum", is a disease with a worldwide distribution. In the United States it is mainly found in the Mississippi and Ohio River areas, most commonly in bird and bat feces. Signs include weight loss, cough, fever, enlarged lymph nodes, and gastrointestinal symptoms. Coccidioidomycosis, caused by "Coccidioides immitis", is found in arid and semi-arid regions of Central and South America, Mexico, and southwestern United States. Signs include weight loss, fever, cough, enlarged lymph nodes, and lameness.

Veterinary parasitology studies both external and internal parasites in animals. External parasites, such as fleas, mites, ticks and mosquitoes can cause skin irritation and are often carriers of other diseases or of internal parasites.
Genetic conditions are a problem in some dogs, particularly purebreeds. For this reason many of the national kennel clubs require that dogs with certain genetic illnesses or who are deemed to be carriers cannot be registered. Some of the most common conditions include hip dysplasia, seen in large breed dogs, von Willebrand disease, a disease that affects platelets that is inherited in Doberman Pinschers, entropion, a curling in of the eyelid seen in Shar Peis and many other breeds, progressive retinal atrophy, inherited in many breeds, deafness, and epilepsy, known to be inherited in Belgian Shepherd Dogs, German Shepherd Dogs, Cocker Spaniels, and St. Bernards.

Subaortic stenosis, or SAS, is a genetic ailment that causes a narrowing of the passage of blood between the heart and the aorta. This leads to heart problems and sometimes sudden death. It affects larger breeds such as the Newfoundland Dog and the Golden Retriever. In some dogs, such as collies, the blue merle or harlequin coloring is actually the heterozygote of a partially recessive gene preventing proper development of the nervous system; therefore, if two such dogs are mated, on the average one quarter of the puppies will have severe genetic defects in their nervous systems and sensory organs ranging from deafness to fatal flaws.

Skin diseases are very common in dogs. Atopy, a chronic allergic condition, is thought to affect up to 10 percent of dogs. Other skin diseases related to allergies include hot spots and pyoderma, both characterized by secondary bacterial infections, food allergy, ear infections, and flea allergy dermatitis. Canine follicular dysplasia is an inherited disorder of the hair follicles resulting in alopecia (baldness). Mange is an infectious skin disease caused by mites. Endocrine diseases such as hypothyroidism and Cushing's syndrome can also manifest as skin problems like alopecia or recurring bacterial infections. Another class of integumentary malady is hygromas, a swelling typically on or near the elbow joint. Nutrition may also play a role in skin disease, as deficiencies in certain nutrients may result in scaling, redness, oiling, balding, and/or itching of the skin.(See dog skin disorders for specific nutrients that impacts skin)

Physical elements of certain dog breeds also affect susceptibility of individuals to skin problems, such as wrinkled skin or excessive skin folds. For instance, skin-fold dermatitis is a skin infection more prevalent in breeds such as the bulldog, cocker spaniel, and English Springer spaniel.

Orthopedic diseases in dogs can be developmental, hereditary, traumatic, or degenerative. Because of the active nature of dogs, injuries happen frequently. One of the most common of these is an anterior cruciate ligament injury, a condition which often requires surgery. Bone fractures are a frequent occurrence in outdoor dogs due to trauma from being hit by cars. Degenerative joint disease is common in older dogs and is one of the most likely reasons for prescription of non-steroidal anti-inflammatory drugs.

Hereditary orthopedic diseases are mainly found in purebred dogs. Hip dysplasia is a common problem that primarily affects larger breeds. Hip dysplasia is a defect in the shape of the hip joint which can, depending on the degree of hip luxation, be quite painful to the dog as it ages. Over time it often causes arthritis in the hips. Dysplasia can also occur in the elbow joint. Luxating patellas can be a problem for smaller breeds. It can cause lameness and pain in the hind legs.

Developmental orthopedic diseases include panosteitis and hypertrophic osteodystrophy. Panosteitis occurs in large and giant breed dogs usually between the age of five and fourteen months and manifests as fever, pain, and shifting leg lameness. Hypertrophic osteodystrophy is also seen in young large and giant breed dogs and is characterized by pain, lameness, fever, and swelling of the long bone metaphysis.

Both benign and malignant tumors are seen in dogs. Common benign tumors include lipomas, non-viral papillomas, sebaceous gland adenoma, and perianal gland adenomas.

Frequently seen cancers include lymphoma, melanoma, mast cell tumors (which are considered to be potentially malignant, even though they may have benign behavior), and osteosarcoma (bone cancer).

Certain breeds are more likely to develop particular tumors, larger ones especially. The Golden Retriever is especially susceptible to lymphoma, with a lifetime risk of 1 in 8. Boxers and Pugs are prone to multiple mast cell tumors. Scottish Terriers have eighteen times the risk of mixed breed dogs to develop transitional cell carcinoma, a type of urinary bladder cancer.

Due to the indiscriminate nature of a dog's appetite, gastrointestinal upset is a frequent occurrence in dogs. The most common symptoms are anorexia, vomiting, and diarrhea. Foreign body ingestion can lead to acute obstruction of the gastrointestinal tract, a very dangerous condition. Acute pancreatitis can also result from dietary indiscretion.

Gastric dilatation volvulus, or gastric torsion and bloat, primarily affects breeds with deep, narrow chests, such as Great Danes, St. Bernards, German Shepherds, Standard Poodles and Irish Setters. The stomach twists on its supporting ligaments, sealing off the exits, and the contents begin to generate gas pressure which is very painful and rapidly causes shock and necrosis of large areas of stomach tissue. It can be fatal within a few hours. Dogs who have experienced bloat are very susceptible to recurrences. Treatment involves stabilization and abdominal surgery to tack the dog's stomach down to prevent recurrence (gastropexy).

Eye diseases are common in dogs. Cataracts, canine glaucoma, and entropion are seen in dogs. Canine-specific eye diseases include progressive retinal atrophy, Collie eye anomaly, sudden acquired retinal degeneration, and cherry eye. Injury to the eye can result in corneal ulcers.

The frequency of bilateral glaucoma with a genetic base in purebred dogs is higher than in any species except humans. Cataracts in dogs either have a genetic base or can also be caused by diabetes. Nuclear sclerosis resembles a cataract but is actually a normal age-related change.

Signs of vestibular disease include head tilt, circling, nystagmus (an abnormal movement of the eyes), and difficulty or inability to stand. These clinical signs are similar to those seen in humans experiencing vertigo. Vestibular disease may have many causes. Elderly dogs are susceptible to an idiopathic (meaning due to unknown causes) form of vestibular disease commonly called "old dog vestibular disease" or idiopathic peripheral vestibular disease. The signs may improve rapidly or take a few days. Less commonly, vestibular signs can also be caused by inner ear disease, a brain tumor, a stroke, or other causes. The major risk with idiopathic peripheral vestibular disease is that the dog is often unable to eat, drink, or go outside to urinate or defecate. These cases must receive supportive therapy of intravenous fluids and nutrition; a light sedative is sometimes administered, as the dog may be very stressed by the experience.

Older, small breeds of dogs are prone to congestive heart failure due to degeneration of the mitral valve. This condition is known to be inherited in Cavalier King Charles Spaniels. Degenerative valve disease is the most common form of heart disease in dogs. Mitral insufficiency leads to turbulent blood flow and increased pressure in the left atrium. This causes increased pressure in the pulmonary blood vessels and pulmonary edema (a build-up of fluid in the lungs). Decreased output of blood by the left ventricle causes the body to compensate by increasing sympathetic tone and activating the renin–angiotensin–aldosterone system (RAAS). Increased sympathetic tone leads to increased peripheral vascular resistance and increased heart rate and contractility of the heart muscle. Chronic elevation of sympathetic tone damages the heart muscle. Activation of the RAAS results in increased retention of water and sodium by the kidneys, vasoconstriction, and other effects that result in increased blood volume. It also results in an increase in diastolic pressure and leads to pulmonary edema. Treatment for congestive heart failure has historically focussed on two types of drugs that address these concerns: diuretics (especially furosemide), which decrease blood volume, and ACE inhibitors, which interrupt the RAAS. Recently, pimobendan - which increases the force with which the heart muscle contracts, and is also a vasodilator - is being more widely used in the treatment of congestive heart failure caused by valvular disease. A major veterinary study, called the QUEST study (QUality of life and Extension of Survival Time), published in September 2008 found that dogs with congestive heart failure receiving pimobendan plus furosemide had significantly better survival outcomes than those receiving benazepril (an ACE inhibitor) plus furosemide. However, ACE inhibitors and pimobendan have different mechanisms of action, and many veterinary cardiologists recommend they be used concurrently. Within the past decade, a new surgical technique has been developed for mitral valve repair that replaces or strengthens the mitral valve chords with polytetrafluoroethylene (PTFE) prostheses and tightens the mitral valve ring to reduce or eliminate regurgitation.

Cardiomyopathy, or disease of the heart muscle, is also seen in dogs and is associated with large breeds (the exception being Cocker Spaniels, a medium-sized breed). Dilated cardiomyopathy is seen in Great Danes, Irish Wolfhounds, St. Bernards, Dobermanns, Boxers, and other large breeds. Dobermanns, in addition to heart muscle failure, are prone to ventricular arrhythmias. Boxer dogs are predisposed to a unique cardiomyopathy with clinical and histological changes analogous to human arrhythmogenic right ventricular cardiomyopathy (ARVC). The disease has been termed “Boxer cardiomyopathy” or “Boxer ARVC”, and is characterized by development of ventricular tachyarrhythmias. Affected dogs are at risk of syncope and sudden cardiac death. Myocardial failure and congestive heart failure are rare manifestations of this disease.

Other diseases affecting dogs include endocrine diseases, immune-mediated diseases, and reproductive diseases. Diabetes mellitus, Cushing's syndrome, Addison's disease, and hypothyroidism are the most common endocrine diseases. Immune-mediated hemolytic anemia is a devastating disease that causes severe anemia in dogs through destruction by the immune system. It has been associated with vaccinations and certain drugs, although many cases are idiopathic. A similar but less severe immune disease is immune-mediated thrombocytopenia, characterized by destruction of platelets by the immune system. Clinical signs include bruising and petechiae (pinpoint bruising, often seen in the mouth). Common reproductive diseases include pyometra (distension of the uterus with pus), mammary tumors, and benign prostatic hyperplasia.

Psychological anxieties affecting dogs include noise phobia and separation anxiety.

Some common sources of toxins that pets encounter include some plants, human medications and cosmetics, cleaning products, and even some foods.

Some foods consumed safely by humans are harmful to dogs:

Cocoa within chocolate contains theobromine, a chemical stimulant that, together with caffeine and theophylline, belongs to the group of methylxanthine alkaloids. Dogs are unable to metabolize theobromine effectively. If they eat chocolate, the theobromine can remain in their bloodstreams for days, and dogs may experience fast heart rate, severe diarrhea, epileptic seizures, heart attacks, internal bleeding, and eventually death. "One ounce of milk chocolate per pound of body weight is a potentially lethal dose in dogs." In case of accidental intake of chocolate by especially a smaller dog, contact a veterinarian or animal poison control immediately; it is commonly recommended to induce vomiting within two hours of ingestion. If chocolate ingestion is suspected (mostly dark or baking chocolate), hydrogen peroxide can be used to safely induce vomiting, then making a trip to the veterinarian is suggested. Large breeds are less susceptible to chocolate poisoning, but can still die after eating four ounces of chocolate.

Carob treats are often available as dog treats; these are unrelated to chocolate and are safe.

Grapes and raisins can cause acute kidney failure in dogs (see also grape and raisin toxicity in dogs). The exact mechanism is not known, nor is there any means to determine the susceptibility of an individual dog. While as little as one raisin can be toxic to a susceptible dog, some other dogs have eaten as much as a pound of grapes or raisins at a time without ill effects. The affected dog usually vomits a few hours after consumption and begins showing signs of renal failure three to five days later. A mycotoxin is suspected to be involved, but one has not been found in grapes or raisins ingested by affected dogs. The reason some dogs develop renal failure following ingestion of grapes and raisins is not known. The most common pathological finding is proximal renal tubular necrosis.

Onions cause hemolytic anemia in dogs (and cats). Allyl propyl disulfide has been reported as being considered to be the main cause of onion poisoning in dogs. Thiosulfate has also been reported as being implicated. Thiosulfate levels are not affected by cooking or processing. Occasional exposure to small amounts is usually not a problem, but continuous exposure to even small amounts can be a serious threat. Also garlic contains thiosulfate, even if to a significantly lesser extent, and it is also known to cause diarrhea and vomiting.

Nutmeg is highly neurotoxic to dogs and causes seizures, tremors, and nervous system disorders which can be fatal. Nutmeg's rich, spicy scent is attractive to dogs which can result in a dog ingesting a lethal amount of this spice. Eggnog and other food preparations which contain nutmeg should not be given to dogs.

Macadamia nuts can cause non-fatal stiffness, tremors, hyperthermia, and abdominal pain. The exact mechanism is not known. Most dogs recover with supportive care when the source of exposure is removed.

Hops, a plant used in making beer, can cause malignant hyperthermia in dogs, usually with fatal results. Certain breeds, such as Greyhounds, seem particularly sensitive to hop toxicity, but hops should be kept away from all dogs. Even small amounts of hops can trigger a potentially deadly reaction, even if the hops are "spent" after use in brewing.

Ingestion of yeast, for example in uncooked bread dough, can cause intestinal obstruction. The yeast can also cause fermentation internally, resulting in ethanol (alcohol) poisoning.

Xylitol is a sugar substitute used in chewing gum, chewable vitamins, candy, toothpaste, and other products. Although a small preliminary study indicated xylitol may be safe for dogs, other studies show significant toxicity. There have been cases of foods, candies and gums containing xylitol causing toxic or even fatal liver damage in dogs.

Some dogs have food allergies just as humans do; this is particular to the individual dog and not characteristic of the species as a whole. An example is a dog becoming physically ill from salmon; many humans likewise have seafood allergies.

Some common household chemicals are particularly dangerous to dogs:Poisoning with pain medications is common. Aspirin, paracetamol (acetaminophen, Tylenol), ibuprofen (Advil), and naproxen (Aleve) can all cause severe clinical signs in dogs, including vomiting blood, diarrhea, and abdominal pain. Specifically, aspirin can cause metabolic acidosis and bleeding disorders, acetaminophen can cause liver disease, ibuprofen can cause kidney disease, and naproxen can cause ulcers in the stomach, which can perforate. Treatment depends on the clinical signs.

Most diseases that affect dogs or humans are not transferable between the two species. Diseases that can be transmitted from animals to humans are terrmed zoonoses. A well-known zoonosis is rabies, a viral infection transmitted through a bite. A common bacterial zoonosis is leptospirosis, transmitted through urine. Some of the most important zoonoses are parasitic. Zoonotic intestinal parasites transmitted through contact with feces include "Toxocara canis" (the canine roundworm), which causes toxocariasis, visceral larva migrans, and ocular larva migrans, and hookworms, which can cause cutaneous larva migrans. Zoonotic skin parasites include scabies, caused by the mite "Sarcoptes scabiei". The most common zoonotic fungal disease is ringworm, caused in this case by "Microsporum canis".

Vaccinations are an important preventative animal health measure. The specific vaccinations recommended for dogs varies depending on geographic location, environment, travel history, and the activities the animal frequently engages in. In the United States, regardless of any of these factors, it is usually highly recommended that dogs be vaccinated against rabies, "canine parvovirus", canine distemper, and infectious canine hepatitis (using "canine adenovirus type 2" to avoid reaction). The decision on whether to vaccinate against other diseases, including leptospirosis, Lyme disease, "Bordetella bronchiseptica", "parainfluenza virus", and "canine coronavirus", should be made between an owner and a veterinarian, taking into account factors specific to the dog.

Dental disease is one of the most common diseases in dogs. Accumulation of plaque and subsequently tartar leads to gingivitis and then periodontitis (gum disease). Periodontitis leads to loss of the bony attachment of the teeth and tooth loss. Preventive measures include tooth brushing, providing an appropriate diet (avoiding tinned and other soft foods and providing dental chew treats) and dental scaling and polishing. Cavities are uncommon in dogs.

Once-a-month topical products or ingestible pills are the most commonly used products to kill and prevent future parasite infestations.

Feeding table scraps to a dog is generally not recommended, at least in excess. Just as in humans, a dog's diet must consist of the appropriate mix of nutrients, carbohydrates, and proteins in order to give them the minerals and vitamins that they need. Dogs get ample correct nutrition from their natural, normal diet; wild and feral dogs can usually get all the nutrients needed from a diet of whole prey and raw meat. In addition, a human diet is not ideal for a dog: the concept of a "balanced" diet for a facultative carnivore like a dog is not the same as in an omnivorous human. Dogs will usually eat all the scraps and treats they are fed: usually too much food. While not all human delicacies are acutely toxic to dogs (see above), many have the same chronically unfortunate results as they do for humans. Beef and dairy are common triggers of food allergies in dogs.

Obesity is an increasingly common problem in dogs in Western countries. As with humans, obesity can cause numerous health problems in dogs (although dogs are much less susceptible to the common cardiac and arterial consequences of obesity than humans are). According to a study published in the Journal of Veterinary Internal Medicine, the prevalence of obesity in dogs is between 22 and 40 percent.

Obesity may also be caused by some diseases, such as Cushing's disease, or hypothyroidism.

Dog treats are often given to pets as a reward for something they did or just to let them chew on a bone, which works their jaw muscles and helps keep their teeth clean. Although dog treats carry high benefits for dogs' teeth, they can also be a source of problems when given excessively. The human food treats are usually the ones that cause the most trouble for dogs.

Dog treats given excessively can be a cause of obesity. The type of food fed has a direct bearing on the tendency of a dog to become overweight. Table scraps, treats, even premium high-energy dog foods can contribute to obesity. Therefore, it is highly important to closely monitor the quantity of treats that a dog gets especially when the dog's activity is diminished. Dog treats are more likely to be linked to obesity in old dogs, since in their old age they are less likely to be active and exercising. On the other hand, active dogs require and use more calories, so dog treats are not a cause of concern in younger and highly active dogs.

Some dogs may attempt to consume feces. Some consume their own or other dogs' feces; others seem to prefer cat feces (which, due to the feline digestive system, are high in protein and consumed by many animals in the wild) This can be harmful if the feces has any pathogens or parasites or contain excreted drugs.

It is not yet clear whether or not vitamins and supplements should be administered in dogs—opinions among veterinarians vary widely. While some think that vitamins and supplements are necessary and can improve the health of a dog, others believe that they are unnecessary and may harm the dog. According to the U.S. Food and Drug Administration (FDA), dogs receive a complete and balanced diet from the commercially processed dog food alone. Pet owners who give their dogs homemade diets may incorporate extra vitamins and supplements.

Between approximately 10 and 30 percent of dogs in the United States receive nutritional supplements. A survey of U.S. pet owners in 2006 found that the most commonly used supplements were multivitamins and chondroprotective agents. The use of natural supplements or multivitamins in conjunction with proper nutrition and exercise may contribute to overall health and immune system support in dogs.

Overdoses of vitamins can be harmful in dogs. As an example, calcium in excess can cause bone problems, especially in the large-breed dogs. Over-supplementation of vitamins A and D can cause vitamin toxicity in dogs. Excess vitamin A can cause dehydration, joint pain and can also harm the blood vessels, while too much vitamin D can cause muscular atrophy, or loss of appetite.

Spaying (females only) and neutering (both genders but more commonly males) refers to the sterilization of animals, usually by removal of the male's testicles or the female's ovaries and uterus, in order to eliminate the ability to procreate, and reduce sex drive. Neutering has also been known to reduce aggression in male dogs, but has been shown to occasionally increase aggression in female dogs.

Animal control agencies in the United States and the ASPCA advise that dogs not intended for further breeding should be spayed or neutered so that they do not have undesired puppies.

Because of the overpopulation of dogs in some countries, puppies born to strays or as the result of accidental breedings often end up being killed in animal shelters. Spaying and neutering can also decrease the risk of hormone-driven diseases such as mammary cancer, as well as undesired hormone-driven behaviors. However, certain medical problems are more likely after neutering, such as urinary incontinence in females and prostate cancer in males. The hormonal changes involved with sterilization are likely to somewhat change the animal's personality, however, and some object to spaying and neutering as the sterilization could be carried out without the excision of organs.

It is not essential for a female dog to either experience a heat cycle or have puppies before spaying, and likewise, a male dog does not need the experience of mating before neutering.

Female cats and dogs are seven times more likely to develop mammary tumors if they are not spayed before their first heat cycle. The high dietary estrogen content of the average commercial pet food may be contributing factors in the development of mammary cancer, especially when these exogenous sources are added to those normal estrogens produced by the body. Dog food containing soybeans or soybean fractions have been found to contain phytoestrogens in levels that could have biological effects when ingested longterm.