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What is Hydrocodone/paracetamol and explain in detail?
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, decreased rate of breathing, 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 paracetamol works is unclear but may involve blocking the creation of prostaglandins.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 2020, it was the sixteenth most commonly prescribed medication in the United States, with more than 30 million prescriptions. It is not available in the United Kingdom, though the combination codeine/paracetamol is. It is sold under the brand names Vicodin and Norco among others.

Uses
Medical
Hydrocodone/paracetamol is a fixed-dose combination consisting of the opioid hydrocodone and the non-opioid analgesic paracetamol. It is indicated for relief of moderate to severe pain of acute, chronic, or postoperative types. Hydrocodone/paracetamol 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.

Recreational
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 DEAs National Forensic Laboratory Information System (NFLIS) and System to Retrieve Information from Drug Evidence (STRIDE).

Pregnancy and breastfeeding
Pregnancy category C: Risk in pregnancy cannot be ruled out. Animal controlled studies have not been conducted with this medication.Low concentrations of paracetamol is excreted through breast milk, however, hydrocodones excretion is unknown.

Kidney and liver impairment
Use with caution due to possible risk of toxicity.

Side effects
Most common
Lightheadedness
Dizziness
Euphoria
Sedation
Nausea and vomiting
Headaches

Less common
Central nervous system: drowsiness, confusion, lethargy, anxiety, fear, unease, dependence, mood changes, impairment of mental and physical performance
Gastrointestinal system: constipation
Genitourinary system: inability to urinate, bladder spasms
Respiratory depression: decreased rate and effort of breathing
Hearing impairment, permanent hearing loss
Dermatological: rash, itching

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

Allergy warning
"Do not take hydrocodone bitartrate and paracetamol 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 paracetamol tablets and contact your healthcare provider immediately."

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

Interactions
Hydrocodone may demonstrate an enhanced respiratory depressant effect when combined with other sedatives such as other opioids, benzodiazepines, nonbenzodiazepine sedatives, psychotropics, and anticonvulsants.Concurrent use of paracetamol with alcohol products may increase the risk of acute liver failure.

Monitoring
Laboratory function tests should be used to monitor therapy in people with severe liver or renal disease.

Pharmacology
Hydrocodone
Mechanism of action: Hydrocodone acts primarily as an agonist at the mu-opioid receptors, but is also a weak agonist against the delta opioid and kappa opioid receptors.
Absorption/distribution: The oral formulation can be absorbed from the gastrointestinal tract and remain 20–50% bound to plasma proteins. The onset of analgesia is about 20 to 30 minutes with duration of 4 to 8 hours and t1/2 of 3 to 4 hours.
Metabolism/excretion: It is metabolized to norhydrocodone by cytochrome P450 3A4 and to hydromorphone, also biologically active, by cytochrome P450 2D6. For individuals who have a defect in the gene encoding CYP2D6, the clearance of the drug will be lower and less metabolite such as hydromorphone will be formed; however, the effect on analgesia remains unknown.

Paracetamol
Mechanism of action: Paracetamol acts to inhibit COX enzyme, which is responsible for prostaglandin synthesis. Prostaglandins increase the perception of pain. Inhibition of prostaglandin production helps to alleviate pain.
Absorption/distribution: The half-life of oral paracetamol is 1.25 to 3 hours and peak level is reached by 10–60 minutes after ingestion.
Metabolism/excretion: Paracetamol is metabolized primarily in the liver via glucuronidation and sulfation to mostly non-toxic metabolites and some highly reactive metabolites, which is inactivated by glutathione. 85% of the oral dose is excreted renally. At high doses, the supply of glutathione cannot meet its demand, thus results in the accumulation of highly reactive compounds leading to liver damage.

Society and culture
In May 2017, professional golfer Tiger Woods was arrested by the police for driving under the influence. Woods said that this was due to four prescription drugs that he was taking for a back operation, one of which was Vicodin.

Legal status
On 30 June 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 paracetamol component, which is also the main ingredient in commonly used nonprescription drugs such as Tylenol