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Hydrocodone / Paracetamol

Combination of
Hydrocodone	Opioid analgesic
Paracetamol	Anilide analgesic
Clinical data
AHFS/Drugs.com	entry
Licence data	US FDA:link
Pregnancy cat.	C (US)
Legal status	Schedule III (US)
Routes	Oral
Identifiers
CAS number	330988-71-1 Y
ATC code	?
PubChem	CID 11247932
ChemSpider	9422965 Y
Y (what is this?)  (verify)

Hydrocodone/paracetamol (also known as hydrocodone/acetaminophen) is a combination of two analgesic products hydrocodone and paracetamol (acetaminophen) used to relieve moderate to severe pain.^[1] It is usually found in tablet form, produced and marketed under the trade names Vicodin, Vicodin ES, Vicodin HP, Anexsia, Anolor DH5, Bancap HC, Zydone, Dolacet, Lorcet, Lortab, and Norco, as well as generic brands. Hydrocodone also comes in a combination with ibuprofen, available under the trade name Vicoprofen.

Medical uses[link]

Hydrocodone/paracetamol, like other opioid analgesics, is used to manage pain. It is most commonly prescribed for relief of moderate to moderately severe pain of acute, chronic, or post-operative types.

Formulations[link]

Hydrocodone/paracetamol is made as a mixture of hydrocodone and paracetamol. Paracetamol acts as an analgesic/antipyretic. Hydrocodone is a semi-synthetic opioid analgesic.

Pregnancy[link]

This drug is classified under pregnancy category C. Although not enough research has been done to deem this drug safe for pregnant women, if taken in the time before delivery, it may give rise to respiratory depression in the baby. Mothers using any opioids regularly during pregnancy run the risk of their babies being substance-dependent and, therefore, going through withdrawal symptoms after birth. Withdrawal symptoms include excessive crying, vomiting, irritability, tremors, and fever. Nursing mothers should not use this drug, as paracetamol is transferred through breast milk; it is unknown whether hydrocodone is.^[2]

Adverse effects[link]

A diagram showing the side effects of Vicodin (hydrocodone/paracetamol)

Side-effects of hydrocodone/paracetamol are most commonly upset stomach, nausea, and altered mental status (e.g., dizziness, light headedness). Other rarer side-effects include allergic reaction, seizures, clammy skin, paranoia, hallucinations, severe weakness, dizziness, hyperventilation, unconsciousness, jaundice (yellowing of eyes or skin), unusual fatigue, bleeding, bruising, stomach pain,^[3] constipation, dry mouth, decreased appetite, muscle twitches, sweating, hot flashes, itching, tinnitus, hearing loss, decreased urination and altered sex drive. Vicodin also has depressant effects on the central nervous system, which may cause irritability. However, some of the less mundane effects can be desirable effects that are sought after by some. Those effects include euphoria and drowsiness, as well as slowing of the pulse.

Unlike NSAIDs, paracetamol does not cause ulcers. However, paracetamol can cause liver damage, and, thus, dosages should never exceed 4000 mg a day; this is especially important and will be a smaller number of doses when using mixed drugs like Vicodin. It is imperative that users of this drug follow physician-prescribed dosages. Liver damage can manifest, ranging from abdominal pain to outright liver failure, and can necessitate a liver transplant to avoid death.

Pharmacodynamics[link]

Besides the activity of hydrocodone and acetaminophen on their own, there is observed a factor of analgesia related to the two substances in tandem^{[citation needed]} that is not altogether understood, but this independent synergy has been observed to be related to the inhibition of prostaglandins. The pharmacodynamics of a mixed drug such as Vicodin depends on the kinetics of the drugs that comprise it.

Hydrocodone: Acts at μ-opioid receptors.^[4] Hydrocodone is metabolized to hydromorphone by the activity of cytochrome P450 2D6. Cytochrome 3A4 forms the substrate norhydrocodone. Note that this conversion is only somewhat responsible for the effects of hydrocodone.^[5] Hydrocodone passes through the blood–brain barrier (BBB) because of its modifications. The brain is typically where the analgesic effects are being carried out. Many of the side-effects of this drug are caused by the fact that it so readily crosses the blood–brain barrier. The half-life of hydrocodone is approximately 3.8 hrs.

Paracetamol: The major active metabolites are sulphates and glucuronide conjugates. Its main mode of action is to inhibit the activity of the enzyme cyclooxygenase (COX). COX enzymes are necessary for the production of prostaglandins. Prostaglandins are a form of hormone (although rarely classified as such) that are indicated to be mediators of pain, fever, and inflammation. The half-life of paracetamol may be measured either by salivary or by plasma counts. Both measurements give a varying half-life between 1 and 4 hours.^[6] Peak levels are reached between 40–60 minutes after ingestion. It has been proposed that paracetamol aids in the reduction of pain by increasing serotonergic neurotransmissions.^[7] Paracetamol is a peripherally acting drug, and hence does not cross the BBB as readily as hydrocodone.^{[citation needed]}

Society and culture[link]

Manufacture[link]

The principal constituent of Vicodin, hydrocodone, has the same basic structure as morphine but is metabolized by different enzymes. There are three variations of Vicodin, with different amounts of hydrocodone in each. Hydrocodone, like oxycodone, is an intermediate-strength analgesic that has similar effects as morphine; hydrocodone is approximately twice as potent as morphine by mouth for acute use. The tablets are made with less hydrocodone than paracetamol. The theory of using the mix comes from the idea that these drugs alleviate pain using different mechanisms and also that the adverse side-effects of each separate drug are reduced by using reduced dosages of both drugs in order to get the same analgesic effect.^[8]

Both hydrocodone and acetaminophen are white crystalline powders, which are then manufactured into tablet form. Manufacturers of hydrocodone (generic or otherwise) include Abbott Laboratories (makers of trademark Vicodin), Amerisource Health Services Corp, Cardinal Health, Drx Pharmaceutical Consultants Inc, Eckerd Corp, Hospira Inc, Mallinckrodt Pharm. Quality Care, Pdrx Pharmaceuticals Inc, Physicians Total Care Inc, Rx Papoo s Packaging Inc, and Watson Pharmaceuticals.

On January 13, 2011, FDA announced that it is asking manufacturers of prescription acetaminophen combination products to limit the maximum amount of acetaminophen in these products to 325 mg per tablet, capsule, or other dosage unit. FDA believes that limiting the amount of acetaminophen per tablet, capsule, or other dosage unit in prescription products will reduce the risk of severe liver injury from acetaminophen overdosing, an adverse event that can lead to liver failure, liver transplant, and death.^[9]

Legal status[link]

In the United States, Vicodin production is regulated in part by the Controlled Substances Act of 1970. This guarantees that all manufacturing, importing, possession, and distribution of drugs are to be overseen and regulated by the federal government.

In the U.S. Vicodin is a Schedule III drug. Pure codeine and hydrocodone are Schedule II drugs, but, when compounded with paracetamol or with an NSAID, they can become a Schedule III drug. Schedule III drugs are classified by the U.S. government as having the potential to cause moderate or low physical dependence, or a high psychological dependence if misused.

United States[link]

To qualify for treatment as a Schedule III medication in the United States, hydrocodone must be combined with a non-narcotic ingredient in a recognized therapeutic amount. There are four dosage forms recognized by the U.S. authorities:

• per 100 ml (i.e., a liquid), which must have no more than 300 mg of (dissolved) hydrocodone in addition to the therapeutic amount of a non-narcotic ingredient
• per dosage unit (i.e., a solid, pill or capsule), which must have no more than 15 mg of hydrocodone in addition to the therapeutic amount of a non-narcotic ingredient

Proposed U.S. ban[link]

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 painkiller, Percocet, from the market because of "a high likelihood of overdose from prescription narcotics and acetaminophen products". The panel cited concerns of liver damage from their acetaminophen component, which is also the main ingredient in commonly-used nonprescription drugs such as Tylenol.^[10] Each year, acetaminophen overdose is linked to about 400 deaths and 42,000 hospitalizations.^[11]

The U.S. Food and Drug Administration is asking manufacturers of prescription combination products that contain acetaminophen to limit the amount of acetaminophen to no more than 325 milligrams (mg) in each tablet or capsule.^{[12][13][14][15]} Manufacturers will have three years to limit the amount of acetaminophen in their prescription drug products to 325 mg per dosage unit.^[13][15] The FDA also is requiring manufacturers to update labels of all prescription combination acetaminophen products to warn of the potential risk for severe liver injury.^[12][13][15]

Hydrocodone, the narcotic component of Vicodin, is still available in Canada as a single drug and marketed under the trade name Hycodan in syrup and tablet forms by Bristol-Myers-Squibb.^[16]

Popular media[link]

The central character on the popular American television medical drama House habitually uses (and abuses) Vicodin to manage pain stemming from an infarction in his quadriceps muscle incurred some years earlier.

Vicodin is referenced in multiple songs by rapper Eminem such as "Kill You", "Under the Influence", "Deja Vu", "Old Time's Sake", "Underground", "Going Through Changes", "Oh No", and "Cocaine". He also featured a Vicodin pill on the CD of his debut album The Slim Shady LP. The rapper has admitted to an addiction to the painkiller (along with other substances), the hiatus in rapping that it caused, and the subsequent rehabilitation required to return to his career.^[17]

References[link]

External links[link]

• Norco information from Drugs.com
• Norco Website
• Vicodin U.S. DEA Drug Schedule
• Vicodin U.S. Federal Regulations
• U.S. National Library of Medicine: Drug Information Portal - Vicodin

Terra Naomi
Background information
Birth name	Terra Naomi
Born	1979/1980 (age 31–32)[1]
Genres	Rock, alternative rock
Occupations	Singer, songwriter
Instruments	Guitar, piano
Labels	[Independent artist]
Website	www.terranaomi.com
Notable instruments
Vocals, Guitar, Piano

Terra Naomi is an alternative, rock, and pop artist, who rose to fame through a performance of her song "Say It's Possible" on the video sharing site YouTube.^[2] Originally from New York State, but currently based in Los Angeles, she writes and performs her own songs, and plays the guitar and piano.

Biography[link]

Naomi was born in Saratoga Springs, New York and raised on a farm for the first couple of years of her life. The family then moved to Cleveland, Ohio where they lived for six years before finally settling in upstate New York, from where her father, a plastic surgeon, originated. Her mother is a social worker. Naomi has one older brother and one younger brother.

Classical beginnings[link]

Naomi studied classical piano and voice, attending Interlochen Performing Arts Camp in Michigan and Belvoir Terrace Summer Camp in Lenox, Massachusetts. Teachers convinced her to pursue a degree in opera from The University of Michigan.^[3] During this time, Naomi also participated in the Aspen Opera Theater Program.

Change in direction[link]

Naomi moved to New York City after college and began writing songs. During this time she also started playing guitar. She played at various clubs in Manhattan, including The Bitter End, The Sidewalk Cafe and The Living Room. Following a tour of the US in 2003, which started in NYC and ended at the Bumbershoot Festival in Seattle, Naomi moved to Los Angeles to work with producer Paul Fox (XTC, 10,000 Maniacs, Sixpence None the Richer, Edwin McCain, Phish, The Sugarcubes).^[3]

Naomi has come to prominence in the international YouTube community where she broadcast her own "virtual" summer tour during the summer of 2006. The program included live performances from her apartment in Hollywood and question-answer sessions entitled "Ask a Wanna-be Rockstar." Her song, "Say It's Possible," filmed in Terra's Hollywood apartment, recorded on a Sony Handycam, was featured on YouTube in June 2006, causing an instant explosion of interest.^[2] "Say It's Possible," has inspired adoring fans to post hundreds of personal "YouTube covers" in a wide range of styles.^[4] This includes versions from countries in South America, North America and Europe. Fans have also translated and performed the song into Spanish, Italian, and Mandarin Chinese and one used a sock puppet. In March 2007, she received one of the inaugural YouTube Video Awards in the music video category for "Say It's Possible", garnering her appearances on NBC's The Today Show and CBS' The Early Show, as well as coverage on several international news programs.^[5]

Naomi has also been featured in articles for CNBC, Reuters, The Los Angeles Times, The LA Weekly, The Washington Post, Salon.com,^[6] and The Sunday Times (UK).^[1]

In the fall of 2006, Naomi was signed to a publishing deal with Universal Music Publishing Group. This was followed in December 2006 by the announcement that she had been also signed to the major record label, Island Records.

After releasing "Under the Influence," Naomi left Island Records. She is currently finishing her new album To Know I'm Ok. It will be released independently on June 21. It is being funded through fans via Pledgemusic, an "international Direct-to-Fan platform for raising funds."^[7]

Tours and notable performances[link]

Terra Naomi performing at the Hotel Utah Saloon in San Francisco.

Naomi headlined national tours in the United States in 2003, 2004, and 2005, which included dates at the Chicago House of Blues, NYC's Irving Plaza, The Trocadero in Philadelphia, The Abbey^{[disambiguation needed ]} in Chicago, The Gypsy Tea Room in Dallas and The Hotel Cafe in Los Angeles and has also performed shows in Canada and the United Kingdom.^[8] Shows in the United Kingdom included an appearance at the In The City festival in Manchester [5]. She has also opened for Tyler Hilton,^[9] Michael Bolton,^[10] Jay Brannan,^[11] The Fray,^[12] Martha Wainwright^[12] and Natasha Bedingfield.^[13]

In 2007, after being personally invited by Al Gore, Naomi performed "Say It's Possible" at the UK leg of Live Earth at Wembley Stadium in London.^[12] Later that year, YouTube Russia was launched and Naomi was invited to perform and help launch it.^[14]

In November 2009 Naomi began a two week tour of India playing shows in Mumbai, Bangalore and Delhi culminating with a headlining performance at the Mercy Corps Say It's Possible Climate Change Concert in Srinagar, Kashmir. This tour was sponsored by American Center, Levi Strauss & Co. India, Fabindia and Mercy Corps. Naomi's Indian tour was immediately followed by two weeks in Italy playing shows in Fabriano, Perugia, Rome, Imola, Bologna, Rimini, Monte Castello Di Vibio and Montesilvano.^[15] During her stay in Italy she also recorded a duet with italian superstar Elisa.

In early July 2010, Naomi performed at Lilith Fair's San Francisco show after winning a competition sponsored by OurStage.com.^[16] In August she toured Italy again, playing in Rimini, Milano, Padova, Montepulciano and Castiglione del Lago.

In June 2011 Naomi performed the inaugural show for the Haus of Hipstamatic Unplugged Summer Sessions in San Francisco.^[17] The event was the first in a series of unplugged sessions featuring other singer-songwriters such as Michelle Branch and was hosted by Hipstamatic at their office space in SoMa. The music video for "You For Me" was also debuted at the event, which is archived on Ustream.

Discography[link]