Vicodin

For drug information from the FDA, click here

Overview
Vicodin is a trademarked brand narcotic analgesic product containing hydrocodone and paracetamol (acetaminophen or more completely para-acetylaminophenol). It is usually found in tablet form with either the names Vicodin, Vicodin ES, or Vicodin HP imprinted on one side. Analgesics with the same chemical composition and a similar physical appearance are found under many other trade names, including Anexsia, Anolor DH5, Bancap HC, Dolacet, Lorcet, Lortab, and Norco. The hydrocodone/paracetamol drug formula is also available under generic brands. The paracetamol in the formula increases the effects of the hydrocodone. Hydrocodone also comes in a combination with ibuprofen, available under the trade name Vicoprofen.

Ingredients
Vicodin is made as a mixture of hydrocodone and paracetamol. Paracetamol, which is also called acetaminophen, acts as an analgesic/antipyretic. Hydrocodone is a synthetic mixture of the opiate codeine modified by an added hydrogen and the opiate alkaloid thebaine. Codeine acts as an antitussive, antidiarrheal and analgesic, while thebaine is added for its stimulatory effects. Non-active ingredients included in each pill as well: colloidal silicon dioxide, starch, croscarmellose sodium, dibasic calcium phosphate, magnesium stearate, microcrystalline cellulose, povidone, and stearic acid.
 * Vicodin contains 500 mg paracetamol and 5 mg hydrocodone
 * Vicodin ES contains 750 mg paracetamol and 7.5 mg hydrocodone
 * Vicodin HP contains 660 mg paracetamol and 10 mg hydrocodone

Regulation and scheduling
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 is to be overseen and regulated by the federal government.

In the U.S. Hydrocodone is a Schedule III drug. Other drugs on this list include anabolic steroids, dihydrocodeine, dronabinol, phendimetrazine, ketamine, paregoric, and Xyrem; codeine and hydrocodone are also Schedule III but only when compounded with paracetamol or with an NSAID. Schedule III drugs are classified by the U.S. government as potentially causing moderate or low physical dependence or a high psychological dependence if abused. There is a high inclination for abuse of this drug.

Manufacture
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 / paracetamol (acetaminophen) in each. Hydrocodone is a strong drug which has similar effects as morphine, because of this, the pills are made with much 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. Both hydrocodone and acetaminophen are white crystalline powders, which are then manufactured into pill form. There is also a theory that the acetaminophen is added in order to reduce abuse potential, as multiple doses will result in nausea symptoms and stomach complications. 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, Knoll Laboratories Div Knoll Pharmaceutical Co, Mallinckrodt Pharm. Quality Care, Pdrx Pharmaceuticals Inc, Physicians Total Care Inc, Rx Pak Div of Mckesson Corp, Sandhills Packaging Inc, and Watson Pharmaceuticals.

Pharmacokinetics
Besides the activity of hydrocodone and acetaminophen on their own, there is observed a factor of analgesia related to the two substances in tandem which is not altogether understood, but this independent synergy has been observed to be related to the inhibition of prostaglandins. The pharmacokinetics of a mixed drug such as Vicodin depends on the kinetics of the drugs that comprise it. We will look at the two main constituents separately, hydrocodone and paracetamol. Hydrocodone: acts at mu opioid receptors. Hydrocodone must be metabolized to its active state, hydromorphone. This metabolism occurs by the activity of cytochrome P450 2D6. Cytochrome 3A4 forms the active substrate norhydrocodone. Cytochromes are haemoprotiens found in the cells of all living organisms and are involved primarily with the electron transport chain producing ATP. Hydrocodone passes through the Blood Brain Barrier 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 BBB. 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), which are indicated to be mediators of pain, fever and inflammation. The half-life of paracetamol may be measured either by salivary or plasma counts. Both measurements give a varying half-life between 1 and 4 hours. Peak levels are reached between 40–60 minutes after ingestion. It has been proposed that paracetamol aids in the reduction of pain by increasing seratonergic neurotransmissions. Paracetamol is a peripherally acting drug, and hence does not cross the BBB as readily as hydrocodone.

Indications
Vicodin, 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. It can also be used to treat severe cough.

Pregnancy
This drug is classified under pregnancy category C. Although not enough research has been done to deem this drug safe for pregnant women, if the positive effects outweigh the possible negatives, then it can be taken. If taken in the time before delivery, it may give rise to respiratory depression in the baby. Mothers who use 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 and it is unknown if hydrocodone is.

Side effects


Side effects for Vicodin are most commonly upset stomach, nausea, and altered mental status (eg. dizziness, light headedness). Other more rare side effects include allergic reaction, seizures, clammy skin, hallucinations, severe weakness, dizziness, hyperventilation, unconsciousness, jaundice (yellowing of eyes or skin), unusual fatigue, bleeding, bruising, stomach pain, 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. 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. Liver damage can manifest ranging from abdominal pain to outright liver failure, and can necessitate a liver transplant to avoid death. Paracetamol dosages should never exceed 4g a day; this is especially important and may be a smaller number when dealing with mixed drugs like Vicodin. It is imperative that users of this drug follow physician prescribed dosages.

Behavioral effects
Tolerance to this drug may develop rapidly, especially if it is misused. This tolerance will usually manifest itself by analgesic effects wearing off faster, and people needing higher dosages to reach the analgesic effects. It is commonly misused or used excessively because people take too much in order to relieve their pain faster. Taking more of the drug does increase its efficacy but it also increases its addictive properties. When tolerance does develop, people are often forced to seek out more and more Vicodin, but as it is a controlled substance, there are regulations on how much can be legally prescribed. This often leads to societal/legal consequences as people will visit many doctors and/or try to buy the drug illegally. The withdrawal effects of Vicodin include things such as insomnia, night sweats, tremors, and agitation. People looking for the secondary effects of the drug often abuse many forms of prescription drugs. Vicodin is a potentially addictive drug, specifically due to the hydrocodone in it. People who are using Vicodin for non-medicinal purposes are typically using it to get the euphoric effects sometimes associated with it. Ten percent of American high school seniors have abused Vicodin; 4.7 percent report abusing Oxycontin in the past year. There have been reports of severe hearing loss and deafness associated with the abuse of Vicodin. If taken at the normal prescribed dosages, the risk of hearing loss is very minimal. It is interesting to note that in people who use these drugs for recreational purposes there are sex differences. Women tend to feel less "in control on their thoughts" and more report, "feeling bad" more often than men. People given logic examinations while under the influence of this drug showed an increase in incorrect answers, but spent more time on the exams. This suggests that this drug may be aiding in attention. It is again important to note that clinically prescribed dosages do not produce these effects; these effects are related to taking more of the drug than typically prescribed.

Paracetamol/Acetaminophen In The News
On Jun 30 2009 an FDA advisory panel recommended that Vicodin and another painkiller, Percocet, be removed from the market because they have allegedly caused over 400 deaths a year. The problem is with Paracetamol overdose and liver damage.