Hydrocodone effects

Codeine, hydrocodone, morphine, methadone, and oxycodone are substrates of the cytochrome P-450 isoenzyme CYP2D6.47 Inhibition of CYP2D6 results in decreased analgesia of codeine and hydrocodone due to decreased conversion to the active metabolites (e.g., morphine and hydromorphone, respectively) and increased effects of morphine, methadone, and oxycodone. Methadone is also a substrate of CYP3A4, and its metabolism is increased by phenytoin and decreased by cimetidine. CNS depressants may potentiate the sedative effects of opiates. 

Severe pain should be treated with an opioid such as morphine, hydromorphone, methadone, or fentanyl. Moderate pain can be treated effectively in most cases with a weak opioid such as codeine or hydrocodone, usually in combination with acetaminophen. Meperidine should be avoided owing to its relatively short analgesic effect and its toxic metabolite, normeperidine. Normeperidine may accumulate with repeated dosing and can lead to central nervous system side effects including seizures. 

HydroNarcotic Analgesic/NSAID] Uses Mod-severe pain (<10 d) Action Narcotic w/ NSAID Dose 1—2 tabs q4-6h PRN Caution [C, M] Renal insuff -1- effect w/ ACE inhibitors diuretics t effect w/ CNS d ressants, EtOH, MAOI, ASA, TCA, anticoagulants Contra Component sensitivity Disp Tabs SE Sedation, fatigue, GI upset see Hydrocodone Acetaminophen Interactions -1- Effects OF ACEIs, diuretics EMS See Hydrocodone Acetaminophen T risk of bleeding w/ heparin use OD See individual agents... 

Hydrocodone (Hycodan), oxycodone (Roxicodone), dihydrocodeine, hydromorphone (Dilaudid), and oxy-morphone (Numorphan) are derivatives of codeine and morphine. All are indicated for the relief of mild to severe pain or for their antipyretic effects they are often used in combination with nonopioid analgesics. The drugs vary in potency, but their pharmacological effects do not differ significantly from those of codeine or morphine. 

The patient who uses hydrocodone repeatedly may develop a tolerance to the drug s analgesic effect as well as physical dependence. 

Codeine,oxycodone, dihydrocodeine, and hydrocodone are all somewhat less efficacious than morphine (they are partial agonists) or have adverse effects that limit the maximum tolerated dose when one attempts to achieve analgesia comparable to that of morphine. 

Among the compounds that fall within this class are hydrocodone (e.g., Vicodin), oxycodone (e.g., OxyContin—an oral, controlled-release form of the drug), morphine, fentanyl, codeine, and related medications. Morphine and fentanyl are often used to alleviate severe pain, while codeine is used for milder pain. Other examples of opioids prescribed to relieve pain include propoxyphene (Darvon) hydromorphone (Dilaudid) and meperidine (Demerol), which is used less often because of its side effects. In addition to their effective pain-relieving properties, some of these medications can be used to relieve severe diarrhea (for example, Lomotil, also known as diphenoxylate) or severe coughs (codeine). 

Side-effects Hydrocodone induces side-effects similar to codeine and morphine and has an appreciable abuse and dependence potential (Morrison, 1979). 

The abuse of marketed medications has been at the forefront of public awareness in recent years, mostly due to widespread reports concerning OxyContin and hydrocodone.1 While these are highly regulated, prescription-only medications with recognized potential for abuse, even some over-the-counter (OTC) medications have become problematic, either because of their own effects (e.g., ephedrine) or because they are used in the manufacture of other abused substances (e.g., pseudoephedrine, used to make methamphetamine).2 3... 

Semi-synthetic and synthetic opioids (meperidine, hydrocodone, fentanyl, etc.) are the result of many attempts to produce effective yet safer analgesics. The fact that both morphine and codeine are still widely used indicates that the newer opioids have been only moderately successful. However, current knowledge of the opioid system makes the goal of producing the perfect... 

The prototypical opioid is morphine (A.137) (Figure A.39). Isolated in a crude form, called opium, morphine has been recognized as a potent pain killer for thousands of years. Although effective, morphine has a low oral availability (F = 25%). Two common derivatives of morphine include hydrocodone (Vicodin, A.138) and oxycodone (A.139), both of which have oral availabilities of greater than 75%. Oxycodone is often sold in an oral continuous-release form under the trade name of OxyContin. Not all opioids are semisynthetic derivatives of morphine. Dextropropoxyphene (Darvon, A.140) and tramadol (Tramal, A.141) are fully synthetic opioids. Both compounds preserve the pharmacophore of morphine as described in the morphine rule (see Chapter 11). Dextropropoxyphene and tramadol are depicted in Figure A.39 to highlight possible pharmacologically active conformations that resemble morphine. 

Initiate therapy of these drugs, particularly those with a narrow therapeutic index, at the lowest effective dose. Interaction is likely to be important with substrates for which CYP2D6 is considered the only metabolic pathway (e.g. hydrocodone, oxycodone, desipramine, paroxetine, chlorpheniramine, mesoridazine, alprenolol, amphetamines, atomoxetine)... 

Hydrocodone, another codeine congener, is approximately six times more potent than codeine. This agent appears to cause less constipation and less sedation than codeine. It has been suggested that hydrocodone may produce more euphoria than codeine, but this effect has not been substantiated in clinical studies. Hydrocodone is also available in combination with aspirin, acetaminophen, or ibuprofen. 

If additional analgesia is required beyond that afforded by the nonnarcotic analgesics, an opioid such as oxycodone, hydrocodone, or codeine should be used. If opioid side effects are unacceptable or become problematic, the narcotic dose is reduced or an alternative opioid is selected. 

The opioid analgesics of choice for use in the elderly are listed in Box 7-3. For treatment of moderate to severe pain, an effective opioid regimen consists of a combination of acetaminophen with 15 to 60 mg codeine or acetaminophen with 5 to 30 mg oxycodone. Acetaminophen combinations with hydrocodone are also frequently used. If pain persists, an alternative opioid analgesic should be selected. Adjuvants such as caffeine may enhance the analgesic activity of the opioid. 

Heroin was first synthesized from morphine over a century ago. Since then, it has become one of the most abused substances. Research into why it produces such powerful effects has led to the discovery of specific opiate receptors and endogenous opioids (enkephalins and endorphins). These peptides appear to be neurotransmitters involved with the sensation of pain and pleasure. A number of opiates and synthetic opioids are available and can lead to dependency, including morphine, heroin, propoxyphene (Darvon), methadone, meperidine (Demerol), pentazocine (Talwin), hy-dromorphone (Dilaudid), oxycodone (Percodan), and hydrocodone (Vicodin, Damason-P), and codeine. 

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