Morphine methadone

Depressants alcohol, barbiturates Opioids heroin, morphine, methadone... 

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. 

Total Daily Dose Oral Morphine Morphine Methadone Factor... 

Schedule (C-ll) II High addictive potential medical use accepted. No telephone call-in prescriptions no refills. Some states require special prescription form (eg, cocaine, morphine, methadone). 

Acute pain is managed with either nonopioids such as acetaminophen, NSAIDs, or, when severe, opioids such as meperidine, morphine, methadone, hydromor-phone, fentanyl, or sufentanil (Golianu et ah, 2000). The latter are generally used parenterally, and when the patient is converted to oral analgesics, agents such as codeine, oxycodone, and hydrocodone are often used. 

Moreton, J. Edward, Timothy Roehrs, and Naim Khazan. 1976. "Drug Self-Administration and Sleep-Wake Activity in Rats Dependent on Morphine, Methadone, or L-Alpha-Acetylmethadol." Psychopharmacologia 47 237-41. 

Berkowitz, B.A. The relationship of pharmacokinetics to pharmacological activity morphine, methadone and naloxone, Clin. Pharmacokinet. 1976, 1, 219-230. 

Methadone, in general, exerts a pharmacological action similar to that of morphine. Its action on smooth muscle resembles that of meperidine. analgesic potency, but /-methodone is twice as effective. When used in comparable analgesic doses, methadone is as toxic as morphine and exerts the same effects on the pulse rate and respiration as does morphine. Methadone exerts no sedative effect and, hence, is of no value as a preanesthetic agent. 

Cross-tolerance occurs between all opiates that act primarily via the mu receptors. This is the basis of the methadone substitution therapy which is commonly used to withdraw people who are dependent on heroin or morphine methadone is used because of its relatively long half-life (about 12 hours) and its ease of administration in an oral form. Cross-tolerance does not occur between the opiates and other classes of dependence-producing drugs such as the barbiturates, alcohol or the amphetamines, which act through different mechanisms. 

Actions The analgesic activity of methadone is equivalent to that of morphine. Methadone exhibits strong analgesic action when administered orally, in contrast to morphine, which is only partially absorbed from the gastrointestinal tract. The miotic and respiratory depressant actions of methadone have average half-lives of 24 hours. Like morphine, methadone increases biliary pressure, and is also constipating. 

Correct choice = A. Methadone shows an analgesic action similar to that of morphine. Methadone is effective for 15 to 20 hr, whereas morphine acts for 4 to 6 hr. A major advantage of using methadone in the controlled withdrawal of heroin and morphine abusers is that it can be given orally. 

Masking hydrophilic groups also enhances the uptake of drugs into the brain. A classical example is heroin, which is the diacetylated derivative of morphine (Figure 2.7c). Ironically, heroin was invented in an attempt to overcome the addictive effects of morphine. Methadone was later invented to avoid those of heroin. 

Brashear RE. Effects of heroin, morphine, methadone and propoxyphene on the Inng. Semin Respir Med 1980 2 59. 

The major pharmacological actions of methadone, mediated by fi- and 6-receptor interactions, are similar to those of other opioids and include analgesia, sedation, respiratory depression, miosis, antitussive effects, and constipation. Methadone is administered as a racemic mixture (R,S- [ ] -methadone), but the analgesic activity is due almost entirely to the R(-)-isomer. When administered intramuscularly, methadone and morphine have equivalent analgesic potency. In contrast to morphine, methadone retains about 50% of its intramuscular analgesic potency when taken orally. ... 

Prescription regulations for most CNS drugs are based on their abuse liability. The potent opioid analgesics (e.g., morphine, methadone, meperidine, fentanyl) are judged to have the highest potential for abuse, along with CNS stimulants (e.g., amphetamine, cocaine) and short-acting barbiturate (e g., secobarbital). No refills or telephone prescriptions are permissible. 

DAMGO Morphine Methadone Fentanyl Dermorphin crop Levorphanol Etorphine Naloxone Naltrexone j3-funaltrexamine Enkephalin Endorphin... 

In contrast to morphine, methadone, or heroin, definite withdrawal signs... 

Opioids (heroin, morphine, methadone, etc) Lethargy, sedation, coma, bradycardia, hypotension, hypoventilation, pinpoint pupils, cool skin, decreased bowel souncte, flaccid muscles Provide airway and respiratory support. Give naloxone as required... 

In 1915, it was shown that N-allylnorcodeine abolished both heroine- and morphine-indueed respiratory depression. Almost 25 years later (1940), it was observed that N-allylnormorphine (eom-monly known as nalorphine) possessed more marked and signifieant morphine antagonizing aetions. Thirteen years later (1953), it was demonstrated that nalorphine had the ability to arrest severe abstinence syndromes in postaddicts who were earlier treated briefly with either morphine, methadone or heroine. Examples of narcotic antagonists include nalorphine hydrochloride naloxone hydrochloride propiram fnmarate and pentazocine. 

Fig. 8.3 Space-fining ball-and-s(ick (la-4a, lc-4c) and CPK (lb-4b, ld-4d) three-dimensional molecular models of the structures of morphine (la-ld), methadone (2a-2d), meperidine (3a-3d), and fentanyl (4a-4d). (For two-dimensional structures of morphine, methadone, meperidine, and fentanyl refer to Fig. 8.1). Conventional colors used for different atoms are shown in structures la-4a and lb-4b. In structures Ic- c and ld-4d the morphine pharmacophore of a tertiary alkylamine at least three atoms away from, and including, an aromatic ring is shown in blue while the rest of the molecule is shown in light gray. For methadone, the...

PCPA blocks the analgesic actions of morphine, methadone, propoxyphene and meperidine.CNS effects of morphine other than analgesia are blocked by PCPA,35 but the findings of Way et al36 that PCPA blocks symptoms accompanying morphine withdrawal have not been confirmed. 

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