Opioids morphine

Opioids. Morphine [57-27-2] C yH NO, (8) the most prevalent and analgesicaHy potent of the naturally occurring opium alkaloids (qv), has been used as an anesthetic premedication for over one hundred years (93). It has also been used as an iv analgesic for the last four decades, and, since 1969, in high doses as an anesthetic agent (117). 

Epidural analgesia is frequently used for lower extremity procedures and pain (e.g., knee surgery, labor pain, and some abdominal procedures). Intermittent bolus or continuous infusion of preservative-free opioids (morphine, hydromorphone, or fentanyl) and local anesthetics (bupivacaine) may be used for epidural analgesia. Opiates given by this route may cause pruritus that is relieved by naloxone. Adverse effects including respiratory depression, hypotension, and urinary retention may occur. When epidural routes are used in narcotic-dependent patients, systemic analgesics must also be used to prevent withdrawal since the opioid is not absorbed and remains in the epidural space. Doses of opioids used in epidural analgesia are 10 times less than intravenous doses, and intrathecal doses are 10 times less than epidural doses (i.e., 10 mg of IV morphine is equivalent to 1 mg epidural morphine and 0.1 mg of intrathecally administered morphine).45... 

In 1976 Martin proposed the theory that there are three subtypes of opioid receptor on the basis of behavioural studies using a chronic spinal dog model which revealed that the opioids morphine (mu) (1), ketazocine (kappa) (2) and A-allylnormetazocine (SKF 10047) (4) (sigma) had different effects on respiration, heart rate and locomotor activity [13]. Furthermore, these ligands were unable to replace each other to prevent withdrawal symptoms in dogs that had been chronically treated with one of the compounds. 

Analgesics are divided into two groups opioids (morphine-like substances), which predominantly influence the central nervous system (CNS) and nonopioids (nonsteroidal antiinflammatory or fever-reducing drugs—NSAID), which act predominantly on the peripheral nervous system. 

The above mentioned reactions are widely used in alkaloid modification. A good example of alkaloid modifications for clinical curation purposes are opioides. Morphine and codeine are natural products of Papaver somniferum. However, the codeine is naturally produced in small amounts. This is one reason why it is produced synthetically from morphine by modification. As codeine is the 3-0-methyl ether of morphine, the mono-O-methylation occurs in the acidic phenolic hydroxyl. Pholcodine is obtained by modification of morphine through alkylation with A-(chloroethyl)morpholine. Moreover, dihydrocodeine, hydro-morphone and heroine are also obtained from morphine through modifications. 

Schedule II - The drugs at this level also have a high abuse potential and could cause psychic or physical dependence. They may be prescribed but are under stringent control. Schedule II drugs include opioids(morphine), amphetamines and methamphetamines used alone or in combination as well as some barbiturates. 

Despite an intensive research effort over the past two decades involving many innovative approaches in the global academic community and by the pharmaceutical industry, the latter representing an aggregate investment in excess of 2.5 billion, the only new opioid-based pain medications either in clinical development or on the market are alternative dosage forms of the classical opioids, morphine, loperamide, and fentanyl, or compounds such as tramadol. ... 

Opioids Morphine Hydromorphone (Dilaudid) Meperidine (Demerol) Methadone Fentanyl Propoxyphene (Darvocet) Hydrocodone (Vicodin) Oxycodone (OxyContin, Percocet)... 

Severity of pain, route of administration, and patient history of opioid use should guide the selection of an appropriate opioid. Morphine is the prototypical pure agonist to which... 

Opioids morphine, codeine Cigarette smoking Cocaine insufflation... 

Opioids Morphine, Heroin, Methadone, Fentanyls, Other Opioids ... 

Opioids morphine 30H > 60H, buprenorphine, nalorphine, naltrexone, codeine (low) and naloxone. 

Dexamfetamine increased the analgesic effect of morphine and reduced its respiratory depressant effects to some extent in studies during postoperative analgesia and in healthy subjects. Methylphenidate 15 mg daily similarly increased the analgesic effects of various opioids (morphine, hydromorphone, ievorphanol, oxycodone) and reduced the sedative effects in patients with chronic pain due to advanced cancer. Therefore, the analgesic dose of an opioid may be lower than expected in patients on these drugs. 

Gabapentin has been reported to enhance the analgesic effects of morphine and other opioids. Morphine can increase the bioavailability of gabapentin. 

Chloroprocaine can reduce the efficacy of epidural morphine and fentanyl analgesia. Bupivacaine may enhance the local anaesthetic effect of fentanyl, but does not appear to affect respiration. Similarly, Udocaine does not appear to increase respiratory depressant effects of morphine. However, two cases of respiratory depression have been reported with Udocaine and opioids. Morphine given as an intravenous bolus does not alter Udocaine serum levels given as a continuous intravenous infusion. 

For mention of the suggestion that NSAIDs may increase the incidence of myoclonus with high-dose morphine, see Opioids Morphine + Miscellaneous , p.l90. 

FIGURE 17.5 Opioids. Morphine and codeine are natural alkaloids in the opium poppy. Heroin is a synthetic derivative with similar activity as a drug, but it is dangerously addictive. 

Due to morphine s hydrophilic nature, the spinal cord s exposure over time to intrathecal morphine greatly exceeds that of other spinal opioids, leading to a prolonged analgesic effect but also greater rostral spread and the potential for delayed respiratory depression and sedation. Compared to less hydrophilic opioids, morphine has a lower spinal cord distribution volume, slower clearance from the spinal cord into the plasma, and higher bioavailability in the extracellular fluid space of the spinal cord [1]. 

Of six patients with central sleep apnea, who were receiving opioids (morphine equivalent doses of 120 20 mg/day) for chronic pain, four achieved symptomatic improvement when treated with bi-level ventilation, correcting nocturnal hypoxemia and reducing sleep fragmentation P ]. 

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