Opioids addictive potential

The answer is c. (Hardman, pp 528-537.) Morphine is a pure agonist opioid drug with agonist activity toward all the opioid subtype receptor sites. In high doses, deaths associated with morphine are related to the depression of the respiratory center in the medulla. Morphine has a high addiction potential related to the activity of heroin or dihydromorphine. Codeine has a significantly lower addiction potential. 

Opiates and opioid derivatives delay the transit of intraluminal content or increase gut capacity, prolonging contact and absorption. The limitations of the opiates are addiction potential (a real concern with long-term use) and worsening of diarrhea in selected infectious diarrheas. 

Morphine and other opioids work by activating a family of opioid receptors in the brain. These fall into three classes and morphine activates all of them. It has proved possible to design and synthesize opioids that are more-or-less specihc for snbsets of the opioid receptors. However, none of these has proved to have the right set of activities to retain the potent analgesic power of morphine withont the addiction potential and respiratory depression potential. Finding such a molecule remains on ongoing challenge. 

Reward Therapy. A similar (yet nonspecific) approach is to use a medication that stimulates the brain s reward centers. Reward medications usually do not work in quite the same way as the substance of abuse however, the net effect in the final common pathway (i.e., the reward centers) may be the same. For the most part, these reward centers are activated by either dopamine or endogenous opioid agonists. One common feature of most abused drugs is that they stimulate these reward centers. This lies at the heart of their addictive potential. Some attempts have been made to use medications that activate these reward centers in place of the abused substance. The hypothesis is that the addict will have less intense craving for his/her preferred substance of abuse in the presence of these other agents. This is, of course, a relatively nonspecific approach that could theoretically be used to treat the abuse of many different substances. It has not yet, however, demonstrated any utility in the treatment of substance abuse. 

Morphine was isolated from opium in 1806, which was a significant step in scientific pharmacology. For the first time, a powerful, pain-relieving medicine was available whose effects were predictable. However, it eventually became clear that the addictive potential of morphine is equal to that of opium, with many of the same side effects. Undaunted, scientists began the quest, which is ongoing, for the perfect opioid—a drug with the analgesic power of morphine, but with much milder side effects and little or no addictive potential. 

A survey of 59 questions sent to physicians practicing in the state of Texas revealed many areas of concern when prescribing opioids.Ten percent of those surveyed would withhold opioid medications until a patient in severe pain had either a prognosis of less than 1 year or was terminal. Forty percent were extremely concerned regarding potential addiction. More than one-half falsely believed that opioid addiction is a common occurrence with legitimate prescribing. The physicians surveyed also... 

Buprenorphine Opioid Buprenorphine is a synthetic p-opioid partial agonist synthesized in 1967 [229] and initially utilized as an analgesic [230]. It was not used as a maintenance treatment for opioid addiction until the mid-1980s. Studies have showed that buprenorphine s effects were longer-acting and that it had a lower potential for abuse than did morphine [231]. Suboxone is a combination of buprenorphine plus naloxone formulated to prevent misuse. 

Administration (FDA) for the treatment of opioid addiction. Treatment is initiated with buprenorphine alone administered sublingually, followed by maintenance therapy with a combination of buprenorphine and naloxone (Suboxone) to minimize abuse potential. The partial agonist properties of buprenorphine limit its usefulness for the treatment of addicts who require high maintenance doses of opioids. However, conversion to maintenance treatment with higher doses of methadone, a full agonist, is possible. 

Development of physical dependence during the longterm administration of methadone can be demonstrated by drug withdrawal or by administration of an opioid antagonist. Subcutaneous administration of 10 to 20 mg methadone to former opioid addicts produces definite euphoria equal in duration to that caused by morphine, and its overall abuse potential is comparable with that of morphine. 

II Medical use high addiction potential Strong opioid agonists, cocaine, short half-life barbiturates, amphetamines, methylphenidate... 

The efflux transporter P-gp is a major determinant of the pharmacokinetics and pharmacodynamics of loperamide, a potent opiate. The main reason that loperamide does not produce opioid CNS effects at usual doses in patients is a combination of slow dissolution, first-pass metabolism, and P-gp-mediated efflux, which prevents brain absorption, perhaps contributing to its low addiction potential. Loperamide produced no respiratory depression when administered alone, but when administered with a P-gp inhibitor, respiratory depression occurred, which could not be explained by increased plasma loperamide concentrations. This effect demonstrates the potential for important drug interactions by inhibition of P-gp efflux transporter. The lack of respiratory depression produced by loperamide, which allows it to be safely used therapeutically, can be reversed by a drug causing P-gp inhibition, resulting in serious toxic and abuse potential. 

Other constraints are important for more complex products, for which mass is not central, but value. For example, central nervous system stimulants are a new class of substances addressed by production with engineered baker s yeast. Expressing the biosynthetic pathways for the opioids thebaine and hydrocodone, and parts of the morphine pathway in yeast, a first step is taken for easy production of opiates [21, 22]. This opens the possibility for the development of new painldllers with less addictive potential. However, it clearly is a new technology that could be abused with many negative consequences - so some contemplation about how to control these developments seems advisable [23]. Not only are narcotics in the center of interest but stimulants such as caffeine and theobromine have also recently been produced with genetically engineered 5. cerevisiae strains [24]. 

Nalbuphine (trade name in Germany and elsewhere Nubain ) is a mixed agonist-antagonist. The danger of hallucinations and psychotic effects is lower than for other dualistic opioids. The addiction potential is likewise low, so that nalbuphine is not subject to regulatory control as a narcotic. 

Two opioids are used in the treatment and management of opiate dependence levomethadyl and methadone. Levomethadyl is given in an opiate dependency clinic to maintain control over the delivery of the drug. Because of its potential for serious and life-threatening proarrhythmic effects, levomethadyl is reserved for use in the treatment of addicted patients who have no response to other treatments. Levomethadyl is not taken daily the drug is administered three times a week (Monday/Wednesday/Thursday or Tuesday/Thursday/ Saturday). Daily use of the usual dose will cause serious overdose. 

Long -term sequelae of chronic pancreatitis include dietary malabsorption, impaired glucose tolerance, cholangitis, and potential addiction to opioid analgesics. 

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