Opioid abuse potential

Benzodiazepines and similar agents occupy a position of intermediate abuse potential, compared with most other sedative-hypnotics (Griffiths and Weerts 1997). Animal models of abuse habihty indicate that the reinforcing effects of benzodiazepines are less pronounced than are those of the barbiturates, opioids, and stimulants. Differences in abuse potential within the class have not been consistently demonstrated however, most chnicians agree that benzodiazepines with a rapid onset and short duration of action pose the greatest risk in susceptible individuals. 

This class produces analgesia and has a ceiling effect on respiratory depression and lower abuse potential than morphine. However, psychotomimetic responses (e.g., hallucinations and dysphoria with pentazocine), a ceiling analgesic effect, and the propensity to initiate withdrawal in opioid-dependent patients have limited their widespread use. 

High abuse potential with possible medical value in U.S. Cocaine, amphetamines, strong opioid medications... 

Tramadol is a central-acting analgesic, effective for mild to moderate acute and chronic pain. It impairs nociception by a unique mechanism that is not completely understood. In animal models, it binds to the /u. opioid receptor and is a weak inhibitor of serotonin and norepinephrine reuptake, actions similar to those ascribed to the SSRIs and TCAs. Seizures have been reported in patients taking tramadol. Abuse potential is low, but does exist. 

It is centrally acting synthetic analgesic compound that is not derived from natural sources nor is chemically related to opiates. It acts via opioid receptors in CNS to produce analgesia and has no abuse potential. It also inhibits the reuptake of noradrenaline and serotonin. 

Codeine, one of the principal alkaloids of opium, has an analgesic efficacy much lower than other opioids, due to an extremely low affinity for opioid receptors. It is approximately one-sixth as potent as morphine. It has a low abuse potential. In contrast to other opioids, with the exception of oxycodone, codeine is relatively more effective when administered orally than parenterally. This is due to methylation at the C3 site on the phenyl ring (Figure 7.3), which may protect it from conjugating enzymes. It is used in the management of mild-to-moderate pain, often in combination with non-opioid analgesics, such as aspirin or paracetamol. It is valuable as an antitussive and for the treatment of diarrhoea. Side effects are uncommon and respiratory depression, even with large doses, is seldom a problem. 

Nalbuphine hydrochloride is structurally related to oxymorphone and naloxone. It is approximately equipotent with morphine. Nalbuphine is metabolised in the liver to inactive metabolites. The plasma terminal half-life is approximately 5 h. The onset of analgesia is within 2-3 min of intravenous administration and 15 min after intramuscular injection, and lasts 3-6 h with an adult dose of 10 mg. With equi-analgesic doses, similar degrees of respiratory depression to that of morphine occur up to a dose of approximately 0.45 mg-kg-1. With higher doses a ceiling effect occurs. Sedation, possibly mediated by K-receptor activation, occasionally occurs. The incidence of psychotomimetic side effects is lower than with pentazocine. The abuse potential is low, but is can cause withdrawal symptoms in opioid-dependent subjects. It has occasionally been used to reverse opioid-induced respiratory depression. 

Obviously, the risk of causing dependence is an important consideration in the therapeutic use of these drugs. Despite that risk, under no circumstances should adequate pain relief ever be withheld simply because an opioid exhibits potential for abuse or because legislative controls complicate the process of prescribing narcotics. Furthermore, certain principles can be observed by the clinician to minimize problems presented by tolerance and dependence when using opioid... 

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. 

The intestinal inhibitory action of opioids can be used for treatment of diarrhea (De Luca and Coupar, 1996). The clinically most important anti-diarrheal opioid is loperamide (Heel et al., 1978). After oral administration, loperamide acts locally within the gastro-intestinal tract. After parenteral administration, the compound is rapidly inactivated and does not reach the CNS. Therefore loperamide does not show the typical central opioid side-effects, has no analgesic action and has no abuse potential. 

Side-effects Buprenorphine induces p-opioid-type side effects including respiratory depression, drowsiness, nausea and vomiting. In the clinical literature, however, there are only few cases of significant respiratory depression. Reversal of respiratory depression may need higher doses of naloxone (Gal, 1989). Buprenorphine has a limited abuse potential and withdrawal reactions, due to slow receptor dissociation, are mild and delayed. 

Side-effects Dezocin induces j-opioid-type side-effects with nausea, vomiting and drowsiness. Overdoses may be treated with naloxone. The compound has a low abuse potential and is not under narcotic control. Because of its partial antagonistic properties dezocine can precipitate withdrawal in opioid-dependent subjects (Strain et al., 1996). 

Side-effects Typical side-effects of tramadol are nausea, sweating and dizziness. In rare cases seizures after high i.v. doses are reported, mostly in combination with other proconvulsant componds or in patients with reduced seizure theshold (Gardner et al., 2000). Tramadol shows a reduced level of opioid side-effects, especially respiratory depression and constipation are less frequent and severe than with standard opioids such as morphine. Tramadol has a very limited abuse potential and is not subject to narcotic control (Cossmann et al., 1997). 

Schedule V. These drugs have the lowest relative abuse potential. Drugs in this category consist primarily of low doses of opioids that are used in cough medications and antidiarrheal preparations. 

If the FDA recommends not to schedule a drug, then the DEA is powerless to schedule the drug on its own. This occurred in the case of the synthetic opioid tramadol (Ultram), which has a very low abuse potential. The administrator of the DEA then compiles all available data in addition to the HHS recommendation and makes... 

In recent years there has been a major research effort, so far without success, to produce potent, centrally acting analgesics that do not have an abuse potential. The discovery of various types of opioid receptor, which may have different effects on central neurotransmitter function, may ultimately lead to the development of such a drug. In the meantime, the most widely used opioids, for example morphine, heroin (also called diacetylmorphine) and codeine are therapeutically effective but are liable to be abused and produce dependence. The structure of some of the morphine-like analgesics and their antagonists are shown in Figure 15.2. 

Sublingual buprenorphine is an alternative to methadone in treating opiate dependence, but its opioid agonist effects pose the risk of intravenous abuse and subsequent dependence. This abuse potential may be hmited by using a combination of buprenorphine with naloxone, which will precipitate opiate withdrawal when given... 

The mechanism of loperamide toxicity is related to opioid-like activity that causes depression of the central nervous system (CNS). The abuse potential for loperamide is low. 

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