Opiate drugs

The pharmacological and/or adverse effects of a drug can be reversed by co-administration of drugs which compete for the same receptor. For example, an opioid receptor antagonist naloxone is used to reverse the effects of opiates. Drugs acting at the same site with opposite effects also can affect each other, e.g. the reduction in the anticoagulant effect of warfarin by vitamin K. 

Cooper OB, Brown TT, Dobs AS Opiate drug use a potential contributor to the endocrine and metabolic complications in human immunodeficiency virus disease. Clin Infect Dis 37(suppl 2) S132—S136, 2003... 

Opiate drug exposure has a significant impact on HIV infection as well as progression to HIV-associated dementia. On a cellular level it is comprehendible that drugs of abuse such as opioids would reduce the threshold for neurotoxicity such that a marginally toxic insult would now be exacerbated and lead to cell death or injury... 

When Montgomery and I published our article, we thought we had disproven another theory of placebo effects - the theory that placebo effects are produced by the release of endorphins in the brain. In 1978 researchers at the University of California in San Francisco discovered that when placebos reduce pain, they may stimulate the release of endorphins.18 Endorphins, the existence of which had only been discovered a few years earlier, are opioids that are produced naturally by the brain. Just like the opiates that are derived from opium - morphine and codeine, for example - endorphins reduce the sensation of pain. The University of California researchers reasoned that if placebos can mimic the effects of opiate drugs, maybe they do so by stimulating the release of the brain s endogenous opioids. 

Endorphins are found primarily in the limbic system, hypothalamus, and brainstem. Enkephalins and dynorphin (in smaller quantities) are found primarily in the periaqueductal gray matter (PAG) of the midbrain, the limbic system, and the hypothalamus. These endogenous substances mimic the effects of morphine and other opiate drugs at many points in the analgesic system, including in the dorsal horns of the spinal cord. 

Opioid peptide A neuropeptide (e.g., p-endorphin), whose actions are mimicked by opiate drugs. 

The reinforcing effects of opiate drugs involve a number of neuronal pathways [21]. In the VTA, opiates stimulate p-opioid receptors on GABA neurons that synapse on dopamine neurons. This inhibits the GABA neurons, leading to disinhibition of the dopamine neurons and enhanced dopamine release in the nucleus accumbens and other target areas (Fig. 56-3). Opiates also exert dopamine-independent effects in the nucleus accumbens by activating... 

Sacerdote, P. et al., Antinociceptive and immunosuppressive effects of opiate drugs A structure-related activity study, Hr. J. Pharmacol., 121, no. 4, 834—840, 1997. 

Opiate drugs encompass morphine and its many synthetic derivatives including heroin. Opiates act by mimicking endogenously occurring morphine-like neurotransmitter peptides termed the enkephalins or endorphins. 

Alcohol is a socially accepted drug of abuse in Western countries. Due to the high potential for addiction to develop, however, it is actually a hard drug and has a much larger number of victims than the opiate drugs, for example. In the brain, ethanol is deposited in membranes due to its amphipathic properties, and it influences receptors for neurotransmitters (see p. 352). The effect of GABA is enhanced, while that of glutamate declines. 

Figure 4.4 Brain showing binding sites and pathways of opiate drugs. Kairos, Latin Stock/Photo Researchers, inc.

There are many legal medicines that use opiates or opiate-like substances. Most of the opiate-based medicines used today are not made from natural opiates, but are either synthetic or semi-synthetic. Synthetic opiate drugs are not actually opiates at all they are merely different chemicals that act like opiates. Semi-synthetics are those drugs that involve changing the chemical structure of a natural opiate. An example of this is heroin, which is a human-made variation of morphine. Morphine and codeine are the principal natural opiates used as medicines and what follows are descriptions of the other most frequently used opiate-based medicines. 

According to the Controlled Substances Act, the term narcotic drug refers to more than just opiate drugs it also includes opium, poppy straw, derivatives of opium and opiates, cocaine, coca leaves, and extracts that contain cocaine and ecgonine (the major metabolite of cocaine) and its derivatives. These may be directly or indirectly produced by extraction from substances, by chemical synthesis, or by a combination of both methods. 

As far as possible, methadone treatment should mean just that, not methadone plus other medications of potential misuse. The theoretical footing for this is that the majority of the positive evidence for effectiveness relates to methadone alone, although we noted earlier that the main studies did not include individuals who were significant users of non-opiate drugs. 

Rasmussen P. A role for phytotherapy in the treatment of benzodiazepine and opiate drug withdrawal. EurJ Herbal Med 1997 3 11-21. 

Naloxone will block the effects of opiate drugs and is used to treat overdoses. It was found that during trauma the use of naloxone would increase pain and prevent naturally induced analgesia. It was only a matter of time until the endogenous opiates, the endorphins (for endogenous morphine) and enkephalins, were discovered. Now there exists a whole nomenclature of opiate receptor types and their various effects. 

The cause of RLS is still unknown, but likely involves a deficiency in the neurotransmitter dopamine. Scientists suspect a dopamine deficiency is to blame because the most widely prescribed medication for treating RLS is levadopa (also called L-dopa), which the body turns into dopamine. Other medications that seem to alleviate symptoms are opiate drugs such as codeine and oxycodone, but these must only be administered occasionally since they are prone to cause addiction. Finally, some benzodiazepines (discussed in Chapter 6) also help the RLS sufferer get a better night s rest. 

Sequence Determination of the Brain Peptide Leucine Enkephalin A group of peptides that influence nerve transmission in certain parts of the brain has been isolated from normal brain tissue. These peptides are known as opioids, because they bind to specific receptors that also bind opiate drugs, such as morphine and naloxone. Opioids thus mimic some of the properties of opiates. Some researchers consider these peptides to be the brain s own pain killers. Using the information below, determine the amino acid sequence of the opioid leucine enkephalin. Explain how your structure is consistent with each piece of information. 

---