Opioid pharmacological effects

Opioids are easily absorbed subcutaneously and intramuscularly, as well as from the gastrointestinal tract, nasal mucosa (e.g., when heroin is used as snuff), and lung (e.g., when opium is smoked). About 90% of the excretion of morphine occurs during the first 24 hours, but traces are detectable in urine for more than 48 hours. Heroin (diacetyhnorphine) is hydrolyzed to monoacetylmorphine, which is then hydrolyzed to morphine. Morphine and monoacetylmorphine are responsible for the pharmacologic effects of heroin. Heroin produces effects more rapidly than morphine because it is more lipid soluble and therefore crosses the blood-brain barrier faster. In the urine, heroin is detected as free morphine and morphine glucuronide (Gutstein and Akil 2001 Jaffe et al. 2004). 

Young, G.A. Neistada, L. and Khazan, N. Differential neuro-pharmacological effects of mu, kappa, and sigma opioid agonists on cortical EEG power spectra in the rat. Res Commun Psvchol Psvchiatr Behav 6 365-377, 1981. 

Tolerance to many of the effects of the depressants develops. Unlike opioids, barbiturate and benzodiazepine tolerance develops slowly. Also, tolerance is incomplete in some instances or does not influence some pharmacological effects. One such exception is the lack of tolerance to barbiturate lethality. The lethal dose in a tolerant individual is not much different from that of the general population. Cross-tolerance develops to some degree between the depressant classes of drugs. 

It is a potent opioid analgesic. Chemically it is N-phenyl-N-propanamide. It interacts predominantly with opioid p-recep-tor in human brain, spinal cord and other tissues. It exerts its principle pharmacologic effects on the CNS. It is 80-100 times more potent than morphine, both in analgesia and respiratory depression. 

The development of physical dependence is an invariable accompaniment of tolerance to repeated administration of an opioid of the - type. Failure to continue administering the drug results in a characteristic withdrawal or abstinence syndrome that reflects an exaggerated rebound from the acute pharmacologic effects of the opioid. 

The aim of this concept was to synthesize drugs which combine both activities in one molecule. Before in vitro screening was started, excellent correlation between pharmacological effects and L-type channel as well as p opioid binding affinity was ensured (data not shown). 

Members of the group of natural, semisynthetic, or synthetic alkaloid compounds prepared from opium are referred to as opioids. This group includes natural compounds usually denoted opiates, such as morphine and codeine, and the synthetic and semi synthetic compounds such as oxycodone, buprenorphine, fentanyl, methadone, and tramadol. The pharmacological effects and pharmacokinetic parameters of these drugs share many common characteristics and are illustrated with the prototypic drug in this class, morphine. 

We expected that (-)-TAN-67 will be used for the detailed investigation of both the existence and the pharmacological effects of a <5i opioid receptor, and that the (+)-TAN-67-induced nociception may be a unique pharmacological model for the elucidation of pain mechanisms. Moreover, the hyperalgesia produced by (+)-TAN-67 could be one of the neuropathic pain models. We hope that the (+)-TAN-67-induced nociception will be used for the development of analgesics for neuropathic pain, for which morphine indicates little or no effect. 

THC has a variety of pharmacologic effects that resemble those of amphetamines, LSD, alcohol, sedatives, atropine, and morphine. Important opioid interactions include reduction in opioid dependence in CB1 knockout mice lacking the CB1 receptor. 

The opioids produce their pharmacological effects by interacting with a closely related group of peptide receptors, thereby suggesting that endogenous opioid-like polypeptides exist, which presumably have a physiological function. 

The identification of several compounds that have in vitro potencies in the 1-5 nM range at both the mu and delta receptors, such as compounds 54 and 55 (Fig. 11), has provided useful tools to test the pharmacological effects of mixed delta/mu opioid agonists in human clinical trials. 

Naloxone is being used to reverse the potentially lethal respiratory depression caused by neurolept analgesia or opioid overdose. Among other pharmacological effects, naloxone antagonizes the blood pressure drop in various forms of shock [29-32], reverses neonatal hypoxic apnoea [26], counteracts chronic idiopathic constipation [34], reduces the food intake in humans [35, 36] and shows beneficial effects in CNS injuries [37]. 

Heroin s primary toxic principle is its profound ability to depress the central nervous system (CNS). Opioid analgesics bind with stereospecific receptors at many sites within the CNS. Heroin, similar to other opioids, exerts its pharmacologic effect by acting at mu, kappa, and delta receptors in the brain. Although the precise sites and mechanisms of action have not been fully determined, alterations in the release of various neurotransmitters from afferent nerves sensitive to painful stimuli may be partially responsible for the analgesic effect. Activities associated with the stimulation of opiate receptors are analgesia, euphoria, respiratory depression, miosis, and reduced gastrointestinal motility. 

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