Analgesics interaction

Bodnar RJ, Paui D, Pasternak GW. (1991). Synergistic analgesic interactions between the periaqueductai gray and the iocus coeruleus studies with the partial mu-1 agonist ethyiketocyciazocine. Brain Res. 558 224-30. 

Opioid analgesics interact with non-selective monoamine oxidase inhibitors, causing nervous system excitation and hypertension (70). These interactions have been reviewed (SEDA-18, 14). 

Finally, the demonstration that narcotic analgesics interact with brain amines suggests that these analgesics may interact with other psychotropic drugs, like the MAO inhibitors, the tricyclic antidepressants and the neuroleptics. 

P-Endorphin. A peptide corresponding to the 31 C-terminal amino acids of P-LPH was first discovered in camel pituitary tissue (10). This substance is P-endorphin, which exerts a potent analgesic effect by binding to cell surface receptors in the central nervous system. The sequence of P-endorphin is well conserved across species for the first 25 N-terminal amino acids. Opiates derived from plant sources, eg, heroin, morphine, opium, etc, exert their actions by interacting with the P-endorphin receptor. On a molar basis, this peptide has approximately five times the potency of morphine. Both P-endorphin and ACTH ate cosecreted from the pituitary gland. Whereas the physiologic importance of P-endorphin release into the systemic circulation is not certain, this molecule clearly has been shown to be an important neurotransmitter within the central nervous system. Endorphin has been invaluable as a research tool, but has not been clinically useful due to the avadabihty of plant-derived opiates. 

Narcotic analgesic. A drug that alleviates pain by interacting with the morphine receptor. 

The existence of further alternative transcripts of MOP was postulated by the observation that in knockout mice with disrupted exon 1, heroin but not morphine was still analgesically active. Based on earlier observations that the antagonist naloxazone blocked morphine-induced antinociception but not morphine-induced respiratory depression, a subdivision of the MOP in pi and p2 was proposed. However, no discrete mRNA for each of these MOP subtypes has been found. It is, however, possible that subtypes of MOPs result from heterodimerization with other opioid receptors or by interaction with other proteins. 

Discuss the uses, general drug action, general adverse reactions, contraindications, precautions, and interactions of the narcotic analgesics. 

Phenytoin interacts widi many different drugp. For example isoniazid, chloramphenicol, sulfonamides, benzodiazepines, succinimides, and cimetidine all increase phenytoin blood levels. The barbiturates, rifampin, theophylline, and warfarin decrease phenytoin blood levels. When administering the hydantoins with meperidine, die analgesic effect of meperidine is decreased. 

For a detailed description of spectral map analysis (SMA), the reader is referred to Section 31.3.5. The method has been designed specifically for the study of drug-receptor interactions [37,44]. The interpretation of the resulting spectral map is different from that of the usual principal components biplot. The former is symmetric with respect to rows and columns, while the latter is not. In particular, the spectral map displays interactions between compounds and receptors. It shows which compounds are most specific for which receptors (or tests) and vice versa. This property will be illustrated by means of an analysis of data reporting on the binding affinities of various opioid analgesics to various opioid receptors [45,46]. In contrast with the previous approach, this application is not based on extra-thermodynamic properties, but is derived entirely from biological activity spectra. 

Buprenorphine is a weak analgesic [91], which precludes its ability to replace morphine in the treatment of chronic pain. However, development of compounds that interact with /u receptors in a similar manner as buprenorphine but that are more effective agonists and analgesics could lead to the development of drugs that can be used for the treatment of chronic pain but which have little or no abuse potential. 

Portoghese PS. A new concept on the mode of interaction of narcotic analgesics with receptors. J Med Chem 1965 8 609-616. 

Interactions are seen between cocaine and the opioid system in analgesia. A synergistic effect occurs when cocaine is combined with a ju agonist (morphine) in the hot-plate test and a k agonist (U69,593) in the hot-plate test (Waddell and Holtzman 1999). Cocaine enhances morphine analgesia in several analgesic paradigms (e.g., formalin test, hot-plate test, and thermal tail-flick test)... 

Cannabinoids are known to interact with opioid systems. This is particularly relevant to their analgesic effects and is discussed at length in chapter 8. 

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