Clinical Textbook of Addictive Disorders 3rd ed - R. Frances, S. Miller, A. Mack (Guilford, 2005) WW

144 III. SUBSTANCES OF ABUSEAnalgesia is the principal useful effect of the opioids. It seems not to matterwhether the pain is physical or emotional: Relief is significant. The addictionpotential of a given opioid appears to be at least partly related to the analgesicaffect. Analgesia from full opioid agonists increases in a dose-relatedmanner, to a point beyond which larger doses cause greater side effects but nogreater analgesia (Deneau & Mule, 1981). Contravening side effects includerespiratory depression, sedation, seizures, and loss of motor control. Heroin,morphine, and hydromorphone are among the best analgesics because of rapidabsorption into the central nervous system and a relatively higher threshold forside effects. Meperidine and codeine are less effective in this regard. Route ofadministration significantly affects analgesia. Parenteral use is the most efficient,because oral administration subjects the opioid to erratic absorption inthe gastrointestinal tract, as well as passage through the portal system beforereaching the central nervous system. Codeine and methadone are reliablyabsorbed orally; morphine and meperidine are not.Opioids are potent suppressors of the cough reflex, and this antitussiveaction is most often accomplished with codeine or hydrocodone. A related phenomenonis that of respiratory depression. Opioids cause the central respiratorycenter to become less sensitive to carbon dioxide, which in rising concentrationsordinarily stimulates breathing. The mechanism of death in acute opioidoverdose usually is respiratory arrest.Opioids have pronounced gastrointestinal effects. Initially the user mayexperience nausea and emesis due to central stimulation; however, this is followedby depression of the central structures controlling emesis, and evenemetic agents frequently fail to produce vomiting. The intestinal smooth muscleis stimulated to contract by opioids, thus reducing peristalsis. Although thisaction may be desirable in preventing loss of water through diarrhea, the relatedundesirable effect of constipation routinely appears with repeated administration.Smooth muscle contraction in the urinary bladder is also stimulated byopioids, sometimes resulting in an unpleasant sensation of nearly constant urinaryurgency. Although uterine muscle is not significantly affected by opioids,labor is frequently prolonged. Because opioids do cross the placental barrier,newborn infants can show all the adult signs of intoxication, withdrawal, andoverdose.Blood vessels in the periphery are generally dilated as a result of opioidinducedhistamine release; this sometimes causes a blush of the skin, with itching,especially in the face. By a separate mechanism, reflex vasoconstriction isinhibited, resulting in significant orthostasis. Some endocrine effects have alsobeen noted. Thyroid activity, output of gonadotropins, and adrenal steroid outputare all reduced. These effects are caused by opioid actions on the pituitarygland.