Opioid agonists adverse effects

The intoxicating effects of opioids appear to be due to their action as agonists on mu (p) receptors of the opioid neurotransmitter system. Competitive p opioid antagonists such as naloxone and naltrexone acutely reverse many of the adverse effects of opioids. To date we do not have specific antagonists for most other abused substances, so rapid pharmacologic reversal of intoxication is usually not possible. 

Bowdle, T.A. (1998) Adverse effects of opioid agonists and agonist-antagonists in anaesthesia. Drug Saf. 19 173-189. 

Respiratory depression is one of the most prominent adverse effects of p opioid agonists (e.g., morphine). The frequency of breathing and the inspiratory volume can be affected differently by drugs and have to be measured. 

Butorphanol is a synthetic 14-hydroxymorphinan analogue with a low dependence potential and a low propensity to cause opioid adverse effects (1). It is a synthetic OP2 (k) receptor agonist and OP3 ( ) receptor antagonist. 

Conorfone is an opioid analgesic, a codeine derivative, with mixed agonist-antagonist activity (SED-11, 150). It has adverse effects similar to those of codeine, bnt canses more drowsiness (1). 

Drug-related factors There is little evidence suggesting that any one opioid agonist has a substantially better adverse effects profile than any other. 

Studies of the use of the partial opioid agonist butor-phanol to reduce the adverse effects of epidural morphine have not provided evidence of benefit (SEDA-19, 86). Epidural meptazinol has been described as being well tolerated (135). 

Tonazocine is a partial opioid receptor agonist that has not been reported to have adverse effects on the cardiovascular system or to cause clinically significant respiratory depression. When single doses of tonazocine 2,4, and 8 mg were compared in 150 adults postoperatively. 

Diphenoxylate HCI (2.5 mg) and atropine (0.025 mg) are combined in tablets or 5 mL liquid and are used effectively as symptomatic treatment for diarrhea. The typical dose is two tablets or 10 mL every 3 to 4 hours. The combination with atropine enhances the block of acetylcholine-stimulated peristalsis, and the adverse effects of atropine helps to limit the abuse of the opioid. The combination is Schedule V under the Controlled Substances Act. Diphenoxylate itself has low p opioid agonist activity. It is metabolized rapidly by ester hydrolysis to the zwitterionic free carboxylate (difenoxin), which is five times more potent after oral dosing. The zwitterionic properties of difenoxin probably limits its penetration into the CNS and explains the low abuse potential of this agent. High doses of diphenoxylate (40-60 mg) will cause euphoria and addiction. 

General precautions associated with the use of all opioid agonists should be observed with the use of hydrocodone bitartrate respiratory depression and adverse CNS effects are primary concerns, and the use of hydrocodone should be individually tailored in those patients at risk for these complications, if undertaken at all. Particular attention is warranted in... 

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