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[Opioid tolerance and dependence--pharmacological aspects].
I M Jaba1, I Luncanu, O C Mungiu
1Facultatea de Medicină, Catedra de Farmacologie, Toxicologie şi Algeziologie, Universitatea de Medicină şi Farmacie Gr. T. Popa Iaşi.
Summary
Opioid tolerance and dependence can be managed. Combining opioid agonists with calcium channel blockers may prevent tolerance and enhance analgesic effects, offering new therapeutic avenues.
Area of Science:
- Pharmacology
- Neuroscience
Context:
- Prolonged opioid administration leads to tolerance and dependence.
- Tolerance involves neuronal hypersensitivity and altered opioid receptor characteristics.
- Physical dependence manifests as an abstinence syndrome upon opioid cessation.
Purpose:
- To review current understanding and emerging strategies for managing opioid tolerance and dependence.
- To explore pharmacological alternatives and novel therapeutic targets.
Summary:
- Traditional treatments include methadone and opioid antagonists (naloxone, naltrexone).
- Modern alternatives include LAAM, and agonist-antagonists (buprenorphine, nalbuphine).
- Emerging research explores enkephalinase inhibitors, NMDA receptor antagonists, NO synthase inhibitors, and CCK receptor modulators.
- Concomitant administration of sufentanil (opioid agonist) and nimodipine (calcium channel blocker) prevents tolerance and induces opioid hypersensitivity.
Impact:
- Provides insights into mechanisms of opioid tolerance and dependence.
- Highlights current and future pharmacological interventions for opioid management.
- Suggests novel combination therapies for improved pain management and reduced adverse effects.