Pharmacological Strategies for Decreasing Opioid Therapy and Management of Side Effects from Chronic Use
Abstract
:1. Introduction
2. Opioid-Reduction Weaning Protocols in Pediatric Patients
3. Opioids and Common Side Effects
3.1. Dependence and Withdrawal
3.2. Tolerance
3.3. Opioid Induced Hyperalgesia
3.4. Addiction
4. Assessment of Opioid Withdrawal
5. Opioid Weaning Treatments
Sample Clonidine Dosing and Weaning Schedule
- Start with clonidine 4–8 µg/kg/day oral (per os (PO)) divided every 4 h. If not taking oral intake (nil per os (NPO)), give clonidine 1 µg/kg IV q4h.
- Concurrently initiate opioid weaning by reducing daily opioid dose by 5–10% of baseline dose.
- After 48 h on oral or parenteral clonidine without adverse blood pressure effects, convert to clonidine patch 5–10 µg/kg/day, rounding up or down to nearest 50 µg increment.
- The minimum patient weight for patch use is typically about 5 kg. Although doses as high as 2 µg/kg may be tolerated, the physical patch size makes it difficult to use in smaller children. Therefore, for children ≤5 kg, use oral or intravenous (i.v.) clonidine.
- Once ready to wean, reduce the clonidine patch size by 50 µg/day two times a week until the dose is reduced to the 100 µg/day patch size for children >10 kg, or 50 µg/day patch size for children <10 kg. Then leave this last patch on for 14 days and discontinue afterwards.
- Clonidine weaning may occur concomitantly with opioid weaning, provided the opioid parenteral morphine equivalent dose is less than 0.3 mg/kg/day.
6. Adjuvant Therapies for Opioid Reduction Therapy
7. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Term | Definition | Causative Mechanism |
---|---|---|
Dependence | A physiologic and biochemical adaptation of neurons such that removing a drug precipitates withdrawal or abstinence syndrome | Activation of second-messenger protein kinases; changes in neurotransmitter levels; changes in neuronal networks |
Withdrawal | A clinical syndrome that manifests after stopping or reversing a drug after prolonged exposure to that drug | Superactivation of AC; opioid receptor coupling to Gs protein; activation of excitatory amino acid receptors |
Tolerance | Decreasing clinical effects of a drug after prolonged exposure to it | Upregulation of the cAMP pathway; desensitization of opioid receptors |
Addiction | A chronic, relapsing syndrome of psychological dependence and craving a drug for its psychedelic, sedative, or euphoric effects; characterized by compulsion, loss of control, and continued use of a substance despite harmful effects | Activation of dopaminergic reward systems in nucleus accumbens; mechanisms associated with tolerance and dependence |
Weaning schedules | |
---|---|
IV morphine dose | Methadone total daily dose |
<0.05 mg/kg/h | 0.3 mg/kg/day |
0.05–0.1 mg/kg/h | 0.4 mg/kg/day |
0.11–0.2 mg/kg/h | 0.6 mg/kg/day |
0.21–0.4 mg/kg/h | 0.8 mg/kg/day |
>0.4 mg/kg/h | 1 mg/kg/day |
IV fentanyl dose | Methadone total daily dose |
1 µg /kg/h | 0.05 mg/kg/day |
2 µg/kg/h | 0.1 mg/kg/day |
3 µg/kg/h | 0.15 mg/kg/day |
4 µg/kg/h | 0.2 mg/kg/day |
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D’Souza, G.; Wren, A.A.; Almgren, C.; Ross, A.C.; Marshall, A.; Golianu, B. Pharmacological Strategies for Decreasing Opioid Therapy and Management of Side Effects from Chronic Use. Children 2018, 5, 163. https://doi.org/10.3390/children5120163
D’Souza G, Wren AA, Almgren C, Ross AC, Marshall A, Golianu B. Pharmacological Strategies for Decreasing Opioid Therapy and Management of Side Effects from Chronic Use. Children. 2018; 5(12):163. https://doi.org/10.3390/children5120163
Chicago/Turabian StyleD’Souza, Genevieve, Anava A. Wren, Christina Almgren, Alexandra C. Ross, Amanda Marshall, and Brenda Golianu. 2018. "Pharmacological Strategies for Decreasing Opioid Therapy and Management of Side Effects from Chronic Use" Children 5, no. 12: 163. https://doi.org/10.3390/children5120163