Opioid dosing

Personality variables, state of mind at time of withdrawal, and expectations of severity of symptoms all may affect withdrawal severity (Kleber 1981). One study found that merely providing addicts information about the withdrawal syndrome resulted in lower levels of withdrawal symptoms (Green and Gos-sop 1988). Naloxone rapidly induces a severe withdrawal syndrome, which peaks within 30 minutes and then declines rapidly. Until the antagonist is eliminated, only partial suppression of the withdrawal syndrome is possible, and then only by using very high opioid doses, which may cause respiratory depression when naloxone is metabolized. 

Equianalgesic dose of methadone when compared with other opioids will decrease progressively the higher the previous opioid dose... 

The combination of an opioid and nonopioid oral analgesic often results in analgesia superior to monotherapy and may allow for lower doses of each agent. An NSAID with a scheduled opioid dose is often effective for painful bone metastases. 

Opioids dose-dependently reduce the release of acetylcholine in several brain areas, including the hippocampus, striatum, and cerebral cortex... 

No fixed conversion ratio is likely to be satisfactory in all patients, especially patients receiving large opioid doses. 

Ketorolac (Toradol) is an NS AID with very mild antiinflammatory and antipyretic activity. It is a potent analgesic for postoperative pain. Its efficacy is equivalent to that of low doses of morphine in the control of pain. For this reason it is often combined with opioids to reduce opioid dose and related side effects while providing adequate pain relief. It is also used to replace the opioids in some patients with opioid sensitivity. The mechanism of action of ketorolac involves the inhibition of COX and decreased formation of prostaglandins. However, some evidence exists that ketorolac may stimulate the release of endogenous opioids as a part of its analgesic activity. 

Synergistic effects as described for the supraspinal interaction of opioids with either KCOs or serotonin are interesting in terms of providing a rationale for reducing opioid doses by using co-administration regimes, e.g. with tricyclic antidepressants which are known to increase serotonin levels in the synaptic cleft. 

In one study, daily opioid doses significantly decreased in a gene dose-dependent manner with the ABCB1 3435C>T variant [45]. The same study found that a tendency toward increased pain and the OPRM 111 8A>G variant were associated in a dose dependent manner [45], Another study found that pain relief variability was significantly associated with both polymorphisms [46],... 

Two patients who were hospitalized with a diagnosis of opioid dependence received concomitant treatment with methadone 50 mg/day in one case, and levorpha-nol 14 mg/day in the other, each in association with risperidone. After several days, both had symptoms of opioid withdrawal despite having no change in their opioid doses (256). The withdrawal symptoms resolved soon after risperidone was withdrawn. According to the authors, this finding suggests that risperidone may precipitate opioid withdrawal in opioid-dependent patients. 

Opioids with long half-lives, such as pethidine, or slow-release preparations should generally be avoided, as if toxicity does ensue it will be prolonged. However, after continued unproblematic use of a regular opioid dose a slow-release preparation may be tried cautiously in patients with stable liver disease. 

Stool softeners and cathartics can be used in children, as in adults, to relieve symptoms of constipation. Nausea and vomiting generally diminish as opioid therapy is continued, but antihistamines with antiemetic effects, such as hydroxyzine or promethazine, may be helpful as adjuvants to diminish impleasant G1 symptoms. Reducing the opioid dose to minimal analgesic levels may help to limit sedation or drowsiness. Mild respiratory depression, an uncommon side effect in children, may require only that the opioid dose be reduced. 

Catatonia is a rare complication of prolonged epidural opioid administration in cancer pain (SEDA-16, 78). Patients with advanced cancer who were taking opioids had significant but transient cognitive impairment when opioid doses were increased (31). This correlates well with studies of the effects of psychotropic medications on ability to drive (32). 

Patient-controlled epidural analgesia (PCEA) with fentanyl gives superior analgesia and reduces opioid doses, but without a reduction in adverse effects. However, PCEA with sufentanil offers no advantage (SEDA-19, 87). 

Opioid-naive patients with severe pain who require high doses of opioids are at highest risk for respiratory depression, whereas patients receiving chronic opioid therapy rarely experience this problem (20). Fortunately, the occurrence of respiratory depression can often be circumvented with appropriate titration of opioid dose (22)unless there is underlying pulmonary dysfunction such as emphysema or severe obesity (23). 

The opioid dose required for analgesia will be affected by genotype variants. One dose does not fit all. For example, a patient with the variant of OPRMl may require twice the standard morphine dose to be effective. This variability in clinical effect among patients based on genotype emphasizes the need to perform pharmacogenetic assessments in patients, perhaps leading to the concept of pharmacogenetic-based dose adaptation [49]. 

Galvagno AM, Correll D J, Narang S. Safe oral equianalgesic opioid dosing for patients with moderate to severe pain. Resid Staff Physician 2007 53(4) 17-25. 

Gives patient some control over their pain therapy. PCA allows the patient to self-administer small opioid doses. The PCA-Plus pump allows the patient to receive a continuous infusion together with a set number of self-administered doses per hour. PCA helps to eliminate wide peak and trough fluctuations so that levels remain in a therapeutic range. Children as young as 6 or 7 years of age can master the use of PCA. 

Effective in the management of severe postoperative, chronic, or cancer pain. Spinal opioids can be administered by a single bolus injection into the epidural or subarachnoid space or by continuous infusion via an indwelling catheter. Dosage requirement by these routes is significantly less than with IV administration (epidural opioid doses 10-fold lower than IV doses intrathecal opioid doses 100-fold lower than IV doses). Morphine, hydromorphone, fentanyl, and sufentanil are effective when administered intrathecally. The most commonly used local anesthetic in continuous epidural infusions is bupivacaine. Fentanyl, morphine, or hydromorphone is usually combined with bupivacaine for epidural infusions. 

Methadone PO 2.5-10 mg q 3-4 h (acute)"" IM 2.5-10 mg q 3-4 h (acute)"" PO 5-20 mg q 6-8 h (chronic)"" Effective in severe chronic pain Sedation can be major problem Some chronic pain patients can be dosed every 12 hours The equianalgesic dose of methadone when compared with other opioids will decrease progressively the higher the previous opioid dose has been... 

Lynch ME, Clark AJ. Cannabis reduces opioid dose in the treatment of chronic non-cancer pain. J Pain Symptom Manage (2003) 25,496-8.. 

O Connor AB, Zwemer FL, Hays DP, Feng C. Intravenous opioid dosing and outcomes in emergency patients a prospective cohort analysis. Am J Emerg Med 2010 28(9) 1041-50.e6. 

Opioid tolerance is a well-known phenomenon, which involves increasing dosage requirements with repeated opioid dosing in order to maintain the same analgesic effect. This effect is a common reason for dose escalation in pain patients, fii humans, tolerance can be divided into associative and nonassociative forms. 

Patients maybe advanced to step 3 of the ladder in situations where pain has progressed to severe or very severe intensity, and is inadequately controlled with weak opioids. At this step, potent opioids including morphine, hydromorphone, oxymorphone, and transdermal delivered (TDS) fentanyl are commonly prescribed. In general, sustained-release opioids are provided daily or twice daily for basehne pain control with immediate-release opioids taken as needed for breakthrough pain. Total daily opioid dose is increased as required, thereby allowing patients to gain freedom from pain. 

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