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Respiratory
depression is the chief hazard from all opioid usage. Respiratory
depression occurs most frequently in elderly or debilitated
patients, usually following large initial doses in non-tolerant
patients, or when opioids are given in conjunction with other
agents that depress respiration. Common opioid side effects
are constipation, nausea, sedation, dizziness, vomiting, headache,
dry mouth, sweating, and weakness.
Oxycodone should be used with extreme caution in patients with
significant chronic obstructive pulmonary disease and in patients
having a substantially decreased respiratory reserve, hypoxia,
hypercapnia, or preexisting respiratory depression. In such
patients, even usual therapeutic doses of oxycodone may decrease
respiratory drive to the point of apnea. In these patients alternative
non-opioid analgesics should be considered, and opioids should
be employed only under careful medical supervision at the lowest
effective dose.
Oxycodone causes miosis, even in total darkness. Pinpoint pupils
are a sign of opioid overdose but are not pathognomonic. Marked
mydriasisrather than miosis may be seen due to hypoxia in overdose
situations.
Gastrointestinal
Tract and Other Smooth Muscle
Oxycodone causes a reduction in motility associated with an
increase in smooth muscle tone in the antrum of the stomach
and duodenum. Digestion of food in the small intestine is delayed
and propulsive contractions are decreased. Propulsive peristaltic
waves in the colon are decreased, while tone may be increased
to the point of spasm resulting in constipation. Other opioid-induced
effects may include a reduction in gastric, biliary and pancreatic
secretions, spasm of sphincter of Oddi, and transient elevations
in serum amylase.
Cardiovascular
System
Oxycodone may produce release of histamine with or without associated
peripheral vasodilation. Manifestations of histamine release
and/or peripheral vasodilation may include pruritus, flushing,
red eyes, sweating, and/or orthostatic hypotension.
Concentration--Efficacy
Relationships (Pharmacodynamics)
Studies in normal volunteers and patients reveal predictable
relationships between oxycodone dosage and plasma oxycodone
concentrations, as well as between concentration and certain
expected opioid effects. In normal volunteers these include
pupillary constriction, sedation and overall "drug effect"
and in patients, analgesia and feelings of "relaxation."
In non-tolerant patients, analgesia is not usually seen at a
plasma oxycodone concentration of less than 5&endash;10
ng/mL.
As with all opioids, the minimum effective plasma concentration
for analgesia will vary widely among patients, especially among
patients who have been previously treated with potent agonist
opioids. As a result, patients need to be treated with individualized
titration of dosage to the desired effect. The minimum effective
analgesic concentration of oxycodone for any individual patient
may increase with repeated dosing due to an increase in pain
and/or the development of tolerance.
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