Critical Point #1: Tramadol has a dual analgesic mechanism of action (MOA) and unpredictable pharmacokinetics.
MOA #1: Tramadol is metabolized in the liver by CYP2D6 to its primary active metabolite O-desmethyltramadol (M1).
Tramadol (parent compound) has very low affinity for m-opioid receptors.
M1 binds m-opioid receptors with ~300-fold higher affinity than tramadol and is more potent in producing analgesia.
MOA #2: Tramadol inhibits serotonin and norepinephrine reuptake suggesting analgesic activity by inhibition of central nervous system pain transmission.
Variation in CYP2D6 activity leads to unpredictable metabolism and production of active metabolites resulting in phenotypic differences in toxicity and efficacy.
Critical Point #2: Common misconception? Tramadol is a weak opioid and has a more favorable safety profile.
Tramadol has atypical risks compared to other opioids due to inhibition of serotonin and norepinephrine uptake, including serotonin syndrome.
Hypoglycemia is a potential serious complication reported with use in both diabetic and non-diabetic patients.
New-onset seizures have been reported in patients taking therapeutic doses.
Physical dependence and addiction are possible consequences of tramadol use.
Abrupt cessation can cause unpleasant opioid andSSRI-like withdrawal symptoms.
Guest Post By:
DeAnna W. Turner, PharmD, BCPS
Clinical Pharmacist Emergency Medicine
Methodist Hospital Emergency Medicine Department
San Antonio, Texas
References:
Drug Enforcement Administration Diversion Control Division. Drug and Chemical Evaluation Section. Tramadol (Trade Names: Ultram®, Ultracet®). October 2018 update. Accessed April 25, 2019. Link is HERE
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Post Peer Reviewed By: Salim R. Rezaie, MD (Twitter: @srrezaie)
