Template:DangerousInteractions/PhenylpropylamineOpioids

• Amphetamines - Stimulants facilitate the activity of the monoamine neurotransmitters, i.e., dopamine, norepinephrine and serotonin, in the central (CNS) and peripheral nervous systems. Because Tramadol has SNRI activity and it also has slight serotonin releasing properties, mixing these two drugs may cause serotonin syndrome.
• Cocaine - Stimulants facilitate the activity of the monoamine neurotransmitters, i.e., dopamine, norepinephrine and serotonin, in the central (CNS) and peripheral nervous systems. Because Tramadol has SNRI activity and it also has slight serotonin releasing properties, mixing these two drugs may cause serotonin syndrome.
• DXM - Dextromethorphan has SRI properties. Because Tramadol has SNRI activity and it also has slight serotonin releasing properties, combining these two drugs will cause serotonin syndrome.
• GHB/GBL - The two substances potentiate each other strongly and unpredictably, very rapidly leading to unconsciousness. While unconscious, vomit aspiration is a risk if not placed in the recovery position
• MAOIs - Coadministration of monoamine oxidase inhibitors (MAOIs) with certain opioids has been associated with rare reports of severe adverse reactions. There appear to be two types of interaction, an excitatory and a depressive one. Symptoms of the excitatory reaction may include agitation, headache, diaphoresis, hyperpyrexia, flushing, shivering, myoclonus, rigidity, tremor, diarrhea, hypertension, tachycardia, seizures, and coma. Death has occurred in some cases.
• Benzodiazepines - Central nervous system and/or respiratory-depressant effects may be additively or synergistically present. The two substances potentiate each other strongly and unpredictably, very rapidly leading to unconsciousness. While unconscious, vomit aspiration is a risk if not placed in the recovery position blackouts/memory loss likely.
• MXE - MXE can potentiate the effects of opioids but also increases the risk of respiratory depression and organ toxicity.
• Alcohol - Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. Place affected patients in the recovery position to prevent vomit aspiration from excess. Memory blackouts are likely
• Nitrous - Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. While unconscious, vomit aspiration is a risk if not placed in the recovery position. Memory blackouts are common.
• Tramadol - Increased risk of seizures. Tramadol itself is known to induce seizures and it may have additive effects on seizure threshold with other opioids. Central nervous system- and/or respiratory-depressant effects may be additively or synergistically present.
• Grapefruit - While grapefruit is not psychoactive, it may affect the metabolism of certain opioids. Tramadol, oxycodone, and fentanyl are all primarily metabolized by the enzyme CYP3A4, which is potently inhibited by grapefruit juice. This may cause the drug to take longer to clear from the body. it may increase toxicity with repeated doses. Methadone may also be affected. Codeine and hydrocodone are metabolized by CYP2D6. People who are on medicines that inhibit CYP2D6, or that lack the enzyme due to a genetic mutation will not respond to codeine as it can not be metabolized into its active product: morphine.