Metabolization of Fentanyl
Fentanyl is a potent opioid analgesic derived from phenylpiperidine that interacts predominantly with the μ opioid receptor. Its main therapeutic effects are analgesia and sedation.
Fentanyl is 60 to 100 times more potent than morphine. It has greater liposolubility, which explains its rapid effect (from 1 to 3 minutes), and its short duration due to its rapid redistribution. However, when given on a long-term basis, it may accumulate in the fatty tissue and thus modify its pharmacokinetic profile to an opiate with a longer half-life than morphine. It is metabolized in the liver, so it can accumulate in patients with hepatic dysfunction. It has no active metabolites. Fentanyl does not release histamine, providing greater hemodynamic stability than morphine.
Both the lower effective concentration of fentanyl and the concentration that produces adverse reactions will increase with the development of increased tolerance. The tendency to develop tolerance varies considerably between individuals.
Fentanyl is contraindicated in patients with known intolerance to the drug or other morphinomimetics, in traumatic brain injury, increased intracranial pressure and / or coma.
As with other strong opiates:
- Respiratory depression is dose related and may be reversed with the administration of a narcotic antagonist (naloxone), but additional doses of this antagonist may need to be administered since respiratory depression may have a longer duration of action than other opioid antagonists.
- Muscle stiffness, including stiffness of the thoracic muscles, may occur. Can be avoided if the following measures are taken: slow intravenous injection (usually sufficient for low doses), premedication with a benzodiazepine and administration of muscle relaxants.
- Non-epileptic myoclonic movements may occur.
- Opioids can cause hypotension, especially in patients with hypovolemia. Appropriate measures should be taken to maintain a stable blood pressure.
- Patients receiving long-term opioid treatment or having a history of opiate abuse may require higher doses.
The most serious adverse reaction to fentanyl is respiratory depression.
Other side effects are:
- Psychiatric disorders: somnolence, sedation, nervousness, loss of appetite, depression.
- Cardiac disorders, uncommon: tachycardia, bradycardia.
- Respiratory, thoracic and mediastinal disorders,uncommon: dyspnea, hypoventilation.
- Skin and subcutaneous tissue disorders: sweating, pruritus.
- General disorders at administration site: skin reactions at the point of application.
- Undesirable effects of administration on the neuroaxis included delayed respiratory depression, nausea / vomiting, pruritus and urinary retention.
- Following administration of fentanyl with a neuroleptic such as droperidol, the following adverse reactions can be observed: tremor, nervousness, postoperative hallucinatory experiences and extrapyramidal symptoms.
The simultaneous use of barbituric acid derivatives should be avoided since the respiratory depressant effect of fentanyl may increase.
Simultaneous use of other CNS depressants may produce additive depressant effects and there may be cases of hypoventilation, hypotension, and also profound sedation or coma. The above mentioned CNS depressants include: opiates, antipsychotics, hypnotics, general anesthetics, skeletal muscle relaxants, sedative antihistamines and alcoholic drinks.
Fentanyl, a high clearance active substance, is rapidly and extensively metabolised primarily by CYP3A4; therefore concomitant prescription of fentanyl with other CYP3A4 inhibitor / inducer drugs is not recommended.
It is usually recommended to discontinue administration of monoamine oxidase inhibitors (MAOs) two weeks prior to any surgical intervention.
- Fentanest ®
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