Fentanyl (Efficacy)

Fentanyl is an opioid drug used in medicine for its analgesic and anesthetic action. The presence of the CYP3A4*1G allele of the CYP3A4 cytochrome may affect the plasma concentration of the drug and affect its efficacy.

Fentanyl is a potent phenylpiperidine-derived opioid analgesic 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 (1 to 3 minutes), and its short duration due to its rapid redistribution. However, when administered for a prolonged period of time, it can accumulate in fatty tissue and thus change its pharmacokinetic profile to an opioid with a longer half-life than morphine. It is metabolized in the liver, so it may accumulate in patients with hepatic dysfunction. It has no active metabolites. It 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 increasing tolerance. The tendency to develop tolerance varies considerably among individuals.

CONTRAINDICATIONS


Fentanyl is contraindicated in patients with known intolerance to the drug or other morphinomimetics, head trauma, increased intracranial pressure and/or coma.

PRECAUTIONS


As with other strong opioids:

  • Respiratory depression is dose-related and can be reversed with administration of a narcotic antagonist (naloxone), but additional doses of this antagonist may be necessary since respiratory depression may have a longer duration of action than other opioid antagonists.
  • Muscle stiffness may occur, including rigidity of the thoracic muscles, which can be avoided if the following measures are taken: slow intravenous injection (which is usually sufficient for low doses), premedication with a benzodiazepine and administration of muscle relaxants.
  • Non-epileptic myoclonic movements may occur.
  • Opioids may cause hypotension, especially in patients with hypovolemia. Appropriate measures should be taken to maintain stable blood pressure.
  • Patients receiving prolonged opioid therapy or with a history of opioid abuse may require higher doses.

SIDE EFFECTS


The most serious adverse reaction to fentanyl is respiratory depression.

Other side effects include:

  • Psychiatric disorders: drowsiness, sedation, nervousness, loss of appetite, depression.
  • Cardiac disorders: rare: tachycardia, bradycardia.
  • Respiratory, thoracic and mediastinal disorders: rare: dyspnea, hypoventilation.
  • Skin and subcutaneous tissue disorders: sweating, pruritus.
  • General disorders and alterations at the site of administration: skin reactions at the point of application.
  • Undesirable effects of administration on the neuraxis: include delayed respiratory depression, nausea/vomiting, pruritus, urinary retention.
  • The following adverse reactions may be observed after administration of fentanyl with a neuroleptic such as droperidol: tremor, nervousness, postoperative hallucinatory experiences and extrapyramidal symptoms.

DRUG-DRUG INTERACTIONS


Concomitant use of barbituric acid derivatives should be avoided, since the respiratory depressant effect of fentanyl could be increased.

Concomitant use of other CNS depressants could produce additive depressant effects and hypoventilation, hypotension and also deep sedation or coma could occur. The CNS depressants mentioned above include: opioids, antipsychotics, hypnotics, general anesthetics, skeletal muscle relaxants, sedative antihistamines and alcoholic beverages.

Fentanyl, a high-clearance active substance, is rapidly and extensively metabolized mainly by CYP3A4, so concomitant prescription of fentanyl with other CYP3A4 inhibitor/inducer drugs is not recommended.

It is usually recommended to discontinue administration of monoamine oxidase (MAO) inhibitors two weeks prior to any surgical intervention.

BRAND NAME


  • Fentanyl ®

Genes analyzed

CYP3A4

Bibliography

Barratt DT, Bandak B, Klepstad P, et al . Genetic, pathological and physiological determinants of transdermal fentanyl pharmacokinetics in 620 cancer patients of the EPOS study. Pharmacogenet Genomics. 2014 Apr;24(4):185-94.

Ren ZY, Xu XQ, Bao YP, et al . The impact of genetic variation on sensitivity to opioid analgesics in patients with postoperative pain: a systematic review and meta-analysis. Pain Physician. 2015 Mar-Apr;18(2):131-52.

Saiz-Rodriguez M, Ochoa D, Herrador C, et al.Polymorphisms associated with fentanyl pharmacokinetics, pharmacodynamics and adverse effects. Basic Clin Pharmacol Toxicol. 2019 Mar;124(3):321-329.

Tanaka N, Naito T, Yagi T, et al.Impact of CYP3A5*3 on plasma exposure and urinary excretion of fentanyl and norfentanyl in the early postsurgical period. Ther Drug Monit. 2014 Jun;36(3):345-52.

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