Fentanyl: Everything You Need To Know

Fentanyl is a morphine-derived analgesic drug that is indicated for the relief of chronic pain in cancer patients, neuropathies, and many other diseases.

In fact, it is the most potent opiate available for medical use. However, it produces a considerable degree of addiction and has been responsible for numerous deaths from overdose.

Pharmacokinetics of fentanyl: what happens to the drug in our body?

Fentanyl can be marketed in parenteral, transmucosal and transdermal forms, the latter being the most widely used. When applied this way, the drug is well absorbed, reaching its maximum concentration in the blood after 12-24 hours. In addition, this achieves a continuous release of fentanyl for 72 h.

On the other hand, it must be taken into account that it is bound in a high proportion to plasma proteins, approximately 80-85%. This characteristic is important, since if it is administered together with another drug that also binds to these proteins in a high proportion, they can move between them.

If this interaction occurs, fentanyl levels in the blood can increase considerably, producing undesirable effects or even producing toxicity.

Regarding its metabolism, it does not appear to be metabolized in the skin, since 92% of a transdermal dose can be found unchanged in the blood. However, it is metabolized in the liver through oxidation reactions. Its metabolites and the rest of the unchanged drug are eliminated in the urine.

Mechanism of action: how does the drug exert the effect?

It is a drug that owes its analgesic effect to the high degree of affinity it has for morphine receptors. Morphine receptors are protein structures to which morphine and drugs derived from it bind to trigger their action.

In this way, the activation of these receptors  induces a high intensity analgesia. The effect of fentanyl is much greater than that of other pain reliever drugs such as ibuprofen.

Specifically, fentanyl selectively binds to μ-morphine receptors. This receptor, like the other types of morphine receptors, is coupled to G proteins. By binding, it blocks the action of the enzyme adenylate cyclase and consequently, levels of cAMP decrease.

Adenylate cyclase is an enzyme that is part of the G protein signaling cascade. When the signal reaches the receptor, which is coupled to this protein, the message is transmitted, thanks to the G protein, to adenylate cyclase to introduce it into the cell and trigger the corresponding action.

In this case, the objective is to block potassium (K) channels in the cell membrane, preventing the pain signal from being transmitted.

Adverse reactions

Treatment with fentanyl can develop undesirable effects on the body, the most significant of which is respiratory depression. However, it can also produce others quite frequently (10-25% have been observed) such as:

• Nausea and vomiting
• Constipation.
• Drowsiness.
• Euphoria and sweating.

On the other hand, there are also a series of symptoms that can appear although less frequently. They have been observed in 1-9% of patients treated with fentanyl. These are, for example, seizures, urinary retention, hypertension, muscle stiffness or mood disorders.

On the other hand, its administration is completely contraindicated in patients who are allergic to morphine, those with respiratory depression (if it is not controlled it can cause death) and in patients with COPD.

Fentanyl addiction, tolerance and dependence

It must be taken into account that both fentanyl and the other drugs derived from morphine have addictive effects. Addiction is the compulsive desire to get the drug or drug. This effect appears easily in recreational use and does not appear frequently in patients who use it as a treatment.

However, being constantly under the effects of this pain reliever, there are people who can develop tolerance to its effects. This degree of tolerance varies from one individual to another.

However, tolerance and physical dependence are two very common effects of using fentanyl as a drug to relieve pain.

Pharmacological tolerance is the need to increase the doses of the drug to maintain the relief of pain that it produced at the beginning of the treatment. It presents as a decrease in the duration of analgesia and is treated by increasing the dose of the drug.

As for dependence, we must distinguish between physiological and psychological dependence. The first is due to an abrupt withdrawal of fentanyl administration after chronic use. When this happens, a series of symptoms is triggered that constitute the withdrawal syndrome.

Psychological dependence is a behavioral syndrome characterized by the desire for the corresponding dose as well as avoiding the discomfort derived from not being able to consume it.