How Genes Influence The Breakdown Of Fentanyl?

What Is Fentanyl?

Fentanyl is a drug used to treat sudden and extreme pain episodes and is a synthetic opioid.

Opioids are drugs used for pain relief and are natural substances extracted from the opium poppy plants.

Synthetic opioids are manufactured artificially and act the same way as other natural opioid drugs.

Fentanyl is about 100 times more potent (strong) than morphine, one of the most common opiate medications prescribed for pain in the United States.

It is also about 30-50 times stronger than heroin, another popular opioid drug made from morphine.

Fentanyl makes it to the World Health Organization’s Model List of Essential Medicines 2021.

It is known by brand names Actiq, Sublimaze, Fentora, and Duragesic.

What Does Fentanyl Look Like?

Fentanyl, in powder form, is light-brown to off-white in color.

When mixed with other drugs, it can leave brown spots or patches on the mixture.

Medically, fentanyl is available as lozenges, under the tongue tablets, buccal (pills placed between cheeks and gum), and skin patches.

What Does Fentanyl Taste Like?

Compared to other opioid drugs like heroin, fentanyl is slightly sweeter.

What Is Fentanyl Used For?

In people already on pain medications, fentanyl may be used to treat sudden and intense episodes of pain that regular analgesics cannot handle. Analgesics are pain-relieving medications.
Fentanyl helps handle cancer-related pain. During medical procedures, it is also regularly used as an anesthetic (a substance causing temporary loss of sensations).
Fentanyl may also be used to handle trauma-related pain and chronic pain caused due to injuries and wounds.

How Does Fentanyl Work?

Fentanyl works like any other opioid medication by targeting the Mu-opioid receptors.

The Mu-opioid receptors are a part of the Central Nervous System (CNS) and are associated with pain sensations and emotions.

By attaching itself with these receptors, fentanyl prevents the neurotransmitters from sending pain signals.

Fentanyl is highly soluble and hence easily penetrates the CNS than other opioids.

How To Test For Fentanyl?

Illegally produced fentanyl is mixed with other drugs to make them more potent, increasing the risk of fentanyl-related side effects.

You can use fentanyl test strips to check the presence of this drug.

These strips can identify whether or not a drug contains fentanyl.

How Long Does Fentanyl Stay In Urine?

Fentanyl can be detected in the urine for anywhere from 24 hours to 72 hours after using it.

Side Effects Of Fentanyl

Some of the common side effects of fentanyl are:

Abdominal pain
Heartburn
Dizziness
Dry mouth
Sleep disorders
Back and chest pain
Swelling in the arms and legs
Weight loss

Some of the more severe side effects of fentanyl are:

Hallucinations, agitation, and other severe mood disorders
Rapid heartbeat
Muscle twitching and stiffness
Sexual conditions like lack of erection and decreased sexual drive
Breathing difficulties
Low blood pressure

Why Is Fentanyl So Dangerous?

Fentanyl is more dangerous than other opioid drugs because it is highly potent (strong).

Even small unmonitored doses can lead to drug addiction, drug overdose, and extreme side effects.

How Long Does Fentanyl Stay In Your System?

Fentanyl may remain in the system and be detected in the urine for up to 72 hours after using it.

Experts may detect the drug even after three months in the hair samples.

Is Fentanyl Stronger Than Heroin?

Yes. Fentanyl is about 30-50 times stronger than heroin and is often added to illegal heroin to improve its efficacy.

Interactions With Other Drugs

Fentanyl may interact with many drugs, leading to changes in drug efficacies or worsened side effects.

Notify your doctor if you use any of the below medications with fentanyl.

Voriconazole and fluconazole (antifungal medications)
Anticholinergic drugs (drugs used to block acetylcholine action)
Baclofen (muscle relaxant)
CYP3A4 inhibitor and inducer drugs
Diuretics (used to treat high blood pressure)
Estrogen medications
Metformin (used to treat high blood sugar)
Nitrous oxide (used to induce sedation)
Other opioid drugs

Fentanyl: Gene-Drug Interactions

The ABCB1 Gene

The ATP Binding Cassette Subfamily B Member 1 gene (ABCB1 gene) provides instructions for producing the ABC proteins.

These proteins control the accumulation of different drugs in the body’s cells.

rs1045642 is a Single Nucleotide Polymorphism (SNP) in the ABCB1 gene.

People with the AA and AG genotypes of this SNP may need lower doses of fentanyl to handle pain when compared to people with the GG genotypes.

Genotypes	Implications
AA	Lower doses of fentanyl are sufficient to handle pain
AG	Lower doses of fentanyl are sufficient to handle pain
GG	Higher doses of fentanyl are needed to handle pain

The OPRM1 Gene

The opioid receptor mu 1 gene (OPRM1 gene) provides instructions for producing the mu-opioid receptor.

This receptor controls the opioid system and is the primary target area for fentanyl and other opioid medicines.

rs540825 is an SNP in the OPRM1 gene.

People with the TT genotype of this SNP have an increased risk of experiencing vomiting as a result of fentanyl usage when compared to people with the AA and AT genotypes.

Genotypes	Implications
TT	Increased risk of experiencing vomiting with fentanyl use
AT	Decreased risk of experiencing vomiting with fentanyl use
AA	Decreased risk of experiencing vomiting with fentanyl use

The RHBDF2 Gene

The Rhomboid family member 2 gene (RHBDF2 gene) provides instructions for producing the RHBDF2 protein.

This protein plays a role in the secretion of the Tumor Necrosis Factor (TNF).

TNF is associated with the immune system, and high levels of TNF may increase pain and inflammation.

rs12948783 is an SNP in the RHBDF2 gene.

People with the AA and AG genotypes of this SNP have a decreased risk of experiencing lower drug efficacy (poor pain management) when treated with opioid medications like fentanyl when compared to people with the GG genotypes.

Genotypes	Implications
AA	Decreased risk of lower drug efficacy (poor pain management) when treated with fentanyl
AG	Decreased risk of lower drug efficacy (poor pain management) when treated with fentanyl
GG	Increased risk of lower drug efficacy (poor pain management) when treated with fentanyl

The ADRB2 Gene

The Adrenoceptor Beta 2 gene (ADRB2 gene) provides instructions for producing the ADRB2 protein.

This protein plays a role in several body functions, including muscle relaxation, insulin secretion, dilating blood vessels, and controlling motor nerves.

rs1042718 is an SNP in the ADRB2 gene.

People with the AA and AC genotypes of this SNP may experience severe hypotension (low blood pressure) when treated with a combination of fentanyl, remifentanil, propofol, and sevoflurane than people with the CC genotype.

Remifentanil, propofol, and sevoflurane are drugs used to induce anesthesia.

Genotypes	Implications
AA	May experience severe hypotension (low blood pressure) when treated with a combination of fentanyl, remifentanil, propofol, and sevoflurane
AC	May experience severe hypotension (low blood pressure) when treated with a combination of fentanyl, remifentanil, propofol, and sevoflurane
CC	May experience a lesser severity of hypotension (low blood pressure) when treated with a combination of fentanyl, remifentanil, propofol, and sevoflurane

Recommendations To Safely Use Fentanyl

Risk Of Respiratory Depression

One of the common reasons for fentanyl-related deaths is respiratory depression.

Respiratory depression is a sudden reduction in the ability to breathe.

Fentanyl may lead to respiratory depression anytime during the therapy, but the risk is very high in the initial usage periods.

Users should rush to the ER or call 911 if they experience the below symptoms after using fentanyl.

Shallow breathing
Difficulty in breathing
Dizziness due to lack of oxygen
Bluish tint to the skin
Reduced pupils
Vomiting

Studies show that the high potency of fentanyl increases the risk of respiratory depression.

Risk Of Central Sleep Apnea

Central Sleep Apnea (CSA) is a condition that causes breathing to stop and start repeatedly while sleeping.

Studies show a dose-dependent relationship between the use of fentanyl and the risk of developing CSA.

Chronic users of the drug have a higher risk of developing this sleep disorder.

Risk Of Fertility And Sexual Problems

Almost all opioid medications can cause fertility problems.

According to studies, chronic use of fentanyl may decrease sperm motility (the ability of the sperm to move towards the egg) in men.

A 2018 study asked 11,517 opioid users about changes in their sexual desire.

The study reports that people who used opioid drugs like fentanyl for more than six months experienced a reduction in sexual desire.

If you are a chronic user of fentanyl, then talk to your doctor about its potential effects on your sexual life and fertility rate.

Usage In People With Existing Mental Health Disorders

According to some studies, people with existing mental health disorders may overuse opioid drugs like fentanyl.

These studies also suggest that as a cyclic effect, overuse of opioid drugs worsens the symptoms of depression and other mental health disorders.

Usage In Pregnant And Lactating Women

The use of opioid medications during pregnancy may increase the risk of Neonatal Opioid Withdrawal Syndrome (NOWD) or Neonatal Abstinence Syndrome (NAS).

When a pregnant woman uses opioid drugs, the fetus is exposed to them too.

Shortly after birth, the lack of the drug may lead to withdrawal symptoms in the infants.

Breathing difficulties
Excessive crying and crankiness
Increased muscle tone
Seizures
Tremors
Fever
Poor feeding

According to experts, fentanyl may be secreted in breastmilk and lead to adverse effects in the infant.

If you are pregnant or lactating, talk to your doctor and weigh the risks and benefits before using the drug.

Fentanyl Overdose

Fentanyl overdose is a common problem in the United States.

Unintentional overdose of the medically prescribed drug and the overuse of illegally sold fentanyl can both lead to severe side effects, including death.

Reports state that the rate of fentanyl overdose deaths has increased from 0.5 per 100,000 people in 2011 to 5.9 per 100,000 people in 2016.

If you think you have overdosed on the drug, dial 911 right away.

Fentanyl Addiction

All opioid drugs have an increased risk of causing addiction.

Since fentanyl is a more potent drug, the risk of addiction is higher.
If you think you are addicted to the drug, contact de-addiction centers near you and get professional help.

Handling Withdrawal Symptoms

Fentanyl is a strong opioid drug, and it is easy to get dependent on it with chronic usage.

Discontinuing the medication suddenly can lead to withdrawal symptoms like the below.

Nausea
Vomiting
Hot and cold flushes
Anxiety and other mood disorders
Tremor
Restlessness
Muscle cramps
Stomach disorders
Sleeping disorders
Muscle spasms

Consult your doctor if you plan to discontinue the medication.

You may have to slowly reduce the dosage before you are completely off the drug.

How Long Does Fentanyl Withdrawal Last?

Fentanyl withdrawal symptoms may start within 12-30 hours after quitting and may be severe for the first few days.

The symptoms should slowly get better within a week.

How Much Fentanyl Is Fatal?

The fatality rate of fentanyl varies depending on how a person’s body processes the drug.

Few people may be able to handle slightly higher doses better than others. Usually, 2 milligrams of fentanyl is considered lethal.

Genetic Testing

Genetic testing helps your doctor determine your response to fentanyl based on your genotype.

This can help them prescribe an appropriate dosage of the drug to manage your condition.

Analyze Your Genetic Response to Fentanyl

Summary

Fentanyl is a synthetic opioid drug that is used to treat extreme episodes of pain and is also used as an anesthetic.
Fentanyl targets the opioid receptors and prevents them from sending pain sensations to the brain.
Some of the side effects of fentanyl are abdominal pain, vomiting, weight loss, sleep disorders, and sexual disorders.
Fentanyl may interact with antifungal drugs, muscle relaxants, CYP3A4 inducer and inhibitor drugs, diuretics, and other opioid drugs and may lead to changes in drug efficacies or worsen the side effects.
Changes in the ABCB1, OPRM1, RHBDF2, and ADRB2 genes may increase or decrease the side effects of fentanyl or affect the drug's effectiveness.
People with existing health conditions, allergies, and those who are pregnant are advised to inform their physician about the same before starting the course.
Fentanyl, being 30-50 times stronger than heroin, can be highly addictive.
Genetic testing can help your doctor understand the dosage requirements suitable for you and analyze your risk for potential drug reactions.