How Genes Influence The Breakdown Of Diclofenac?

What Is Diclofenac?

Diclofenac is a Non-Steroidal Anti-Inflammatory Drug (NSAID) that helps treat pain and inflammation in the body.

Diclofenac is sold under brand names Voltaren, Cambia, Zipsor, Cataflam, and Dyloject among others.

It is available as capsules, tablets, and oral powder/solutions and comes in immediate-release, delayed-release, and extended-release variants.

Diclofenac is also available as a 1% topical gel for external application.

Except for the topical solution, other forms of diclofenac are not available over-the-counter.

This is one of the most common drugs prescribed in the United States to handle pain. There were 10,115,975 prescriptions of diclofenac given out in 2019.

How To Pronounce Diclofenac?

Diclofenac should be pronounced dai-klow-fuh-nak.

How to Pronounce Diclofenac? (CORRECTLY)

Courtesy: Julien Miquel’s YouTube channel

Is Diclofenac A Muscle Relaxer?

Diclofenac is an anti-inflammatory drug and not a muscle relaxant. However, it may be often used with muscle relaxants to bring down spasm pains.

What Is Diclofenac Used For?

Diclofenac is a drug to treat pain and inflammation in the body.

It is prescribed to handle the symptoms of osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis (a type of arthritis causing stiffness and inflammation in the spine).
It may also be used to treat migraine headaches, menstrual pain, and postoperative pain in some instances.

Diclofenac may be prescribed to handle inflammation and pain associated with certain kinds of cancers too.

Is Diclofenac A Strong Painkiller?

Diclofenac is an effective painkiller, and studies show that it can be more effective than similar drugs like ibuprofen or paracetamol in reducing postoperative pain.

What Kind Of Pain Does Diclofenac Relieve?

Diclofenac treats joint pain and inflammation associated with arthritis and other muscular pains and aches.

It may also treat gout pain, dental pain, migraine headaches, and postoperative pain.

What Is Diclofenac Sodium Topical Gel Used For?

The Diclofenac Sodium Topical Gel can externally treat arthritis pain in the knees, wrists, ankles, elbows, and other joints.

How Does Diclofenac Work?

Like most other NSAIDs, Diclofenac works by inhibiting the cyclooxygenase (COX) enzyme.

This enzyme helps convert arachidonic acid (a type of polyunsaturated omega 6 fatty acid) into prostanoids.

Prostanoids play a role in the inflammation process.

There are two types of COX enzymes produced in the body – COX1 and COX2.

Diclofenac is both a COX-1 and COX-2-inhibitor.

However, studies show that the extent of inhibition of COX-2 is up to 4 times that of COX-1.

By inhibiting COX, diclofenac prevents inflammation.

This drug is one of the few NSAIDs that can cross the blood-brain barrier and bring down inflammation in the spinal cord.

How Long Does Diclofenac Take To Work?

Depending on the dosage consumed, it may take anywhere from 1 to 4 hours for the drug to reach peak levels in the blood.

Side Effects Of Diclofenac

Some of the common side effects of diclofenac are:

Gastrointestinal issues like diarrhea, constipation, bloating, or gas
Dizziness
Nausea
headaches
Ringing in the ears
Increased blood pressure levels

In addition, the topical solution may cause skin irritation in a few.

Some of the more severe side effects of diclofenac are:

Myocardial infarction (MI) and heart failure
Stroke
Kidney problems
Liver damage
Increased risk of bleeding

How Long Does Diclofenac Stay In Your System?

The half-life of diclofenac is about 2 hours.

The drug may stay in the system for 4-5 hours before being eliminated.

Does Diclofenac Make You Sleepy?

No, diclofenac does not contain active ingredients to make you sleepy.

In fact, some studies suggest that NSAIDs may disrupt sleep because of their prostaglandin-inhibiting properties.

If you notice excessive tiredness or sleepiness after taking diclofenac, talk to your doctor about it immediately.

Does Diclofenac Cause Weight Gain?

Abnormal and rapid weight gain could be one of the rarer side effects of diclofenac, and you need to right away contact your doctor about this.

Why Is Diclofenac Bad For The Heart?

While inhibiting prostanoids, diclofenac also inhibits the functioning of a group of hormones called prostaglandin I2 (PGI).

PGI is a type of prostanoid, and it plays a role in protecting the heart by reducing blood pressure and preventing the formation of plaques in blood vessels.

PGI-inhibition may be harmful to the heart and increase the risk of heart attacks and strokes.

Interactions With Other Drugs

Diclofenac may interact with other drugs and lead to changes in drug efficacies or severe side effects.

Notify your doctor if you use diclofenac along with the below medications.

Antibiotics (to treat bacterial infections)
Antifungal medications (to treat fungal infections)
Blood thinner medications
Angiotensin-converting enzyme (ACE) inhibitors (used to treat high blood pressure)
Beta-blockers (used to treat heart conditions)
Diuretics (used to treat high blood pressure)
HIV medications
Other NSAIDs

Can I Take Tylenol With Diclofenac?

Yes, diclofenac can be combined with Tylenol to improve the effects of analgesia (the inability to feel pain) and handle acute pain.

However, do not combine medications without consulting your doctor.

How Long After Diclofenac Can I Take Ibuprofen?

Since diclofenac and ibuprofen are similar NSAIDs, they should not usually be taken together.

You may need to wait for at least 6-8 hours before considering taking ibuprofen.

This gives enough time for diclofenac to clear out from the system.

Can I Take Aspirin While Taking Diclofenac?

Combining aspirin and diclofenac may increase the risk of side effects, including internal bleeding, gastrointestinal troubles, and dizziness.

You should not combine these medications unless your doctors suggest you to.

Diclofenac: Gene-Drug Interactions

The ABCC2 Gene and Diclofenac

The ATP binding cassette subfamily C member 2 gene (ABCC2 gene) provides instructions to produce the Multidrug Resistance Protein 2 (MRP2).

This protein plays a role in clearing out drugs from the organs and tissues in the body.

It also helps in clearing out diclofenac.

rs717620 is a Single Nucleotide Polymorphism (SNP) in the ABCC2 gene.

People with the T allele of this SNP have an increased risk of developing hepatotoxicity (liver damage) on diclofenac use compared to people with the C allele.

Allele	Implications
T	Increased risk of developing hepatotoxicity on diclofenac use
C	Decreased risk of developing hepatotoxicity on diclofenac use

The UGT2B7 Gene

The UDP-Glucuronosyltransferase-2B7 gene (UGT2B7 gene) provides instructions for producing the UGT2B7 enzyme.

This enzyme helps in the clearance of many xenobiotic drugs (substances not found naturally in the body), including diclofenac.

The UGT2B7*2 allele of this gene is associated with an increased risk of developing Drug-Induced Liver Injury (DILI) on using diclofenac.

Studies show that people with this allele had almost 6-times a lower clearance rate of diclofenac glucuronidation, this drug’s metabolite.

*2 is a star allele of this gene. Star alleles are used to name different haplotypes.

A haplotype is a group of gene changes that are inherited together.

Recommendations To Use Diclofenac

Usage With Existing Heart Conditions

Doctors may not advise people with existing heart conditions to use diclofenac, especially long-term.

This drug may worsen heart conditions and increase the risk of developing heart attacks and strokes.

Your doctor will weigh the risks and benefits and plan your drug dosage.

Usage With Existing Renal Or Liver Conditions

Extended use of diclofenac may lead to kidney and liver damage.

Though rare, the risk is higher in patients with existing kidney and liver conditions.

Consuming On An Empty Stomach

All NSAIDs increase acid production and lead to gastric problems like acidity, nausea, abdominal pain, and ulcer formations.

You can prevent the extent of these problems by consuming the tablet after meals.

If you use diclofenac regularly, you may also be asked to take antacids to handle these effects.
However, compared to other NSAIDs, diclofenac has a lesser risk of developing gastrointestinal conditions.

Usage In Geriatric Patients

Diclofenac is not a very popular drug prescribed for the elderly because of its ability to cause heart and gastric problems.

In fact, diclofenac makes it to the American Geriatrics Society’s list of ‘potentially inappropriate medication use in older adults.’

Usage In Pregnant Women

Diclofenac use during pregnancy may lead to an increased risk of miscarriages.

A nationwide study in Denmark analyzed the effects of diclofenac used in pregnant women.

The study reported that 28.3% of women who used diclofenac during pregnancy had a miscarriage.

Diclofenac Toxicity

Diclofenac overdose may lead to the below symptoms and need immediate medical attention.

Dizziness
Seizures
Metabolic acidosis (excess acid in the body fluids), leading to renal problems
Coma
Heart attacks

Allergic Symptoms

Though rare, some people may develop allergic reactions to diclofenac and may need immediate medical attention. Some of the symptoms to look out for are:

Flushing
Increased heart rate
Breathing difficulties
Hives
Low blood pressure

Genetic Testing

Genetic testing can help understand a person’s risk of developing liver toxicity and damage by using diclofenac.

This will help make dosage planning easier, and doctors can decide between using this drug or a safer alternative.

Analyze Your Genetic Response to Diclofenac

Diclofenac With Coffee

Caffeine in coffee may slow down the rate of blood clotting.

Diclofenac may also cause a clotting disorder and increase the risk of bleeding.

Therefore, talk to your doctor if you consume coffee while on the drug.

Diclofenac And Driving

Diclofenac may cause dizziness in a few.

If you are using the drug for the first time or have changed the dosages, monitor your symptoms before deciding to drive.

Summary

Diclofenac is an NSAID used to treat pain and inflammation seen in conditions like arthritis, gout, migraines, spondylitis, and post-surgeries.
Diclofenac works by inhibiting prostanoids, a chemical that plays a role in inflammation.
Some people may experience side effects like nausea and dizziness when on diclofenac. Rarely, the drug may also cause heart attacks, strokes, kidney and liver damage.
Common drug interactions seen with diclofenac occur due to antibiotics, antifungal medications, beta-blockers, blood thinners, or ACE inhibitors consumption.
Changes in the ABCC2 and UGT2B7 genes increase the risk of liver toxicity and liver damage in people who use diclofenac.
People with existing medical conditions, allergies, and those who are pregnant are advised to notify their doctor of the same before consuming diclofenac.
Genetic testing can help understand the risk of liver damage and toxicity in people who use diclofenac.