Gene Talk
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Gene Talk

How Genes Influence The Break Down Of Acamprosate

How Genes Influence The Break Down Of Acamprosate

What Is Acamprosate?

Acamprosate is a drug used to treat alcoholism or Alcohol Use Disorder (AUD). AUD is one of the leading causes of morbidity and premature mortality worldwide.

AUD is characterized by problems with controlling one’s alcohol intake, being excessively occupied with alcohol, and having withdrawal symptoms when alcohol consumption is reduced or stopped.

This disorder can cause a significant impact on your daily activities.

Acamprosate is the first drug that was developed specifically to maintain alcohol abstinence in alcoholics. It is available as Acamprosate Calcium (Campral).

What Is Acamprosate Used For?

Most other medications used to treat Alcohol Use Disorder (AUD) work by reducing the pleasurable effects of alcohol on the brain or giving rise to side effects that act as a deterrent for alcohol use.

Acamprosate is one of the three medications approved by the FDA for treating alcoholism. It works by reducing the brain’s dependence on alcohol by interacting with the neurotransmitter systems.

Apart from managing alcoholism, Acamprosate is also used to reduce symptoms like insomnia, anxiety, and restlessness.

How Does Acamprosate Work?

Unlike other medications used to treat alcoholism, Acamprosate is non-habit forming and will not lead to prescription drug abuse.

In patients with alcoholism, there is an imbalance between the neuronal excitation and inhibition regulated by glutamine in the brain.

Excitation and inhibition are the two forces that are responsible for the function of the nervous system.

This results in alcohol withdrawal symptoms like headaches, nausea, tremors, anxiety, hallucinations, and seizures.

Acamprosate interacts with glutamate and GABA neurotransmitters in the Central Nervous System (CNS) to restore the balance between excitation and inhibition.

It binds to the GABA B receptors and indirectly affects the GABA A receptors to restore the balance.

What Are The Side Effects Of Acamprosate?

Acamprosate is a safe drug. It may cause mild side effects, which subside as the treatment progresses. Since this drug is not metabolized in the liver, it has no liver-related side effects, as seen in most drugs.

Some common side effects of Acamprosate are:

- Hypersensitivity reaction to the drug
- Diarrhea
- Insomnia
- Anxiety
- Nervousness
- Nausea and vomiting
- Flatulence
- Headache and dizziness
- Muscle weakness and fatigue

Other severe side effects of Acamprosate that require urgent medical attention include:

- Severe anxiety
- Depression
- Behavioral or mood changes
- Suicidal thoughts
- Swelling in your hands and feet
- Increased heartbeats
- Fluttering in your chest
- Fainting
- Hearing and vision changes
- Decreased urination

Drug Interactions Of Acamprosate

Though a majority of drugs undergo metabolism in the liver, Acamprosate does not. Therefore, it is less likely to cause any drug-drug interactions via the cytochrome P450 inhibition mechanism.

Drug metabolism is the process of modifying drugs in the body so that they can be eliminated more easily. Most of the drug metabolism occurs in the liver, as the enzymes that facilitate the reactions are concentrated there.

Cytochrome P450 is a family of enzymes that are responsible for detoxifying chemical substances from the body. These enzymes can be induced or inhibited by different drugs called cytochrome P450 inducers and inhibitors, respectively. Thus, any alteration in this system results in drug-drug interactions.

When acamprosate is taken with other drugs used to treat alcoholism like diazepam, disulfiram, or antidepressants, it does not cause adverse effects.

A clinical trial showed that co-administering naltrexone with Acamprosate increased the rate and extent of acamprosate absorption. Thus, this combination of drugs is an excellent way to increase the bioavailability of Acamprosate without changing its tolerability.

Acamprosate: Gene-Drug Interactions

GRIN2B Gene And Acamprosate

The GRIN2B or Glutamate Ionotropic Receptor NMDA gene provides instructions for the production of GluN2B protein. This protein is found in the nerve cells in the brain, mainly during brain development before birth.

The brain contains many protein receptors like the NMDA receptors. The NMDA receptors also play a role in learning and memory. These NMDA receptors are glutamate-gated channels that allow the flow of positive ions when glutamate attaches to them.

Alcohol binds to the NMDA receptor inhibiting cognition, short-term memory formation, motor coordination, and overall regular CNS function.

Alcohol withdrawal increases the number of NMDA receptors at the surface, increasing the vulnerability of neurons to excitotoxicity (prolonged activation) and generating hyperexcitability.

https://www.xcode.life/wp-content/uploads/2021/11/nmda_alcohol_neuron_acamprosate.jpg

Image: Effects of alcohol withdrawal on NMDA receptors

rs2058878 is a single nucleotide polymorphism or SNP in the GRIN2B gene. The A allele of rs2058878 is associated with prolonged abstinence from alcohol during the first three months of Acamprosate treatment.

Recommendations For Safe Consumption Of Acamprosate

- Appropriate Dosage

To avoid an overdose of the drug, the recommended dosage of Campral (Acamprosate Calcium) is two tablets of 333 mg each. However, a lower dose may be effective in some patients. This dosage is ideal for patients who eat three meals a day regularly.

- Pre-existing Kidney Disorders

Acamprosate is predominantly excreted by the kidneys. So, the risk of toxic accumulation and reactions to the drug is high in patients with impaired renal function and kidney disorders.

For patients with moderate renal impairment (creatinine clearance of 30–50 mL/min), a starting dose of one 333 mg tablet taken three times daily is recommended.

Acamprosate is not recommended in patients with severe renal impairment (creatinine clearance of ≤ 30 mL/min).

Since renal function decreases in elderly patients, appropriate dosage selection is crucial in the senior age group.

- Pregnancy and Lactation

If you are pregnant or lactating, you must inform your doctor about the same before taking Acamprosate.

Campral is considered to be a Pregnancy Category C drug. Pregnancy Category C drugs are known to cause harm to the fetus in animal studies, but there is an inadequate number of studies on humans.

Acamprosate calcium was found to be teratogenic (causes fetal abnormalities and malformations) in animal studies. It also increases the risk of stillbirths.

These studies also report that acamprosate is released into breast milk. Though there have been no studies on humans to prove the same, it is best to inform your doctor if you are lactating before taking the medication.

- Genetic Testing

A genetic test gives a deeper insight into how your body reacts to a particular drug. It can help your medical practitioner recommend the appropriate dose for you.

Analyze Your Genetic Response to Acamprosate

Summary

- Acamprosate is a drug used in patients who are on alcohol withdrawal as it helps them maintain abstinence.
- Acamprosate works on reducing the brain’s dependence on alcohol by interacting with the neurotransmitter receptors in the brain.
- In alcoholics, there is an imbalance between the excitation and inhibition of nerve cells in the brain. Acamprosate restores this imbalance by binding to GABA B and A receptors.
- Though Acamprosate is a safe drug, it can cause side effects.
- Acamprosate does not get metabolized in the liver, so it does not interact with drugs that are metabolized there. It also does not interact with other drugs used in the management of alcoholism.
- rs2058878, an SNP in the GRIN2B gene, influences the duration of alcohol abstinence. The A allele of this SNP is associated with prolonged abstinence during the first three months of Acamprosate treatment.
- To ensure safe consumption of Acamprosate, it is advisable to stick to the recommended dosage of two tablets of 333 mg per day.
- Individuals who have pre-existing kidney disorders, older adults, pregnant and lactating women must inform their doctor before taking acamprosate.

References:

- https://en.wikipedia.org/wiki/Acamprosate
- https://medlineplus.gov/druginfo/meds/a604028.html
- https://www.rxlist.com/campral-drug.htm
- https://www.nami.org/About-Mental-Illness/Treatments/Mental-Health-Medications/Types-of-Medication/Acamprosate-(Campral)
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4350512/

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