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.
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.
Compared to other opioid drugs like heroin, fentanyl is slightly sweeter.
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.
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.
Fentanyl can be detected in the urine for anywhere from 24 hours to 72 hours after using it.
Some of the common side effects of fentanyl are:
Some of the more severe side effects of fentanyl are:
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.
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.
Yes. Fentanyl is about 30-50 times stronger than heroin and is often added to illegal heroin to improve its efficacy.
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.
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 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 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 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 |
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.
Studies show that the high potency of fentanyl increases the risk of respiratory depression.
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.
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.
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.
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.
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 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.
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.
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.
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.
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 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
https://reference.medscape.com/drug/sublimaze-fentanyl-343311#0
https://medlineplus.gov/druginfo/meds/a605043.html
https://www.drugabuse.gov/publications/drugfacts/fentanyl#ref
https://en.wikipedia.org/wiki/Fentanyl#Detection_in_biological_fluids
https://pubchem.ncbi.nlm.nih.gov/compound/Fentanyl#section=NLM-Curated-PubMed-Citations
https://www.cdc.gov/opioids/basics/fentanyl.html
https://www.medicalnewstoday.com/articles/260580#research
https://americanaddictioncenters.org/fentanyl-treatment/how-long-in-system
https://medlineplus.gov/ency/article/007313.htm
https://www.jpsmjournal.com/article/S0885-3924(03)00495-0/fulltext
https://oxfordtreatment.com/substance-abuse/fentanyl/lethal-dose/
https://americanaddictioncenters.org/withdrawal-timelines-treatments/fentanyl
https://www.dea.gov/resources/facts-about-fentanyl
https://www.genecards.org/cgi-bin/carddisp.pl?gene=ABCB1
https://www.genecards.org/cgi-bin/carddisp.pl?gene=ADRB2
https://en.wikipedia.org/wiki/RHBDF2
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Diuretics are a class of antihypertensive drugs that help your kidneys get rid of extra salt and water via urine.
They are usually the first line of drugs used to control blood pressure in hypertensive patients.
Diuretics are also called ‘water pills’ as they help your kidneys pump out extra water from the blood, decreasing the fluid in your blood vessels.
This fluid reduction helps lower your blood pressure, making it easier for your heart to pump.
There are different types of diuretics, and each one acts on the kidneys differently.
Some diuretic medications have a combination of two or more drugs.
The three primary types of diuretics are – thiazides, loop diuretics and potassium-sparing diuretics.
Each of these diuretic groups has a different mechanism of action.
To pronounce diuretic correctly, you must say it as ‘dai - ur - eh - tuhk.’
How to Pronounce Diuretic? (CORRECTLY)
Courtesy: Julien Miquel’s YouTube channel
Though coffee does increase urine production, it does not dehydrate.
So, coffee is a mild diuretic.
Pineapple juice is a known diuretic that helps flush out toxins from the digestive system.
Beer is alcohol, and all types of alcoholic drinks are diuretics because they cause your body to expel fluids from the excretory system quicker than most other liquids.
Alcohol can also cause dehydration.
Chocolate contains caffeine and theobromine, both of which cause diuresis.
Diuretics are usually prescribed to you if you suffer from one of the following conditions:
This improves circulation and relieves pressure on the heart in case of heart failure.
Loop diuretics are usually prescribed in these cases.
Diuretics facilitate the elimination of excess fluid from the body.
This can help reduce your water weight.
However, this does not help lose fat, and as a result, it cannot be used for weight loss.
Different types of diuretics have different mechanisms of action.
Thiazide diuretics stimulate your kidneys to pull salt and extra water from the blood and increase urine output.
Common thiazide diuretics include hydrochlorothiazide and chlorthalidone.
Some side effects of thiazide diuretics include headache, loss of appetite, and hair loss.
They are considered the most potent diuretics and prevent reabsorption of both sodium and chloride.
These diuretics are effective because they act directly on the loop of Henle portion of the renal tubule (in the kidneys).
Some commonly used loop diuretics are furosemide and bumetanide.
Few people may experience side effects like diarrhea, dizziness, or an upset stomach when taking loop diuretics.
These diuretics reduce the body’s fluid levels while preventing excessive loss of potassium, a vital mineral.
This group of diuretics is recommended for people who have low potassium levels in the body or are taking medications that may deplete potassium levels.
Triamterene and amiloride are two commonly used potassium-sparing diuretics.
Some people may experience side effects like gas, nausea, and headache on taking potassium-sparing diuretics.
Two other types of diuretics that are used less often are:–
This group of diuretics works by increasing the excretion of sodium, potassium, and bicarbonate, along with water, from the renal tubules.
The diuretic property of carbonic anhydrase inhibitors are usually mild, and hence, these drugs are not commonly used.
Some examples of carbonic anhydrase inhibitors include acetazolamide, dichlorphenamide, and methazolamide.
These diuretics work by preventing the resorption of water, sodium, and chloride by increasing the osmotic pressure within the kidney.
Diuretics begin working around 1-2 hours after you take them.
There are plenty of natural diuretics.
These include coffee, dandelion extract, parsley, hibiscus, green and black tea.
Black seed (Nigella sativa) is one of the most effective natural diuretics.
Diuretics are generally well-tolerated and considered safe.
However, they may cause side effects in some individuals.
The most common side effects are:
Some rare but serious side effects of diuretics include:
Diuretics act directly on your kidneys as they are responsible for eliminating extra fluid and salts from the body.
In some cases, excessive elimination of water can result in dehydration, which can be bad for your kidneys.
If you are suffering from a kidney ailment, it is best to inform your doctor before taking a diuretic.
Diuretics can react with other drugs when they are taken together. Some significant interactions of diuretics with other drugs are:
Antidiabetic drugs
When thiazide diuretics are given with antidiabetic drugs like insulin, they may decrease the blood levels of the antidiabetic drug.
In this case, the antidiabetic drug dosage may need to be increased.
Digoxin
Digoxin is a cardiac glycoside used to manage heart failure symptoms and atrial fibrillation.
Digoxin with thiazide and loop diuretics may cause side effects like weakness, cramps, and irregular heartbeat.
Lithium-containing drugs
Lithobid (a mood-stabilizing medication used to treat manic disorders and bipolar disorder) and other lithium-containing drugs with thiazide or loop diuretics may induce lithium toxicity due to decreased elimination of lithium from the body.
ACE inhibitors and NSAIDs
Taking potassium-sparing diuretics with angiotensin-converting enzyme (ACE) inhibitors of NSAIDs may result in severely elevated potassium levels.
This condition is called hyperkalemia and may cause muscle weakness, fatigue, and reduced heart rate (bradycardia).
Other antihypertensive drugs
Diuretics are a class of antihypertensive drugs and may be prescribed with other similar drugs to bring down blood pressure levels.
However, combining diuretics with other antihypertensive drugs may cause electrolyte imbalance in the body, especially reduced potassium levels.
Phosphodiesterase 4D or the PDE4D gene provides instructions for producing the enzyme cAMP-specific 3',5'-cyclic phosphodiesterase 4D.
This enzyme plays an essential role in regulating inflammation in the body and is associated with hypertension.
rs702553 is a single nucleotide polymorphism or SNP in the PDE4D gene. This SNP has been linked to arterial blood pressure.
Individuals with TT genotype of SNP rs702553 had significantly lower mean arterial blood pressure than AA and AT genotypes upon treatment with a diuretic.
NEDD4-like E3 ubiquitin-protein ligase or the NEDD4L gene belongs to the NEDD4 family of genes.
This gene contains instructions for producing an enzyme that plays a role in sodium transport and regulates the reabsorption of sodium in the kidneys.
The NEDD4L gene has a strong effect on the efficacy of thiazide diuretics.
SNPs in the NEDD4L gene have been associated with hypertension.
Individuals with the AA genotype of rs4149601 and hypertension have a decreased response to diuretics compared to those having the AG or the GG genotypes.
Before taking diuretics, it is recommended that you inform your doctor about your medical history.
Some crucial conditions that need to be mentioned include diabetes, pregnancy, pancreatitis, kidney problems, liver problems, lupus or history of lupus, gout, menstrual problems, and a tendency to get dehydrated.
Inform your doctor about allergies to sulfa drugs like Septra and Bactrim before taking any diuretic.
Diuretics cause the elimination of water and minerals like sodium and potassium.
If you are taking loop or thiazide diuretics, eating potassium-rich foods like bananas, sweet potatoes, spinach, lentils, etc., can ensure that you are getting enough for your body functions.
However, if you take potassium-sparing diuretics, avoid potassium-rich foods, low-sodium milk, or salt substitutes to prevent potassium overload.
Genetic testing helps your doctor determine your response to different diuretics based on your genotype.
This can help them prescribe an appropriate dosage of the diuretic drugs to manage your hypertension.
Analyze Your Genetic Response to Diuretics
While taking diuretics, you will have to urinate more often.
The goal is to avoid getting dehydrated while on diuretics.
Your doctor will also guide you about how much water you should consume every day when taking diuretics.
You will need to visit your doctor for regular checkups to monitor your hydration and potassium levels and determine how your kidneys are working.
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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.
Diclofenac should be pronounced dai-klow-fuh-nak.
How to Pronounce Diclofenac? (CORRECTLY)
Courtesy: Julien Miquel’s YouTube channel
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.
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.
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.
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.
The Diclofenac Sodium Topical Gel can externally treat arthritis pain in the knees, wrists, ankles, elbows, and other joints.
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.
Depending on the dosage consumed, it may take anywhere from 1 to 4 hours for the drug to reach peak levels in the blood.
Some of the common side effects of diclofenac are:
In addition, the topical solution may cause skin irritation in a few.
Some of the more severe side effects of diclofenac are:
The half-life of diclofenac is about 2 hours.
The drug may stay in the system for 4-5 hours before being eliminated.
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.
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.
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.
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.
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.
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.
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.
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 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.
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.
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.
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.
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.’
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 overdose may lead to the below symptoms and need immediate medical attention.
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:
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
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 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.
https://www.drugs.com/diclofenac.html
https://en.wikipedia.org/wiki/Diclofenac#Mechanism_of_action
https://en.wikipedia.org/wiki/Prostaglandin-endoperoxide_synthase_2
https://pubmed.ncbi.nlm.nih.gov/25078485/
https://clincalc.com/DrugStats/Drugs/Diclofenac
https://en.wikipedia.org/wiki/Prostacyclin
https://medlineplus.gov/druginfo/meds/a689002.html
https://www.ncbi.nlm.nih.gov/books/NBK557879/
https://www.drugs.com/tips/diclofenac-patient-tips
https://supp.ai/i/caffeine-diclofenac/C0006644-C0012091
https://www.rxlist.com/coffee/supplements.htm
https://pubmed.ncbi.nlm.nih.gov/20814155/
https://www.mayoclinic.org/drugs-supplements/diclofenac-oral-route/side-effects/drg-20069748?p=1
https://www.pharmgkb.org/combination/PA166156619,PA166163692/variantAnnotation
https://medlineplus.gov/genetics/gene/abcc2/
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Gabapentin is a prescription medication used as an antiepileptic drug (anticonvulsant) to control seizures.
Its action is similar to GABA or gamma-aminobutyric acid.
GABA, a neurotransmitter, reduces the excitability of the nerve cells in the brain and subsequently reduces seizures and pain transmission.
It is also used to treat nerve pain experienced in shingles caused by the herpes zoster virus in adults.
Some gabapentin-containing medications like Horizant are also used in relieving symptoms of Restless Leg Syndrome (RLS).
Restless Leg Syndrome is a condition that causes discomfort in the legs and a constant strong urge to move the legs, especially at night, while sitting down or sleeping.
Gabapentin is available as capsules, tablets, and an oral solution. It is routinely found in antiepileptic drug formulations with other medications.
Though some studies have reported misuse and abuse of gabapentin, it is not a narcotic substance.
There have also been reports of people experiencing gabapentin withdrawal symptoms when they discontinued the drug after taking higher than recommended dosages.
Gabapentin is used for the following:
In adults and children over the age of three, gabapentin is routinely used to treat partial seizures.
Shingle is a painful rash caused by the herpes zoster virus.
This virus causes chickenpox and often remains inactive in the spinal nerve root (nerves that connect the spinal cord to the peripheral nervous system).
When this virus gets reactivated due to stress many years later, it causes shingles.
The nerve pain caused by shingles is also called postherpetic neuralgia.
Gabapentin is used in the treatment of restless leg syndrome.
Depending upon your condition and its severity, your doctor will prescribe the appropriate dosage of the drug.
Gabapentin and Xanax (alprazolam) are both used to treat anxiety, but these drugs belong to different classes.
While gabapentin is an anti-seizure or anticonvulsant drug, Xanax is a benzodiazepine used to treat anxiety disorders and panic attacks.
Since gabapentin and Xanax belong to different drug classes, their mechanism of action differs.
Gabapentin brings about seizure control by reducing the abnormal nerve excitement in the brain, which triggers a seizure.
Research states that the drug binds to a specific site on the voltage-gated calcium channels.
These channels play crucial roles in many body functions like neurotransmitter release, muscle contraction, nerve cell excitation, etc.
When gabapentin binds to this specific site on these calcium channels, they relax the nerves and relieve nerve pain and seizures.
Gabapentin and tramadol are pain relievers, but they relieve different kinds of pain.
Gabapentin relieves postherpetic neuralgia, a type of nerve pain that follows shingles, while tramadol is an opioid pain reliever used to manage moderate to severe pain.
There are limited reports of gabapentin abuse, and those that exist have been found in people who have been prescribed the drug, probably in higher doses.
There are no reported instances of snorting gabapentin.
Gabapentin is a safe drug but may cause side effects in some individuals. Some common side effects of the drug include:
If you experience any of the following severe side effects on taking gabapentin, call your doctor immediately:
Gabapentin has a renal route of excretion, i.e., it is excreted via urine.
Though gabapentin is given to patients with kidney disease and those undergoing dialysis, the dosage of the drug varies.
In very rare cases, gabapentin may cause renal toxicity or failure.
Constipation is a rare side effect of gabapentin but may occur in some individuals.
Clinical trial data states that of all adults who take gabapentin, around 4% of them experience constipation as a side effect.
Since 2% of people taking a placebo in the clinical trial also reported constipation, the percentage of people who experience constipation as a side effect is less than 4%.
Existing research about gabapentin-induced hair loss is limited.
Few studies suggest that hair loss may be a lasting effect of gabapentin treatment.
A 2015 study stated that alopecia (hair loss) was a common side effect of many antiepileptic drugs, but gabapentin was not part of the study.
Gabapentin is known to interact with the following drugs:
There have been no documented instances of gabapentin interaction with ibuprofen (a non-steroidal anti-inflammatory drug or NSAID drug).
So, you can take ibuprofen with gabapentin.
It is always recommended to inform your doctor before doing so.
Tylenol can be safely taken with gabapentin as there have been no known interactions or adverse effects on taking them together.
However, it is advisable to inform your doctor before taking these two drugs together.
Xanax and gabapentin can interact to increase side effects of gabapentin, such as dizziness, confusion, drowsiness, and difficulty in concentrating.
Some older adults may experience motor coordination, thinking, and justice issues.
It is, therefore, recommended not to take Xanax with gabapentin.
Solute Carrier Family 7 Member 5 or SLC75 is a gene found on chromosome 16.
This gene gives instructions for producing amino acids like phenylalanine, tyrosine, leucine, arginine, and tryptophan.
rs440803 is a single nucleotide polymorphism or SNP in the SLC7A5 gene.
The AG genotype of this SNP is associated with an increased risk of adverse events when treated with gabapentin in people with neuropathic pain as compared to people with the GG genotype.
There is no evidence of any association of adverse events between the AA genotype of the SNP and gabapentin.
Inform your doctor about any medical conditions that you may have to avoid serious adverse effects on taking gabapentin.
People with breathing or lung problems may experience severe breathing difficulties when taking gabapentin.
People with Chronic Obstructive Pulmonary Disorder (COPD) and asthma must inform their doctor about their condition before taking gabapentin.
People with mental illnesses like depression may experience suicidal thoughts and behaviors when taking gabapentin.
If you suffer from other medical conditions like diabetes, kidney trouble, liver problems, etc., you must inform your doctor about the same before taking gabapentin.
This information helps your doctor determine the safe dosage of gabapentin for you.
Inform your doctor if you are allergic to gabapentin or gabapentin enacarbil before taking the drug.
It is also important to tell your doctor about your allergies as sometimes, gabapentin formulation may contain active ingredients that can trigger an allergic reaction.
Drinking alcohol while taking gabapentin can increase sleepiness, drowsiness, and dizziness.
You must, therefore, limit or avoid alcohol intake before starting on gabapentin.
After taking gabapentin, your seizures may be under control, and you may feel fine.
However, you must not stop taking gabapentin suddenly and without your doctor’s consent, as it may cause increased seizures.
There is no known information about how gabapentin can affect your unborn child.
Therefore, inform your doctor if you are pregnant or plan to get pregnant while taking gabapentin.
Gabapentin can pass into breast milk.
So, you must inform your doctor if you are breastfeeding to avoid any adverse reaction in your baby.
Genetic testing helps your doctor determine if you are at risk of developing an adverse reaction to gabapentin.
Analyze Your Genetic Response to Gabapentin
Taking gabapentin in excess can cause an overdose, which may prove fatal.
Common symptoms of gabapentin overdose include severe drowsiness, speaking trouble, and weakness.
Overdosing on gabapentin usually occurs when the drug is taken with other opioids, addictive substances, or alcohol.
Know Your Response To Drug Therapies Using Your 23andMe, AncestryDNA Raw Data!
Azathioprine is an immunosuppressant drug that works by bringing down the activity of the immune system.
It is sold under the brand names Imuran and Azasan and is added to the World Health Organization's (WHO’s) List of Essential Medicines for 2021.
It is available as oral pills or injected in the vein; the dosage depends on the specific requirement.
Azathioprine is used to prevent organ rejection after kidney transplantation.
It is also used to treat certain autoimmune diseases like Multiple Sclerosis (MS), Rheumatoid Arthritis (RA), Ulcerative Colitis, and Crohn's Disease.
It is usually used with Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), corticosteroids, and other immunosuppressant drugs.
No. Azathioprine is not a steroid.
Instead, it is a steroid-sparing drug.
When taken in combination with steroid drugs, it can decrease the required steroid dosage.
Azathioprine is a purine analog drug.
Purines are organic compounds required for DNA and RNA production.
The immune system needs DNA and RNA to produce White Blood Cells (WBCs) to fight invaders.
By reducing the number of purines in the body, azathioprine lowers WBC production by the immune system, leading to immunosuppression.
The effects of azathioprine appear gradually.
For autoimmune conditions, it may take anywhere from 6-12 weeks to start working.
For certain autoimmune skin conditions, it may even take up to a year for the drug to show results.
Azathioprine is an effective treatment option for Crohn’s and helps decrease the dependency on steroids.
A study of 272 Crohn's disease patients treated with azathioprine reported that the remission rate (remaining symptom-free) for patients treated with the drug for more than six months was 64%.
Some of the common side effects of azathioprine are:
Some of the more severe side effects of azathioprine are:
About 3.3% of patients on azathioprine may experience pancreatitis (inflammation of the pancreas) in the first six months of treatment.
People who take azathioprine for more than ten years may have a higher risk of developing certain types of cancers, including skin and lymphoma and myelotoxicity (damage to bone marrow).
No, azathioprine, by itself, may not lead to weight gain.
However, when used with other steroid drugs, the steroids may cause weight gain.
Azathioprine may interact with other drugs and lead to changes in drug efficacy or worsen the side effects.
Talk to your doctor if you take azathioprine with any of the following medications:
Yes, prednisone and azathioprine can be taken together and are prescribed to improve Crohn’s Disease symptoms.
Studies show that the combination is more effective for treating Crohn’s than prednisone alone.
The Nudix hydrolase 15 gene (NUDT15 gene) provides instructions for producing the NUDT15 protein.
This protein helps in the metabolism of purine analog drugs like azathioprine.
rs116855232 is a Single Nucleotide Polymorphism (SNP) in the NUDT15 gene.
Inflammatory Bowel Disease patients with the TT and CT types of this SNP have an increased risk of developing myelosuppression (a condition causing decreased bone marrow activity) compared to patients with the CC type.
| Genotype | Implications |
| TT | Increased risk of myelosuppression on azathioprine usage |
| CT | Increased risk of myelosuppression on azathioprine usage |
| CC | Decreased risk of myelosuppression on azathioprine usage |
The thiopurine S-methyltransferase gene (TPMT gene) provides instructions for producing the TPMT enzyme.
This enzyme helps break down drugs like azathioprine and decrease immune system activity.
Drugs like azathioprine get converted into active (toxic) forms called thioguanine nucleotides (TGNs) in the body.
The TPMT enzyme helps quickly convert the toxic substance into a non-toxic compound.
Excess of TGNs in the body may lead to life-threatening conditions of myelosuppression.
There are different metabolizer types identified based on the enzyme activity, and these metabolizer types can affect azathioprine efficacy and dosage levels in the body.
| Phenotype | Implication | Recommendations for using azathioprine |
| Normal metabolizers | Low concentrations of TGN metabolites | Normal doses can be used |
| Intermediate metabolizers | Slightly higher concentrations of TGN metabolites | Start with a reduced dosage before dosage adjustment |
| Poor metabolizers | Very high concentrations of TGN metabolites | Consider alternative medications or start with very low doses |
There are multiple star alleles noted in the TPMT gene.
Star alleles are used to name different haplotypes.
A haplotype is a group of gene changes that are inherited together.
Tumor Necrosis Factor (TNF) blockers are drugs used to block the activity of TNF.
TNF is a protein that causes inflammation and worsens the symptoms of different autoimmune conditions.
A combination of TNF blockers and immunomodulatory drugs like azathioprine may increase the risk of developing hepatosplenic T-cell lymphoma (HSTCL).
HSTCL is a very aggressive T-cell lymphoma common in young children and adolescents.
A 2011 study reports an increased risk of developing HSTCL in autoimmune patients who receive a combination of TNF blockers and immunomodulators.
Azathioprine hypersensitivity is a rare but serious condition in about 2% of the patients treated with the drug.
The following symptoms of azathioprine sensitivity occur just weeks after administering the drug.
Azathioprine use in pregnancy may affect the unborn fetus and lead to congenital abnormalities.
A 2003 population-based cohort study in the Danish population reports a 7-fold increased risk of congenital abnormalities in pregnant women who used azathioprine.
They also had a 20-fold increased risk of experiencing perinatal mortality (miscarriages).
Some studies also report an increased risk of congenital abnormalities in children whose fathers were on azathioprine before conception.
There are reports of azathioprine being expressed in breastmilk.
If you are a lactating mother, talk to your doctor to weigh the risks and benefits of breastfeeding while on the drug.
Since azathioprine may lead to liver or kidney damage, it needs to be used with caution in people with existing liver or kidney conditions.
The doctors may adjust the dosage accordingly and recommend periodical Complete blood count (CBC) and Liver Function Tests (LFT) to rule out liver and kidney damage.
People with active infections may not be recommended to use azathioprine until the condition goes away.
Since the drug is an immunosuppressant, it may worsen the effects of the infection.
A meta-analysis studied the relationship between azathioprine usage and the risk of Squamous Cell Carcinoma (SCC) of the skin.
SCC is a very common type of skin cancer due to UV exposure.
According to the study, using azathioprine significantly increased the risk of developing SCC.
If you are on azathioprine, limit sun exposure and avoid tanning booths and beds.
You may also be asked to use sunscreens regularly to bring down the risk of developing SCC.
Azathioprine overdose may lead to vomiting, fever, rashes, and chills in the body.
If you think you have overdosed on the drug, rush to the nearest Emergency Room or dial 911.
Genetic testing will help understand how quickly the body converts TGNs into inactive forms, making dosage planning more customized.
It can also help doctors understand the risk of developing myelosuppression and decide between using azathioprine and other immunosuppressants.
Analyze Your Genetic Response to Azathioprine
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https://www.drugs.com/drug-interactions/azathioprine.html
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https://medlineplus.gov/druginfo/meds/a682167.html
https://www.ncbi.nlm.nih.gov/books/NBK542190/
https://my.clevelandclinic.org/health/drugs/9407-azathioprine
https://en.wikipedia.org/wiki/Azathioprine#Interactions
https://www.webmd.com/melanoma-skin-cancer/melanoma-guide/squamous-cell-carcinoma
https://www.healthline.com/health/drugs/azathioprine-oral-tablet
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The heart capacity is a measure of the amount of blood your heart pumps every minute. It is calculated using the following equation:
Heart Capacity = heart rate x stroke volume
Stroke volume is the amount of blood your heart pumps every time it beats. The capacity of the heart to pump enough blood every minute ensures all organs receive oxygen and essential nutrients.
For a normal individual who is resting, the heart pumps 5-6 liters of blood every minute.
When exercising, your muscles rapidly use up oxygen. In order to keep up with demand, your heart pumps faster, and hence your heart rate increases. In order to keep up with demand, your heart pumps faster, and hence your heart rate increases. When your heart rate increases, your heart capacity or cardiac output increases.
Exercising is considered important for the heart’s health. Here are some of the benefits of exercise for heart capacity.
Just like how exercise strengthens the rest of your body muscles, it strengthens the heart muscle too. A stronger heart pumps blood better.
With regular exercise, your body can receive/absorb oxygen from the blood better. This puts less strain on the heart when it pumps blood.
Studies show that with regular exercise, the blood vessels dilate to allow more blood flow.
Blood pressure is a very critical factor that talks about your heart’s health. By exercising, your blood pressure slowly drops down to normalcy without putting excess pressure on the heart’s pumping capacity.
An increase in your Resting Heart Rate (RHR) is associated with increased mortality. Exercise helps bring down the resting heart rate. The RHR for athletes can be as low as 40 bpm.
The CREB1 gene encodes the CAMP Responsive Element Binding Protein 1, which plays an important role in several biological pathways. Variations in the gene are proven to cause various diseases, including memory disorders and Huntington’s disease.
The rs2253206 SNP in this gene causes changes in heart rate while exercising. The AA genotype causes heart rate improvements because of exercises. The AG and GG genotypes show no such positive relation.
Just like how exercise changes your heart capacity, other non-genetic factors increase or decrease your heart’s ability to pump blood.
Hormones - Certain hormones affect the contraction of the heart and hence affect stroke volume.
Stress - Norepinephrine is a chemical released in the body when you are stressed. This chemical right away increases heart rate, which in turn increases heart capacity. Epinephrine is another chemical the body produces when the person experiences fear or anger. This also increases the heart rate and pumping capacity.
Changes in body temperature - Increased body temperature can cause increased heart rate and heart capacity
Sex - Women have a higher heart rate than men, and hence their heart pumps blood faster.
Age - The heart rate and capacity to pump blood is the fastest at birth and reduces slowly as people age.
It is quite normal for the heart capacity to increase during exercise and other external factors. However, when the heart capacity or cardiac output is consistently high, it can lead to pulmonary edema (fluid accumulation in the lungs). This can be a life-threatening condition.
If exercising causes abnormal increases in heart rate and heart capacity, you may have to slow down the intensity of working out and give the body adequate resting time to stabilize.
When the heart capacity is lower than normal, it gets difficult for the other parts of the body to receive oxygen. For maintaining your heart’s pumping capacity, the heartbeat increases to pump more blood with every passing minute.
The adrenaline glands release adrenaline that reaches the heart and pushes it to beat faster. Consistently lowered capacity and higher heart rate can weaken the heart muscles with time.
Start slow
Exercise definitely helps your heart capacity improve. However, start slow and let the heart get used to all the physical exertion. As your capacity improves, you can start training intensively.
Listen to your heart
Does exercising leave you tired, breathless, or dizzy? Get the core problem checked before you continue to exercise. If you are genetically designed to experience high blood pressure or abnormally high heart rate because of exercise, you could feel worse after a workout session.
Moderation is the key
A healthy individual who is not trained by a professional should consider moderate exercises over high-intensive training.
Improve your recovery heart rate after exercise
Aim to improve your heart rate recovery after exercise. Follow a mix of light, moderate, and intense exercises to get your heartbeat to normalcy quickly.
https://wa.kaiserpermanente.org/healthAndWellness?item
https://medicalxpress.com/news/2018-09-genes-heart.html
https://www.health.harvard.edu/heart-health/what-your-heart-rate-is-telling-you
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https://www.medpagetoday.com/blogs/skeptical-cardiologist/83528
https://www.uofmhealth.org/health-library/tx4080abc
https://www.theonlinelearningcenter.com/assets/carter/46/course_01/module_04/mod_04.pdf
