ACE inhibitors (Angiotensin-Converting Enzyme inhibitors) are drugs used to relax the veins and arteries in order to lower blood pressure. They also help reduce blood volume and the heart’s demand for oxygenated blood.
ACE inhibitors bring down the activity of the angiotensin-converting enzyme. This enzyme controls fluid volumes in the body. It converts a hormone called angiotensin I into a more active form called vasoconstrictor angiotensin II.
This conversion causes constriction of blood vessels and increased blood flow. These lead to an increase in blood pressure.
ACE inhibitors reduce the conversion of angiotensin I into vasoconstrictor angiotensin II and hence relax blood vessels.
Image: Action of ACE Inhibitors
Studies have reported that ACE Inhibitors can reduce the chances of developing heart failure that occurs due to high blood pressure.
Beta-blockers and diuretics are similar drugs used to treat high blood pressure and related health conditions.
Beta-blockers work by reducing the effects of the adrenaline hormone. This causes the heart to beat slowly and relaxes veins and arteries.
Diuretics reduce the amount of water in the blood, thereby reducing blood volume and blood pressure.
Angiotensin II Receptor Blockers (ARBs) also work very similarly to ACE inhibitors. These drugs can offer better inhibition of angiotensin II and are becoming popular types of antihypertensive medications.
Digoxin is another drug commonly prescribed for reducing heart rate. Digoxin is usually used along with other kinds of heart medicines to treat symptoms of heart failure. It is preferred when ACE inhibitors or beta-blockers cannot be used.
The common side effects of ACE inhibitors are:
Other extreme side effects of ACE inhibitors are:
ACE inhibitors can interact with many drugs and can lead to extreme side effects. Inform your doctor if you are on the following medications.
Angioedema is a condition that causes rapid swelling beneath the skin. Studies report that up to one-third of all emergency visits for angioedema are by those who use ACE inhibitor drugs.
The XPNPEP2 gene contains instructions for the production of X-Prolyl Aminopeptidase 2 protein. The gene plays a role in the functioning of bradykinin, a molecule that helps relax the blood vessels.
rs3788853 is a Single Nucleotide Polymorphism (SNP) in the XPNPEP2 gene.
According to a study, the A allele of this SNP is associated with low aminopeptidase P (APP) activity.
Low APP activity leads to increased bradykinin production, which increases the risk of developing angioedema in black men.
However, this relationship was not found in women or white men.
|A||Increased risk of developing angioedema in black men|
|C||Normal risk of developing angioedema|
The ADRB2 gene (Adrenoceptor beta 2 gene) helps produce the beta-2 adrenergic receptor. This receptor is activated by adrenaline and is associated with mental health conditions like anxiety and phobias.
A study analyzed the association between ACE inhibitors and changes in the ADRB2 gene. 336 participants were treated with ACE inhibitor drugs. The time taken to reach a Mean Arterial Pressure (MAP) of 107 mmHg was noted.
rs2053044 is an SNP in the ADRB2 gene. People with the GG genotype of this SNP reached the MAP about 12 days later than those with the AA or AG genotype.
|GG||Lowered response to ACE inhibitors in reducing blood pressure|
|AG||Normal response to ACE inhibitors in reducing blood pressure|
|AA||Normal response to ACE inhibitors in reducing blood pressure|
The NOS3 gene (Nitric Oxide Synthase 3 gene) helps produce the endothelial NOS (eNOS) or nitric oxide synthase 3 enzyme. This enzyme plays a role in Nitric Oxide (NO) synthesis.
rs3918226 is an SNP in the NOS3 gene. According to a study, people with the T allele of this SNP responded better to enalapril, a type of ACE inhibitor. An opposite effect was observed in those with the A allele.
|T||Better response to ACE inhibitors|
|A||Lowered response to ACE inhibitors|
ACE inhibitors are more effective for people younger than 55. This is because young individuals have higher levels of renin in the blood.
Renin is a type of enzyme released by the kidney - higher levels of this enzyme are associated with higher blood pressure in younger adults.
ACE inhibitors effectively bring down renin levels.
People older than 55 are less responsive to renin, and hence, ACE inhibitors don’t make an impressive difference to blood pressure levels.
ACE inhibitors lead to lowered blood flow, which can be problematic in those with existing circulatory problems.
Low blood volume and hypotension can lead to ischemia (inadequate blood supply to organs), myocardial infarction, stroke, and even kidney failure.
ACE inhibitors also cause kidney failure in those with existing renal artery stenosis (narrowed/blocked arteries that lead to the kidneys) or chronic kidney disease.
People with diabetes (both type 1 and type 2) are at increased risk of developing hyperkalemia with ACE inhibitor intake.
Genetic testing can help understand how a person is likely to respond to ACE inhibitor treatment. It gives insights into how a person’s body reacts to the drug and identifies if dosage alterations are needed to improve the efficiency of the medicine and reduce its toxicity risk.
Analgesics, also called painkillers or pain relievers, are a group of medications that relieve pain and inflammation without making you drowsy. They are available as over-the-counter and prescription drugs.
There are different classes of analgesics, but the two most commonly used ones are Non-steroidal Anti-inflammatory Drugs (NSAIDs) and opioid analgesics (narcotics).
Analgesics are always prescribed based on how strong they are. The WHO recommends using the analgesic ladder, a step-wise approach to pain relief.
According to this ladder, non-opioid analgesics (like acetaminophen and NSAIDs) are prescribed for mild-to-moderate pain, weak opioids (like codeine tramadol) for moderate-to-severe pain, and stronger opioids (oxycodone and morphine) for severe pain.
Image: WHO Analgesic Ladder
Analgesics may be used to relieve pain and inflammation due to various reasons:
Different analgesics have different mechanisms of action.
NSAIDs bring about pain relief by blocking the effect of cyclo-oxygenase enzymes.
These enzymes play a role in producing prostaglandins, chemicals responsible for pain and inflammation at the injury site.
When there is a reduction in prostaglandin production, pain and inflammation are reduced.
Other analgesics that have a similar mechanism of action to NSAIDs include acetaminophen, aspirin, and COX (cyclo-oxygenase) inhibitors.
Though paracetamol is known to work similarly to NSAIDs (blocking the cyclo-oxygenase enzymes), it does not reduce inflammation.
Opioids work by binding to opioid receptors in the central nervous system or CNS, gut, and other parts of the body and altering how your brain perceives pain.
As a result, you feel less pain, and in a way, these drugs increase your pain tolerance.
Some examples of opioids are codeine, fentanyl, methadone, naloxone, and oxycodone.
Though analgesics are widely used, they may cause side effects in some individuals when used too often or in large doses.
Some side effects of analgesics are:
Opioid analgesics may also cause any of the above side effects in addition to causing physical dependence.
Some signs that you may be addicted to an opioid analgesic are:
If you experience any of the side effects mentioned above, you must consult your doctor. If you notice any of the following side effects, stop taking the NSAIDs or analgesic drugs and report to your doctor immediately:
Some drugs that cause significant interactions with analgesics are:
Antacids and food are both known to delay the absorption of analgesics, which means the slow effect of the analgesic on pain.
Drugs bound to proteins such as phenytoin, warfarin, and phenylbutazone compete with the binding site of salicylates (a subclass of NSAIDs). This reduces the efficacy of the analgesic.
Consuming beta-blockers with salicylates can affect their metabolism (breaking down and processing the drug) and elimination from the liver.
Some NSAIDs interactions with other drugs that may cause adverse reactions are:
Taking NSAIDs with blood thinners like warfarin can increase the risk of bleeding.
When combined with ACE inhibitors (medicines used to treat high blood pressure and heart problems), analgesics may cause kidney failure. The same adverse effect may be seen when analgesics are consumed with diuretics (medicines that remove excess fluid from the body).
When two NSAIDs like a low-dose aspirin are combined with another NSAIDs drug, there may be a greater risk of ulcer formation or bleeding in the gastrointestinal tract.
Taking analgesics with antibiotic isoniazid may cause liver damage. So, it is best to avoid taking these drugs together.
Always inform your doctor about your current medications to avoid adverse effects due to analgesic interaction with other drugs you may be taking.
The KCNJ6 gene contains instructions for producing an enzyme called Potassium Inwardly Rectifying Channel Subfamily J Member 6. This enzyme allows a greater inflow of potassium ions into the cell.
In doing so, this gene regulates body processes like heart rate and the activity of nerve cells.
Certain changes in the KCNJ6 gene have been associated with analgesic requirements in patients who have undergone surgery.
Patients having a change (variation) called 1032A/A in the KCNJ6 gene required more analgesics than those with the other variations - 1032A/G and 1032G/G.
This is because 1032A/A is associated with lower levels of the enzyme and insufficient analgesic effects.
The COMT gene provides instructions for making the enzyme catechol-O-methyltransferase.
The COMT gene has 3 types named Val/Val, Val/Met, Met/Met. The three types each produce different levels of the COMT enzyme.
The COMT gene has been associated with postoperative pain treatment using opioid analgesics.
According to a study, individuals having the Val/Met type required less opioid analgesia in the first 24 hours after surgery.
This was not seen with individuals carrying the Va/Val and Met/Met types.
The OPRM1 gene gives instructions for making a mu-opioid receptor protein.
These receptors form a part of the body’s system that regulates pain, reward, and addictive behaviors.
A study found that individuals with the 118G or GG type of the OPRM1 gene require more postoperative analgesics than those with the AA or the AG types.
Analgesics like NSAIDs, opioid analgesics and acetaminophen are all metabolized in the liver.
So, if you suffer from any liver disease or condition, you must inform your doctor.
To avoid adverse reactions or severe side effects of analgesics, people with chronic liver diseases, especially hepatitis and cirrhosis, must avoid consuming analgesics.
Analgesics are known to interact with different drugs. Therefore, to avoid adverse reactions, you must inform your doctor about any medicines or supplements you are currently taking before taking analgesics.
Alcohol and analgesics are both known to irritate the stomach lining.
Drinking alcohol while taking NSAIDs may increase your risk for gastrointestinal lining damage and bleeding.
So, if you are taking analgesics, especially NSAIDs, you must avoid drinking alcohol.
Always take an analgesic when necessary and in the minimum dose possible that relieves your pain.
It is also important to take the painkiller only as long as it is needed.
Genetic testing can be beneficial in determining how your body may respond to analgesics and identify your risk for any side effects.
Amprenavir is an antiviral drug used to treat the Human Immunodeficiency Virus (HIV) infection.
This drug was approved by the Food and Drug Administration (FDA) in 1999 and is available as capsules or oral solutions.
The drug is sold under the brand name Agenerase.
Amprenavir was discontinued in 2007.
However, a prodrug version of the same, called Fosamprenavir, is available now.
A prodrug is a substance that is converted into an active drug form in the body after the person consumes it. Sometimes when the actual drug is poorly absorbed or leads to severe side effects, a prodrug form of the same is developed.
The prodrug is created to ensure maximal absorption by the target cells and bring down the risk of adverse effects.
In this case, Fosamprenavir, on administration, is metabolized into amprenavir and directly targets the virus.
No. You will need a prescription to be able to buy the drug.
Amprenavir belongs to a class of drugs called protease inhibitors. Protease is a type of enzyme that the virus makes.
This HIV-1 protease enzyme makes the virus infectious and, as a result, harmful.
Protease inhibitors attach themselves to the virus’s protease and prevent it from functioning. As a result, the virus remains infectious.
An adult will need 1200 mg of the drug twice a day, and the drug is available in the form of 50 mg or 150 mg capsules.
Some of the common side effects of amprenavir are:
About 27% of people may develop skin rashes and itchy skin when amprenavir is administered.
In addition, a severe skin condition called Stevens-Johnson Syndrome (losing the outer layer of the skin) may occur in 1% of people using the drug.
16% of people who use amprenavir may also experience psychiatric disorders, including mood swings and depression.
Amprenavir oral solution can lead to the following side effects:
Like other protease inhibitors, Amprenavir may lead to increased cholesterol levels, insulin resistance, and worsening diabetes.
Yes, protease inhibitors are safe to use under the guidance of a healthcare provider. However, make sure to talk to your doctor about your existing health conditions and the drugs you use to prevent the risk of side effects.
Amprenavir may interact with other drugs and lead to changes in drug efficacy or worsening of the adverse effects. Therefore, notify your doctor if you use amprenavir along with the following medications.
The SLCO1B1 gene (Solute Carrier Organic anion transporter family member 1B1 gene) provides instructions for producing the organic anion transporting polypeptide 1B1 (OATP1B1) protein.
This protein transports drugs, toxins, hormones, and other substances from the blood to the liver for elimination.
rs4149056 is a Single Nucleotide Polymorphism (SNP) in the SLCO1B1 gene.
In people with HIV infection, the CC and CT types of this SNP may lead to reduced blood amprenavir levels.
In contrast, TT type may lead to increased blood amprenavir levels.
However, this association was only found in people of European descent.
Low levels of amprenavir may not be sufficient to fight HIV effectively, while high drug levels may lead to an increased risk of developing adverse side effects.
Knowing specific gene changes can help plan the right drug dosage to maintain optimal drug levels in the body.
|CC||Decreased blood amprenavir levels in people of European descent with HIV|
|CT||Decreased blood amprenavir levels in people of European descent with HIV|
|TT||Increased blood amprenavir levels in people of European descent with HIV|
Studies in animals show that usage of amprenavir during pregnancy may be associated with an increased risk of abortion and low birth weight in babies.
Talk to your doctor and weigh the benefits and risks of using amprenavir if you are pregnant.
Animal studies also show that amprenavir is secreted in the milk of lactating animals. This is not confirmed in humans, though.
Hence, talk to your doctor and understand the risks of the same.
Doctors generally don’t recommend mothers with HIV to breastfeed because of the risk of postnatal transmission of the virus from the mother to the baby.
People with existing liver conditions must use amprenavir with caution.
The Child-Pugh score is an assessment to determine the extent of liver damage.
People with a Child-Pugh score of 5-8 should bring down amprenavir dosage to 450 mg/twice a day.
Those with a score of 9-12 should decrease the dosage to 300 mg/twice a day.
The oral amprenavir solution contains high amounts of propylene glycol. This colorless liquid is harmful in large doses.
Doctors recommend patients choose the capsules over the oral solution for this reason.
Also, the oral solution is not recommended for pediatric patients below four and the elderly.
Studies show that a high-fat diet may decrease the absorption of amprenavir. Therefore, patients are advised to monitor their fat intake while on the drug.
Certain hormonal birth control pills can interfere with amprenavir and reduce its efficacy. Talk to your doctor if you are on birth control pills and are prescribed amprenavir.
If you think you have overdosed on Amprenavir, make sure you call 911 or visit the nearest Emergency Room right away.
Genetic testing will help find out if you have SLCO1B1 gene changes. This can help plan the right dosage of amprenavir, preventing both lowered drug efficacy and drug overdose.
Acetaminophen is a common drug prescribed for pain and fever. It is both an analgesic (pain relievers) and antipyretic (used to treat fevers).
Acetaminophen is sold under the brand names Paracetamol, Tylenol, and Panadol.
Acetaminophen is used to treat fever, flu, common cold, headaches, body aches, toothaches, menstrual pain, and even arthritis pain. It is available without the need for a prescription in most parts of the world.
As of 2018, acetaminophen was the 20th most prescribed drug in the United States.
Acetaminophen works by changing the way the body experiences pain and increased temperature.
This drug works by blocking the release of certain chemicals that signal pain sensations to the brain. As a result, the person does not feel the intensity of pain.
Acetaminophen also communicates to the heat-regulating center of the brain and asks it to lower the body’s temperature. This helps bring down the fever.
This drug is usually available as oral pills. In some cases, it may also be administered intravenously.
Most people can tolerate acetaminophen well. However, some may develop some allergic reactions.
Some studies report that the use of acetaminophen during pregnancy increases the risk of childhood asthma in babies.
Acetaminophen overdose can lead to severe liver damage. Here are some of the symptoms of Acetaminophen overdose:
Acetaminophen can interact with many other drugs and can cause increased side effects or nullify the effects of the drugs. Make sure you notify your doctor if you use the below medications.
The TRPV1 gene contains instructions for the production of a protein called transient receptor potential cation channel subfamily V member 1. This protein helps the body sense pain.
It is activated in response to high temperature, acidic conditions, and upon consumption of certain foods like hot peppers or mustard.
Acetaminophen is converted into an intermediary metabolite called N-arachidonoylphenolamine (AM404) by the fatty acid hydrolase.
Studies show that this metabolite activates the TRPV1 protein, contributing to the pain-relieving effects of this drug.
Glucuronidation is an essential detoxification pathway for acetaminophen clearance from the body.
The UGT1A gene (UDP glucuronosyltransferase 1 family, polypeptide A cluster gene) helps produce the UGT1A enzyme that helps in acetaminophen glucuronidation.
rs8330 is a Single Nucleotide Polymorphism or SNP in the UGT1A gene.
The G allele of this SNP is associated with increased acetaminophen glucuronidation and a lower risk of acetaminophen overdose.
|GG||Very high acetaminophen glucuronidation activity and very low risk of acetaminophen overdose|
|CG||Moderately high acetaminophen glucuronidation activity and lesser risk of acetaminophen overdose|
|CC||Normal acetaminophen glucuronidation activity and a normal risk of acetaminophen overdose|
The OPRM1 gene (opioid receptor mu 1 gene) helps produce the mu (μ) opioid receptor protein. This protein is a part of the opioid system in the body that regulates pain.
rs1977791 is an SNP in the OPRM1 gene. People with the G allele of this SNP require a higher dose of medication for pain relief compared to the A allele carriers.
About 19% of the global population has this minor G allele.
|G||Require higher doses of acetaminophen for pain relief|
|A||Require normal doses of acetaminophen for pain relief|
According to the Food and Drug Administration (FDA), adults should not consume more than 4g of acetaminophen in a day or 325 mg/dose. For children younger than 12, the recommended dosage limit per day is 75mg/kg of body weight.
If you are consuming acetaminophen for the first time, carefully watch out for allergy symptoms like shortness of breath, itching, hives, and swelling.
Acetaminophen is usually safe for pregnant and breastfeeding women. However, it is always safer to inform your doctor about your pregnancy.
Acetaminophen overdose can cause dangerous side effects in people with existing liver problems. Talk to your doctor before consuming the drug.
It may not be safe to use acetaminophen in combination with allergy, cold, and cough medications in children younger than two. Do not combine medications unless instructed by the pediatrician.
Genetic testing will help understand an individual’s response to acetaminophen and give insights on how quickly the drug is cleared from the body and dosages that may lead to toxicity.
Genetic testing can make dosage planning more precise and customized to a person’s genetic changes.
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).
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.
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.
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:
Other severe side effects of Acamprosate that require urgent medical attention include:
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.
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.
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.
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.
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.
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.
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.
Abacavir is an oral medication used to treat infections associated with the Human Immunodeficiency Virus (HIV). It belongs to a class of drugs called reverse transcriptase inhibitors that prevent the multiplication of HIV. It is routinely used with other medications as part of Highly Active Antiretroviral Therapy (HAART).
HIV needs to form new DNA to produce new viruses and multiply. The virus uses an enzyme called reverse transcriptase (RT) to create the new viral DNAs in the host (humans, animals).
This enzyme is usually found in retroviruses like Human Immunodeficiency Virus or HIV.
When Abacavir is consumed, it gets converted into its active form called carbovir triphosphate in the body. This compound is similar to deoxyguanosine triphosphate, a compound used by the HIV virus to make new DNA.
The RT enzyme now uses carbovir triphosphate instead of deoxyguanosine triphosphate for making DNA. This interferes with viral replication, slowing down the multiplication of HIV.
Abacavir does not kill HIV and is not a cure for the disease either.
Some common side effects of Abacavir are:
Serious side effects of the drug include:
Abacavir shows interactions with other drugs, so it is essential to inform your doctor about the medications you may be taking. Some medicines that may interact with Abacavir are:
The HLA-B gene is a part of the Human Leukocyte Antigen (HLA) complex family. This complex helps the body’s immune system differentiate between proteins made by the body and infectious pathogens like bacteria and viruses.
There are many types of the HLA-B gene that allow the immune system to respond to a wide range of pathogens. The HLA-B gene alleles are numbered as HLA-B *x, where x is a numerical figure. For example, HLA-B*57, HLA-B*35, etc.
Closely related alleles that are categorized together are numbered as HLA-B *57: 01 to HLA-B*57:60 (if there are around 60 very similar alleles that are subtypes of HLA-B57)
HLA-B*57:01 allele increases the risk of hypersensitivity reactions to Abacavir across different ethnicities.
In addition, the presence of HLA-B*57:01 significantly increases the risk of hypersensitivity reactions with Abacavir usage.
Abacavir is, therefore, not indicated or prescribed for patients with HLA-B*57:01 allele and those with a prior history of hypersensitivity reaction to Abacavir.
rs2395029 is a single nucleotide polymorphism or SNP in the HLA-B gene. The G allele of this SNP is 99.9% predictive of the presence of an HLA-B*5701 allele in Caucasian and Hispanic populations.
|GG||HLA-B*57:01 homozygote likely if the individual is Caucasian or Hispanic. High risk for hypersensitivity to drugs like Abacavir|
|GT||Most likely a carrier of the HLA-B*57:01 if the individual is Caucasian or Hispanic.|
|TT||No risk of sensitivity to abacavir|
Before taking Abacavir, you must inform your doctor if you have a history of liver or kidney problems.
Abacavir may increase your risk for heart attack, and you must consult your doctor if you have any cardiovascular condition that can precipitate an attack.
It is also essential to inform your doctor about your history of alcohol consumption, smoking, hypertension, diabetes, and high cholesterol levels.
If you are on medications like methadone or other retrovirals for HIV, you must inform your doctor and pharmacist to avoid untoward drug interactions.
The recommended dosage of Abacavir is 300 mg orally twice a day or 600 mg once a day (for healthy adults, adolescents, and children weighing at least 25 kg). The drug is available as a solution (20 mg/mL) and tablet (300 mg).
Before taking Abacavir, you must inform your doctor if you are allergic to the drug or have a history of allergies to any substance or other medications.
Inform your doctor if you are pregnant before starting on Abacavir. Treatment using this drug can lower the transmission of HIV to your fetus.
This drug can pass into breast milk. Therefore, avoiding breastfeeding may be recommended during treatment with the drug.
Screening for the HLA-B*57:01 allele is recommended for all patients according to the FDA drug label for Abacavir.
Methadone is an opioid (or narcotic) drug and a controlled substance - this drug has a risk of misuse and may cause dependence.
Methadone is also available as the brand-name drug Methadose. It is used as an oral soluble tablet.
Methadone is used to treat moderate to severe pain.
It is sometimes prescribed in cases where the patient has an addiction to another opioid. Methadone helps prevent withdrawal symptoms.
Methadone relieves pain by changing the way your brain and the nervous system respond to pain. It does so by working on the pain receptors.
Methadone relieves pain much slower than other painkillers like morphine.
Some common side effects of methadone are:
Some serious side effects are:
Opioid medication can interact with many other drugs and cause dangerous side effects. Make sure you notify your doctor if you use other:
Methadone maintenance treatment is the use of methadone for a prolonged period of time to treat pain in patients who have faced addiction issues with other opioids like heroin.
The UGT2B7 gene is located at chromosome 4q13. It contains instructions for the production of UDP-Glucuronosyltransferase-2B7.
It is associated with withdrawal symptoms, treatment efficacy, and side effects in methadone maintenance treatment.
rs4292394 is a single nucleotide polymorphism or SNP in the UGT2B7 gene. It is associated with opioid withdrawal when undergoing methadone maintenance treatment.
|GG||May have increased severity of opiate withdrawal symptoms|
|CG||May have decreased severity of opiate withdrawal symptoms|
|CC||May have decreased severity of opiate withdrawal symptoms|
The CYP3A enzymes are the most abundant of the CYP450 isozymes, comprising ∼40% of the hepatic CYP450 content.
The CYP3A4 gene contains instructions for the production of the Cytochrome P 450 3A4 enzyme. CYP3A4 plays a role in the metabolism of 40–60% of all drugs ingested.
A few studies have reported the role of CYP3A4 polymorphisms in methadone toxicity.
rs4646437 is an SNP in the CYP3A4 gene. Studies have demonstrated that the CYP3A4 enzyme expression and activity are increased in females carrying the T allele.
Increased levels of CYP3A4 result in increased conversion of methadone to inactive metabolites (substances that result from the metabolism of methadone). This increases the risk of fatal methadone intoxication in the female population with the T allele.
Notify your doctor of any health conditions you may have, like heart, lung, or kidney disease, as methadone may not be safe to consume in these cases.
Make sure your doctor knows all the drugs you are currently on/have had in the recent past in order to avoid drug interactions.
Women who are pregnant or breastfeeding may take methadone; however, methadone can cross the placenta and can go into the breast milk. So seek the advice of your medical practitioner if you are pregnant or breastfeeding.
The correct dosage varies according to the purpose - whether to treat pain, for detoxification of opioid addiction, or for maintenance of opioid addiction.
In case you take too much or experience symptoms of overdosing like slow pulse, cold, clammy skin, slowed breathing, or dizziness, immediately call your doctor or local poison control. If the symptoms are severe, call 911.
Methadone can cause severe allergic reactions. If you have trouble breathing or experience swelling of your tongue and throat, seek medical attention immediately.
Acetylcholine is a parasympathomimetic drug that is used for ophthalmological applications. Parasympathomimetic drugs are also called cholinomimetic drugs, and these activate the parasympathetic nervous system (PSNS).
The sympathetic nervous system is a part of the brain that is involved in the "fight or flight" response, and the PSNS is the "rest and digest" side.
The PSNS uses acetylcholine, a neurotransmitter (chemical messenger) that helps in brain-body coordination. Cholinomimetic drugs delay the breakdown or promote the release of acetylcholine.
Acetylcholine in drug form is available as eye drops. It is used to create rapid miosis (shrinking of the pupil) during cataract surgery after the lens is placed or during general eye surgery.
This drug has no value when intravenously administered as it is quickly deactivated by a group of enzymes in the Central Nervous System called cholinesterase. The eye drop form, however, helps quicken recovery after eye surgery.
When administered inside the eyes, Acetylcholine controls nerve impulse transmission and causes rapid shrinking of the pupil.
A nerve impulse is the way nerve cells (neurons) communicate with one another. Nerve impulses are mostly electrical signals.
About 0.5-2 ml of the 1% solution is introduced into the eyes, and miosis occurs (pupil shrinks to less than 2mm). Miosis lasts for about 10 minutes
Some common side effects of acetylcholine are:
Rarer side effects of acetylcholine are:
Acetylcholine can interact with certain drugs and lower the efficiency of the drug or cause extreme side effects. Therefore, make sure to notify your doctor if you are on any of the following drugs.
The ACE gene (angiotensin-converting gene) helps produce the ACE enzyme.
The ACE enzyme regulates blood pressure and fluid balance in the body by constricting the blood vessels.
In a study, researchers introduced enalaprilat, an ACE inhibitor drug, to 56 patients with atherosclerosis (a condition caused by the build-up of fat and cholesterol).
ACE inhibitor drugs interfere with the ACE enzyme activity and relax the blood vessels.
Image: Action of ACE Inhibitors
These patients were then administered acetylcholine. Changes in the coronary blood flow, vascular resistance, and epicardial diameter were then measured.
People with the DD and ID types of the ACE gene had a better blood flow and relaxation of blood vessels than those with the II type.
|DD||Increased coronary blood flow|
|ID||Increased coronary blood flow|
|II||Lowered coronary blood flow|
As a topical eye solution, acetylcholine is very unstable. Therefore, the solution has to be prepared and used immediately.
Acetylcholine overdose can lead to cardiovascular complications or constriction of the airways. Drugs that can counteract this constriction effect have to be kept ready while administering acetylcholine.
Rarely, some people can have an allergic response to acetylcholine and develop the below symptoms.
If you experience any of the above-mentioned symptoms when treated with acetylcholine, notify your doctor immediately.
Genetic testing can help understand how your body responds to acetylcholine. This can enable your doctor to administer the drug at correct dosages with proper precautions.
Around 6.2 million Americans of 65 years and above are ravaged by Alzheimer's. Alzheimer's is characterized by amyloid plaques in the brain. A new study found that people taking certain drugs for type 2 diabetes had less amyloid protein in the brain. Further, people taking these drugs also displayed a slower cognitive decline.
Alzheimer’s is one of the ten leading causes of death in the US. Medically, Alzheimer’s is a progressive neurological disorder, i.e., the nerve cells in the brain start to die, and the brain shrinks.
The area of the brain to get affected earliest is the hippocampus, which is responsible for memory. However, the onset of disease can occur much earlier than the appearance of the first symptoms.
Gradually, neuronal cell death progresses to other areas of the brain. This leads to severe memory impairment and loss of ability to carry out everyday tasks.
To date, there is no cure or treatment for Alzheimer’s. Further progression of the disease ultimately results in death due to severe loss of brain function involving dehydration, malnutrition, or infection.
Xcode Life’s Gene Health Report analyzes 50+ genetic markers for Alzheimer’s disease to give possible predisposition and recommendations. Check your Alzheimer’s Disease risk here.
Biological markers or biomarkers are characteristics that can be objectively measured as an indicator of a pathological or normal physical process.
For Alzheimer’s, scientists usually look for two proteins as the disease’s biomarkers.
Amyloid plaques are stacked forms of the beta-amyloid protein fragment. Beta-amyloid is a protein fragment cut from the amyloid protein precursor (APP). Usually, these protein fragments are cleansed from the brain by microglia.
Image Source: Brain Blogger
The image here depicts amyloid plaques formed around nerve cells in the brain.
In Alzheimer's patients, the beta-amyloid does not get eliminated and starts forming clusters in the brain. In their early cluster stage, the beta-amyloid starts destroying synapses or nerve junctions - leading to memory loss in the individual. Upon forming plaques, the beta-amyloid protein contributes towards brain/nerve cell death.
Tau proteins are part of the neuron’s (nerve cell) internal support and transport system.
Image Source: Utah Public Radio
In Alzheimer’s, the tau proteins change their shape and structure to form tangles in the neuronal fibers. These tangles disrupt normal tau protein functioning and become toxic for the cells, thus leading to cell death.
The most prevalent genetic risk factor for Alzheimer’s is the ApoE (apolipoprotein E) gene. The 4 type of this gene is known to confer the highest risk factor and is present among 50% of Alzheimer’s patients.
The ApoE gene present on chromosome 19 makes a protein that helps transport cholesterol and other fat molecules through the bloodstream.
While there are two other types of the ApoE gene ( 2 & 3), only the 4 variant is associated with increased risk for Alzheimer’s. Having one or both copies of ApoE 4 in the body increases Alzheimer’s risk. The prevalence of individuals carrying one copy is about 25%, while only 2-3% carry both copies.
Know your ApoE gene Status with Xcode Life’s Gene Health Report.
Alzheimer’s is one of the diseases where age, especially old age, plays a significant role. Although Alzheimer’s development is not part of the normal aging process, old age increases the risk.
MCI is characterized by a decline in memory and associated thinking abilities, disrupting an individual's normal societal or work-environment functioning. Usually, an MCI diagnosis with primary memory deficit leads to Alzheimer's associated dementia.
Certain factors which pose a risk for cardiac problems also increase Alzheimer’s risk. Some of them are
Additionally, people with type 2 diabetes are at a higher risk of Alzheimer's disease. This may be due to higher blood sugar levels which have been linked to amyloid plaque buildup.
DPP-4 inhibitors or gliptins are oral diabetes drugs used to block the enzyme dipeptidyl peptidase-4. DPP-4i acts on incretins (a group of hormones that stimulate the release of insulin). In addition, it reduces glucagon (a hormone that increases blood sugar levels), thereby decreasing blood sugar levels.
Studies revealed an increased risk of inflammatory bowel and hypoglycemia when combined with another class of diabetic drug, sulphonylureas (like glipizide and glimepiride), in type 2 diabetic patients.
Know your body’s predisposition to the metabolism of DPP-4i and sulphonylurea drugs with Xcode Life’s pharmacogenomics report, Personalized Medicine.
Scientists at the American Academy of Neurology explored the effect of DPP-4i use in Alzheimer’s patients who may/may not suffer from type 2 diabetes (T2D).
The study involved 282 people with either pre-clinical, early, or probable diagnosis of Alzheimer's. Individuals were of an average age of 76 and were followed for a six-year period. These people comprised of:
Researchers measured the amyloid content in the individuals’ brains using a brain scan.
Study participants were made to take a common thinking and memory test called Mini-Mental State Exam (MSME) every 12 months for 2.5 years to track cognitive decline. The test consisted of questions like counting backward from 100 by sevens or copying a picture on paper. The score ranged from zero to thirty.
Between the three subgroups, Alzheimer’s individuals having T2D and on DPP-4i drugs:
Further adjustment of factors that could affect MSME scores, the same Alzheimer’s individuals with T2D and using DPP-4i drugs scored even lower decline by 0.77 points per year.