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.
Analyze Your Genetic Response to Acetylcholine
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.
A previous study exploring the effect of DPP-4i use on dementia among type 2 diabetes patients revealed an increased impact on dementia, albeit not in Alzheimer’s patients.
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.
Pharmacogenomics, sometimes called as pharmacogenetics, is the study of how genes affect a person’s response to drugs. It is a combination of two fields - pharmacology (the science of drugs) and genomics (the study of genes and their functions).
Just like how genes determine our eye color, height, etc. they also partly influence how our body responds to drugs. Some chemical changes in these genes can elicit unwanted side effects upon drug consumption.
The long-term goal of pharmacogenomic research is to design drugs best suited for each person, in order to avoid these undesirable side effects.
Genes influence multiple steps involved in your response to drugs. They include:
Drug Receptors: Some drugs require a type of protein called the receptors, to which they bind and get activated. Your genes can influence the number and effectiveness of these receptors.
Example: T-DM1 is a drug used to treat breast cancer. This drug works by attaching to a receptor called the HER-2 receptor. However, not all breast cancer cells express this receptor. So, this drug may not be effective for all individuals with breast cancer.
Drug Uptake: Certain drugs are activated only after they are taken into the cells and tissues. If your genetic makeup leads to reduced uptake of the drug, it may accumulate in other parts of the body.
Example: Statins are a class of drugs commonly used to treat high cholesterol levels. For the drug to work, it must be transported to and taken up by the liver efficiently. SLCO1B1 gene influences this process. A change in this gene results in a reduced transport of statins to the liver. This can result in statin buildup in muscles resulting in pain and weakness.
Drug breakdown/metabolism: If your genetic makeup results in a faster breakdown of drugs, it gets clear from the body faster. This may warrant an increased dosage of the drug or a different drug. On the other hand, if your drug metabolism is slow, it stays in your body for a longer period. In this case, a lower dosage may do the work.
Example: Amitriptyline is an antidepressant drug. Two genes, namely, CYP2D6 and CYP2C19, are involved in its metabolism. If you carry a change that slows down or boosts the metabolism, you may need to alter the drug dosage accordingly.
Patients can respond differently to the same medicine.
Commonly used drugs to treat some medical conditions need not be effective for everyone. Some examples are:
- Antidepressants drugs (SSRIs) are ineffective in as many as 38% of patients who are prescribed these drugs
- Asthma drugs are ineffective in as many as 40% of patients who are prescribed these drugs
- Diabetes drugs are ineffective in as many as 43% of patients who are prescribed these drugs
- Arthritis drugs are ineffective in as many as 50% of patients who are prescribed these drugs
- Alzheimer’s drugs are ineffective in as many as 70% of patients who are prescribed these drugs
- Cancer drugs are ineffective in as many as 75% of patients who are prescribed these drugs
- Cardiac Arrhythmias drugs are ineffective in as many as 40% of patients who are prescribed these drugs
Source: Brian B Spear, Margo Heath-Chiozzi, Jeffrey Huff, Clinical application of pharmacogenetics, Trends in Molecular Medicine, Volume 7, Issue 5, 2001, Pages 201-204, ISSN 1471-4914, https://doi.org/10.1016/S1471-4914(01)01986-4.
The purpose of pharmacogenomic testing is to find out if a medication is right for you. A pharmacogenomic test will help in knowing:
Efficacy - Whether a medication may be an effective treatment for you.
Dosage - What is the best dose for you for specific medications.
Toxicity - Whether you could have serious side effects from a medication.
CYP enzymes or the Cytochrome P450 enzymes are the major drug-metabolizing enzymes in the body. The P450 enzymes contain a protein called heme (iron-containing compound) and are commonly present in hepatocytes (cells of the liver). This is why drugs are mostly broken down or metabolized in the liver.
From a clinical perspective, the most commonly tested CYPs are:
Changes in CYP enzymes can influence the metabolism and clearance of drugs.
The CYP450 Test categorizes individuals into one of the four known metabolic profiles, called “predicted phenotypes.”
What are the limitations of a CYP test?
- Pharmacogenomic research is still in its infancy. Therefore, tests are available only for certain drugs.
- Any change in medication will require a new CYP test - this is because different enzymes are responsible for metabolizing different drugs
- The test reveals how genes affect the drugs and not what the drug does to the body (for example, we cannot determine how the drugs change certain receptors in the brain to alleviate the symptoms)
- Some drugs are metabolized and cleared by more than one CYP enzyme. For example, antidepressant drugs like the SSRIs (Selective Serotonin Reuptake Inhibitor) are metabolized by serotonin receptor molecules as well. This can limit the predictive value of the test.
Who should take the PGx test ?
If you answer yes to any of the below questions, you are an ideal candidate for a PGx test.
1. Are you currently taking four or more medications monthly?
2. Have you or anyone in your family ever been hospitalized for taking medication?
3. Have you or anyone in your family ever felt ill after taking a new medication?
4. Has your doctor changed your dose of medication due to a lack of response or a reaction to the medication?
5. Do you take your prescribed medication, and you still aren’t feeling better?
6. Are you taking or is your doctor considering prescribing to you pain medicine, tamoxifen, or Plavix?
7. Do you take herbal supplements regularly in addition to your medication?