Drugs and Genetics: The Genetic and Non Genetic Relation with Various Responses to Medications

My project about the relation of medication with genetics and why some people react to similar medication differently than other people.
Anay Shroff
Grade 9

Problem

Why do some people respond to medical drugs different than others and how is this related to genetics?

Method

Hypothesis:

If I research about why some people respond to medical drugs differently than others, then, I think I will find that it is because of their genetic properties, because, the way you react to a medicine is based on the way that your body is built and the things that your body can and can not tolerate and these things are based on your genetic makeup.

Method:

There are a couple of areas I went deeper in with this project. Firstly, I looked at medicine as a whole and look at the general reason(s) behind people reacting differently to medications.  I  then looked at non prescribed medicine and find out why some people react differently than others to non prescribed medications. Then looked at prescription medicine and look at the reasons behind different reactions and effects of prescription medication. Finally, I looked at at some measures to prevent reactions to medications.

Research

Intro

There are two different types of things that can happen if a medicine doesn’t work as intended. These are: a change in the effectivity of the medicine, and adverse drug reaction occurring.

Adverse drug reactions

Adverse drug reactions (ADRs) are a type of reaction to medicines that can happen when taking a medicine. They are possible when there is a genetic mutation or when a certain patient related factor is causing the reaction. ADR is defined as “a response to a drug which is noxious and unintended.” For most ADRs there are lots of factors that are related to genetics, and other things related to factors of the patient or the medicine itself. Most of the ADRs that occur are because of the extension of the desired effects of a medicine.

Change in effectivity

A change in effectivity for a medicine is when the medicine is either less effective than intended or more effective than intended. Generally, problems occur where the medicine is less effective than intended and there are not a lot of cases where medicines are more effective than intended to be at a certain dosage. Genetic related factors and patient related factors are the two predominant reasons that a change in the effectivity of a medicine occurs.

Medicine in general and reasons why they cause reactions and changes in effectivity

Genetic Related Factors that can cause ADRs or change the effectivity of the medicine:

Genetic Mutations

In general, different responses to medicine have a lot to do with differences in genetics. Every person has a genome that contains anywhere between 20,000 to 25,000 genes. Each gene has hundreds to millions of DNA nucleotides. All it takes is a single DNA mutation that is associated with an increased, or decreased, response to a certain drug that changes the effect of that drug on the patient’s body. It depends on what, and where, the mutation is. (Lohner, 2023)

Every gene in the human body is made up of DNA (deoxyribonucleic acid). DNA is a type of genetic code that is made up of four different types of nucleotides. These are: adenine (A), thymine (T), guanine (G), and cytosine (C). DNA code is turned into mRNA (messenger ribonucleic acid) in our bodies in the process of transcription. Transcription works by DNA initially turning into pre-mRNA. In order to turn this into the final mRNA code, a process called splicing removes certain pieces of the pre-mRNA called that are called introns. Other pieces called exons are left in and reassembled, which become part of the final mRNA code. After this, the mRNA goes through a process that is called translation which turns it into amino acids. Every three mRNA nucleotides code into one amino acid. This set of three nucleotides is called a codon. In the end, a sequence of DNA becomes a sequence of amino acids that is joined together in a long chain called a protein. Proteins are the ones that are responsible for most of the functions of our cells.

While introns are labeled as DNA that don’t ultimately code for a protein, they are still very important for the generation of a functional protein. Inside the introns, instructions are there for how the pre-mRNA should be converted into mRNA for a given gene. As a result of these processes, a mutation in one single DNA nucleotide (called an SNP) can prevent a gene from turning into a protein or can create a non-functional protein (Lohner, 2023). In a gene's exon, if a single DNA nucleotide is mutated, this could be able to cause the wrong amino acid to be formed, which would result in the protein not working. This is because, different amino acids are different in many ways, like in size and in the electric charges they have. These characteristics of the amino acids have an effect on how they interact with each other and other molecules that surround them such as water. These seemingly small differences are able to cause very large consequences in how we respond to a drug and the effectiveness of that drug in our body. (Lohner, 2023)

Drugs interact with signalling pathways called biochemical pathways in very specific ways. Signalling pathways involve a lot of different proteins that are all affecting each other in a controlled and specific manner to have an effect on our bodies as a whole. It is possible that the drug may not function as it should if the protein that the drug is interacting with has been mutated a way that the medication cannot interact with the protein or if the protein is not being made at all. For example, the drug clopidogrel (also known as Plavix) is used to prevent blood clots. In order for clopidogrel to prevent blood clots, the intestine has to absorb the drug. After this occurs, clopidogrel must become active in the liver by interacting with a series of proteins. In the end it has to bind platelets to, which are important in forming blood clots (by binding to platelets, it stops the blood clots from forming). If anywhere in this process there is a protein is not functioning normally, or there is a protein that’s not where it’s supposed to be, the clopidogrel may not have its desired effect. (Lohner, 2023)

Overall the genetic factors are mostly the same as when it comes to the effectivity of medicines and genetics. When there is a genetic mutation in the body, the risk of an ADR is present because the medicine is not able to properly interact with the body as a result of the genetic mutation. For this same reason, the effectiveness of the medicine can also be lowered.

Differences in RGS Proteins

 RGS proteins are a major class of proteins within the cells of the body that regulate signals coming in from cell surface receptors. People commonly have differences in these proteins that cause the cells in their body to respond differently when the same cell receptor is stimulated by the same drug. These RGS proteins provide an important braking function (Kirill, 2020) for a group of cell receptors called G-protein-coupled receptors (GPCRs). GPCRs, control hundreds of essential functions in the cells of our body, and have an impact for dozens of diseases such as heart problems, vision impairments, and mood disorders. As a result, GPCRs are the main group of cell receptors that are targeted by a medication. More than one third of all medicines that have been approved by the FDA target GPCRs (Kirill, 2020).

When GPCRs are activated, they initiate signalling within the cells that they are in by carrying proteins called G-proteins. RGS proteins (regulator of G-protein signalling) work by deactivating G-proteins and turning off the signalling. This shutoff device (Kirill, 2020) limits the G-protein signalling to only a brief amount of time and allows the cells to reset and accept new signals. Without RGS proteins, the GPCR-initiated signal stays on for too long which causes the cell to become dysfunctional. Genetic variation in the RGS proteins has the possibility to disrupt normal GPCR signalling because there is no braking function to the GPCR signalling. This explains why different individuals that have been treated with the same GPCR-targeting drug often differ widely in their responses (Kirill, 2020).

Patient related factors that can cause ADRs or change the effectivity of the medicine

Age

All medicines can cause ADRs, but not all patients develop the same level and/or the same type of ADRs. Age is a very important factor which affects the occurrence of ADRs. For elderly patients who have multiple medical problems and are taking multiple drugs, the risks are elevated for and ADR to occur because there are more chances for two medicines to react with each other (Muaed, 2013). Those who have a history of ADRs, and those with a reduced capacity to eliminate drugs from their body after the intended use is complete are also at high risk for ADRs. Elderly and young patients are also particularly vulnerable to ADRs because the drugs are less likely to be studied extensively in these extremes of age. Age can also be a factor because of dosage requirements and if the incorrect dose is given, an ADR can be caused or the effectivity of the medicine can be altered.

Gender

The biological differences of males and females can also have an effect on the action of many drugs. There are several anatomical differences between males and females including body weight, body composition, gastrointestinal tract factors, liver and metabolism factors and these can all cause differences in whether ADRs occur or not (Muaed, 2013). All of these factors can also have an effect on how effective the medicine is for that patient.

Body weight and fat distribution

Medicines are distributed to and from the blood and various tissues in the body such as fat, muscle, and brain tissue. After a drug has been absorbed into the body’s bloodstream, it circulates through the entire body. As the blood recirculates, the drug moves from the body’s bloodstream into the body’s different tissues. Once absorbed, most of the medicines do not spread evenly in the body. Some of them dissolve in water while others stay within the blood and the fluid that surrounds the cells. The drugs that dissolve in fat tend to concentrate in the fattiest tissues of the body. Some drugs leave the bloodstream very slowly, because they have bonded tightly with the proteins that are circulating in the blood (Muaed, 2013). Others leave the bloodstream very quickly and enter other tissues, because they are less tightly bound to the blood proteins.  The ones that more tightly bound can act as a reservoir for the drug and can potentially cause reactions. If the ones that are less tightly bound leave too quickly, they can result in reduced effectivity of the medicine for the patient.

Drug related factors that can cause ADRs or change the effectivity of the medicine

Polypharmacy

Taking several drugs, whether they are prescription or over-the-counter can contribute to the risk of having an ADR or the risk of the effectiveness of the drug dropping (Muaed, 2013). The number and severity of ADRs also increases as the number of drugs taken increases. The prescription of too many medicines for one patient adds a possibility of increased risk of ADRs. If there are more drugs being taken, it is also possible that they interact with each other and lower the effectivity of all the medicines involved.

Drug dose and/ or frequency

Drug dosing has an effect on the development of ADRs in many ways. For example, some drugs need to be taken in the morning while others need to be taken in the evening. Some need to be taken at bedtime. Dosing also needs to be considered as a factor which might have some effect on the development of ADRs. Dosing and frequency can also have change the effectiveness of a medicine. If a medicine is taken at the improper time, it is possible that the medicine will not be as effective. Also, if the dosage is improper for the patient, the effectivity of the medicine will change (Muaed, 2023).

 

Prescription Medications and reasons why they cause reactions and changes in effectivity

Effectiveness of the medicine:

The main factor that influences prescription medicine effectiveness is resistance being built up to the medicine. This is a big issue for prescription medicines because they are often higher dose and are used for longer periods of time for treatment. If resistance is built to a certain medication then the medication will no longer work or will work but not very effectively. This is a very big thing, especially for bacterial infection medications. Normally for bacteria related medicines, if the body develops resistance to the medicine then it is possible that the specific medication used for the treatment of the problem will not be effective anymore. This could occur because of the body’s and the disease’s genetic make-up but happens most often because of using a medicine with certain ingredients repeatedly. For example, if the same antibiotic is given for every bacterial infection, the bacteria in the body can build resistance to that medicine which makes it useless after. The patient profile of past medical history and treatment comes into play more than genetics for the effectiveness of medicine on a patient. These issues tend to occur on prescription medicine more than others because of the prescription medicines being higher dose and containing ingredients that are stronger and have a bigger impact on the body (Dr.Jasmin, 2023).

Normal Reactions to medication:

Reactions to prescription medicines are more related to the genetics of the body and the type of body the medicine is given to and the patient profile doesn’t come into play as much. Reactions are based on the patient’s body and are more based on genetics when it comes to ingredients (Dr.Jasmin 2023). Some body types and genetic makeups don’t allow for a certain medicine’s ingredients to be handled by the body so there is a reaction.

Allergic Reactions

Allergic reactions are very common to prescription medicines because they have more distinct, stronger, and powerful ingredients which have a greater possibility to cause allergic reactions or trigger the body’s immune system. Allergy symptoms are the caused by a chain or reactions that originate in the immune system (AAAI, 2020). The immune system is the part of the body that controls how our body reacts to substances that are foreign to the body. It decides on whether to allow the substance into the body, or think of it as a threat and cause a reaction.  For example, if you have an allergy to a particular medication, your immune system identifies that medicine as a threat or invader formally known as an allergen. The immune system may have several different types of reactions. Most of the allergic reactions that happen are in the timeframe of a couple of hours to two weeks of taking the medicine however, rashes may develop up to six weeks after starting certain types of medications. Most allergic reactions are also with medicines that the patient has been exposed to in the past (AAAI, 2020). A patient is more likely to have a reaction to a medicine that they have used before than to a medicine that is brand new for them.  

Immunoglobulin E

One of the types of immune reactions is caused by the production of antibodies known as Immunoglobulin E or IgE that are specific to the drug (AAAI, 2020). These antibodies travel to cells in the body that release hormones that trigger an immediate allergic reaction within the body. This reaction causes all the symptoms of allergic reactions such as runny and stuffy nose, and dry cough. This reaction can occur in a matter of minutes after taking the medicine or can take hours to occur which can lead to it being picked up fairly easily.

T-Cell expansion

The other and more common type of immune response/ allergic reaction to a drug is caused by the expansion of cells in our body called T-Cells. T cells are a type of white blood cell in the body that help the body fight against infections and send signals to the immune system, when a foreign substance is detected. The T-Cells often detect the medicine and label it as an intruder or allergen which causes a full immune response.  These responses caused by T-cells often take weeks to fully start so they are much tougher to pick up. It is also harder to figure out which drug caused the response because there is so much time between the drug being taken and the reaction taking place (AAAI, 2020).


Anaphylaxis

The worst form of immediate allergic reactions is anaphylaxis. It is the worst because it causes the most symptoms and the strongest symptoms of all the types of allergic reactions. Symptoms of anaphylaxis are wheezing, light-headedness, facial or throat swelling, vomiting and shock (AAAI, 2020). Most reactions that are anaphylactic occur within one hour of taking the medication or receiving an injection containing the medication. It is possible though for the reaction to start several hours after the medicine is taken. The most common cause for anaphylactic reactions is antibiotics (AAAI, 2020). More recently, things like chemotherapy drugs and monoclonal antibodies have also shown to cause anaphylaxis.

Delayed Allergic Reactions

Delayed allergic drug reactions are reactions that are caused several hours to days after the medicine is taken. They are more dangerous to the body because the most severe forms not only cause rashes but can also cause various other organs of the body to be involved. These can include organs such as the liver, kidneys, lungs, and heart. Stevens - Johnson syndrome and Toxic epidermal necrolysis (TEN) are two types of delayed allergic reactions. Blisters are a symptom of these reactions. Other symptoms include erosion to surfaces of eyes, lips and mouth and my also include dryness in these particular areas. Many medications can cause these severe delayed reactions. Some of these are medications for epilepsy (seizures), antibiotics, medication for depression and medication for gout.

Other Factors for both Effectiveness and Reactions to prescription medicine:

Genetic differences

The liver has a collection of enzymes that break down many drugs so they can be removed from the body after their intended use is completed. The DNA or genetic material of cells contains the blueprint on how to create these enzymes that break down the drugs. Some people have small errors in their DNA called polymorphisms. These errors result in the enzymes not working as they are intended to. This is an issue with specifically prescription medicine because they are often harder to break down because they are stronger and more powerful (White, 2021). These errors when they occur can cause the body to not have the ability to break down drugs any more. This would result in more of the drugs being in the blood stream than there should be. If this rising blood concentration is more than the amount that can be tolerated by our bodies, serious reactions can occur. This can also reduce the effectivity of the medicine because the medicine can often end up in the wrong place which means that it won’t help treat the issue that the patient is having (White, 2021).

Drug interactions

One big factor when it comes to prescription medicine specifically is the interaction of several medicines that are being taken together. This is a big factor because if different medicines with different properties are being taken at the same time, they can cause the effectivity to be reduced and/or reactions to occur. This is because, if one medicine has properties opposite to the other, they will just cancel each other out and none of the medicines will be effective. If two medicines with conflicting properties are taken, it can also lead to reactions because the two medicines aren’t interacting with each other properly. (White, 2021) This is a very important factor for prescription medications because they are often higher dose and contain more stronger and powerful ingredients which can conflict with each other easier than other lower dose medicines.

Inflammation

When the body has acquired an infection or is injured, the inflammatory response of the body brings white blood cells to the site of infection/ injury and increased blood flow in that area to sterilize and repair the problem. Inflammation is meant to last for only short periods of time until the infection or injury is dealt with and is healed but. It is possible that the immune systems of some people may attack areas unaffected by the injury or infection and result in chronic inflammation. Inflammation from an infection/ injury or a chronic inflammatory disease could also impact how well the enzymes can metabolize drugs. The liver is one of the major organs that create special proteins to help with an immune response and help the body heal injuries. When the liver is busy making all of these proteins during an immune response, it does not have the capacity to make as many of these drug-metabolizing enzymes as it can normally (White, 2021). This would result in a decline in drug break down. This decline in break down could mean that there is more of the drug in the blood stream and could cause reactions. It could also cause the drug to be less effective if the drug is not reaching the intended place it should be.

Liver and Kidney Damage

Liver and Kidney damage are also major factors that affect drug metabolizing capabilities. The same things can happen if there is a decline in drug break down and can ultimately cause reactions or reduced effectivity. This decline in break down could again result in more of the drug being in the blood stream and could lead to reactions (White, 2021). It could also cause the drug to be less effective for the same reason that the drug would not be reaching the intended place it should be.

Body Size

Body size is also a major factor affecting drug response and effectivity. Drug concentration in our bodies is determined by the dose given to the patient and also the amount of body fluids that the patient has. If the same dose of a drug is given no matter what the patient’s body size is, it could result in there being more concentration of the medicine in the patient’s body. This could ultimately lead to reactions and a reduction in effectiveness. This is the main reason why lower doses are given to a child patient than an adult patient. The child patient has a smaller body size and therefore needs a smaller concentration of the drug in their body to be able to have the same effect as an adult patient.

Lack of Receptors for the drug to bond with

Some people don’t have many receptors in the body that are capable with binding with the drug and helping with the drug’s effectiveness. Other people have the receptors but they are dysfunctional and don’t bond properly with the drug. This could be due to genetic mutations or other disease that the patient has. As a result of this, the effectivity of the drug would be reduced because less receptors are able to bond with the drug so the drug is able to help with the issue less than it would be able to otherwise if the receptors were working.

Over the Counter Medications and reasons why they cause reactions and changes in effectivity

Medicines that don’t require a doctor’s prescription to be sold to patients are known as Over the Counter or OTC medicines.  OTC medicines help treat a wide variety of illnesses and their symptoms including things like pain, cold and cough, viral infections, diarrhoea, acne, and various other health problems .The Main factor that influences adverse drug reactions and effectivity for Over the counter medicines having is when they are not used correctly. The medicines are often not used how they should be because there are no specific instructions provided by a doctor on how to use them. All of them do include usage instructions but not all people follow these instructions on the packaging. The misuse of an OTC medicine means taking the medicine in a way or dosage other than what is directed on the package or mixing multiple OTC medicines to get a new medicine.

OTC medicines are less powerful and stronger than prescription medicines so if used in the correct way, there is a very low possibility that an adverse drug reaction will occur or the effectivity will be reduced. There are reactions caused by OTC medicines but these are not as serious as the ones produced by prescription medicines most of the time. Human error is the main reason that adverse reactions are caused to OTC drugs. The effectiveness of the OTC drugs however depends much on the same factors as prescription medicine effectiveness. These are factors like age, dosage, and ingredients of the medicine.

Examples of Human errors causing ADRs for OTC medicines

DXM

DXM or Dextromethorphan is an opioid OTC medicine that is used for cough and cold symptoms (NIDA, 2017). This medicine does not have an effect on pain reduction and does not act on the opioid receptors in the body.  In normal circumstances, the drug does not have a large potential to be able to cause an ADR. When taken in a dosage that is way more than recommended, DXM is able to cause a depressant effect and sometimes a hallucinogenic effect or an effect which alters a person’s perception of reality (NIDA, 2017). Repeatedly taking higher doses of DXM can cause an addiction to be formed and can cause major damage to the body in places such as the brain which can even put the body in life threatening scenarios.

Loperamide

Loperamide is an opioid medicine that is for diarreha control and is designed to not enter the brain (NIDA, 2017). When taken in amounts that are much larger than recommended and/or combining it with other substances, it can cause the medicine to react in a way that is similar to other much more harmful opioids that are not meant as medicines. These other opioids are dangerous because they bind to the opioid receptors in the brain which cause the brains activity to be stimulated. These opioid receptors are located in the brain stem which is responsible for controlling important things such as blood pressure and breathing. If the medicine is used in the wrong way, it can change the way these activities occur and can possibly cause death (NIDA, 2017).

Adverse effects

Sometimes OTC medicines can cause unpleasant effects called adverse effects. These effects are not adverse drug reactions and most of the time are not life threatening. These effects can also lead to a reduction if effectivity of the OTC medicine.  These effects include side effects, drug-drug interactions, food-drug interactions, and allergic reactions (Rich, 2022).

Side effects

Side effects are effects on the body that OTC medicines have which don’t help the symptoms of the problem in the body. Most side effects are unpleasant for the patient. Side effects can also lead to decreased effectivity of the medicine if there are more side effects than good effects.  A few examples of side effects are nausea, dizziness, or bleeding in the digestive tract (Rich, 2022). Sometimes, side effects can be useful but these types of side effects are uncommon. Side effects are different from drug allergies because side effects occur to most people who take the medicine while allergies only occur to a few.

Drug-drug interactions

Each medicine has a different process of being absorbed and used in the body. When two medicines are used together, the way they affect the body can change. This is called a drug-drug interaction. It can be unpleasant for you, somewhat harmful to the body, and can severely reduce the effectivity of the medicines involved.  These types of reactions can also increase the side effects caused to the body and they get worse the more medicines taken together that shouldn’t be. Drug- drug interactions happen not only between two or more OTC medicines but can also happen between two or more prescription and OTC medications (Rich, 2022).

Duplication:

When you take 2 medicines that have similar active ingredients it is known as duplication. Duplication causes there to be more medicine than there needs to be in the body.  An example of this is when you take Ibuprofen (a painkiller/ cold reliever) plus an anti-inflammatory medicine containing similar ingredients. Too much of either the anti-inflammatory or Ibuprofen can hurt your kidneys and/or liver.

Opposition

Opposition is when you take two more medications that have opposite effects on the body. These medicines can react with each other and can cause the effectiveness of one or all medicines involved to be reduced. For example, decongestants may raise your blood pressure and if you take them with a high blood pressure medicine, they can work the medicine that lowers your blood pressure (Rich, 2022).

Alteration

Alteration is when one multiple medicines are taken and one medicine changes how the other medicine is absorbed or processed by the body. For example, an aspirin based medicine can change the way some blood-thinning medicines work (Rich, 2022).

Drug-food interactions

Food can change how the body processes some OTC or prescription medicines. This is called a drug-food interaction. Sometimes, medicines that you are taking can be impacted by the things in the food or drinks that you are consuming.  This can prevent the medicine from working the intended way. For example, medicines taken by mouth such as pills are normally absorbed through the lining of the stomach. The nutrients from the food that you eat are also absorbed in the exact same way. If you take a medicine with food that you aren’t supposed to take with food, the way the body absorbs the medicine can be changed (Rich, 2022). Food does not affect all OTC medicines but what you eat and when you eat it does have an impact with some OTC medicines.

Allergic reactions

Some people have allergies to certain OTC medicines. This is not very common with OTC medicines though because they generally have less powerful ingredients as they are self-prescribed. Signs of an allergic reaction are itching, hives, or trouble breathing.  Reactions to a medicine can occur at any point during the use of the medicine. For example, if you take a medicine and have no effect the day you take it, if you take the same medicine a month later, you might have an allergic reaction (Rich, 2022).

Prevention of Adverse Drug Reactions

Prevention of major drug reactions

Most major drug reactions are genetic related. When new medicines are created, they are tested on a large group of people to determine if there is a minority inside of that group that reacts to the specific medicine in question.  Companies use a genetic screening process to screen for known SNPs across the genome. The SNPs that are identified to interrupt or react with the medicine can be used to prevent reactions. When prescribing medication, doctors are able to screen patients that are potential users of the medicine to see if the patients have any of the SNPs that are known for reacting to the drug. If they are identified in the potential users, the doctor can prescribe a different medicine or warn the patient about how they might potentially react to the medicine and how to treat those reactions. By knowing this ahead of time, doctors expect what will happen and aren’t encountered with any surprises.

The prevention of major drug reactions is a shared responsibility of the doctor who prescribes the medicine, the company who makes the medicine, and the patient who takes the medicine (Gwee, 1993). To ensure a reaction doesn’t occur, steps such as SNP screening are a big help but small things like taking the right pill at the right time from the patients end also make a difference. Following the instructions on the packaging and not using it if you fall into one of the categories that the medicine is not recommended for can also save you from the potential of an ADR. Patients also need to make sure to follow the doctor’s prescription and not self-prescribe medication which makes sure that the person prescribing the medicine knows the potential risks and benefits.

Prevention of minor reactions

Most minor drug reactions are cause by patient related factors. All medicines are able to cause minor reactions/ side effects but these aren’t often very serious and go away after a short time. The most common reason a minor drug reaction is caused is a problem in dosage of medication. If you take the wrong dosage or are given the wrong dosage, a drug reaction could occur. Side effects depend on the other hand depend more on the, age of the patient, and the ingredients of the medicine. They may also depend on gender of the patient and if the patient has any other health problems. In most situations, older adults are more likely to have side effects than younger adults. Side effects/ minor drug reactions normally only happen a medicine is started, the dose of a medicine is changed, and/ or the medicine isn’t taken anymore/ is swapped for another medicine with other ingredients.

Age is a very major factor when it comes to drug reactions and it is highly considered by doctors when prescribing a medicine. Age changes the dosage of the medicine (Varn, 2016). As people get older, they also have multiple medicines they need to take which means there is a higher possibility of ingredients mixing and causing reactions. Another factor is that as your age increases, your body’s fat stores also increase while the total amount of water in your body decreases. This can result in fat-soluble drugs to remain in the body longer. It can also cause higher concentrations of water-soluble drugs in your body due to less water being present. Changes that occur in your liver and kidneys as you age can also have an effect on how medications affect you. As you age, your liver and kidneys wear more which result in there being a longer time between you taking the medicine and the medicine exiting your body.  Digestive system changes can also affect how quickly medications enter and leave your blood stream. These are all factors considered when doctors are choosing which medicine to prescribe.

Pharmacogenetics

Pharmacogenetics is a new and cutting edge technology which studies how genes have an effect on you reacting to certain drugs (Medline Plus, 2023). Differences in genes as previously mentioned can be the reason why some people have a great effect from the medicine while others don’t have any effect. Genes can also be the reason why some people have serious reactions effects from a medicine and others have none. Pharmacogenetic testing is a way of providing information about your genes to your health care provider to help them choose the medicine and dosage that are the best for you. This testing uses a sample of your blood, saliva, or cells swabbed from your cheek. Pharmacogenetic testing is a type of precision medicine (Medline Plus, 2023). Precision medicine is when information about your genes, environment, and lifestyle is used to find out which way of disease treatment will be the best for you and also to find out which way of disease prevention is best for you. Pharmacogenetics, pharmacogenomics, and pharmacogenomic testing are all other names for pharmacogenetics.

 

 

Data

Effectivity of Antibiotics on a Bacterial Infection (credit to Dr.Jasmin at Medwin Hospital)

This case study is based on a 68 year old patient who had developed a whole body infection and sepsis.

The patient in this case study has had to use antibiotics on several occasions for various different bacterial infections. The patient had undergone a knee surgery and had acquired a bacterial infection as a result of that surgery and improper post operative care. The bacteria’s name was Acinetobacter baumannii. The infection soon spread to the whole body and that was when the use of high dose antibiotics was started. For this patient, one specific high dose antibiotic called Colistin was given for a very long period of time to try and fight against the bacteria that had caused this infection. After this, the patient was then switched to another antibiotic that was called Minocycline. This antibiotic was also very high dose. This switch occurred roughly a month after the use of Colistin was started. After switching, the patient was moved to a different hospital where they tried Colistin again for a couple of days. After this proved ineffective they conducted an antibiotic resistivity test which involves trying several antibiotics and seeing which ones are effective. The one that ended up causing a benefit was the one that was a local antibiotic that wasn’t widely used yet and was a locally developed antibiotic that was called Doxycycline.

There are various things that can be taken from this case study. When given for the second time, Colistin proved ineffective when used the second time. This was because the bacteria causing the infection for the patient had become resistant and immune to that medicine. The patient’s condition also got worse because Colistin is not recommended for extended periods of usage and can cause harm to the body if used for extended periods of time(1.5 months in this case in total). Therefore, the medicine wasn’t effective when it was used the second time. This is one of the major factors when determining the effectivity of a medicine on a patient. The second hospital had tried various antibiotics that also didn’t work for the patient because that patient had a history with having to use antibiotics on several occasions and this was also a reason behind why this antibiotic did not benefit the patient. The last antibiotic (Doxycycline) used was the one that helped the patient recover. This was because the patient hadn’t been exposed for that particular antibiotic in the past because it was not used that often. The fact that it was a locally developed antibiotic also helped because it was developed in consideration with the people in the place where the treatment was taken place. Various factors such as ethnicity, and location were addressed when that antibiotic was made as it was a locally developed medicine that considered the factors of the people in that region. This also helped with the recovery because the antibiotic would be more specific to that patient’s body and the factors of that patient which would help speed up recovery as well as improve chances of recovery.

NIH national library of medicine Case Study on Antibiotics causing IBS

This case study is based on a 50 year old female who was experiencing symptoms of Gastroenteritis who had a 20-year history of functional gastrointestinal symptoms (Mark et al, 2007), and reoccurring abdominal cramping.

The patient complained of severe diarrhoea, moderate bloating, gas, and abdominal pain. A previous evaluation in 2004 resulted in a diagnosis of Irritable bowel syndrome (IBS). Additionally, in August 2005, the patient's symptoms increased after experiencing acute viral gastroenteritis, a disease related with the digestive system. She had a medical history of anxiety but no major health problems such as diabetes or any other problems.

The patient used dicyclomine (an antibiotic for intestinal and digestive system infections) 10 mg daily, which was started by a doctor in June 2004. Prior to that, the patient had been taking alprazolam (anxiety medicine) but had later discontinued. Her response to dicyclomine was rated as 50% better than without any medicine and was very successful as she had not taken that medicine in the past and her body had not been exposed to it in the past. The patient also received a trial of chlordiazepoxide (an anxiety medicine) 5 mg plus clidinium (a stomach and intestinal medicine) 2.5 mg twice daily with a 60% response from the medicine which was better than the other medicine. She later discontinued this medicine because of drowsiness which was one of the side effects she experienced. She was advised to contact a specialist who started the next part of her treatment (Mark et al, 2007).

As a result of not having used any of these medicines before, the patient responded well to the treatment because there was no resistant built up to the medications, specifically the antibiotics. Also, the medicine was one that was commonly used for the age group, and location that the patient was in which resulted in the medicine being effective and there not being any adverse reactions to the drug. There was also no genetic issues which was most likely due to her not having any sort of genetic mutation in the parts of the body that these specific drugs targeted. Some of the medicines also had better responses than others and there were several reasons for this. The clidinium having a better response than the dicyclomine was because of her body accepting and reacting to the clidinium better, and that could also have a relation with her genetics as well. The clidinium was also only 5 mg per day staggered into two doses so this could have also been a factor because her body may be capable of only handling a certain amount of the medicine at a certain time and the staggering of the two doses would be able to fix that issue. Overall, we were able to see various factors including genetics that had a role in the effectiveness of the clidinium being more than the effectiveness of the dicyclomine for the patient.

Case study of VEGFR TKIs (Vascular endothelial growth factor receptor tyrosine kinase inhibitors) and reactions to it from Health Canada

Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR TKIs) are a type of prescription medicine that is used in Canada. There are currently 8 VEGFR TKIs that are used and prescribed by doctors in Canada. These are Sutent (sunitinib), Inlyta (axitinib), Iclusig (ponatinib), Stivarga (regorafenib), Votrient (pazopanib), Nexavar (sorafenib), Caprelsa (vandetanib) and Lenvima (lenvatinib). These medicines are used for the treatment of types of cancers such as kidney, liver, thyroid, and soft tissue cancers. They are also used for certain types of blood cancers like leukemia and lymphoma.

The reaction occurring in this scenario is that this specific medicine was causing artery dissections and artery aneurysms. An artery dissection is a tear of the inside lining of an artery and an artery aneurysm is a balloon-like bulge in the wall of the artery. A rupture of the aneurysm could lead to bleeding and if not treated properly can lead to death. These disorders of the arterial wall occur more frequently in the aorta, the largest artery of the body, but they can also develop in any other artery in the body. High blood pressure plaque build-up inside arteries are major risk factors for artery dissections and/or aneurysms.

There was 1 Canadian report of artery dissection and 1 Canadian report of artery aneurysm suspected to be linked with the use of this medicine (Health Canada, 2018). There were also 208 international reports of artery dissections and/or aneurysms suspected to be linked to the use of VEGFR TKIs. Of the 210 reports in total of both issues, 80 reports were further reviewed because they had more information about what exactly was going on. Of the 80 reports, 46 were further assessed to find if VEGFR TKIs use was the cause of the artery dissections and/or aneurysms. 43 were artery dissections and 3 were artery aneurysms. 10 deaths were reported in total with 9 linked to artery dissections and 1 linked to artery aneurysm (Health Canada, 2018). When narrowed down, three of these deaths were found to be in relation with the use of this medication.

There are several reasons for this occurring. The medicine itself may have some sort of ingredients that are causing these problems to the patients’ arteries. Also, the three deaths that occurred could have also had similar reactions to the medicines because of factors such as related genetics. There could be many other reasons as well but the predominant reason is the medicine itself having an ingredient that triggers an arterial problem for patients.

Case study of Fibristral and reactions to it from Health Canada

Fibristal (5 mg ulipristal acetate) is a prescription medication which is used in Canada for the treatment of uterine fibroids. These are non-cancerous tumours that have developed in the womb. Each course of the treatment lasts for three months and the medicine has been used in Canada since 2013 with more than sixty-three thousand refills of the prescription in 2017.

The reaction that this medication was causing was that there were serious livery injuries occurring in the patients who were using the medicine. In the reports, the medication was known to causing liver injuries that often led to there being the need of a liver transplant. There were thirty-one reports of which seven were Canadian and twenty-four were international. A possible link between liver injuries and this medicine was found in most of the reports that were made. Twenty cases overall had a link to fibristral and five of these cases were Canadian. Of the twenty cases that had a possible link, eleven cases, two of which were Canadian reported the use of other medications or medical conditions which could have also contributed to liver injury. There were also four international cases of liver injury that was very severe and required a liver transplant (Health Canada, 2018). Only one of the cases had the result in death of these.

It was determined that there was not enough information that was able to prove fibristral as the cause of the liver injury but if it were the cause of injury, there could be a couple reasons why. Age is one of the main reasons because this medicine is used in people who are middle aged because they are the ones who experience uterine fibroids. Location could also be a factor but is not very strong of a factor because this medicine is not used by doctors in the United States and is not used very often in Europe. Genetics has a low chance of being a factor because this has occurred in multiple different people and there are links between the medicine and the reaction for around two thirds of the reports that were made.

 

Conclusion

In conclusion, this project has shown many things that we can learn about effectiveness and reactions of medication and their genetic aspects. Both the research and case studies proved that genetics isn’t the only factor when it comes to determining the effectivity and/or chances of reactions.  The patient profile, patient related factors, medicine related factors and interaction related factors all influence the likelihood of reactions and a drop in effectiveness for a medicine and are as important to consider as the genetic factors. The main genetic aspect that was common in all categories for reactions and change in effectivity of medications was genetic mutations and SNPs in the body. In the data shown in the project, we can also see that the patient profile and genetics of the patient play an equal role in determining the effectivity and whether or not a reaction will occur for a patient to a certain medicine. There are a lot of small scale factors that are taken for granted when we think of medicines such as interactions between multiple medicines and the possibility of incorrect dosage or human error which are all factors able to impact the effectiveness and chance of reaction for a medicine. Even the simplest thing like taking the medicine at a different time of day then you are supposed to or with a certain food item that you aren’t supposed to take it with can be the difference between a proper medicine and a medicine that doesn’t work as intended.

Going back to the main question of the genetic relation with medicine effectivity and reactions, the research speaks for itself when we look at the impact of genetics on these factors. Yes, genetics does have a major role but other factors have just as big of an impact on reactions and effectivity of a medicine. My hypothesis was that genetics would be the predominant factor in determining effectivity and reactivity for a medicine and this was not true. Things like patient profile and other patient and drug related factors are just as important and are sometimes even more important than genetic factors. These factors often are the main ones to influence the drug reactions, especially for OTC medications. This research also shows how if the right steps are taken, medicine effectivity can be kept as high as possible and reactions can be prevented. Just remembering to take the right medicine at the right time can increase effectiveness and decrease the chances of a reaction occurring. Major precautions such as pharmacogenetics testing can also help to make sure that reactions for medicines are kept low. As long as the prescriber, the provider and the patient of the medicine are all informed and educated about the specific conditions, reactions can be kept to a minimum. To sum up, medicines effectiveness and reactiveness are two major parts of medicine and need to be taken into account when deciding what medication is best for you.

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Acknowledgement

I would like to acknowledge a couple of people for this science fair project. Firstly I would like to acknowledge Dr. Jasmin from the Medwin hospital in Vadodra, India. He helped set me in the right direction by giving me basic information on effectiveness and reactions related to medicine. Thank you!  I would also like to acknowledge my science fair coordinator and my science teacher Mr, DeGelder for giving me full support and feedback about how to make my project better.  I would also like to acknowledge the people at the CYSF for giving youth like me oppirtunities to do these reseach projects and for empowering youth to learn more about science. Lastly, i'd like to thank my parents for their constant support throughout this project.