YSN-ASM Science Café KL
Are Your Meds Suitable for You?

The Young Scientists Network-Academy of Sciences Malaysia (YSN-ASM) organised another Science Café session, this time with Dr Baharudin Ibrahim, YSN-ASM Member and Lecturer from the School of Pharmaceutical Sciences, USM Penang.

According to the World Health Organisation (WHO), the definition of health is the state of complete physical, mental, and social wellbeing, and not merely the absence of disease and infirmity. Medicines are chemicals used in the maintenance of health and the prevention, diagnosis, alleviation, or cure of disease or promote physical or mental wellbeing.

Commencing the session, Dr Baharudin brought viewers on a journey of pharmacokinetics, which is the study of how medications move inside the body. Upon ingestion, the medication will be absorbed via the stomach and intestines into the blood, where it then goes to the liver. This is called first-pass metabolism: enzymes in the liver convert prodrugs (biologically inactive compounds that can be metabolised in the body to produce a drug) into active metabolites, or convert active medicines into inactive forms. After this process, the medication will then go to all parts of your body, but it will only take effect at the site with the right receptors.

Sometimes, medication will also cause other effects, because the receptors where drugs get attached may be present in other organs as well. Dr Baharudin used cetirizine and loratadine (antihistamines for the treatment of allergies) as examples. These medications will block the histamine receptors in the lungs to stop phlegm overproduction. However, these receptors are also available in the brain; when the medication goes to the brain, it will also attach to the receptors in the brain, causing drowsiness as a side effect.

After a medication has completed its function, it will return to the liver to be bio-transformed into substances that can be eliminated more easily. Lastly, the drug is eliminated from the body through urine (via the kidneys) or bile (via the liver).

After explaining pharmacokinetics, Dr Baharudin explained why some factors may necessitate the adjustment of dosage or even change of medications. Organ dysfunction, especially the liver or kidneys, is a common factor. The kidneys are in charge of eliminating waste products. If they are damaged, drug metabolites may not be eliminated properly and will accumulate in the body. On the other hand, the liver is in charge of converting medications into safe substances before they are eliminated. If the liver is compromised, it cannot metabolise the drug properly, causing accumulation and poisoning in the long run.

Taking other medications, consuming herbal supplements or eating certain foods also necessitates changing the dosage or type of medication. For example, if two drugs compete to be metabolised in the liver, one of it will not be metabolised and it will accumulate in the liver. An example of medication-herbal supplement interaction mentioned by Dr Baharudin is the interaction of warfarin (an anticoagulant) with ginseng (a common herbal supplement). Ginseng causes warfarin to be ineffective, or may even increase the drug’s toxicity. He also uses warfarin to illustrate drug interaction with green leafy vegetables. Taking these two together will render warfarin less effective because taking too much green vegetables may counter the effects of warfarin. Hence, Dr Baharudin advices patients to inform their doctors or pharmacists if they are taking other medications, herbal supplements, or specific foods.

Besides that, age is an important factor in determining the type and dosage of medications. For instance, infants absorb and process medications differently due to organs such as the liver and stomach that are not fully developed; therefore, some medications may be harmful to infants. As we reach adulthood, our organs will be more developed, but it will deteriorate as we reach old age; again, the liver and kidneys will become less efficient in metabolising medicines and causes accumulation of drugs in the body.

Dr Baharudin also explained that age can also increase the chances of experiencing side effects when we take medications. Older adults may take more medications and have more health problems than younger adults, causing a higher likelihood of older adults experiencing harmful interactions between different medications.

Is it true that taking medicine for extended time will damage or overburden the liver?

Not every medicine will damage the liver; a majority of medications are actually safe at the right doses, even in the long term. However, some medications will eventually damage the liver in the long run. Therefore, discuss with your doctor or pharmacist if you start to experience side effects from taking the medication.

What effects do medications have on the gut microbiome?

Microbiome is the the genetic material of all the microbes – bacteria, fungi, protozoa and viruses – that live on and inside the human body. Dr Baharudin explained that most infections come from the bacteria that live within our bodies. Our body, especially in the gut, is full of microorganisms that live symbiotically within us.

When we take medications that do not affects organisms, the gut microbiome will be fine; taking medications that affect organisms will affect the gut microbiome in the long run. However, antibiotics (a medication that affects organisms) are usually taken short-term; after completing a cycle of antibiotics, the gut microbiome will replenish and return it to normal.

Why do some medicines need to be taken before or after food?

Ideally, medications are required to be taken before food. This is to minimise interaction between the medication and the food. However, some medications such as painkillers will upset the stomach; these can irritate the stomach and may cause ulcers. Therefore, it is better to take painkillers with food to avoid any harm to the stomach. If a medication has clear and known interactions with food and it is best absorbed on an empty stomach, doctors or pharmacists will advise to take that medication without food.

What is the difference between taking medicines orally and via injections?

To address this question, Dr Baharudin reminds viewers about the absorption part of pharmacokinetics. when taken orally, medications will go to the stomach first; when taken via injection, the medication bypasses the stomach (unless it is injected directly there). When medication is injected, there is no first-pass metabolism and the medication will not be absorbed by the stomach or intestines and does not go to the liver. Instead, it will go directly to the heart and be delivered via blood circulation. Similarly, topical application of medication via the skin will also bypass the stomach and liver; it will go through the skin straight to the heart and then distributed throughout the body.

Dr Baharudin explained that some medicine requires to be delivered via injection for fast action: the delay of the medicine by passing through the stomach and the liver may cause danger for the patients that require the medicine to be delivered to the target area as soon as possible.

Why do similar medications have different names, and how do we know which is the best?

Dr Baharudin gives an example of a common medicine: Panadol. The active ingredient in Panadol is paracetamol, a common painkiller and antipyretic (a medication used to reduce fever). There are different brands of medications that have paracetamol as their active ingredient (e.g. Uphamol, Pamol, etc). Whenever a company develops a new drug, they will give it a name and they will patent it for about 10 to 20 years. Throughout the duration of the patent, no other company is allowed to develop the same drug. After the patent expires, other companies can develop the same drug provided they use the exact same active ingredient in the same dosage (e.g. 500 or 600mg). The new drug must also provide the same effect.

Following the Q&A session, Dr Baharudin talked about precision/personalised medicine. It is based on the concept that every patient has a unique biology and pathophysiology that should be reflected in the choice of medicine. Some people are allergic to seafood, gluten, or peanuts; some have inability to digest lactose (I.e. lactose intolerance).

In precision/personalised medicine, medical practitioners try to tailor medications to the patient. The approach with which precision/personalised medicine is practiced is called omics. Omics aims at the collective characterisation and quantification of pools of biological molecules that translate into the structure, function, and dynamics of an organism or organisms. We all have genes that shows certain characteristics; this is how people have different coloured eyes and hair. To have certain characteristics one needs to possess certain genes. Similarly, certain genetic profiles change the way someone absorbs, metabolises, distributes, and eliminates medicine.

The omics approach includes genomics (study of genes), transcriptomics (study of messenger RNA or mRNA), proteomics (study of proteins) and metabolomics (study of metabolites). Studying the above may enable more understanding of how the body affects medications. Dr Baharudin used the medications clopidogrel and gentamicin to illustrate these effects. Clopidogrel is a medication used to prevent platelets from clumping together and forming blood clots in the blood stream. Clopidogrel is a pro-drug, meaning that it is consumed in an inactive form and will be activated by specific enzymes in the body. Malaysians have a variant types of gene that makes us unable to produce the right structure of the enzyme necessary to metabolise clopidogrel. This causes Malaysians to not be able to utilise clopidogrel fully. This might make it necessary for patients to take clopidogrel in higher doses or change to another medicine.

Dr Baharudin then used gentamicin (an antibiotic) to illustrate the relationship between omics and medication side effects. Certain people have certain receptors in the kidneys that can re-absorb gentamicin; instead of being eliminated in the kidneys, it is absorbed again by the kidneys and will accumulate there, causing nephrotoxicity (toxicity in the kidneys). However, this only exists in about 1% of the population. Studying omics will enable researchers to identify people with this genetic anomaly. With precision/personalised medicine, the efficacy and side effects of medicines can be determined in individuals.

Aside from the Five Rights of Optimum Treatment, Dr Baharudin also stated one more “right” that is typically hard to follow by patients: Right Attitude. It may be challenging for patients to have the right attitude due to the following reasons:

• They cannot afford the medication.
• They do not understand the instructions.
• They forget to take the medicine.
• They cannot tolerate the given dosage.
• Sensory impairments inhibit proper consumption.
• Their medication regimen interferes with daily activities.
• Their medication regimen is too complex.
• They feel that the medication is not working.
• They are experiencing side effects.