Synthetic Chemical Medicines

1. General features

Almost everyone in the developed world will receive chemical medicines at some point in their lives. These agents include the most commonly used treatments and are taken for illnesses ranging from relatively minor ailments to serious conditions. Most of the medicines that can be bought over the counter (OTC), without a prescription are chemical, and include treatments for common disorders such as headaches, seasonal allergies and muscle pain. Although they are available without a prescription, care must be taken to follow the package leaflet instructions because they can be harmful if used incorrectly. Many of these medicines have different brand names but contain the same active ingredients. Many chemical medicines, however, require a prescription from a doctor. Prescription-only chemical medicines are used for a variety of more serious illnesses, including infection, high cholesterol, high blood pressure, other cardiovascular disorders, inflammation, depression and anxiety, gastrointestinal disease, fertility problems, sleep disorders and cancer. In many cases, primary care doctors will prescribe treatments, but some chemical medicines are only prescribed by specialist doctors, such as oncologists.

Chemical medicines tend to be less specific than more modern biologic treatments. This has the advantage that they may be effective for more than one illness. Medicines that act on a range of targets, however, can also produce more side effects. This is apparent in chemotherapy, where medicines that target cancer cells also affect healthy cells. Overall, however, chemical medicines are effective with a broad range of uses. Given that chemical medicines are usually stable, they tend to have a shelf life of around three to five years and often do not need special conditions for storage. The packaging and package leaflet will provide information on the expiry date and storage instructions. The stable nature of these medicines generally means that hospitals and pharmacies will have a good supply and can prescribe or administer the medicine without having to order or await delivery.

2. How do chemical medicines work?

After chemical medicines are taken (e.g. by being swallowed, absorbed through the skin, inhaled or injected), the active ingredient of the medicine enters the circulation and is carried in the blood to the intended target. Once it has reached the part of the body where it is needed, it will interact with the local cells to produce the desired effects.

Most chemical medicines are recognised by a specific type of cell and will either act on the cell surface or will be taken inside the cell. This occurs because the cells in our bodies have molecules on the surface called receptors. Medicines attach to their target receptors, much like a key fit into a lock, and this triggers a response in the cell, resulting in the turning on (stimulation) or turning off (inhibition) of an effect (Figure 2).

Figure 2. Active substances bind to cell receptors and enhance cellular activity by continually occupying receptors. Similarly, this can cause blockade of cellular activity by preventing the natural chemical from binding to the receptor .

Some medicines work in the same way as molecules naturally occurring in the body, for example, morphine and similar medicines mimic the actions of endorphins (chemicals produced naturally in the body to reduce pain). Morphine can reduce pain by binding to the same receptors as endorphins. Pain is felt because cells in the nervous system send pain signals to the brain, usually because of injury or illness. By binding to pain receptors on cells of the nervous system, morphine can instruct them to turn off the pain signals.

Other medicines work by blocking the receptors on cells, so that naturally occurring molecules cannot exert their normal effect. An example of this is the family of medicines called beta-blockers, which are used to treat heart conditions and other illnesses. In normal circumstances, the hormones adrenaline and noradrenaline are released in times of stress and, by binding to the beta receptors, they can overstimulate the heart. When a patient at risk of high blood pressure or a heart attack takes a beta blocker, the medicine binds to beta receptors and blocks them, meaning that adrenaline and noradrenaline cannot reach the receptors and overstimulate the heart.

Some medicines attach to only one type of receptor, but others can attach to several different types of receptors throughout the body, which often explains how effective each medicine is in reaching its target. Medicines that are very specific to one receptor often have a better side-effect profile than medicines that are less specific. Even for very specific medicines, binding to the receptor is temporary and, after a while, the molecules will let go of the receptor and leave the body. A new dose may be needed to continue the medicine’s effect, which is why many medicines are given with instructions about how often they should be taken.

3. How are chemical medicines discovered?

By studying a disease, scientists can understand what causes the illness and which cells and their receptors are involved. This research can help scientists to develop new medicines to treat diseases and to relieve symptoms.

Once a target receptor molecule or an enzyme has been identified, scientists begin to look for potential substances that will interact with the target to correct disease-related activity. This research can involve searching through enormous libraries of millions of molecules that have been developed by pharmaceutical companies to speed up medicines development. Large-scale testing of potentially useful molecules from the libraries (also called high-throughput screening) is conducted to discover which ones will bind to the target receptor.

Although this process will help to identify potential active substances, more work is needed to select the molecules that are likely to bind to the target, but not to other receptors, because this may cause side effects. The most promising molecules that are discovered will then be modified in many ways to try to make an effective medicine that has few side effects. It is also important that the molecule has other properties that will allow it to be used as a medicine. For example, the active ingredients in medicines that need to be swallowed must be able to reach their target without being broken down by the digestive system.

When scientists find a molecule with the desired properties of a potential medicine, testing in animals is necessary. If this testing shows the substance is safe, testing in humans follows. Finally, regulatory authorities will consider whether or not to approve the medicine for use in humans.

The ideal molecules should:

• Hit the target (ideally only the target and no other healthy cells or enzymes).
• Have few side effects.
• Be absorbed by the body.
• Reach the right part of the body to hit the target.
• Remain in the body long enough to have an effect.
• Be able to be manufactured in large quantities.
• Be stable and have a long shelf life.
• Be convenient for patients to use.

4. Mode of administration

The active ingredients of chemical medicines are usually relatively simple molecules. Advances with medicines formulations made it possible that many can be taken orally as tablets or liquids, applied as creams, lotions, eye drops, nasal sprays (topical) or patches on the skin (transdermal) which means that patients can take them at home. For example, eye infections are often treated with a topical eye-drop formulation of an antibiotic, rather than with a tablet, to allow the medicine to act where it is most effective. Some chemical agents, however, must be injected under the skin (subcutaneous), into a muscle (intramuscular) or directly into the blood stream (intravenous). The different ways of administering medicines can help to ensure the medication is delivered at the right speed. Some medicines need to act very quickly, such as salbutamol in the case of an asthma attack which is inhaled. Other medicines should work slowly and over several hours. Medicines such as growth hormone can be injected into the fat under the skin because there are few blood vessels there and the medication can take up to 24 hours to find its way into the bloodstream to reach the target.

5. Example - Pain medicines

Medicines that are available without prescription for pain relief (e.g. for a headache or muscle ache) are all chemical agents. These medicines are designed to work quickly with few side effects. They are most often taken as a single or short course of tablets, although some are available as creams. They act by blocking the chemical triggers of pain and by reducing inflammation. Examples include acetylsalicylic acid, ibuprofen and paracetamol. Other pain relief medicines that are more powerful can only be prescribed by doctors, because the patient must be carefully monitored and the medicine can be harmful. These medicines include opium and morphine derivatives (e.g. codeine), which are very effective but are associated with side effects, including vomiting and skin reactions. Such medicines will only be given when the doctor considers pain to be a major issue and are generally administered to patients with long-term (chronic) pain.

6. Example - Cardiovascular medicines

There are many cardiovascular diseases for which chemical medicines play an important role, both in treatment and prevention. One of the most common types of medicine used in this setting is from the chemical class of molecules called statins (1).

These medicines lower cholesterol levels in the blood, which reduces the risk of cardiovascular disease. Statins are effective and have been widely used since their introduction in the late 1980s. They generally have good side-effect profiles, but there is still some risk of side effects, including muscle problems and the potential for diabetes mellitus to develop. Many different types of statins are available and doctors will select the most appropriate based on effectiveness, risk of side effects and cost. But researchers say the absolute benefit or risk depends on each person's own health and risk factors (baseline characteristics) and should always be determined individually. Other cardiovascular medicines include the angiotensin-converting enzyme (ACE) inhibitors, which are used to reduce blood pressure, another risk factor for cardiovascular disease. These agents have been used for several decades and are an important first-line treatment for managing high blood pressure. Side effects can include a dry cough, dizziness and headache.

In general, cardiovascular medicines are intended to achieve long-term results and thus treatment is taken over a long time period. Given that the medicine is generally taken as a tablet, it does not inconvenience patients with regular hospital visits, although the effects of the medicine have to be assessed regularly by a doctor or nurse, who will record changes in blood pressure.

(1) Access the Article BMJ 2019 - Statins for the primary prevention of cardiovascular disease: an overview of systematic reviews by Paula Byrne, John Cullinan, Amelia Smith and Susan M Smith

7. Example - Others

The range of illnesses and diseases that can be treated with chemical medicines is long and they will not all be discussed here. To summarise, some of the other common chemical formulations are used to treat digestive diseases, respiratory illnesses, sleeplessness, fertility problems, skin complaints, viral infections and bone disorders.