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10 Medicines That Work But We Don’t Know Why

Pharmaceutical companies run exhaustive trials before they can release a drug onto the market. This is a matter of common sense. No one wants a repeat of the thalidomide scandal of the 1950s and ’60s when some women took thalidomide for morning sickness. The result of the “biggest man-made medical scandal ever” was 10,000 children born with severe deformities.

Authorities closely monitor the research and development of new drugs to ensure they are as safe as possible and that doctors, pharmacists, and patients are aware of any possible side effects. But knowing that a drug is effective is not the same as knowing exactly how it works. The body is a complex mechanism that we still don’t fully understand. Here are 10 medicines that work, but we don’t know why.

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10 Abatacept

In 2015, Science magazine reported that some years before, a team of doctors in Cincinnati treated a sick 12-year-old boy. He had a rare genetic disease that wrongly triggered his immune system, causing considerable damage to his lungs and intestinal system. He had been sick for years, and doctors desperately sought a cure.

On this visit to the hospital, the staff assessed him to see if he might benefit from a bone marrow transplant. They decided that their patient was too sick for the procedure. Doctors gave him Abatacept, knowing that it would do him no harm and might ease his pain.

People who take Abatacept will probably know this drug under its brand name Orencia. Doctors usually prescribe it for conditions such as rheumatoid arthritis.

Doctors fully expected the boy in Cincinnati to die, but he returned six months later in better health. The success of this drug, in this case, was a mystery.

9 Tylenol

Also known as acetaminophen, Tylenol is a favorite in American bathroom cabinets. It’s an effective painkiller that is perfectly safe as long as you stick to the suggested dose. Everybody knows Tylenol, but nobody is certain how it works.

There are three possibilities:

  1. It might block an enzyme that makes our bodies feel pain.
  2. It could be working on the endocannabinoid system. If this is true, then Tylenol functions like THC in marijuana which is also effective for pain treatment.
  3. It might be affecting signals from the neurotransmitter serotonin. Serotonin is a chemical that brain cells produce and contributes to many cognitive functions.

It’s perfectly possible that Tylenol is doing all three things at once, or even none of these.

8 Lithium

Bipolar disorder, once known as manic depression, is a lifelong condition that causes mood swings from severe depression to euphoria. Doctors prescribe lithium, under brand names such as Eskalith or Lithobid, as a widely-recognized and effective treatment for the condition.

Lithium can reduce the severity and frequency of mania and cut the risk of suicide when the sufferer is in a depressive state. Sufferers from bipolar disorder can take lithium over a long period as maintenance therapy. A doctor will ensure that their patient keeps a constant lithium level in the body.

We know that lithium acts on the central nervous system, but we are unclear about what it does exactly. It might reinforce those connections in the brain that regulate mood and behavior, smooth out fluctuations, and ensure that the system works more constantly.

Lithium, the same metal that we use in new batteries, is present in trace amounts in biological systems. Nobody knows what it does.

7 Ulipristal

Ulipristal, marketed as Esmya, prevents pregnancy when someone has had unprotected intercourse or their contraceptive has failed. Ulipristal will prevent or delay the release of an egg. However, it may also change the lining of the uterus. It works, but we are not sure how.

A person should take this medicine within five days of having unprotected sex. It is a particular drug that the user should only take because of this specific circumstance. It is important to note that ulipristal has no effect whatsoever on sexually transmitted diseases.

6 Paxlovid

There’s a lot of information floating around on the internet and social media about medications and which ones work or don’t work. People often seek a solution to the condition and are willing to try anything they think might help—including antibiotics that can’t possibly treat a virus. Pharmaceutical companies were rushing to find a medicine that might work on the coronavirus and, at the same time, be cheap and easy to administer. In November 2021, Pfizer announced that their drug, Paxlovid, could cut the hospitalization rate by almost 90%.

Clinical trials showed that Paxlovid was safe, but questions remained. Paxlovid affects an enzyme in the body that helps proteins in the virus develop into their final, dangerous state. Stop the enzyme from working, and you stop the virus from developing. But how it stops this replication is still not understood.

Paxlovid looks very promising, but it includes a drug called ritonavir that can affect how the body metabolizes other drugs. Anyone who takes Paxlovid must inform their doctor if they take medicines for other conditions. The exact effects that Paxlovid might cause are not fully known.

5 Valdecoxib

Under its brand name Bextra, this was a popular treatment for rheumatoid arthritis and related conditions. In 2005, the Food and Drug Administration (FDA) decided that its risks outweighed its benefits and stopped its sale. Bextra was effective but could cause heart, skin, and stomach problems.

Valdecoxib is a good example of a drug that researchers designed to address a particular problem. In a class of NSAIDs called COX-2 inhibitors, it works by somehow stopping the body’s production of a substance that causes pain and inflammation. However, it had broader effects than expected, even though other COX-2 inhibitors didn’t—at least to the same degree. Pharmaceutical companies routinely run trial after trial until they think that they are certain that they know what they are dealing with. This is why it takes so long to get FDA approval. But it can take years for the full range of side effects to emerge.

4 Febuxostat

Gout is an incredibly painful condition. Traditionally, people thought of it as a condition that only affected the rich, but no physical ailment is ever restricted to a specific class of people. Gout results from having too much uric acid in the body, causing crystals to form around the joints.

Febuxostat (under the brand name Uloric, among others) is a long-term treatment that cuts the production of uric acid. Doctors will usually only prescribe febuxostat for sufferers who can’t tolerate allopurinol. They know that the drug is very effective against gout, but what is less well-understood is why some people suffer debilitating side effects. These can include liver problems, pain in the joints, nausea, and skin rash. In some cases, patients suffer from anaphylactic shock, which can be fatal.

3 Tofacitinib

Sold under the most common brand name, Xeljanz, this is another medicine that doesn’t work as its developers had hoped. A doctor might prescribe this medicine to patients with rheumatoid arthritis who can’t tolerate the more widely-used Methotrexate.

Initial clinical trials revealed that a few subjects contracted upper respiratory tract infections, diarrhea, and headaches. After years of trials, the FDA approved the drug in 2012. Then, in 2014, a study showed that tofacitinib also converted white fat tissues into brown. Brown fat tissues are more active and break down more easily than white. This unexpected result suggested that the drug might be an effective obesity treatment. If this were true, it would suggest that the already expensive drug had an enormous potential market.

It also suggests that researchers didn’t really know how the drug worked. Some patients ended up with cancer or pulmonary embolisms. It’s worth pointing out that these side effects are very rare, but they do occur.

2 Paroxetine

You might know this medicine under its common brand names, Seroxat or Paxil. It is an antidepressant, but doctors may prescribe it for various disorders, such as obsessive-compulsive disorder, panic attacks, posttraumatic stress, and social anxiety. It is also a useful treatment for premature ejaculation and menopausal hot flashes.

Paroxetine is a selective serotonin reuptake inhibitor. This mouthful might suggest that scientists know what it does. Well, yes and no. They know that paroxetine is effective, but they are not sure why. The best guess is that it increases the level of serotonin in the brain. The body produces serotonin from an essential amino acid called tryptophan.

Such foods as cheese, nuts, and red meat contain tryptophan. Your general well-being depends on having an optimal level of serotonin in your system. This chemical affects your physiological functions, behavior, cognition, learning, memory, and mood. Researchers don’t really know how paroxetine works because they don’t fully understand the complex functions of serotonin.

1 Aspirin

Aspirin’s popularity dipped in the sixties as other painkillers came onto the market. But then scientists realized that “aspirin” wasn’t just a painkiller. It was also very effective as a blood thinner and could reduce the likelihood of heart attacks or strokes. Some doctors suggest that regular use of low-strength aspirin may be beneficial, though others are cautious.

Recent research in Sweden suggests that aspirin has another beneficial effect. With access to a database that contained details of 80,000 cancer patients, a Swedish team discovered that if a patient with colon or lung cancer had regularly taken low-strength aspirin before diagnosis, his tumor tended to be less advanced. Doctors can deal with less-advanced tumors more effectively.

This correlation was sufficiently marked that the team was sure that the link was not due to a statistical anomaly. The puzzle now was to work out why aspirin might have this effect. The jury is still out, but it could be that aspirin’s anti-inflammatory properties slow the damage to DNA that can lead to cancer.

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