OTC painkillers - are we taking too many?

Ibuprofen tablets. Ragesoss, CC3.0 license

A study published in the journal Pharmacoepidemiology & Drug Safety in January 2018 found that people are taking too much ibuprofen.

Ibuprofen is part of a group of drugs known as NSAIDs (non-steroidal anti-inflammatory drugs). Another popular over-the-counter NSAID is naproxen. They are generally used to treat pain, often chronically. Another well known pain killer that is not an NSAID is acetaminophen, more popularly known by its brand name Tylenol (which is manufactured by the company that sponsored this study).

NSAIDs do have side effects, especially if the daily dose limit is exceeded. The drugs act to reduce inflammation, which has effects on blood pressure, the heart, liver, and kidneys. And it's important to follow dosing guidelines, as they've been established based on toxicity studies.

However, the study authors were quoted in the New York Post as recommending NSAIDs become prescription only, pushing acetaminophen as a safer option (though that drug has liver toxicity and a known history of being pulled from shelves). It's a bit of an extreme conclusion based on a single week of self-reporting and limited findings. For example, less than 10% of subjects recorded exceeding the dose with NSAIDs, and they also exceeded the dosing on other drugs they took in that same time period at near the same levels.

So maybe the conclusion should be that we need to communicate dosing better, or find better pain killers in general, rather than limit the availability of what currently works for people. And because of the conflicts of interest regarding the sponsorship of the work, this study just comes across as industry shill.

Why does cortisone work?

Cortisone is an anti-inflammatory hormone. It's injected into areas that are inflamed - swollen joints, painful plantar fasciitis - or used systemically (e.g., allergy). It may also be used cutaneously as a cream (hydrocortisone) in the case of rashes. Sometimes it's a broader name given to corticosteroid injections, which are various types of steroid hormones.

Essentially, the drug utilizes the natural system of the body to alleviate pain caused by inflammation by getting rid of the inflammation.

Natural cortisone production

The adrenal gland naturally produces cortisone, which is then metabolized to cortisol, the major stress hormone in humans. A synthetic version of cortisone was developed after researchers noticed that women experienced alleviation of their rheumatoid arthritis during pregnancy (a state in which cortisol is not cleared as quickly). The cortisone injections, which are sometimes combined with local anesthetics to reduce pain, are used to treat adrenal insufficiency and inflammatory disorders, but hydrocortisone also plays a role in chemotherapy for cancer.

How cortisone exerts actions

Steroids like cortisone treat inflammation by decreasing the production of pro-inflammatory mediators in the body. The actions are carried out by its metabolite, cortisol. Briefly, this molecule binds to receptors in the cytoplasm of cells and then travels to the nucleus of the cell to affect DNA transcription. More specifically, cortisol is a glucocorticoid and binds the glucocorticoid receptor. The glucocorticoid complex translocates to the nucleus and binds the glucocorticoid response element to affect the expression of pro-inflammatory genes. Cortisol also has effects on metabolism and the immune response. 

 

We take advantage of their properties and inject them locally to increase their effects in that area (and some injections contain pain relievers that help) and systemically to give the system a boost. The hormone is metabolized to cortisol once it is in the body - the infamous stress hormone.

How cortisol affects inflammation

Specific actions of glucocorticoids such as cortisone in inflammation include blockade of the secretion of certain interleukins by macrophages, which reduces the number of circulating T cells and prevents B-cell proliferation. The production of lipocortin is stimulated, which prevents phosphatidyl choline from being converted to arachidonic acid. This blocks the synthesis and release of the pro-inflammatory mediators known as prostaglandins and thromboxanes by the enzyme cyclooxygenase (COX), which prevents vasodilation. The lack of arachidonic acid also blocks the actions of leukotrienes in the immune response.

Cortisone injections in local inflammation

Under normal conditions, the body regulates inflammatory responses via endogenous (i.e. produced by the body) hormones like cortisol. The endocrine system is stimulated by the stressors (there are many theories about inflammation and stress), which results in the secretion of hormones to counteract it. The actions of cortisol affect nearly every tissue and cell in the body. This is a systemic response. When the inflammation is localized, such as in plantar fasciitis, cortisone injections can help the body alleviate the inflammation at a more local level. Injection of the hormone into, for example, a swollen and inflamed joint can act on the cells in that area, reducing the inflammatory mediators and local inflammation. However, there are side effects due to the myriad actions of the molecule, which requires a limit on how often a person can be treated with the injections.

 

 

Preventing meningitis

Meningitis is inflammation of the lining of the central nervous system, often by infection. It can be transmitted as viruses, bacteria, fungi, or parasites. The most common form of the disorder is viral meningitis, which tends to resolve on its own. On the other hand, bacterial meningitis can be severe and lead to brain damage, hearing loss, or learning disabilities if not properly treated. Good hygiene is the general practice for preventing the transmission of meningitis. Vaccines are available against the common bacterial causes, including Hib and meningococcus and recommended for college students due to the close quarters they live in.

Read more about how meningitis is transmitted below the jump.

Benign to malignant: Lymphadenopathy is a common symptom

Lymphadenopathy of the neck. Source: James Heilman, MD

 

Lymphadenopathy is the presence of enlarged lymph nodes, and it is often accompanied by tenderness, redness, and warmth at the location of the swollen node. This disorder can occur in a broad range of benign and malignant conditions, ranging from exposure to a virus to cancer. Lymph nodes are present throughout the body, mostly at points of entry and drainage in the lymph system, including the neck, groin, abdomen, and armpits. The lymph nodes filter the lymph (which contains excess tissue fluid and immune cells) as it circulates throughout the body, so swollen nodes indicate an active immune response. Depending on the cause, lymphadenopathy can be localized or generalized.

Normal lymph nodes

The human body contains hundreds of lymph nodes. Usually, the nodes below the jaw (i.e. submandibular), in the armpits (i.e. axillary), and the groin region (i.e. inguinal) can be felt in healthy adults. The lymph nodes contain a germinal center of B cells and macrophages. When an immune response is triggered, the germinal center enlarges with the replicating immune cells. Nodes larger than 1 cm in diameter are considered abnormal, though any knot or lump that appears may be indicative of lymphadenopathy. Clinicians have a standard evaluation technique they use to determine the extent and severity of enlargement, which eventually can aid in diagnosis. Children commonly have this condition due to their high exposure to “benign self-limited disease”, such as viruses. Essentially, some lymph node somewhere in the body is going to become enlarged for any immune reaction.

Localized lymphadenopathy

Localized lymphadenopathy is the most common form of lymph node swelling, occurring at a specific location on the body, either unilaterally or bilaterally (one side of the body versus both sides). The most common cause of localized lymph node swelling is a nearby lesion, such as strep throat causing cervical lymphadenopathy and an infection in an extremity leading to axillary or inguinal lymphadenopathy on the relevant side (the affected arm and leg, respectively). The most common lymph nodes to be enlarged are the cervical lymph nodes due to the exposure of the throat to inhaled and ingested pathogens. However, localized swelling of the supraclavicular lymph nodes may indicate malignancy, specifically the abdomen or chest if not present with generalized lymphadenopathy as noted in the clinician’s evaluation technique.

Generalized lymphadenopathy

Generalized lymphadenopathy is the enlargement of many lymph nodes at various points throughout the body. This is indicative of a systemic disorder. One example is a cancer of the immune system, called Hodgkin’s lymphoma, in which the lymph nodes enlarge much like tumor growth. HIV infection and metastatic cancer also cause a generalized immune response. Other diseases/disorders that cause a generalized response are tuberculosis, fungal infection, viral infection, connective tissue diseases, and autoimmune reactions.

Lymphadenitis

Lymphadenitis is inflammation of the lymph node, causing enlargement. This may be due to invasion of the lymph node by metabolite-laden macrophages or malignant cells. This form of enlargement is seen in lipid storage diseases. Infection of the lymph nodes (which can also lead to inflammation) is a common complication of many bacterial infections.

Does alcohol treat rheumatoid arthritis?

Image source: Andre Karwath

Rheumatoid arthritis is a degenerative joint condition resulting in pain and disability from an autoimmune inflammatory process. Alcohol is thought to act as an anti-inflammatory. Studies have been somewhat contradictory about the effect of alcohol on rheumatoid arthritis, though a few recent studies have shown promise for the home remedy. 

• A 2008 study from Sweden and Denmark on 2700 men and women showed that moderate alcohol consumption (1-4 drinks per week) may reduce the risk of developing rheumatoid arthritis by roughly 20%. 
• A 2010 study published in the journal Rheumatology looked at alcohol consumption and symptom severity in more than 850 patients with rheumatoid arthritis, comparing them to more than 1000 people without the disease. Those who consumed alcohol more frequently had lower levels of inflammation, joint pain, and disability than those who drank less frequently. 

The 2010 study was the first dose-dependent relationship shown for these variables in humans. The researchers also found that non-drinkers were four times more likely to develop the disease than drinkers.

These studies would indicate that patients with rheumatoid arthritis could benefit from moderate alcohol consumption. However, alcohol and RA medications do not mix.

• RA patients usually take methotrexate to slow the progression of the disease. The drug is already associated with liver cirrhosis, which may be due to alcohol consumption by those taking it. 
• RA patients also take NSAIDs (non-steroidal anti-inflammatory drugs), such as naproxen, aspirin, and ibuprofen, to handle the pain and swelling, which can cause stomach and intestinal bleeding when consumed with alcohol. 
• In addition, some patients are treated with prednisone, a steroid, to treat the symptoms of the disease. This drug also reacts adversely with alcohol in the form of stomach and liver irritation.

Overall, the studies regarding alcohol will not benefit those who are already controlling their rheumatoid arthritis with pharmaceutical therapy, and consuming alcohol to prevent the disorder may exacerbate other conditions. Much more work is needed to fully understand the risks, benefits, and mechanisms seen in the studied populations.

Causes of pancreatitis

Pancreatitis is the term used to describe inflammation of the pancreas, which may occur in the short (acute) or long term. The inflammation is caused by activation of the enzymes released by the pancreas before they leave the gland, often by blockage of the ducts. Pancreatitis occurs most often in the context of alcohol abuse (70 percent of acute cases in the U.S.) and is thought to have a genetic component. Both acute and chronic forms of pancreatitis occur more often in men than women, and children are rarely affected. The inflammation occurs as a complication of a number of diseases, and even some medical treatments.

Another bad clinical trial?

I was reading my backlog of The Scientist and ran across this newsblog entry about the death of a healthy man during a clinical trial for RhuDex, an anti-inflammatory treatment for rheumatoid arthiritis. Although I am usually trigger happy about pointing fingers at the pharmaceutical industry for early testing and gung-ho releases, I am not sure they are to blame on this one. My comments were posted there were as follows: Only 1 person in all the trials exhibited heart problems. Though this may indicate what could occur in a larger treated population, or what could occur if healthy individuals are mistakenly treated with the drug, it is not an indictment of the drug itself. Not yet. Heart problems can go unseen for decades and strike out of the blue in otherwise healthy individuals. I agree with others that caution is needed in proceeding, but cannot condemn the drug, the company, or the testing facility without more information about the man's death (and I'm usually all for holding pharma accountable). Also, this was voluntary. To clear his debts means he signed up for the cash, voluntarily. It was still his choice to pay his bills this way. Though there is some question as to the ethics of offering money to trial volunteers, and it is an ongoing discussion in the medical community, if they're healthy and taking a drug to help determine the side effects they deserve some sort of compensation for that effort. Looking further for more recent information, it turns out that the man had an unknown history of heart disease:

According to the investigation, the patient had suffered several small infarctions over the past years. In addition, the autopsy revealed coronary arteriosclerosis and myocardial hypertrophy existing for years.

These findings clearly prove impairment of cardiac function in this patient that had developed for many years. From MediGene's point of view, this is backing the assessment that a causal correlation between the death of the patient, which MediGene deeply regrets, and the administration of the trial medication is unlikely.