A new study found that NSAIDs (e.g. naproxen, ibuprofen, etc.) can increase one’s risk for cardiovascular disease (e.g. myocardio infarction, stroke, etc.). This is a cohort observational study based on the data of 31 trials of 116,429 patients.

The mechanism for how this happens is not known though the most well-known hypothesis is that NSAIDs interfere with the production of prostacyclin and thromboxane A2 (i.e. inhibit them) and this imbalance somehow increases thrombotic events.

Last May, I went to Honduras with a non-profit and provided primary health care to the locals. One of the antibiotics we had was Augmentin, which I remember, was prescribed for a kid with a bacterial infection. I remember asking the doc on the trip why he prescribed Augmentin instead of Penicillin. He said that Augmentin works for bacteria that are resistant to Penicillin.

It turns out Augmentin is a b-lactamase inhibitor. b-lactam is common to all penicillins. Structurally, it’s the part that looks like a square with an N and a carbonyl group. The bacteria that are resistant to penicillins produce an enzyme, b-lactamase, which hydrolyzes the b-lactam ring, rendering the whole molecule (of penicillin) innocuous. Augmentin inhibits this enzyme and makes the pencillin effective again!

Image courtesy of www.wiley.com.

Pranactin-Citric is part of the urea breath test (UBT) kit that tests for presence of H. pylori in your GI tract. It’s a powder that contains ¹³C-urea. This powder is mixed with water and then ingested by the patient (it tastes deliciously tangy).

The test basically utilizes the fact that H. pylori produces large amounts of the enzyme urease, which converts urea into carbon dioxide and ammonia.

(NH₂)₂CO + H₂O —> CO₂ + 2NH₃

(urea)

In the stomach the ammonia goes through several more steps which essentially neutralizes gastric acid and therefore allows the bacteria to survive.

NH₃ + H₂O —> NH₄⁺ + OH^-

OH^- + CO₂ —> HCO₃^-

HCO₃^- is bicarbonate, which is the conjugate base of carbonic acid. This helps neutralize gastric acid.

Anyway, back to the test. The patient first does a baseline breath test which shows the ¹²CO₂ level in his/her breath. Then, after ingesting the Pranactin-Citric solution, which contains carbon 13, the breath test is performed again. This time, IR spectroscopy reveals how much ¹³CO₂ there is. If H. pylori is present, the ratio of ¹³CO₂ to ¹²CO₂ would increase. In a person without H. pylori, the ratio of ¹³CO₂ to ¹²CO₂ should be about 1:1.

Some vocabulary from a paper I read:

• morbilliform - resembling dusky red eruption of measles.
• exanthem - skin eruption characteristic of measles and scarlet fever.
• adeno- - prefix referring to a gland
• papules - firm bumps on the skin (adj. papular)
• -plast - suffix meaning “pertaining to the formation or development of a”
• pruritus - itching
• neo- - new
• -oma - tumor
• neoplasm - abnormal mass of tissue
• neoplasia - abnormal proliferation of cells (new growth)
• vasculitis - inflammatory destruction of blood vessels.
• chemotaxis - when bodily cells, bacteria, etc. move according to certain chemicals in their environment.

Mifepristone is a synthetic steroid used to terminate pregnancies that are up to 49 days (~8 weeks) along. It works by binding to the progesterone receptor dimers thereby preventing its action.

Recall that progesterone is essential for maintaining a pregnancy by suppressing ovulation and decreasing the maternal immune response. Without it, the uterine lining (decidua) degenerates and sheds eventually, causing the implanted blastocyst to be detached and then expelled. The detachment of the blastocyst causes decreased production of hCG (human chorionic gonadotropin), which maintains the corpus luteum, which supplies the progesterone. In this process, prostaglandin levels increase, making the uterus contract and thereby helping the detached blastocyst to be expelled.

To summarize:

1. Mifepristone binds to progesterone receptors, preventing its action
2. Causes decidua to degenerate, cervix soften
3. blastocyst detaches
4. decreased hCG
5. corpus luteum disintegrate 
6. progesterone production stops
7. prostaglandin levels increase 
8. blastocyst is expelled