I've seen the words distal and proximal but admit I wasn't sure of the meaning.
Distal is frequently defined as "most distant from the point of attachment to the body" with respect to limb locations, etc.
Being of a certain age, however, my friends and I are very familiar with the word statin, and it does come up in conversation - often in the context of how we miss being able to eat grapefruit or drink grapefruit juice.
The reason for this is actually quite interesting, and centres upon an enzyme in the liver known as Cytochrome P450 3A4 (known as CYP3A4 for short). This enzyme is one of the "clearance enzymes" responsible for metabolising assorted toxic substances, and converting them into less dangerous (and more easily excretable) products. Grapefruit juice contains compounds that inhibit CYP3A4, and as a corollary, this can result in a wide range of unexpected side effects when taking certain drugs. In the case of those drugs that are broken down by CYP3A4 liver activity, grapefruit juice affects the clearance of these drugs, and allows them to persist in the bloodstream for longer.
A particularly striking example of the activity involved, centres upon the antihistamine Terfenadine. Inhibition of CYP3A4 by grapefruit juice led to the drug remaining in the bloodstream at elevated concentrations long enough to trigger fatal ventricular tachycardia. While investigating this, scientists found that Terfenadine was actually converted to a different compound, Fenoxfenadine, by the CYP3A4 enzyme, and it was actually
this compound that was exhibiting the antihistamine effect. Switching from Terfenadine to Fenoxfenadine directly allowed the antihistamine benefits of the medication to continue, but without the potentially lethal cardiac issues surrounding Terfenadine, which arise from the fact that it acts as a potassium channel blocker in sufficient doses, the source of its cardiotoxicity issues.
So, back to statins. If this class of drugs are not properly metabolised by the CYP3A4 enzyme in the liver, then their persistence in the bloodstream at elevated doses could have serious effects. It's not merely grapefruit juice that can set off this chain of events, but certain antibiotics too, such as Clarithromycin, which is why, if you're taking statins, it's a good idea to remind your doctor of this if you need antibiotic treatment for various infections, and sometimes, you'll be
strongly advised to suspend taking the statins while taking the antibiotics. The reason for this being that persistent, elevated statin levels beyond a certain threshold, carry with them a quantifiable risk of triggering an uncommon but very nasty condition called rhabdomyolysis, which accounts for the strict control of statin dosage when prescribed. In short, elevated statin interference with muscle metabolism can result in the release of reactive oxygen species in the muscle tissue, leading to cell death and the release of myoglobin into the bloodstream, where it quickly starts compromising renal function. In short, if you're taking statins, and you see your pee discoloured a brown colour, get to a hospital
fast - that brown colour is the myoglobin arising from incipient rhabdomyolysis. Failure to act quickly will see a lurid cascade begin, which starts with progressive renal failure and ultimately leads to large scale metabolic collapse. NOT a pleasant way to go.
I spend too much of my time in the company of medical personnel.
