A long time ago, I had a beautiful relationship with half-life. Half-life meant everything to me. If someone overdosed, half-life would tell me when they were out of the danger zone. Half-life would tell me that everything would be okay in 6-8 hours. With half-life, I was armed with all the information I needed to anticipate the clinical course of an overdose. Half-life promised me the world.
It was a simpler world back then, during the larval stages of my medical training. Half-life and I were in love. All heart-attack related chest pain would present with crushing chest pain that radiates to the left arm. All appendicitis would present with right lower quadrant abdominal pain. My standardized patients told me exactly what I needed to hear during the history portion of the exam. I looked forward to a career with a perfect work-life balance where I would reach the nirvana of job satisfaction and appreciation for my efforts from my patients and colleagues.
As a toxicologist, I have a lot of conversations about half-life, and it made me realize that a lot of people still see half-life the way that I used to. I wanted to write this post to talk a little more about half-life, and the way that we can apply it towards overdose patients.
What is the half-life, if not a wildly successful video game franchise with a fanbase who has an undying faith in the release of Half-Life 3? In terms of medications, half-life describes the amount of time it takes to eliminate half of the concentration of a particular medication. If you take a medication with a half-life of four hours, it will take four hours for the concentration in the body to drop to half. Every four hours, the concentration halves, until, after five half-lives, you have eliminated 95% of the medication.
Most medications have information about a half-life because they are eliminated from our bodies in an organized fashion through first-order elimination. The enzymes available for metabolism outnumber the amount of drug in the body so that the drug interacts with the enzyme in a predictable way. Kind of like a toll booth where the number of available booths outnumbers the cars on the road. Traffic still flows smoothly, so the delays in travel are minimal. First-order elimination is based on drug concentration in plasma, which is how we determine the half-life.
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The purpose of making a "biobetter" biologic is to improve on the salient characteristics of a known biologic for which there is, minimally, clinical proof of concept or, maximally, marketed product data. There already are several examples in which second-generation or biobetter biologics have been generated by improving the pharmacokinetic properties of an innovative drug, including Neulasta() [a PEGylated, longer-half-life version of Neupogen() (filgrastim)] and Aranesp() [a longer-half-life version of Epogen() (epoetin-α)]. This review describes the use of protein fusion technologies such as Fc fusion proteins, fusion to human serum albumin, fusion to carboxy-terminal peptide, and other polypeptide fusion approaches to make biobetter drugs with more desirable pharmacokinetic profiles.
I am having a little bit of trouble with trying to play mods on half-life. I have a non-steam version of Half-Life 1.1, and it runs counter-strike mod perfectly, but when I try to play "Crack-Life" or its campaign brother on Half-Life by clicking "Custom Game", selecting the mod on the menu, and clicking activate, then click "done", and click "new game", it comes up with the typical half-life loading screen it stays like that. The longest I have ever had it stay was for 5-10 minutes but I assume the Half-Life game cant load it. How can I make the mods work? Also, I moved the mods into the folder by accessing their original rar state via 7-zip and double clicking on them to se
