On Learning Antibiotics

 Hey team,

Today is Friday, March 8th and I have a pharmacology exam on antibiotics and some other antimicrobial agents in a few hours. Antibiotics are not something I have put much time into in the past or really seen much of. Of course I know what antibiotics are and vaguely how they work (as in before starting the lectures on the content) but not like my background on psychiatry drugs or even cardiovascular drugs. This was definitely something new and not something that was particularly easy. 

First off there are a TON of antibiotics, some are super similar like all of the beta lactams (penicillins, cephalosporins, ect) but from there they are not. There really are only about 3 mechanisms overall though (cell wall inhibitors, DNA inhibitors and protein synthesis inhibitors)  however there are tons of differences between various agents that ultimately have the same target. Also some drugs have weird ass side effects or weird little quirks that really must be remembered. And there are a ton of different bacteria that infect us that can be grouped into different categories ( gram negative, vs positive, anaerobic vs aerobic, ect) but of course that only scratches the surface of the different ways of categorizing different pathogens. From my perspective the continuity between pathogens we treat with certain antibiotics is not particularly easy to piece together. In learning the drugs for cardiovascular disease, it's somewhat easy to piece together what a certain drug might do given a mechanism or the opposite: given a condition, what mechanism of a drug would help the symptoms. For antibiotics it feels "messier" to say the least. This is probably due to me having little history with antibiotic pharmacology, but I think infections are just plain tricky. With that all said by the end of the 2 or so weeks of rigorously studying these drugs I feel confident in understanding "what the hell is going on" in terms of of what drugs can treat what bugs and discriminating and categorizing them based on overlap of spectrum of activity and mechanism. That feels rather reductionistic (breaking things down to their individual components to better understand how all together a system work) , however that is how my human brain works. Biological systems are complex so breaking them down into smaller, more discriminated characteristics doesn't do justice to the interplay of the complete system. Reductionism works for a car but not a living cell or system. 

To briefly go over some of these drugs for all those nasty bugs, I will clump drugs based on their site of action adding in some important details along the way. My professor (the incredible *Dr. David Rowlee) presented all the agents in somewhat of a historical manner, allowing the class to see the progression of antibiotic discovery and development. So I often remember the drugs somewhat in accordance to their place in history. 

Sulfamethoxazole, a drug that gunks of DNA synthesis is basically always combined with another drug (trimethoprim, another drug that gunks of DNA synthesis in very similar but different way) in a compound called Bactrim actually came out before penicillins which is fun fact. Similarly, the drugs metronidazole and nitrofurantoin also fuck up bacterial DNA by seriously pushing the bacteria's buttons. The quinolones/ fluoroquinolones gunk up DNA replication by blocking DNA to unwind and separate its copies. The bacteria get soooo pissed.  There is also this drug, flucytosine (yes like the DNA nucleotide base) that fakes out the DNA replication by subbing in a laced uracil collapsing everything. 

Penicillin, which has a trillion different varieties (amoxicillin, ampicillin, methicillin, ect) fake out the bacteria's cell wall which is the pride and joy of bacteria (something we (humans/ animals) don't have ). This straight up kills the cell and they get mad. So mad they made their own enzymes that deactivate the drugs. From the penicillins we discovered other drugs that work in this same way (fuck up the cell wall) including cephalosporins, carbapenems, monobactams and glycopeptides. 

Now the last class of drugs I'll mention are the ones that gunk of bacterial protein synthesis. FYI proteins are kind-of the be all end all what a cell does with its DNA. Proteins are synthesized using a little cellular machine called a  ribosome and of course some processed DNA called mRNA which allows the ribosome to make very specific proteins. These drugs won't so much kill the bacteria directly like the ones above, but will stunt the bacteria in its tract and allow the immune system to do the rest. The drugs work by gunking up the ribosome (of course in different and nuanced ways but you already knew that). Amino glycosides, tetracyclines, macrolides, lincosamides, oxazolidinones, chloramphenicol, polymyxins, lafamulin, and mupirocin (jesus that was ugly to type out, I feel your pain in reading that all) are the drugs that fuck up this protein synthesis process. The protein synthesis inhibitors are everywhere and there aren't so much enzymes that directly destroy them like the penicillins, but there are specialized "pumps" that kick the chemicals out before they can reach their target or the bacteria use enzymes that change up the drug by adding in new chemistry groups that ruin all that hard work all those scientists did in the lab to isolate the effective drug in the first place. Truly a tough battle.

That is all I have in me to share today, hope you learned a thing or two. Now I'm gonna go to nutrition lecture and crush that pharmacology exam.

Peace out team,

-J.T. 

*Fun fact Dr. Rowlee was the only person at URI to meet my partner Bella while she came down to see me in RI for a day trip while she was staying in boston!!