Why does penicillin require such a painful jab with a huge needle?

I assume there’s a reason that a shot of penicillin is so awful and getting my flu jab or Covid jab is absolutely nothing and painless.

Antibiotics are given deeper into tissue than are flu or Covid vaccinations (into muscles which have greater innervation than does subcutaneous tissue). The needles are longer and usually a larger gauge with antibiotics. Longer and bigger hurts more. Usually the amount of an antibiotic is greater than the .3ml dab for the Covid jab, so that bigger and longer needle is also jabbed into you longer which is going to seem worse. Then there are differences in the formulations as well, some are more buffered and less irritating, etc. This is more into a pharmacist’s territory, so I’ll quit while I’m ahead.

Penicillin (and derivatives) have been used so much that many infections are spread by organisms that have developed some immunity to it. So injections of antibiotics like Penicillin are often big doses. Thus need bigger needles, need to be injected deeper, might be more likely to have side effects.
(For example, the injection to treat STDs currently is several times as big as originally needed.)

Except it doesn’t need to be injected at all. The last time I had penicillin (for strep throat), it was a liquid that tasted vaguely like strawberries, taken orally a spoonful a day.

There are two common types of penicillin, depending on your disease you may need either the one that is used as an oral medication or the one that is used as an injected medication.

Injection gives a more predictable response, and is suitable for medicines that are destroyed in the stomach, or deactivated by first-pass metabolism.

The amount you can inject into a muscle is limited. If you need more, intravenous injection or oral medication is used. Intravenous injection is more difficult and more dangerous.

The amount you can inject under the skin is even more limited. If you inject too much, you get a blister/delamination/leakage.

AZ and Pfizer are intramuscular injections. I don’t know about the rest.

The one time I got an injection with penicillin, it also stung. However, I can’t remember if there was something else in it, too. If it was the penicillin that stung, is there a reason why?

I actually almost fainted because of it.

Ceftriaxone is commonly given IM, and is usually dissolved with lidocaine because its injection can be very painful. Penicillin is sometimes admixed with procaine, not just as a local anesthetic, but also because it lessens the pain of administration.

Plus, the depot (long-acting) forms are very thick, and require a larger needle for administration.

I have to say, needle tech has become insane. Last time I got poked I literally did not feel a thing.

I mean the vaccine hurt later on that day, but I felt nothing from the needle.

The AstraZeneca and mRNA vaccines are designed to actually enter the muscle cells, it is there that they hijack the cell’s machinery to create the spike protein. So you need to inject well into the muscle. The muscle is the target, not just acting as a buffer. I wouldn’t say the AZ vaccine was particularly painful, but the site gets tender after. Modern flu vaccines are very high tech, needing very small amounts of actual material injected in only a simple saline. Done right you won’t even feel them. Often with little to no reaction after either.
Some injections carry material that needs to be in some form of lipid emulsion carrier, or much more viscous carrier, and need much more volume to be injected. They are going to hurt.

I’m not sure what distinction you’re making here between “local anesthetic” and “lessens pain”.

Isn’t “lipid emulsion carrier” a description of how the mRNA covid vaccines work?

Not really. The mRNA is in a tiny lipid capsule, but that is really working as something akin to a cell membrane rather than a carrier for a chemical that is lipid soluble and needs carrying into you as an emulsion. There is a lot less lipid in the mRNA vaccine.

Sorry about the repetition, Chronos; it was pretty late when I made that post.