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Injections Follow the “Location, Location, Location” Cliché

Skin, fat, muscle (even eyeball): injections in different parts of the body are chosen for good reasons.

The fear of needles is a remarkably common phobia. According to different studies, it is reported in 14 to 38% of adults and in 33 to 63% of children. Even those of us who simply dislike injections would love to live in a world where these needles are unnecessary in healthcare. But there are good reasons why injections are still needed and why that syringe gets aimed in different ways depending on the situation.

Swallowing a pill is pretty easy for most of us but it’s not a delivery panacea. For one, it’s a long commute. The content of the pill has to go down to our stomach, then access our intestines and pass through their wall before ending up in the liver and then being transported to our blood vessels. In situations where a drug is rapidly needed, taking the scenic route doesn’t cut it. Also, the wall of the intestines and the liver can chemically alter many drugs, which means typically that less of the drug reaches our bloodstream. This is fine for many therapeutics but in some cases, when very precise doses are needed, this “first pass effect” as it is called can add too much uncertainty. Moreover, some molecules are simply too big to be absorbed in this way, and some (like antibodies) would get digested by our stomach before reaching their target. This is a big challenge for vaccines and the reason so few can be taken by mouth. So needles, unfortunately, can’t be put aside quite yet.

The question is where to inject the thing the body needs because it’s not as simple as breaking the skin and dropping some liquid into a giant cavity. Our body has layers. The top layer of skin, the one we can see, is known as the epidermis, and underneath it is the dermis. Below that is the subcutaneous tissue (also known as the hypodermis) and it consists mostly of fat and loose connective tissue. And underneath this layer, we find our muscles. An injection can be done in many of these layers, and they each have advantages and disadvantages.

If you’ve ever had a Mantoux test done for tuberculosis, you’ve had an intradermal injection. These are done with the needle almost parallel to the skin and the solution is injected in the dermis, just below the top layer of skin. The reason why these injections are relatively rare is because it takes a very long time for the substance being injected to be absorbed by the body, but the advantage of these superficial injections is that the body’s reaction to them is very visible. This makes them ideal for sensitivity tests, like allergy testing and tuberculosis testing. If your body mounts an immune response to the trigger being injected, it will be seen as a raised bubble of skin.

Subcutaneous injections are done one layer down from intradermal injections and into the subcutaneous tissue. This layer in our body does not have many blood vessels, so it can take a little while for what is injected there to make it into our circulation. But the big advantage of this type of injection, especially compared to those that follow, is that it can be easily carried out on yourself. If you require injections of insulin because of diabetes or of an injectable biologic drug for an autoimmune condition, the subcutaneous route is relatively easy as the syringe or autoinjector pen can be aimed at the thighs or the area around the belly button.

Older readers may remember receiving vaccines straight into the subcutaneous fat of the buttocks. In fact, traditionally all vaccines used to be injected into the subcutaneous tissue (except for the BCG shot), as this route of administration was supported by a study published in 1910. When aluminum salts started to be added to certain vaccines to improve the immune response, it led to an unacceptable number of reactions at the site of injection. Nowadays, very few vaccines are injected into the subcutaneous tissue. For most vaccines, there is a better and faster way to inject them that leads to a superior immune response and fewer injection site reactions: straight into the muscle.

Intramuscular injections go below the skin and fat and directly into the underlying muscle, which is suffused with blood vessels which leads to quicker absorption. Most adult vaccines are given via an intramuscular injection in the upper arm, technically a shoulder muscle called the deltoid. As useful as intramuscular injections are at getting a substance into our blood very quickly with a minimally invasive procedure, the right needle has to be used for the task. Injections into the muscle are typically done perpendicular to the skin in a darting motion but the needle has to be long enough to go through the epidermis, the dermis, the subcutaneous layer, and the muscle. In people with obesity, a slightly longer needle is recommended to ensure that the injection takes place in the muscle and not in the subcutaneous layer, but there is some evidence that this is not always done.

Finally, one of the fastest (but also quite invasive) ways of injecting something into the human body is to use the intravenous (IV) route. Piercing a vein to inject something had been attempted for some time in human history but it only became widespread in practice in the 1900s. And while it’s a fast way of delivering rehydration solutions, nutrition, blood products, electrolytes and some solutions that would irritate the subcutaneous fat or the muscles, it is fairly invasive, requires expertise, and can lead to infections and inflammation if not carried out properly.

There are other routes medical professionals can take with an injection, like the bone marrow of the humerus or tibia if an IV can’t be done. The most surprising route for me was when I learned, a few years ago, that patients with certain diseases affecting the back of the eye were injected with a drug inside the eye itself. These intravitreal injections are done specifically in the large space inside the eye that is filled with a gel-like substance called the vitreous humour. Thankfully, the eye and eyelids are anesthetized prior to the injection.

Apparently, these injections are painless but the mere thought of them, I’m afraid, has me on pins and needles.

Take-home message:
- Some drugs cannot be given by mouth since they are too big to be absorbed in our gut; their concentration would be too imprecise given how they interact with our gut; or they would simply be destroyed by the enzymes inside our gut
- Subcutaneous injections are done in the layer of fat underneath the skin and have the advantage of being easily done by people who need to self-inject medication
- Injections into the muscle have the advantage of a more rapid absorption and a better immune response in the case of vaccines, which tend to be administered in this way


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