George Livingston M.S. in Biochemistry

Introduction

The word parenteral can be broken down into its prefix and root word. The prefix par- means with or alongside, and the root word -enteral refers to the enteric system associated with the gastrointestinal tract. Parenteral routes of administration work with or alongside the gastrointestinal system because medications administered this way bypass the gastrointestinal tract to be injected more directly into tissues or the blood. The enteral routes include oral, sublingual, and rectal [2]. Parenteral is more generally understood in the healthcare community as IV and injections [2]. IV administration is beneficial for many reasons, but just like everything, nothing can be inherently good or bad, for IV administration has its pros and cons. In the same way, there are reasons why other parenteral routes (SC/SQ, IM, and ID) would be more desirable, and there are reasons why they would not be optimal [2]. This risk analysis that is alluded to in the previous sentences is where clinicians will defer to their training of assessing the situation by gathering data before making an informed decision [1]. Some information will be obvious or well known based on current medication costs and availability, understood metabolic mechanisms for specific medications, and common adverse side effects, but other information will have to be acquired on a case by case basis: interactions with other prescribed medications, age, physical condition, allergies, and patient preference [1]. The following discussion will address the risks and benefits of the different parenteral administration methods (IV, SC/SQ, IM, ID) as well as how IV administration can be the better option in certain situations, and how in others, non-IV parenteral administration can be indicated for optimal patient care.

Intravenous

In emergency situations where health care professionals need to utilize rapid intervention, IV administration allows the fastest onset of drug action because the medication directly enters the bloodstream [1,2]. This allows the pharmacokinetics distribution to occur instantly [2,3]. Typically, pharmacokinetics observes 4 steps: absorption, distribution, metabolism, and excretion [3]. IV administration skips the absorption step because it flows directly into the blood. The cardiovascular system is an excellent delivery vessel because it is heavily integrated in almost the entire body, so systemic distribution also occurs relatively quickly. To reiterate, IV is the fastest route for onset of medication action, and medication effects can be observed anywhere from a few seconds or minutes after administration [2]. Lastly, IV is a great way to rehydrate or infuse nutrients directly into a patient, for it allows a steady continuous flow when compared to other parenteral routes, which only deliver the medication, fluid, or nutrient during the initial injection. Therefore, if a patient needs their electrolytes restored, and they cannot eat/drink or are unconscious, then IV is the first line approach [1]. Even patients who are conscious and could eat/drink may be put onto an IV to guarantee the patient is getting sufficient fluid input [1]. One more scenario where an IV may be required is after a major surgery involving the mouth, jaw, throat, or certain parts of the digestive system where it is possible that the patient may not be able to ingest their nutrients and fluids in the traditional manner.
Although IV is a very effective way to deliver medications into the patient’s system, there are some potential adverse effects associated with choosing this route, and there are some scenarios where healthcare professionals should refrain from choosing this method. Patient comfort and preference should be considered when attempting to start an IV, for some patients may be afraid of large needles or very sensitive to pain [1,2]. Age can play an important role in the decision to start an IV as well because older patients will have more fragile veins, and they can be more prone to bleeding, especially if they are on blood thinners [1,2]. Another consideration for not starting an IV to administer medications is the unnecessary risk posed to the patient. There is always a small chance of a patient having air embolisms, phlebitis, and extravasation [2]. These risks are more serious than the risks associated with the other parenteral routes.

Subcutaneous, Intramuscular, Intradermal, and Topical

In routine administrations that are non-emergent, non-IV parenteral administrations may be the best choice for the patient [1]. However, some emergent scenarios could require non-IV parenteral administrations. For example, EpiPens administer epinephrine during anaphylaxis via IM injection. The onset of action can vary depending on which non-IV parenteral method is chosen: IM (5-15 minutes), SC/SQ (10-30 minutes), and ID (slowest, 30-60 minutes) [2]. IM has the fastest onset of action of all non-IV parenteral administration methods, SC/SQ averages double IM’s onset of action, and ID’s onset of action is approximately double that of SC/SQ [2]. These changes in onset of action are accounted for via absorption rate differences in the subcutaneous, dermis, and muscle tissues. This knowledge can be beneficial for choosing which route to administer a medication because clinicians may want the medication to have a shorter or longer release time depending on the situation [1,2].
IM injections have the benefits of being pushed into highly vascularized tissue (muscle). Muscle can also handle larger quantities of volumes compared to other non-IV parenteral routes [1]. Optimal sites for IM injections are large muscles like the gluteal, deltoid, and vastus lateralis. Since muscle has a large amount of capillaries throughout it, the medication will be absorbed into the bloodstream rather expediently [2]. Some risks associated with IM injections are pain at the injection site, bleeding if an artery is hit, nerve damage if the injection is administered incorrectly, tissue damage if the needle is inserted incorrectly, and infection if the needle or field is not sterile [1,2]. It is important to note that any injection (including SC/SQ, IM, and ID) can potentially cause infection if the needle or field is not sterile.
SC/SQ injections are great for administering moderate volumes of medications, and they have some special benefits when compared to other non-IV parenteral routes. The needles used for this method of administration are on the smaller side when compared to the other parenteral routes, so the patient will not experience as much pain [2]. SC/SQ also allows patients to administer their own medications under the right circumstances. With a slower onset of action because of absorption rate differences, SC/SQ can provide a more sustained release of medication [2]. The risks associated with SC/SQ administration are lipoatrophy in long term administration at the same inject site, bleeding if a blood vessel is hit, and localized reactions like inflammation, flushing, and itching [2]. While on the topic of skin, it is worth noting that topical administration of medications is another parenteral route [5]. Some common examples of topical medications are triple antibiotic ointment and lidocaine cream [5]. The associated side effects of topical administration depend heavily on the medication that is being applied, but some common side effects include stinging, burning, itching, symptoms of inflammation, and/or dryness [1,5]. The word “percutaneous” encompasses both SC/SQ and topically applied medications [6].
ID injections only administer very small volumes of medications and utilize thin needles. This means that ID injections are not suitable for all medications because of the limitation on volume [2]. They have a few very specific applications such as allergy testing, viral testing (tuberculosis), and vaccinations using live attenuated viruses [1,2]. Since ID administration releases the slowest of any parenteral route, it can be used for a very slow release of a medication into the blood, and it is ideal for medications that only require a very small volume to be administered. Besides ID not being suitable for medications that require larger volumes, it is also a very technical route and requires precision [1]. Therefore, it is one of the more difficult parenteral routes to master.

Conclusion

Selecting the best parenteral route for medication administration requires healthcare professionals to have a nuanced understanding of the benefits and risks of each type of parenteral route (IV, SC/SQ, IM, and ID). While IV administration offers the fastest onset of action and is crucial in emergencies and other specific situations, it also presents potential risks like discomfort and an increased probability of complications compared to injections. Conversely, non-IV parenteral routes, like SC/SQ, IM, and ID, prove advantageous in emergent and non-emergent scenarios and offer varying onset durations and absorption rates depending on the chosen method. It is worth noting that this research did not cover inhalants even though they technically fall under the scope of parenteral routes. Ultimately, the patient’s care team must holistically assess each situation before determining what method of administration is appropriate, for each parenteral route has its own pros and cons. To optimize patient care and achieve the desired therapeutic outcome, the right administration method must be applied.

References:

[1] Wecker, Lynn. Brody’s Human Pharmacology. Elsevier Health Sciences. Kindle (5th) Edition. 2010.
[2] Kim J, De Jesus O. Medication Routes of Administration. [Updated 2023 Aug 23]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. https://www.ncbi.nlm.nih.gov/books/NBK568677/.
[3] Ernstmeyer K, Christman E, editors. Nursing Pharmacology [Internet]. 2nd edition. Eau Claire (WI): Chippewa Valley Technical College; 2023. Chapter 1 Pharmacokinetics & Pharmacodynamics. Available from: https://www.ncbi.nlm.nih.gov/books/NBK595006/.
[4] Oates JT, Lopez D. Pharmacogenetics: An Important Part of Drug Development with A Focus on Its Application. Int J Biomed Investig. 2018;1(2):111. doi: 10.31531/2581-4745.1000111. Epub 2018 May 27. PMID: 32467882; PMCID: PMC7255432.
[5] Open Resources for Nursing (Open RN); Ernstmeyer K, Christman E, editors. Nursing Skills. Eau Claire (WI): Chippewa Valley Technical College; 2021. Chapter 16 Administration of Medications Via Other Routes. https://www.ncbi.nlm.nih.gov/books/NBK593196/.
[6] Pascher F. Systemic reactions to topically applied drugs. Int J Dermatol. 1978 Dec;17(10):768-75. doi: 10.1111/j.1365-4362.1978.tb05977.x. PMID: 730430.