Complications of parenteral drug administration

Intravenous administration: systemic and vascular risks

The intravenous route guarantees 100% bioavailability since the drug substance immediately and completely enters the systemic circulation. However, this very feature causes the main hazards. First, once the solution has entered the vein, it is no longer possible to reverse its effect—the action occurs almost instantaneously.

Second, the procedure requires strict adherence to sterility and the involvement of qualified medical personnel. Improper injection technique carries a life-threatening risk of embolism. In addition, the direct effect of drugs on the vascular wall can provoke thrombophlebitis, and inadequate asepsis opens the gateway for systemic infectious complications.

Intramuscular injections: local reactions and injuries

The intramuscular route allows for the administration of large volumes of fluids (up to 5–10 ml) and the use of depot formulations, such as oil solutions or suspensions (e.g., estradiol esters, which are absorbed slowly, creating a prolonged effect).

Despite the good blood supply to muscles, this method is associated with a number of local complications:

• The injection itself is often extremely painful.
• If the injection site is chosen poorly, there is a serious risk of mechanical or chemical nerve damage.
• Post-injection infiltrates (indurations) and purulent abscesses can form in the muscle tissue.

Just like intravenous infusions, intramuscular injections require trained personnel and absolute sterility.

Subcutaneous administration: volume limitations and necrosis

Subcutaneous injections are relatively simple to perform, which in some cases allows patients to administer drugs independently (a classic example is insulin). However, this route has strict physical and pharmacological limitations.

The maximum permissible volume of the injected solution must not exceed 2 ml. The main and most severe complication of subcutaneous administration is the risk of tissue necrosis. This occurs when substances with pronounced irritating effects or drugs causing severe vasospasm enter the subcutaneous tissue. For example, the subcutaneous administration of norepinephrine (as well as intramuscularly) is strictly contraindicated precisely because of the high risk of ischemia and subsequent tissue death.

Why do we take the risk of parenteral administration?

Why, despite pain, the risk of abscesses, thrombophlebitis, and the need for sterile conditions, do injections remain indispensable? The answer lies in pharmacokinetics. When taken orally (per os), many drugs are destroyed in the gastrointestinal tract (hormones, polypeptide antibiotics) or have a high first-pass effect through the liver (First-pass effect).

For example, more than 90% of nitroglycerin is eliminated during passage through the liver (the oral dose must be 6.4 mg versus 0.5 mg for sublingual administration). Due to hepatic metabolism, lidocaine is generally ineffective when taken orally, which is why it is administered exclusively parenterally (intravenous drip), accepting the risks of infusion therapy. Parenteral administration bypasses presystemic metabolism, ensures precise dose titration, and achieves an instant effect in emergency conditions.

Alternative routes without injection complications

To avoid complications associated with injections (infiltrates, embolisms, pain) while bypassing the liver and gastrointestinal tract, alternative routes are used:

1. Sublingual and buccal: Delivery of lipophilic substances directly into the systemic circulation via passive diffusion through the oral mucosa. The effect develops in 1–2 minutes (nitroglycerin, captopril), but the absorption area is small—suitable only for highly active substances in small doses.
2. Inhalation: Allows for a high concentration in the respiratory tract ($eta_2$-agonists) and minimizes systemic side effects, although it requires proper technique, and part of the dose is deposited in the oropharynx.
3. Transdermal: Patches and gels provide a prolonged effect without injections, but the drug must be strictly lipophilic and have a low molecular weight. Local skin reactions are possible.

Class and exam questions

What else to study on this topic

• The first-pass effect and its impact on bioavailability
• Absorption mechanisms in sublingual and buccal administration
• Features of the clinical use of drug depot formulations
• Inhalation route: dose distribution and systemic absorption
• Transdermal therapeutic systems: requirements for physicochemical properties of substances

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.