Routes of Injection (Parenteral Administration)

Injection routes diagram showing IV, dermal, subcutaneous, and IM at different tissue depths

Fig. 1.3 - Lippincott Illustrated Reviews: Pharmacology. A: Cross-section showing depth of each injection route. B: Plasma concentration curves comparing IV vs. IM midazolam.

Why Use Parenteral Routes?

Parenteral routes bypass the GI tract entirely, which is useful when:

A drug is poorly absorbed orally (e.g., heparin)
A drug is unstable in the GI environment (e.g., insulin)
The patient is unconscious or cannot swallow
A rapid onset of action is needed
Precise dose control is required

The trade-off: parenteral administration is irreversible, may cause pain, local tissue damage, and carries infection risk.

The Four Major Routes

1. Intravenous (IV)

Depth: Directly into a vein (bypasses all tissue layers)
Onset: Fastest of all routes - nearly immediate when given as a bolus
Absorption: 100% bioavailability - no absorption step required
Volume: Can accommodate large volumes
Types:
- IV bolus - full dose delivered almost instantly
- IV infusion - drug delivered over time, giving lower peak concentrations and longer duration
Examples: rocuronium, many antibiotics, emergency medications
Risks: Hemolysis, thrombophlebitis, air embolism, infection

2. Intramuscular (IM)

Depth: Into muscle tissue (below subcutaneous fat)
Needle angle: 90 degrees
Onset: Faster than SC, slower than IV
Absorption: Via simple diffusion - rate depends on formulation
Types of IM preparations:
- Aqueous solutions - absorbed rapidly
- Depot preparations - suspended in non-aqueous vehicles (e.g., polyethylene glycol, oil); the vehicle diffuses out, drug precipitates at the site, then dissolves slowly over days to weeks - ideal for long-acting formulations
Common sites: Deltoid, vastus lateralis, ventrogluteal, dorsogluteal
Max volume: ~3-5 mL in most sites
Examples: vaccines, antipsychotics (depot), some antibiotics

3. Subcutaneous (SC)

Depth: Into the subcutaneous (hypodermis) fat layer - below dermis, above muscle
Needle angle: 45 degrees (can be 90° in obese patients with longer needles)
Onset: Slower than IM due to lower vascularity of fat
Absorption: Simple diffusion; provides slow, sustained, and constant drug release
Advantages over IV: Minimizes risk of hemolysis or thrombosis
Limitation: Should NOT be used for irritating drugs - risk of severe pain and necrosis
Max volume: ~1-2 mL per site
Examples: insulin, heparin, epinephrine auto-injectors

4. Intradermal (ID)

Depth: Into the dermis (below epidermis, above subcutaneous tissue)
Needle angle: 10-15 degrees (nearly flat to the skin)
Onset: Slowest - minimal vascularity in dermis
Primary uses:
- Allergy skin testing (diagnostic determination)
- Tuberculin (Mantoux) test (TB screening)
- Desensitization therapy
Volume: Very small - typically 0.05-0.1 mL
Expected result: A visible wheal (raised bleb) under the skin confirms correct placement

Quick Comparison Table

Feature	IV	IM	SC	ID
Depth	Vein	Muscle	Fat	Dermis
Needle angle	15-25°	90°	45-90°	10-15°
Onset speed	Fastest	Fast	Moderate	Slowest
Bioavailability	100%	High	High	Low
Max volume	Large	3-5 mL	1-2 mL	0.1 mL
Typical uses	Emergency, large dose	Vaccines, depot drugs	Insulin, heparin	Allergy testing, TB test

Speed of Absorption: IV > IM > SC > ID

The chart in the image illustrates this clearly - IV midazolam reaches a plasma concentration of ~150 ng/mL within ~15 minutes, while the same dose given IM peaks at roughly ~50 ng/mL over a longer, flatter curve.

- Lippincott Illustrated Reviews: Pharmacology, p. 25-26

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