Parenteral Administration of Drugs

Definition

Fig 1.2 - Commonly used routes of drug administration (Lippincott Pharmacology)

Indications / When to Use Parenteral Administration

Advantages

• Provides the most control over the dose delivered to the body
• Achieves 100% bioavailability (intravenous route) - no first-pass metabolism
• Allows rapid onset of action
• Suitable when oral route is unavailable or unreliable

Disadvantages

• Irreversible - once given, cannot be recalled
• May cause pain, fear, local tissue damage, and infections
• Requires sterile technique and trained personnel
• More expensive and less convenient than oral route

The Four Major Parenteral Routes

Fig 1.3A - Injection depths for IV, subcutaneous, intramuscular, and dermal routes. Fig 1.3B - Plasma concentration of midazolam after IV vs IM injection (Lippincott Pharmacology)

1. Intravenous (IV)

• Most common parenteral route
• Drug is delivered directly into a vein
• Bolus: entire dose enters systemic circulation almost immediately - fastest onset
• Infusion: drug is given over a longer period - lower peak concentration, longer duration
• Useful for drugs not absorbed orally (e.g., rocuronium)
• Bioavailability = 100%
• Risks: thrombophlebitis, infection, air embolism, speed shock (if given too rapidly)

Note: Intra-arterial injection is a sub-type of intravascular administration - used for local delivery (e.g., chemotherapy to tumors).

2. Intramuscular (IM)

• Drug is injected deep into a muscle (e.g., deltoid, gluteus, vastus lateralis)
• Aqueous solutions: absorbed rapidly
• Depot preparations: suspended in non-aqueous vehicle (e.g., polyethylene glycol, oil)
  • Vehicle diffuses out of muscle - drug precipitates at injection site
  • Drug then dissolves slowly - provides sustained release over an extended interval
  • Examples: depot antipsychotics (haloperidol decanoate), benzathine penicillin
• Absorption by simple diffusion - slower than IV, faster than SC
• Bioavailability typically 75-100%

3. Subcutaneous (SC)

• Drug is injected into the subcutaneous tissue (beneath the dermis, above the muscle)
• Absorption by simple diffusion - slower than IV and IM
• Provides constant, slow, sustained drug effect
• Minimizes risks of hemolysis or thrombosis associated with IV
• Do not use for drugs that cause tissue irritation - can cause severe pain and necrosis
• Examples: insulin, heparin, vaccines

4. Intradermal (ID)

• Drug is injected into the dermis (the vascular layer beneath the epidermis)
• Very slow absorption due to low vascularity at the injection site
• Used for:
  • Diagnostic testing (e.g., tuberculin skin test / Mantoux test)
  • Allergy testing and desensitization
  • Some vaccines (e.g., BCG)
• Volume injected: very small (0.1 mL)

Comparison Table

Special Considerations

• First-pass effect: parenteral routes (especially IV) completely bypass hepatic first-pass metabolism, resulting in higher plasma concentrations compared to the same oral dose
• Bioavailability of IV = 100% - used as the reference standard
• Lung may serve as a site of first-pass loss for some parenterally administered drugs (by excretion and possibly metabolism)
• Serum drug concentrations show wider variability with IM than IV due to variable absorption rates at the injection site