Routes of Drug Administration

Why This Matters

When you're tested on pharmacology, you're not just being asked to list administration routes—you're being evaluated on whether you understand why a clinician would choose one route over another. The key principles at play here include bioavailability (how much drug actually reaches systemic circulation), onset of action (how quickly effects begin), and first-pass metabolism (the liver's processing of drugs before they reach the bloodstream). These concepts determine everything from emergency treatment protocols to chronic disease management.

Think of administration routes as a decision tree: Does the patient need immediate effects or sustained release? Can they swallow? Do we want local or systemic effects? Does the drug survive the GI tract? Don't just memorize that nitroglycerin goes under the tongue—know that it's given sublingually because it would be destroyed by first-pass metabolism if swallowed. That's the level of understanding that earns full credit on exams.

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Routes That Bypass First-Pass Metabolism

First-pass metabolism occurs when drugs absorbed from the GI tract pass through the liver before reaching systemic circulation, often significantly reducing bioavailability. These routes deliver drugs directly to the bloodstream, avoiding hepatic processing entirely.

Sublingual Administration

• Placed under the tongue for absorption through the highly vascular sublingual mucosa—onset within 1-2 minutes
• Bypasses first-pass metabolism, making it ideal for drugs like nitroglycerin that would be extensively metabolized by the liver
• Requires patient cooperation—drug must dissolve completely without swallowing for maximum effect

Buccal Administration

• Placed between gum and cheek, absorbing through the buccal mucosa into systemic circulation
• Slower onset than sublingual due to less vascular tissue, but useful for sustained-release formulations
• Avoids GI degradation—commonly used for fentanyl lozenges and certain hormone therapies

Transdermal Administration

• Patches deliver medication through the skin into capillaries for continuous, controlled systemic absorption
• Bypasses first-pass metabolism and maintains steady plasma levels over 24-72 hours
• Limited to lipophilic drugs with low molecular weight—examples include fentanyl, nicotine, and estrogen patches

Intranasal Administration

• Absorbed through nasal mucosa directly into systemic circulation, with onset in 10-15 minutes
• Bypasses first-pass metabolism—critical for emergency medications like naloxone (Narcan) for opioid overdose
• Rich blood supply allows rapid absorption; also used for vaccines and migraine medications

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Parenteral Routes: Direct Systemic Access

Parenteral administration refers to any route that bypasses the gastrointestinal tract entirely. These injectable routes offer predictable absorption and are essential when oral administration is impossible or inadequate.

Intravenous (IV) Administration

• 100% bioavailability—drug enters bloodstream directly with immediate onset of action
• Allows precise titration of drug levels and is essential for emergency situations and continuous infusions
• Highest risk for adverse reactions—once administered, the drug cannot be retrieved; requires sterile technique

Intramuscular (IM) Injection

• Injected into muscle tissue (deltoid, vastus lateralis, ventrogluteal) where rich blood supply enables absorption in 10-30 minutes
• Accommodates larger volumes (up to 3-5 mL depending on site) and depot formulations for prolonged release
• Absorption rate varies with blood flow—exercise increases absorption; shock decreases it

Subcutaneous (SC) Injection

• Injected into adipose tissue beneath the dermis, providing slower, more sustained absorption than IM
• Ideal for self-administration—standard route for insulin, heparin, and many vaccines
• Limited volume capacity (typically 1-2 mL); absorption affected by blood flow and injection site

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Enteral Routes: Through the GI Tract

Enteral administration involves the gastrointestinal system. While convenient and cost-effective, these routes subject drugs to digestive enzymes, variable pH, and first-pass metabolism—all of which affect bioavailability.

Oral Administration

• Most common and convenient route—patient swallows tablet, capsule, or liquid for absorption in the GI tract
• Subject to first-pass metabolism, which can significantly reduce bioavailability before drug reaches systemic circulation
• Absorption affected by food, gastric pH, and GI motility—some drugs require empty stomach, others need food

Rectal Administration

• Suppositories or enemas inserted into rectum for local effects or systemic absorption through rectal mucosa
• Partially bypasses first-pass metabolism—lower rectal veins drain directly into systemic circulation
• Useful when oral route unavailable—vomiting patients, unconscious patients, or those with swallowing difficulties

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Topical and Local Routes

These routes deliver medication directly to the site of action, minimizing systemic exposure and side effects. The goal is therapeutic effect at the application site rather than throughout the body.

Topical Application

• Applied directly to skin surface as creams, ointments, lotions, or gels for localized effect
• Minimal systemic absorption when skin is intact—treats conditions like dermatitis, infections, and inflammation locally
• Absorption increases with broken skin, occlusive dressings, or application to thin-skinned areas

Ophthalmic Administration

• Drops, ointments, or gels applied to the eye for local treatment of conditions like glaucoma, infections, and inflammation
• Systemic absorption can occur through nasolacrimal drainage—apply pressure to inner canthus to minimize this
• Proper technique essential—avoid touching dropper to eye; wait 5 minutes between different eye medications

Otic Administration

• Medication instilled into external ear canal for local treatment of infections, inflammation, or cerumen impaction
• Proper positioning required—adults: pull pinna up and back; children: pull down and back
• Temperature matters—solutions should be warmed to body temperature to prevent vertigo

Vaginal Administration

• Inserted as creams, tablets, suppositories, or rings for local or systemic effects
• Common uses include antifungal treatments (miconazole), hormonal therapy, and labor induction (prostaglandins)
• Absorption varies with vaginal pH, menstrual cycle, and presence of infection or inflammation

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Inhalation Route: Pulmonary Delivery

The lungs offer an enormous surface area (approximately 70 square meters) with thin membranes and rich blood supply, enabling rapid absorption for both local respiratory effects and systemic delivery.

Inhalation

• Medication delivered as aerosols, nebulizers, or dry powder directly to respiratory tract for rapid absorption
• Primary use is respiratory conditions—bronchodilators for asthma, corticosteroids for COPD, mucolytics for secretions
• Lower doses achieve therapeutic effect compared to systemic administration, reducing side effects significantly

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Quick Reference Table

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Self-Check Questions

1. A patient experiencing an acute angina attack needs immediate relief. Why is nitroglycerin given sublingually rather than orally, and what pharmacokinetic principle does this illustrate?

2. Compare and contrast IM and SC injection routes: What factors would lead a clinician to choose one over the other for a specific medication?

3. Which three administration routes would be appropriate for an unconscious patient who cannot swallow, and what are the advantages and limitations of each?

4. A question describes two patches—one delivering fentanyl for chronic pain and one applying hydrocortisone for a local rash. Explain why these represent fundamentally different administration concepts despite both being applied to skin.

5. If an FRQ asks you to explain why the same drug might require different doses depending on administration route, which routes would demonstrate the greatest dose differences and why? (Hint: think about bioavailability and first-pass metabolism.)