Medication Routes of Administration

Medications Are Given Many Ways

If you've ever watched ER, , Chicago Hope or any of the other zillion-plus medical dramas on television, then you know that drugs can be administered in various iterations.  Most commonly, drugs are taken as pills, capsules or tablets.  But depending on the site of action, absorption, bioavailability, metabolism, anatomy and so forth, your physician may choose to prescribe you a drug via a parenteral or rectal route of administration, too.

Parenteral refers to any route of drug administration other than via the digestive tract (think sharp needles).  Here are details on not only oral administration but also rectal administration and various forms of parenteral administration.

Oral administration

Oral administration is usually the safest, cheapest and easiest way to administer a drug.  In terms of expenditure of healthcare resources, it's much easier for a physician or other healthcare practitioner to instruct you to take a pill, tablet or capsule on a schedule rather than administering the drug himself.

With oral administration, a chief concern is bioavailability which is defined as the fraction of drug that makes it to its intended site of action.  Bioavailability depends on several factors including:

  • physical characteristics of the drug (water solubility and membrane permeability)
  • the surface area of the gastrointestinal tract
  • irritation of the linings of the gastrointestinal tract
  • associated food intake
  • adverse effects like vomiting
  • destruction of the pill by digestive enzymes
  • destruction of the pill by acid (low gastric pH)
  • intestinal or liver metabolism (first-pass metabolism)

With oral administration, it's important to listen to your physician and take your pills at the right dosage and on schedule.

  Nonadherence is a perpetual concern among clinicians and often underlies decisions on routes of administration.  In other words, many types of medications come in both oral and parenteral forms, and if your physician believes that you may have trouble taking your medication as pills, she may decide to give you an injection.  For example, physicians often treat gonorrhea with a one-time shot of Rocephin rather than prescribing oral cephalosporin medication.

Parenteral injection

There are 5 different type of parenteral injection:

  • subcutaneous or under the skin
  • intramuscular or in the muscle
  • intravenous or through a vein
  • intrathecal or directly into the central nervous system in order to circumvent the blood-brain barrier
  • intra-arterial or through an artery (a rare route of administration)

Under certain circumstances, injection of drugs is preferred to oral administration.  First, sometimes a drug needs to reach its destination in active form.  For example, infliximab, an antibody used to treat rheumatoid arthritis and other autoimmune diseases, must be injected in order to remain active.

  Second, drugs given by injection have more accurate, extensive, and predictable actions.  Third, some people--like those who are uncooperative, unconscious or have digestive issues--can take medication only by injection.

Injection of drugs has disadvantages, too.  First, injections are painful--especially if they're intravenous or intrathecal.  Second, unless subcutaneous or intramuscular, it's difficult for a person to self-administer an injection.  Third, with injections, a sterile environment must be maintained because injection is often a source of iatrogenic or treatment-induced infection.

Of particular note, parenteral administration avoids first-pass metabolism or breakdown by the intestine and liver, and thus injected drugs have greater bioavailability.

Rectal administration

When drugs are administered via the rectum, about half the administered dose will avoid liver metabolism; thus, bioavailability or the amount of drug that enters circulation increases.  Moreover, rectal administration avoids intestinal metabolism by the enzyme CYP3A4 which is located in the upper intestine.  Despite the benefit of decreased first metabolism, however, absorption by rectum is usually incomplete and irregular and irritates the rectal mucosa (ouch!). 

Pulmonary absorption

Gaseous, aerosol and volatile drugs that don't cause irritation are administered via inhaler or nebulizer into the lungs (pulmonary absorption).  The lungs have a large surface area and inhaled drugs pass directly into the blood without first-pass metabolism.  Asthma and allergy inhalers are examples of medications that are absorbed via the pulmonary system.

Topical, transdermal and sublingual application

Some drugs like local anesthetics are applied topically to the mucous membranes: nasopharynx, vagina, mouth, urethra, eyes and so forth.  Drugs applied to mucous membranes are quickly absorbed thus making systemic intoxication a possible adverse effect.

Some fat-soluble (lipophilic) drugs are able to make it past the epidermis or outer layer of skin and into the dermis or second layer of skin where they're absorbed.  These drugs can be applied via the transdermal patch and include medications like the nicotine patch, used for smoking cessation, and fentanyl patch, used to treat chronic pain.

Finally, some medications like nitroglycerin are applied sublingually or directly under the tongue.  Although the surface area under the tongue is small, venous drainage dumps the absorbed meds directly into the superior vena cava and systemic circulation thus bypassing all first-pass metabolism.

Although the route of administration for a prescribed medication is a decision made by your physician, remember that your input is extremely important.  For instance, if you know that you have trouble taking oral medications on time or at all (nonadherence), then injections may be an option.  Moreover, as in the case of chronic pain, you may have a preference for injection or oral pain medications based on your own perceptions of efficacy.

Selected Sources

Buxton IO, Benet LZ. Chapter 2. Pharmacokinetics: The Dynamics of Drug Absorption, Distribution, Metabolism, and Elimination. In: Brunton LL, Chabner BA, Knollmann BC. eds. Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12e. New York, NY: McGraw-Hill; 2011. Accessed May 15, 2015.

Holford NG. Chapter 3. Pharmacokinetics & Pharmacodynamics: Rational Dosing & the Time Course of Drug Action. In: Katzung BG, Masters SB, Trevor AJ. eds. Basic & Clinical Pharmacology, 12e. New York, NY: McGraw-Hill; 2012. Accessed May 15, 2015.

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