The route of administration is determined by the properties of the drug (for example, water or lipid solubility, ionization) and by the therapeutic objectives (for example, the desirability of a rapid onset, the need for long-term treatment, or restriction of delivery to a local site). Major routes of drug administration include enteral, parenteral, and topical, among others
Enteral administration (administering a drug by mouth) is the safest and most common, convenient, and economical method of drug administration. The drug may be swallowed, allowing oral delivery, or it may be placed under the tongue (sublingual), or between the gums and cheek (buccal), facilitating direct absorption into the bloodstream.
Oral administration provides many advantages. Oral drugs are easily self-administered, and toxicities and/or overdose of oral drugs may be overcome with antidotes, such as activated charcoal. However, the pathways involved in oral drug absorption are the most complicated, and the low gastric pH inactivates some drugs. A wide range of oral preparations is available including enteric-coated and extended-release preparations.
Placement under the tongue allows a drug to diffuse into the capillary network and enter the systemic circulation directly. Sublingual administration has several advantages, including ease of administration, rapid absorption, bypass of the harsh gastrointestinal (GI) environment, and avoidance of first pass-metabolism. The buccal route (between the cheek and gum) is similar to the sublingual route.
The parenteral route introduces drugs directly into the systemic circulation. Parenteral administration is used for drugs that are poorly-absorbed from the GI tract (for example, heparin) or unstable in the GI tract (for example, insulin). Parenteral administration is also used if a patient is unable to take oral medications (unconscious patients) and in circumstances that require a rapid onset of action.
In addition, parenteral routes have the highest bio-availability and are not subject to first-pass metabolism or the harsh GI environment. Parenteral administration provides the most control over the actual dose of drug delivered to the body. However, these routes of administration are irreversible and may cause pain, fear, local tissue damage, and infections. The three major parenteral routes are intravascular (intravenous or intra-arterial), intramuscular, and subcutaneous
IV injection is the most common parenteral route. It is useful for drugs that are not absorbed orally, such as the neuromuscular blocker rocuronium. IV delivery permits a rapid effect and a maximum degree of control over the amount of drug delivered. When injected as a bolus, the full amount of drug is delivered to the systemic circulation almost immediately. If administered as an IV infusion, the drug is infused over a longer period of time, resulting in lower peak plasma concentrations and an increased duration of circulating drug levels.
Drugs administered IM can be in aqueous solutions, which are absorbed rapidly, or in specialized depot preparations, which are absorbed slowly. Depot preparations often consist of a suspension of the drug in a non-aqueous vehicle such as polyethylene glycol. As the vehicle diffuses out of the muscle, the drug precipitates at the site of injection.
Like IM injection, SC injection provides absorption via simple diffusion and is slower than the IV route. SC injection minimizes the risks of hemolysis or thrombosis associated with IV injection and may provide constant, slow, and sustained effects. This route should not be used with drugs that cause tissue irritation, because severe pain and necrosis may occur. Drugs commonly administered via the subcutaneous route include insulin and heparin.
Inhalation routes, both oral and nasal provide rapid delivery of a drug across the large surface area of the mucous membranes of the respiratory tract and pulmonary epithelium. Drug effects are almost as rapid as those with IV bolus. Drugs that are gases (for example, some anesthetics) and those that can be dispersed in an aerosol are administered via inhalation. This route is effective and convenient for patients with respiratory disorders (such as asthma or chronic obstructive pulmonary disease), because the drug is delivered directly to the site of action, thereby minimizing systemic side effects.
The blood–brain barrier typically delays or prevents the absorption of drugs into the central nervous system (CNS). When local, rapid effects are needed, it is necessary to introduce drugs directly into the cerebrospinal fluid. For example, intrathecal amphotericin B is used in treating cryptococcalmeningitis
Topical application is used when a local effect of the drug is desired. For example, clotrimazole is a cream applied directly to the skin for the treatment of fungal infections.
This route of administration achieves systemic effects by application of drugs to the skin, usually via a transdermal patch. The rate of absorption can vary markedly, depending on the physical characteristics of the skin at the site of application, as well as the lipid solubility of the drug.
Because 50% of the drainage of the rectal region bypasses the portal circulation, the bio-transformation of drugs by the liver is minimized with rectal administration. The rectal route has the additional advantage of preventing destruction of the drug in the GI environment. This route is also useful if the drug induces vomiting when given orally, if the patient is already vomiting, or if the patient is unconscious. [Note: The rectal route is commonly used to administer anti-emetic agents.]