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Routes of administration

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Routes of administration

A route of administration in pharmacology and toxicology is the path by which a drug, fluid, poison, or other substance is taken into the body.[1] Routes of administration are generally classified by the location at which the substance is applied. Common examples include oral and intravenous administration. Routes can also be classified based on where the target of action is. Action may be topical (local), enteral (system-wide effect, but delivered through the gastrointestinal tract), or parenteral (systemic action, but delivered by routes other than the GI tract).

Classification

Routes of administration are usually classified by application location (or exposition). The route or course the active substance takes from application location to the location where it has its target effect is usually rather a matter of pharmacokinetics (concerning the processes of uptake, distribution, and elimination of drugs). Nevertheless, some routes, especially the transdermal or transmucosal routes, are commonly referred to routes of administration. The location of the target effect of active substances are usually rather a matter of pharmacodynamics (concerning e.g. the physiological effects of drugs[2]). Furthermore, there is also a classification of routes of administration that basically distinguishes whether the effect is local (in "topical" administration) or systemic (in "enteral" or "parenteral" administration).

Application location

Gastrointestinal/enteral

Administration through the gastrointestinal tract is sometimes termed enteral or enteric administration (literally meaning 'through the intestines'). Enteral/enteric administration usually includes oral[3] (through the mouth) and rectal (into the rectum)[3] administration, in the sense that these are taken up by the intestines. However, uptake of drugs administered orally may also occur already in the stomach, and as such gastrointestinal (along the gastrointestinal tract) may be a more fitting term for this route of administration. Furthermore, some application locations often classified as enteral, such as sublingual[3] (under the tongue) and sublabial or buccal (between the cheek and gums/gingiva), are taken up in the proximal part of the gastrointestinal tract without reaching the intestines. Strictly enteral administration (directly into the intestines) can be used for systemic administration, as well as local (sometimes termed topical), such as in a contrast enema, whereby contrast media is infused into the intestines for imaging. However, for the purposes of classification based on location of effects, the term enteral is reserved for substances with systemic effects.

Many drugs as tablets, capsules, or drops are taken orally. Administration methods directly into the stomach include those by gastric feeding tube or gastrostomy. Substances may also be placed into the small intestines, as with a duodenal feeding tube and enteral nutrition.Some enteric coated tablets will not dissolve in stomach but it is directed to the intestine because the drug present in the enteric coated tablet causes irritation in the stomach.

Central nervous system

  • epidural (synonym: peridural) (injection or infusion into the epidural space), e.g. epidural anesthesia
  • intracerebral (into the cerebrum) direct injection into the brain. Used in experimental research of chemicals[4] and as a treatment for malignancies of the brain.[5] The intracerebral route can also interrupt the blood brain barrier from holding up against subsequent routes.[6]
  • intracerebroventricular (into the cerebral ventricles) administration into the ventricular system of the brain. One use is as a last line of opioid treatment for terminal cancer patients with intractable cancer pain.[7]

Other locations

Local or systemic effect

Routes of administration can also basically be classified whether the effect is local (in topical administration) or systemic (in enteral or parenteral administration):

  • topical: local effect, substance is applied directly where its action is desired.[9] Sometimes, however, the term topical is defined as applied to a localized area of the body or to the surface of a body part,[10] without necessarily involving target effect of the substance, making the classification rather a variant of the classification based on application location.
  • enteral: desired effect is systemic (non-local), substance is given via the digestive tract.
  • parenteral: desired effect is systemic, substance is given by routes other than the digestive tract.

Topical

  • epicutaneous (application onto the skin), e.g. allergy testing, typical local anesthesia
  • inhalational, e.g. asthma medications
  • enema, e.g. contrast media for imaging of the bowel
  • eye drops (onto the conjunctiva), e.g. antibiotics for conjunctivitis
  • ear drops - such as antibiotics and corticosteroids for otitis externa
  • through mucous membranes in the body

Enteral

In this classification system, enteral administration is administration that involves any part of the gastrointestinal tract and has systemic effects:

Parenteral

Choice of Route of Administration

The options are limited by the available forms of any given drug. Still, there are advantages and disadvantages to consider with any route of administration.

Oral

The oral route is generally the most convenient and carries the lowest cost.[12] However, some drugs can cause gastrointestinal tract irritation.[13] For drugs that come in delayed release or time-release formulations, breaking the tablets or capsules can lead to more rapid delivery of the drug than intended.[12]

Topical

By delivering drugs almost directly to the site of action, the risk of systemic side effects is reduced.[12] However, skin irritation may result, and for some forms such as creams or lotions, the dosage is difficult to control .[13]

Inhalation

Inhaled medications can be absorbed quickly, and act both locally and systemically.[13] Proper technique with inhaler devices is necessary to achieve the correct dose. Some medications can have an unpleasant taste or irritate the mouth.[13]

Inhalation by smoking a substance is likely the most rapid way to deliver drugs to the brain, as the substance travels directly to the brain without being diluted in the systemic circulation.[14] The severity of dependence on psychoactive drugs tends to increase with more rapid drug delivery.[14]

Injection

The term injection encompasses intravenous (IV), intramuscular (IM), and subcutaneous (SC) administration. [15]

Injections act rapidly, with onset of action in 15-30 seconds for IV, 10-20 minutes for IM, and 15-30 minutes for SC.[16] They also have essentially 100% bioavailability, and can be used for drugs that are poorly absorbed or ineffective when given orally.[12] Some medications, such as certain antipsychotics, can be administered as long-acting intramuscular injections.[17] Ongoing IV infusions can be used to deliver continuous medication or fluids.[18]

Disadvantages of injections include potential pain or discomfort for the patient, and the requirement of trained staff using aseptic techniques for administration.[12] However, in some cases patients are taught to self-inject, such as SC injection of insulin in patients with insulin-dependent diabetes mellitus. As the drug is delivered to the site of action extremely rapidly with IV injection, there is a risk of overdose if the dose has been calculated incorrectly, and there is an increased risk of side effects if the drug is administered too rapidly.[12]

Uses

  • Some routes can be used for topical as well as systemic purposes, depending on the circumstance. For example, inhalation of asthma drugs is targeted at the airways (topical effect), whereas inhalation of volatile anesthetics is targeted at the brain (systemic effect).
  • On the other hand, identical drugs can produce different results depending on the route of administration. For example, some drugs are not significantly absorbed into the bloodstream from the gastrointestinal tract and their action after enteral administration is therefore different from that after parenteral administration. This can be illustrated by the action of naloxone (Narcan), an antagonist of opiates such as morphine. Naloxone counteracts opiate action in the central nervous system when given intravenously and is therefore used in the treatment of opiate overdose. The same drug, when swallowed, acts exclusively on the bowels; it is here used to treat constipation under opiate pain therapy and does not affect the pain-reducing effect of the opiate.
  • Enteral routes are generally the most convenient for the patient, as no punctures or sterile procedures are necessary. Enteral medications are therefore often preferred in the treatment of chronic disease. However, some drugs can not be used enterally because their absorption in the digestive tract is low or unpredictable. Transdermal administration is a comfortable alternative; there are, however, only a few drug preparations that are suitable for transdermal administration.
  • In acute situations, in emergency medicine and intensive care medicine, drugs are most often given intravenously. This is the most reliable route, as in acutely ill patients the absorption of substances from the tissues and from the digestive tract can often be unpredictable due to altered blood flow or bowel motility.

See also

References

External links

  • The 10th US-Japan Symposium on Drug Delivery Systems
  • FDA Center for Drug Evaluation and Research Data Standards Manual: Route of Administration.
  • FDA Center for Drug Evaluation and Research Data Standards Manual: Dosage Form.
  • A.S.P.E.N. American Society for Parenteral and Enteral Nutrition
  • Medical Subject Headings (MeSH)

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