Auricular, buccal, conjunctival, cutaneous, dental, electro-osmosis, endocervical, endosinusial, endotracheal, enteral, epidural, extra-amniotic, extracorporeal, hemodialysis, infiltration, interstitial, intradermal, intralesional, intraluminal, intramuscular, intravenous, IV, nasal, ophthalmic, oral, otic, parenteral, rectal, subcutaneous, sublingual, suppository, topical, transdermal patch, vaginally.

The route of administration is defined as the path by which a drug or other substance enters the body. The pharmacokinetic properties, such as absorption, distribution, metabolism, and excretion, of a drug are critically influenced by the route of administration.

The United States Food and Drug Administration recognizes 111 distinct routes of administration.

The development of alternative methods of drug administration has improved the ability of physicians to manage specific problems.

Routes of administration can broadly be divided into four categories: topical, enteral, parenteral and other.

Topical: Usually for a local effect, a substance is applied directly where its action is desired.

Epicutaneous (application onto the skin), e.g. allergy testing, topical 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 conjuncitivitis

Ear drops, such as antibiotics and corticosteroids for otitis externa

Intranasal, e.g. decongestant nasal sprays

Enteral: Desired effect is systemic (non-local) where substance is given via the digestive tract.

By mouth (orally), many drugs as tablets, capsules, or liquids (syrup, suspension, elixir)

By gastric feeding tube, duodenal feeding tube, or gastrostomy, many drugs and enteral nutrition

Rectally, various drugs in suppository or enema form

Parenteral: Desired effect is systemic where substance is given by routes other than the digestive tract. Parenteral administration generally has the greatest bioavailability because it avoids an absorption phase as well as possible inactivation by first-pass metabolism by the liver. It can be further divided into two subgroups: parenteral by injection or infusion and other parenteral excluding oral route of administration.

Parenteral by injection or infusion

Intravenous (into a vein), e.g. many drugs, total parenteral nutrition (TPN)

Intraarterial (into an artery), e.g. vasodilator drugs in the treatment of vasospasm and thrombolytic drugs for treatment of embolism

Intramuscular (into a muscle), e.g. many vaccines, antibiotics, and long-acting psychoactive agents

Intracardiac (into the heart), e.g. adrenalin during cardiopulmonary resuscitation (not commonly performed anymore)

Subcutaneous (under the skin), e.g. insulin

Intraosseous infusion (into the bone marrow) is, in effect, an indirect intravenous access because the bone marrow drains directly into the venous system. This route is occasionally used for drugs and fluids in emergency medicine and pediatrics when intravenous access is difficult

Intradermal, (into the skin itself) is used for skin testing some allergens, and also for tattoos

Other parenteral administration

Intraperitoneal, (into the peritoneum) is predominantly used in veterinary medicine and animal testing for the administration of systemic drugs and fluids due to the ease of administration compared with other parenteral methods.

Transdermal (diffusion through the intact skin), e.g. transdermal opioid patches in pain therapy

Transmucosal (diffusion through a mucous membrane), e.g., sublingual nitroglycerin

Inhalational, e.g. inhalational anesthetics

Other:

Intraperitoneal (infusion or injection into the peritoneal cavity), e.g. peritoneal dialysis

Epidural (synonym: peridural) (injection or infusion into the epidural space), e.g. epidural anesthesia

Intrathecal (injection or infusion into the cerebrospinal fluid), e.g. antibiotics, spinal anesthesia

Intramuscular: Intramuscular injection is an injection of a substance directly into a muscle. It is used for particular forms of medication, which are administered in small amounts. Depending on the chemical properties of the drug, the medication may either be absorbed fairly quickly or more gradually. Intramuscular injections are often given in the deltoid, vastus lateralis, ventrogluteal and dorsogluteal muscles. When the gluteal muscles are used, injections should be made on the upper, outer quadrant of the buttock to avoid damaging the sciatic nerve.

Intramuscular injection is similar to subcutaneous injection, except that medication is delivered deeper into tissue, and a larger needle is usually used. Drugs in aqueous solution are rapidly absorbed. However, very slow constant absorption can be obtained if the drug is administered in oil or suspended in other repository vehicles. It can be used for relatively irritant drugs and larger volumes can be administered.

Intraosseous: Intraosseous infusion is the process of injection directly into the marrow of the bone. The needle is injected right through the bone and into the soft marrow interior.

Intravenous: Intravenous therapy, or IV therapy, is the administration of liquid substances directly into a vein. It can be intermittent (an IV bolus), or continuous (an intravenous drip). The simplest form of intravenous access is a syringe with an attached hollow needle. The needle is inserted through the skin into a vein, and the contents of the syringe are injected through the needle into the bloodstream. This is most easily done with an arm vein, especially one of the metacarpal veins. This is the most common intravenous access method in both hospitals and paramedic services.

Therapeutic effects of medication delivered by IV injection are extremely rapid, as the initial absorption step is bypassed. Drug levels are accurately controlled, and it is suitable for large volumes of drugs.

A peripheral IV line consists of a short catheter inserted through the skin into a peripheral vein. A peripheral vein is any vein that is not in the chest or abdomen. Arm and hand veins are typically used although leg and foot veins are occasionally used. Veins in the scalp are sometimes used in infants. .

Central IV lines flow through a catheter with its tip within a large vein, usually the superior vena cava or inferior vena cava, or within the right atrium of the heart. This has several advantages over a peripheral IV. It can deliver fluids and medications that would be overly irritating to peripheral veins because of their concentration or chemical composition, such as chemotherapy drugs and total parenteral nutrition. Medications delivered by a central IV reach the heart immediately, and are quickly distributed to the rest of the body.

Compared with other routes of administration, the intravenous route is the fastest way to deliver fluids and medications throughout the body. Some medications, as well as blood transfusions and lethal injections, can only be given intravenously.

Oral: Orally, drugs are often taken as tablets or capsules. A tablet is a mixture of active substances and binders, usually in powder form, pressed into a solid. A capsule is a mixture of similar ingredients enclosed within a gelatinous outer shell. Medicines to be taken orally are very often supplied in tablet form. Medicinal tablets and capsules are usually intended to be swallowed, and are of a suitable size and shape. A coating may be applied to hide the taste of the tablet's components.

Rectal: Drugs given rectally may be in the form of enemas or suppositories. An enema is the procedure of introducing liquids into the rectum and colon via the anus. The main uses of enemas are as laxatives or to clean the lower bowel prior to examination or surgery. Enemas may also be used for the administration of substances into the bloodstream. This may be done in situations where it is undesirable or impossible to deliver a medication by mouth, such as antiemetics given to reduce nausea. The topical administration of medications into the rectum, such as corticosteroids and mesalamine used in the treatment of inflammatory bowel disease, may be accomplished by an enema. Administration by enema avoids having the medication pass through the entire gastrointestinal tract, therefore simplifying the delivery of the medication to the affected area and limiting the amount that is absorbed into the bloodstream.

A suppository is a medicine that is inserted either into the rectum (rectal suppository), the vagina (vaginal suppository), or into the urethra where it melts. Vaginal suppositories are used to treat gynecological ailments, especially vaginal infections such as candidiasis, or yeast infections. Rectal suppositories are used for laxative purposes, to treat hemorrhoids by delivering a moisturizer or vasoconstrictor, and for general medical administration purposes. The substances in the suppository are absorbed by the rectal mucosa and enter the bloodstream. Urethral suppositories are used to treat infections or erectile dysfunction. Suppositories are used especially for small children, for they may be easier to administer than tablets or syrups, or for patients experiencing intractable vomiting.

Subcutaneous: Subcutaneous injection is useful when slow and continuous absorption is required. The formulation must be isotonic and at physiological pH. Certain drugs are irritating and can cause severe injection site pain and tissue necrosis, so it is common practice to alternate between injection sites. The rate of distribution of the drug is largely dependent on blood flow and can therefore be slowed by including a vasoconstrictor. Warming or vigorous massage of the injection site will increase distribution of medication.

Transdermal: A transdermal patch is a medicated adhesive patch that is placed on the skin that delivers a time-released dose of medication through the skin and into the bloodstream. The most common transdermal patch, the nicotine patch, contains nicotine and is used to quit the habit of tobacco smoking. Transdermal patches are used to deliver a wide variety of pharmaceuticals; recent developments are their use in the delivery of hormonal contraceptives (see contraceptive patch) and antidepressants.

Transdermal drug application can significantly alter drug kinetics. The bioavailability of a transdermal drug differs depending on the site of application, the thickness and integrity of the skin, the size of the drug molecule, the permeability of the membrane of the transdermal delivery system, the state of skin hydration, the thickness of the adipose (fat) tissue under the application site, the pH of the drug, and the alteration of blood flow in the skin caused by varying body temperature.

Transmucosal: Drug absorption through a mucosal surface is generally efficient because the stratum corneum epidermidis, the major barrierto absorption across the skin, is absent. Mucosal surfaces areusually rich in blood supply, providing the means for rapid drugtransport to the systemic circulation and avoiding, in most cases,degradation by first-pass hepatic metabolism. The amount of drug absorbed depends on drug concentration, vehicle of drug delivery, mucosal contact time, venous drainage of the mucosal tissues, degree of the drug's ionization and the pH of the absorption site, size of the drug molecule, and relative lipid solubility.

Respiratory tract mucosal absorption is useful for the treatment of pulmonary conditions and for delivery of drugs via systemic circulation. One of the oldest examples is inhalation anesthesia. Administration may be accomplished by inhalation of vaporized, nebulized, powdered, or aerosolized drug, as well as by directinstillation. Metered-dose inhalers and nebulizers are often used to treat asthma and chronic obstructive pulmonary disease related symptoms.

Nasal mucosal administration is rapid and relatively painless. Vasopressin and corticosteroids were among the first drugs to be administered by this route.

Oral transmucosal administration involves sublingual (under the tongue) and buccal (inside the cheek) tablets. Oral transmucosal absorption is generally rapid because of the rich vascular supply to the mucosa and the lack of a stratumcorneum epidermidis. This minimal barrier to drug transport resultsin a rapid rise in blood concentrations. The oral transmucosalroute has been used for many years to provide rapid blood nitratelevels for the treatment of angina pectoris

Central IV lines carry higher risks of bleeding, bacteremia, and gas embolism than peripheral lines.

IV injection can be a dangerous route. Drugs must be in aqueous solution, and must be carefully injected. Once injected, the drug cannot be removed.

Thrombocytopenia (low platelet counts) and coagulopathy (bleeding tendency) are contraindications for intramuscular injections, as they may lead to hematomas.

The potential for toxic effects of the drug and difficulty in limiting drug uptake are major considerations for nearly alltransdermal delivery systems, especially in children because skinthickness and blood flow in the skin vary with age. Episodes ofsystemic toxic effects, including some fatalities in children,have been documented with use of transdermal patches, often secondary to accidentalabsorption through mucous membranes

Problems with respiratory mucosal administration include drug metabolism in the respiratory tract decreasing systemic effects, possible conversion to carcinogens, and local toxic effects of the drug, such as edema, cell injury, or altered tissue defense.

Until appropriate studies of the neurotoxicity of drugs and their carriers are completed, it would seem prudent not to administerdrugs unapproved for use by nasal mucosa absorption, particularly when additionaldoses are contemplated.

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 cannot be used enterally because their absorption in the digestive tract is low or unpredictable. Transdermal administration is a comfortable alternative; there are, however, few drug preparations suitable for transdermal administration. Therefore, if a drug is not absorbed well in the gastrointestinal tract due to stomach acids or liver inactivation, it may have to be administered parenterally.

Some routes can be used for topical as well as systemic purposes, depending on the circumstances. 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).

A single drug 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, 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 caused by opiate pain therapy and does not affect the pain-reducing effect of the opiate.

There is no definite answer for the best route of administration. It depends on the individual characteristics of the patient, the drug, and the condition being treated. Therefore, careful examination by physician is recommended to pick the best administration route for each individual.

This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Berlin C, Notterman D, Ward R. Alternative Routes of Drug Administration Advantages and Disadvantages. America Academy Of Pediatrics 1997;100:143-152. aappolicy.aappublications.org

FDA CDER Data Standards Manual. 1 June 2006. www.fda.gov