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Drug Administration

by Jennifer Le, PharmD, MAS, BCPS-ID

Drugs are introduced into the body by several routes. They may be

  • Taken by mouth (orally)

  • Given by injection into a vein (intravenously), into a muscle (intramuscularly), into the space around the spinal cord (intrathecally), or beneath the skin (subcutaneously)

  • Placed under the tongue (sublingually) or between the gums and cheek (buccally)

  • Inserted in the rectum (rectally) or vagina (vaginally)

  • Placed in the eye (by the ocular route) or the ear (by the otic route)

  • Sprayed into the nose and absorbed through the nasal membranes (nasally)

  • Breathed into the lungs, usually through the mouth (by inhalation) or mouth and nose (by nebulization)

  • Applied to the skin (cutaneously) for a local (topical) or bodywide (systemic) effect

  • Delivered through the skin by a patch (transdermally) for a systemic effect

Each route has specific purposes, advantages, and disadvantages.

Oral route

Many drugs can be administered orally as liquids, capsules, tablets, or chewable tablets. Because the oral route is the most convenient and usually the safest and least expensive, it is the one most often used. However, it has limitations because of the way a drug typically moves through the digestive tract. For drugs administered orally, absorption may begin in the mouth and stomach. However, most drugs are usually absorbed from the small intestine. The drug passes through the intestinal wall and travels to the liver before being transported via the bloodstream to its target site. The intestinal wall and liver chemically alter (metabolize) many drugs, decreasing the amount of drug reaching the bloodstream. Consequently, these drugs are often given in smaller doses when injected intravenously to produce the same effect.

When a drug is taken orally, food and other drugs in the digestive tract may affect how much of and how fast the drug is absorbed. Thus, some drugs should be taken on an empty stomach, others should be taken with food, others should not be taken with certain other drugs, and still others cannot be taken orally at all.

Some orally administered drugs irritate the digestive tract. For example, aspirin and most other nonsteroidal anti-inflammatory drugs (NSAIDs—see Nonopioid Analgesics : Nonsteroidal Anti-Inflammatory Drugs) can harm the lining of the stomach and small intestine to potentially cause or aggravate preexisting ulcers (see Peptic Ulcer). Other drugs are absorbed poorly or erratically in the digestive tract or are destroyed by the acid and digestive enzymes in the stomach.

Other routes of administration are required when the oral route cannot be used, for example:

  • When a person cannot take anything by mouth

  • When a drug must be administered rapidly or in a precise or very high dose

  • When a drug is poorly or erratically absorbed from the digestive tract

Injection routes

Administration by injection (parenteral administration) includes the subcutaneous, intramuscular, intravenous, and intrathecal routes. A drug product can be prepared or manufactured in ways that prolong drug absorption from the injection site for hours, days, or longer. Such products do not need to be administered as often as drug products with more rapid absorption.

Through the Skin

Sometimes a drug is given through the skin—by needle (subcutaneous, intramuscular, or intravenous route), by patch (transdermal route), or by implantation.

For the subcutaneous route, a needle is inserted into fatty tissue just beneath the skin. After a drug is injected, it then moves into small blood vessels (capillaries) and is carried away by the bloodstream. Alternatively, a drug reaches the bloodstream through the lymphatic vessels (see Figure: Lymphatic System: Helping Defend Against Infection). Protein drugs that are large in size, such as insulin, usually reach the bloodstream through the lymphatic vessels because these drugs move slowly from the tissues into capillaries. The subcutaneous route is used for many protein drugs because such drugs would be destroyed in the digestive tract if they were taken orally.

Certain drugs (such as progestins used for birth control—see Hormonal Methods of Contraception) may be given by inserting plastic capsules under the skin (implantation). Although this route of administration is rarely used, its main advantage is to provide a long-term therapeutic effect (for example, etonogestrel that is implanted for contraception may last up to 3 years).

The intramuscular route is preferred to the subcutaneous route when larger volumes of a drug product are needed. Because the muscles lie below the skin and fatty tissues, a longer needle is used. Drugs are usually injected into the muscle of the upper arm, thigh, or buttock. How quickly the drug is absorbed into the bloodstream depends, in part, on the blood supply to the muscle: The sparser the blood supply, the longer it takes for the drug to be absorbed.

For the intravenous route, a needle is inserted directly into a vein. A solution containing the drug may be given in a single dose or by continuous infusion. For infusion, the solution is moved by gravity (from a collapsible plastic bag) or, more commonly, by an infusion pump through thin flexible tubing to a tube (catheter) inserted in a vein, usually in the forearm. Intravenous administration is the best way to deliver a precise dose quickly and in a well-controlled manner throughout the body. It is also used for irritating solutions, which would cause pain and damage tissues if given by subcutaneous or intramuscular injection. An intravenous injection can be more difficult to administer than a subcutaneous or intramuscular injection because inserting a needle or catheter into a vein may be difficult, especially if the person is obese.

When given intravenously, a drug is delivered immediately to the bloodstream and tends to take effect more quickly than when given by any other route. Consequently, health care practitioners closely monitor people who receive an intravenous injection for signs that the drug is working or is causing undesired side effects. Also, the effect of a drug given by this route tends to last for a shorter time. Therefore, some drugs must be given by continuous infusion to keep their effect constant.

For the intrathecal route, a needle is inserted between two vertebrae in the lower spine and into the space around the spinal cord. The drug is then injected into the spinal canal. A small amount of local anesthetic is often used to numb the injection site. This route is used when a drug is needed to produce rapid or local effects on the brain, spinal cord, or the layers of tissue covering them (meninges)—for example, to treat infections of these structures. Anesthetics and analgesics (such as morphine) are sometimes given this way.

Sublingual and buccal routes

A few drugs are placed under the tongue (taken sublingually) or between the gums and teeth (bucally) so that they can dissolve and be absorbed directly into the small blood vessels that lie beneath the tongue. These drugs are not swallowed. The sublingual route is especially good for nitroglycerin, which is used to relieve angina, because absorption is rapid and the drug immediately enters the bloodstream without first passing through the intestinal wall and liver. However, most drugs cannot be taken this way because they may be absorbed incompletely or erratically.

Rectal route

Many drugs that are administered orally can also be administered rectally as a suppository. In this form, a drug is mixed with a waxy substance that dissolves or liquefies after it is inserted into the rectum. Because the rectum’s wall is thin and its blood supply rich, the drug is readily absorbed. A suppository is prescribed for people who cannot take a drug orally because they have nausea, cannot swallow, or have restrictions on eating, as is required before and after many surgical operations. Drugs that can be administered rectally include acetaminophen (for fever), diazepam (for seizures), and laxatives (for constipation). Drugs that are irritating in suppository form may have to be given by injection.

Vaginal route

Some drugs may be administered vaginally to women as a solution, tablet, cream, gel, suppository, or ring. The drug is slowly absorbed through the vaginal wall. This route is often used to give estrogen to women during menopause to relieve vaginal symptoms such as dryness, soreness, and redness.

Ocular route

Drugs used to treat eye disorders (such as glaucoma, conjunctivitis, and injuries) can be mixed with inactive substances to make a liquid, gel, or ointment so that they can be applied to the eye. Liquid eye drops are relatively easy to use but may run off the eye too quickly to be absorbed well. Gel and ointment formulations keep the drug in contact with the eye surface longer, but they may blur vision. Solid inserts, which release the drug continuously and slowly, are also available, but they may be hard to put in and keep in place. Ocular drugs are almost always used for their local effects. For example, artificial tears are used to relieve dry eyes. Other drugs (for example, those used to treat glaucoma [see Table: Drugs Used to Treat Glaucoma], such as acetazolamide and betaxolol, and those used to dilate pupils, such as phenylephrine and tropicamide) produce a local effect (acting directly on the eyes) after they are absorbed through the cornea and conjunctiva. Some of these drugs then enter the bloodstream and may cause unwanted side effects on other parts of the body.

Otic route

Drugs used to treat ear inflammation and infection can be applied directly to the affected ears. Ear drops containing solutions or suspensions are typically applied only to the outer ear canal. Before applying ear drops, people should thoroughly clean the ear with a moist cloth and dry it. Unless the drugs are used for a long time or used too much, little of the drugs enters the bloodstream, so bodywide side effects are absent or minimal. Drugs that can be given by the otic route include hydrocortisone (to relieve inflammation), ciprofloxacin (to treat infection), and benzocaine (to numb the ear).

Nasal route

If a drug is to be breathed in and absorbed through the thin mucous membrane that lines the nasal passages, it must be transformed into tiny droplets in air (atomized). Once absorbed, the drug enters the bloodstream. Drugs administered by this route generally work quickly. Some of them irritate the nasal passages. Drugs that can be administered by the nasal route include nicotine (for smoking cessation), calcitonin (for osteoporosis), sumatriptan (for migraine headaches), and corticosteroids (for allergies).

Inhalation route

Drugs administered by inhalation through the mouth must be atomized into smaller droplets than those administered by the nasal route, so that the drugs can pass through the windpipe (trachea) and into the lungs. How deeply into the lungs they go depends on the size of the droplets. Smaller droplets go deeper, which increases the amount of drug absorbed. Inside the lungs, they are absorbed into the bloodstream.

Relatively few drugs are administered this way because inhalation must be carefully monitored to ensure that a person receives the right amount of drug within a specified time. In addition, specialized equipment may be needed to give the drug by this route. Usually, this method is used to administer drugs that act specifically on the lungs, such as aerosolized antiasthmatic drugs in metered-dose containers (called inhalers), and to administer gases used for general anesthesia.

Nebulization route

Similar to the inhalation route, drugs given by nebulization must be aerosolized into small particles to reach the lungs. Nebulization requires the use of special devices, most commonly ultrasonic or jet nebulizer systems. Using the devices properly helps maximize the amount of drug delivered to the lungs. Drugs that are nebulized include tobramycin (for cystic fibrosis), pentamidine (for Pneumocystis jirovecii pneumonia), and albuterol (for asthma attacks).

Side effects can include those that occur when the drug is deposited directly in the lungs (such as cough, wheezing, shortness of breath, and lung irritation), spread of the drug into the environment (possibly affecting people other than the one taking the drug), and contamination of the device used for nebulization (particularly when the device is reused and inadequately cleaned). Using the device properly helps prevent side effects.

Cutaneous route

Drugs applied to the skin are usually used for their local effects and thus are most commonly used to treat superficial skin disorders, such as psoriasis, eczema, skin infections (viral, bacterial, and fungal), itching, and dry skin. The drug is mixed with inactive substances. Depending on the consistency of the inactive substances, the formulation may be an ointment, cream, lotion, solution, powder, or gel (see Treatment of Skin Disorders : Topical Preparations).

Transdermal route

Some drugs are delivered bodywide through a patch on the skin. These drugs are sometimes mixed with a chemical (such as alcohol) that enhances penetration through the skin into the bloodstream without any injection. Through a patch, the drug can be delivered slowly and continuously for many hours or days or even longer. As a result, levels of a drug in the blood can be kept relatively constant. Patches are particularly useful for drugs that are quickly eliminated from the body because such drugs, if taken in other forms, would have to be taken frequently. However, patches may irritate the skin of some people. In addition, patches are limited by how quickly the drug can penetrate the skin. Only drugs to be given in relatively small daily doses can be given through patches. Examples of such drugs include nitroglycerin (for chest pain), scopolamine (for motion sickness), nicotine (for smoking cessation), clonidine (for high blood pressure), and fentanyl (for pain relief).

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