Tetracyclines

Definition
Purpose
Description
Recommended dosage
Precautions
Side effects
Interactions

Definition

Tetracyclines are broad-spectrum antibiotics that kill bacteria, which are one-celled microorganisms that commonly multiply by cell division. Tetracyclines are also used to treat infections caused by such subcategories of bacteria as rickettsiae and spirochetes. The older tetracyclines became less useful in the early 2000s because many bacteria have developed resistance to this group of drugs; however, a new subgroup of tetracyclines known as glycylcyclines was introduced in June 2005 to treat infections that are resistant to other antibiotics, including the older tetracyclines. The name tetracycline comes from the four (tetra in Greek) hydrocarbon rings found in the chemical structure of these antibiotics.

Tetracyclines are classified as antibiotics, which are chemical substances produced by a microorganism that are able to kill other microorganisms without being toxic to the person, animal, or plant being treated. They were first discovered in the 1940s when a scientist at Lederle Laboratories isolated chlortetracycline from a bacterium in the soil known as Streptomyces aureofaciens; the drug was given the trade name Aureomycin. Oxytetracycline (Terramycin) was then derived from the bacterium Streptomyces rimosus. After the chemical structure of oxytetracycline was worked out, researchers were able to make synthetic tetracyclines in the laboratory. In the early 2000s, some tetracyclines are derived directly from a bacterium known as Streptomyces coelicolor, while others are made in the laboratory from chlortetracycline or oxytetracycline. One of these semi-synthetic drugs, minocycline, was used to develop tigecycline (Tygacil), the first glycylcycline to receive regulatory approval for use in the United States. Tigecycline was the first new tetracycline to be approved since the early 1980s.

Purpose

Tetracyclines are called broad-spectrum antibiotics, because they can be used to treat a wide variety of infections. Physicians may prescribe these drugs to treat eye infections, pneumonia, gonorrhea, syphilis, chlamydia, bubonic plague, anthrax, brucellosis, malaria, Rocky Mountain spotted fever, urinary tract infections, travelers’ diarrhea, Lyme disease, and other infections caused by bacteria. These drugs are also used to treat acne and rosacea (a chronic inflammatory skin condition marked by flushing and redness). Tigecycline is used to treat skin and soft-tissue infections, as well as infections inside the abdomen. The tetracyclines will not work, however, for colds, flu, and other infections caused by viruses.

Description

Tetracyclines are available only with a physician’s prescription. They are sold in capsule, tablet, liquid, and injectable forms. Some commonly used medicines in this group are tetracycline (Achromycin V, Sumycin), demeclocycline (Declomycin), minocycline (Minocin), oxytetracycline (Terramycin), and doxycycline (Doryx, Vibramycin, Vivox). Tigecycline (Tygacil) is not available in oral form, but must be given as a slow intravenous infusion over a period of 30–60 minutes.

Tetracyclines have been used for treatment of gum infections in dental surgery. In orthopedic surgery, they have been used as markers to identify living bone. The patient is given a tetracycline antibiotic for several weeks prior to surgery. Some of the tetracycline is absorbed into the bone during this period. Since tetracyclines glow under ultraviolet light, this absorption helps the surgeon distinguish the living bone from the dead tissue that must be removed.

Tetracycline may also be mixed with bone cement for prevention of infection in bone surgery. In nasal surgery, tetracycline ointments are used to help prevent postsurgical infections.

Recommended dosage

The recommended dosage depends on the specific tetracycline, its strength, and the disease agent and severity of infection for which it is being taken. Patients should check with the physician who prescribed the drug or the pharmacist who filled the prescription for the correct dosage.

To make sure an infection clears up completely, patients should take the full course of antibiotic medication. It is important to not stop taking the drug just because symptoms begin to improve.

Tetracyclines are most effective at constant levels in the blood. To keep blood levels constant, the medicine should be taken in doses spaced evenly throughout the day and night. It is important to not miss any doses.

These medicines work best when taken on an empty stomach with a full glass of water. The water will help prevent irritation of the stomach and esophagus (the tube-like structure that runs from the throat to the stomach). If the medicine still causes stomach upset, the patient may take it with food. Tetracyclines should never be taken with milk or milk products, however, as these foods may prevent the drugs from working properly. Patients should not drink or eat milk or dairy products within one to two hours of taking tetracyclines (except doxycycline and minocycline).

Precautions

There are specific warnings that apply to tetracycline preparations taken by mouth to treat infections; they do not apply to topical ointments or tetracyclines mixed with bone cement. Also, these warnings apply primarily to tetracycline itself. Some members of the tetracycline family, particularly doxycycline and

KEY TERMS

Antibiotic— A chemical substance produced by a microorganism that is able to kill other microorganisms without being toxic to the host. Antibiotics are used to treat diseases in humans, other animals, and plants.

Bacterium (plural, bacteria)— A one-celled microorganism that typically multiplies by cell division and whose nucleus is contained within a cell wall. Most diseases treated with tetracyclines are caused by bacteria.

Brucellosis— An infectious disease transmitted to humans from farm animals, most commonly goats, sheep, cattle, and dogs. It is marked by high fever, pains in the muscles and joints, heavy sweating, headaches, and depression.

Glycylcyclines— The name of a new subgroup of tetracyclines derived from minocycline, a semi-synthetic tetracycline. As of 2007, the only drug in this class approved for use is tigecycline.

Gonorrhea— A sexually transmitted disease (STD) that causes infection in the genital organs and may cause disease in other parts of the body.

Microorganism— An organism that is too small to be seen with the naked eye.

Orthopedics— The medical specialty concerned with treatment of diseases of bone.

Rickettsia (plural, rickettsiae)— A microorganism belonging to a subtype of gram-negative bacteria that multiply only within the cells of a living host. Rickettsiae are usually transmitted to humans and other animals through the bites of ticks, fleas, and lice. They are named for Howard Ricketts (1871-1910), an American doctor.

Rocky Mountain spotted fever— An infectious disease that is caused by a rickettsia and spread by ticks. Its symptoms include high fever, muscle pain, and spots on the skin.

Rosacea— A chronic inflammatory skin condition primarily affecting the skin of the nose, forehead, and cheeks, marked by flushing and reddening of the affected areas.

Salicylates— A group of drugs that includes aspirin and related compounds. Salicylates are used to relieve pain and reduce inflammation or fever.

Spirochete— A spiral-shaped bacterium. Spirochetes cause such diseases as syphilis and Lyme disease.

minocycline, have different adverse effects and precautions. Patients should consult their physician or pharmacist about these specific drugs.

Taking outdated tetracyclines can cause serious side effects, particularly damage to the kidneys. Patients should not take these medicines when:

• the color, appearance, or taste have changed
• the drug has been stored in a warm or damp area
• the expiration date on the label has passed

Outdated tetracyclines should be thrown out. Patients should check with their physician or pharmacist if they have any doubts about the effectiveness of their drugs.

Patients should not take antacids, calcium supplements, such salicylates as Magan or Trilisate, magnesium-containing laxatives, or sodium bicarbonate (baking soda) within one to two hours of taking tetracyclines. Patients should also not take any medicines that contain iron (including multivitamin and mineral supplements) within two to three hours of taking tetracyclines.

Some people feel dizzy when taking these drugs. Tetracyclines may also cause blurred vision or interfere with color vision. Because of these possible side effects, anyone who takes these drugs should not drive, use machines, or do anything else that might be dangerous until they have found out how the drugs affect them.

Birth control pills may not work properly while tetracyclines are being taken. To prevent pregnancy, women should use alternative methods of birth control while taking tetracyclines.

Tetracyclines may increase the skin’s sensitivity to sunlight. Even brief exposure to sun can cause severe sunburn or a rash. During treatment with these drugs, patients should avoid exposure to direct sunlight, especially high sun between 10 a.m. and 3 p.m.; wear a hat and tightly woven clothing that covers the arms and legs; use a sunscreen with a skin protection factor (SPF) of at least 15; protect the lips with a lip balm containing sun block; and avoid the use of tanning beds, tanning booths, or sunlamps. Sensitivity to sunlight and sunlamps may continue for two weeks to several months after stopping the medicine, so patients must continue to be careful about sun exposure.

Tetracyclines may permanently discolor the teeth of people who took the medicine in childhood. The drugs may also slow down the growth of children’s bones. Tetracyclines should not be given to infants or children under eight years of age unless directed by the child’s physician.

Special conditions

People with certain medical conditions or who are taking other medicines may have problems if they take tetracyclines. Before taking these drugs, the patient must inform the doctor about any of these conditions.

FOOD OR MEDICATION ALLERGIES. Anyone who has had unusual reactions to tetracyclines in the past should inform his or her physician before taking the drugs again. The physician should also be told about any allergies to foods, dyes, preservatives, or other substances.

PREGNANCY AND LACTATION. Pregnant women should not take tetracyclines during the last four months of pregnancy. These drugs can prevent the baby’s bones and teeth from developing properly and may cause the baby’s adult teeth to be permanently discolored. Tetracyclines can also cause liver problems in pregnant women.

Women who are breastfeeding should also not take tetracyclines. The drugs pass into breast milk and can affect the nursing baby’s teeth and bones. They may also make the baby more sensitive to sunlight and may increase its risk of contracting fungal infections.

OTHER CONDITIONS. Before using tetracyclines, people with any of these medical problems should make sure their physicians have been informed:

• diabetes
• liver disease
• kidney disease

Side effects

The most common side effects of tetracyclines are stomach cramps or a burning sensation in the stomach, mild diarrhea, nausea, or vomiting. These problems usually go away as the body adjusts to the drug and do not require medical treatment. Less common side effects, such as a sore mouth or tongue and itching of the rectal or genital areas, may occur. These reactions do not need medical attention, however, unless they do not go away or are bothersome.

Other rare side effects have been reported, including inflammation of the pancreas, impairment of the kidneys, skin peeling, headache, intracranial hypertension, and ulceration of the esophagus. Anyone who has unusual symptoms during or after treatment with tetracyclines should consult his or her physician.

Interactions

Tetracyclines may interact with other medicines. When an interaction occurs, the effects of one or both of the drugs may change or the risk of side effects may be greater. Anyone who takes tetracyclines should give the doctor a list of all other medications that they take on a regular basis, including over-the-counter (OTC) drugs, herbal preparations, traditional Chinese medicines, or other alternative medicines. Standard medications that may interact with tetracyclines include:

• antacids
• calcium supplements
• medicines that contain iron (including multivitamin and mineral supplements)
• laxatives containing magnesium
• digoxin
• cholesterol-lowering drugs, including cholestyramine (Questran) and colestipol (Colestid)
• salicylates
• penicillin compounds
• birth control pills

Herbal preparations containing St. John’s wort have been reported to increase sensitivity to sunlight in patients taking tetracyclines. People who have been using St. John’s wort to relieve mild depression should discontinue it while they are taking tetracyclines.

Resources

BOOKS

Deglin, Judith Hopfer, and April Hazard Vallerand. Davis’s Drug Guide for Nurses, 10th ed. Philadelphia: F. A. Davis, 2007.

Neal, Michael J. Medical Pharmacology at a Glance, 5th ed. Malden, MA: Blackwell Publishing, 2005.

Pelletier, Kenneth R., MD. The Best Alternative Medicine, PartI, Chapter 6, “Western Herbal Medicine.” New York: Simon & Schuster, 2002.

PERIODICALS

Gottehrer, N. R. “Managing Risk Factors in Successful Nonsurgical Treatment of Periodontal Disease.” Dentistry Today 22 (January 2003): 64–69.

Kasbekar, N. “Tigecycline: A New Glycylcycline Antimicrobial Agent.” American of Health-System Pharmacy 63 (July 1,2006): 1235–1243.

Moore, D. E. “Drug-Induced Cutaneous Photosensitivity: Incidence, Mechanism, Prevention and Management.” Drug Safety 25 (2002): 345–372.

Rose, W. E., and M. J. Rybak. “Tigecycline: First of a New Class of Antimicrobial Agents.” Pharmacotherapy 26 (August 2006): 1099–1110.

Wormser, G. P., R. Ramanathan, J. Nowakowski, et al. “Duration of Antibiotic Therapy for Early Lyme Disease. A Randomized, Double-Blind, Placebo-Controlled Trial.” Annals of Internal Medicine 138 (May 6, 2003): 697–704.

ORGANIZATIONS

American Society of Health-System Pharmacists (ASHP). 7272 Wisconsin Avenue, Bethesda, MD 20814. (301) 657-3000. http://www.ashp.org (accessed April 10, 2008).

United States Food and Drug Administration (FDA). 5600 Fishers Lane, Rockville, MD 20857-0001. (888) INFO-FDA. http://www.fda.gov (accessed April 10, 2008).

U.S. Pharmacopoeia (USP). 12601 Twinbrook Parkway, Rockville, MD 20852–1790. (800) 227–8772. http://www.usp.org/ (accessed April 10, 2008)

Nancy Ross-Flanigan

Sam Uretsky, PharmD

Rebecca Frey, PhD

Tetralogy of Fallot seeHeart surgery for congenital defects

Therapeutic abortion seeAbortion, induced