Tetracyclines

What are tetracyclines?

Tetracyclines are a family of related oralantibioticsoften used to treat skin diseases. There has been over 50 years' experience with these medications, which were originally derived from the soilbacteriumStreptomyces aureofaciens.

The original base medicines, chlortetracycline, tetracycline, and oxytetracycline, have been replaced by products that are better absorbed and morelipophilic, with excellent tissuedistribution. These include:

• Doxycycline
• Lymecycline
• Minocycline
• Sarecycline.

Doxycycline is the most commonly prescribed tetracycline.

Chemically modified tetracyclines are underdevelopmentto reduce antibiotic activity and to increase their non-antibiotic, anti-inflammatoryeffect.

What are tetracyclines used for?

Tetracyclines are broad spectrum antibiotics often used to treat skin, chest,urethral, and pelvicinfections. Doxycycline is indicated in a wide range of infections includingsyphilis,Lyme disease, Qfever,Rocky Mountain spotted fever, andplague. It is also widely used formalariaprophylaxis.

Doxycycline is also effective at controlling non-infectious, inflammatory skin andmucosaldiseases, including:

• Acne vulgaris
• Rosacea
• Periorificialdermatitis
• Hidradenitis suppurativa
• Recurrentaphthousstomatitis
• Bullouspemphigoid
• Granulomatousdisorders such assarcoidosis
• Pyodermagangrenosum
• Acutefebrileneutrophilicdermatosis
• Pityriasislichenoides chronica.

It is important to note that the use of tetracyclines does not increaseStaphylococcus aureusresistance (seeMRSA).

How do tetracyclines work?

As antibiotics, tetracyclines interfere withproteinsynthesisof易受影响bacteria.

They are alsoanti-inflammatoryagents.

• Theyinhibitmatrix metalloproteinases(MMP), hydrolases, and phospholipase A2 — theseenzymesare active indermalinflammatory skin disorders.
• They reduce production of pro-inflammatorycytokinessuch asTNF-a, IL-1B, and IL-6.
• They are antioxidants, reducingfree radicalproduction andnitric oxide.
• They inhibitangiogenesisandgranulomaformation.

What is the usual dose?

The antibiotic dose of doxycycline is 100 mg once or twice daily. It should be taken while upright, with plenty of water.

Lower doses of doxycycline have been shown to be effective in rosacea (20 mg twice daily or 40 mg once daily). The lowest dose of doxycycline available in New Zealand is 50 mg. The effect of low-dose doxycycline in other skin disorders is unknown and it is quite common for an antibiotic dose to be prescribed.

Atopicalfoamformulationof minocycline was approved for use in acne by the Food and Drug Administration in the US in 2019.

How long are tetracyclines taken for?

Infections are treated for 7 to 28 days, depending on the condition.

Inflammatory disorders take several weeks or months to respond to tetracyclines such as doxycycline. They are often prescribed for months or years for inflammatory skin disorders. They are not curative for these conditions.

There is a lag period of one to three weeks between the change in dosage and its effect on the skin. If the skin problem becomes worse following a dose reduction, return to the previous higher dosage and continue on it or as advised by your doctor.

What are the side effects and risks of tetracyclines?

Tetracyclines must not be taken by pregnant or breastfeeding women, or by children under 12 years, because they discolour growing teeth and may cause enamel hypoplasia (malformed permanent teeth). Staining of permanent teeth is usually temporary but canpersistfor lifelong. Staining can also affect bones.

Doxycycline is usually tolerated very well, particularly in a subantibiotic dose.Allergycan occur, but it’s rare. There are some important precautions.

• It must be taken when upright and with copious water, to reduceoesophagitis. Wait about an hour before lying down
• Patients should protect skin andnailsfrom sun exposure, as it is aphotosensitiserand can cause unexpectedsunburnor acute painful甲脱离
• It can cause nausea, vomiting, and diarrhoea; it is better tolerated when taken after food than on an empty stomach
• Women prone tovulvovaginalcandidiasis(thrush) with broad-spectrum antibiotics should considerprophylactictreatment with intermittenttopicalorsystemicazole antifungal agent

Minocycline has an increased risk of severe adverse effects compared to doxycycline, so it best to avoid minocycline as a first-line agent. These include:

• Drughypersensitivitysyndrome
• Autoimmunereactions
• Dizziness and headache (intracranialhypertension)
• With prolonged use,bluepigmentationof skin and nails

Minocycline is less likely than doxycycline to cause光敏性.

Drug interactions with tetracyclines

Important drug interactions of tetracycline and its derivatives include:

• Risk of raised intracranial hypertension is increased if taken with other drugs with the same side effect such assystemicretinoids(acitretin,isotretinoin,alitretinoin)
• Reducedbioavailabilityof tetracyclines with iron, aluminium, magnesium, calcium,rifampicin, celestipol, andanticonvulsants
• Increasedrenaltoxicity智慧h diuretics
• May increaselithiumconcentrations, which can lead to toxicity

Effect on contraceptives

There is little evidence that tetracyclines reduce theefficacyof theoral contraceptive pillunless they cause gastrointestinal upset. However, to be absolutely safe, extra precautions should be taken, particularly in the first four weeks of starting the antibiotics. Discuss this with your doctor.

If youdevelopside effects, advise your doctor. You may need to stop taking the tetracycline or change brand.