How hydrocortisone works
Hydrocortisone (“cortisol”) is produced by the body from cholesterol in the adrenal cortex. The amount of the hormone produced is mainly regulated by hormones of the pituitary gland (hypophysis).
A lot of hydrocortisone is produced, especially in stressful situations, to ensure, among other things, that the body remains efficient. Such stress can result for the body not only from a hectic daily routine, but also, for example, from lack of sleep, addictions and infections.
In any kind of stress, energy reserves are mobilized in the body (i.e. fat is broken down), easily utilizable sugars are formed in the liver, and proteins are broken down more frequently. In addition, the immune system, inflammatory reactions and wound healing, which cost the body a lot of energy, are slowed down.
The concentration peak in the morning is used, for example, when taking oral corticosteroid preparations in order to interfere as little as possible with the natural rhythm. In diabetics, on the other hand, the morning release is associated with elevated blood glucose levels (“dawn phenomenon”).
After its release, hydrocortisone travels through the bloodstream to the various tissues. There it penetrates into the cells and ensures that proteins are increasingly formed that support the stress-related effects described. In order to terminate its effect, hydrocortisone is converted into the inactive, i.e. non-effective, cortisone in some tissues such as the kidney and the intestine.
Therapeutic use is made of both the hormonal effect (taken as a tablet) and the anti-inflammatory and anti-allergic effect (e.g. ointment, cream) of hydrocortisone.
Absorption, degradation and excretion
However, it persists longer in the tissues, where its duration of action is eight to twelve hours.
Hydrocortisone is finally broken down in the liver and then excreted in the urine via the kidneys. Two days after ingestion, 90 percent of the active ingredient has left the body again.
When applied externally, for example as an ointment, only insignificant amounts of the active ingredient enter the bloodstream.
When is hydrocortisone used?
Hydrocortisone is used in the following cases:
- orally as a replacement therapy for a lack of natural hydrocortisone in the body (Addison’s disease)
- externally in inflammatory skin diseases, eczema and psoriasis
- rectally for anal eczema or for the treatment of inflammatory diseases of the lower colon (such as ulcerative colitis, Crohn’s disease)
In this modified form, hydrocortisone shows better penetration and prolonged release when applied to the skin and better water solubility when used as an injection (for acute conditions). The main chemical forms are hydrocortisone acetate and hydrocortisone butyrate.
Depending on the disease, hydrocortisone can be used for short or long term.
How hydrocortisone is used
Hydrocortisone is used either topically – i.e., directly on diseased areas of the body – or systemically – i.e., swallowed or injected, which allows the active ingredient to reach every tissue in the body through the blood.
An eye ointment containing the active ingredient is applied to the conjunctival pocket (after pulling down the lower eyelid) or externally to the edge of the eyelid for a maximum of two weeks, two to three times a day, depending on the doctor’s instructions.
Rectal foam for inflammatory bowel disease is applied once or twice daily at the beginning, then only once every two days after a few weeks.
Systemic use of hydrocortisone is by taking tablets, with dosage mimicking daily blood level fluctuations: Most of the active ingredient is taken in the morning (about two-thirds to three-quarters of the total daily amount), and the remaining amount is taken in the afternoon.
What are the side effects of hydrocortisone?
No side effects are to be expected with short-term, low-dose therapy.
This is different with longer or high-dose therapy, where the so-called “Cushing’s threshold” is exceeded. This is an individually dependent dose of administered corticosteroid above which side effects occur, as they do in Cushing’s disease (pathologically elevated hydrocortisone blood level).
The consequences of exceeding the Cushing’s threshold for a longer period of time can be: Moon face, truncal obesity, bull neck, high blood pressure, high blood sugar, increased thirst and frequent urination, bone loss, muscle breakdown, back and joint pain, delayed wound healing and increased susceptibility to infection.
What should be considered when using hydrocortisone?
Contraindications
If indicated, there is in principle no absolute contraindication apart from a known hypersensitivity to the active substance or one of the other components of the drug – i.e. no circumstance that absolutely precludes the use of the active substance.
Caution is advised if hydrocortisone is used systemically and certain diseases are present at the same time or a vaccination is planned. Your doctor will take this into account when prescribing if you inform him/her.
Drug interactions
Especially when hydrocortisone is taken in higher doses, disturbances in the salt and water balance of the body may occur, for example due to increased potassium excretion.
The blood sugar-increasing effect of hydrocortisone weakens the blood sugar-lowering effect of many diabetes medications.
The effect of coumarin-type anticoagulants such as phenprocoumon and warfarin can also be weakened. Close monitoring of coagulation is recommended, especially at the beginning of use.
The combination of hydrocortisone with non-steroidal anti-inflammatory drugs (NSAIDs), which are often taken as painkillers (e.g. ibuprofen, naproxen, acetylsalicylic acid/ASS, diclofenac) increases bleeding in the gastrointestinal tract.
Hydrocortisone is metabolized with the involvement of the enzyme CYP3A4. Substances that strongly inhibit this enzyme or stimulate its formation (inducers) may therefore enhance or attenuate the effect of hydrocortisone. Examples of strong CYP3A4 inhibitors are:
- antifungal agents (such as ketoconazole, itraconazole, and voriconazole)
- some antibiotics (such as erythromycin, clarithromycin)
- some HIV drugs (such as ritonavir)
Examples of CYP3A4 inducers that may attenuate the effect of hydrocortisone include:
- anti-epileptic drugs (such as phenytoin, carbamazepine, phenobarbital, primidone)
- some antibiotics (like rifampicin, rifabutin)
- some HIV medicines (like efavirenz, nevirapine)
Age restriction
In appropriately adjusted doses, hydrocortisone can be administered at any age.
Pregnancy and lactation
Hydrocortisone may be taken as replacement therapy (substitution therapy) during pregnancy and lactation under medical supervision. If possible, treatment with greatly increased dosages should not be given during this time.
External application of hydrocortisone is also possible in all phases of pregnancy as well as during breastfeeding (excluding the breast area).
How to obtain medication with hydrocortisone
Preparations containing hydrocortisone for oral administration, for injection, for rectal application as a foam or suppository and in concentrations above 0.5 percent require a prescription in all three countries.
How long has hydrocortisone been known?
Hydrocortisone, cortisone and related substances were discovered by the American chemist Edward Calvin Kendall, who received the Nobel Prize in Medicine for them in 1950. Hydrocortisone was marketed as early as 1949 and is now also available as a generic drug.