Corticosteroids Chemische Eigenschaften,Einsatz,Produktion Methoden
Verwenden
Corticosteroids, synthetic steroid drugs made from the natural hormone hydrocortisone, and
particularly prednisone, are frequently used for combination therapy for treating severe and
chronic lymphocyte leukemia, Hodgkin’s and non-Hodgkin’s lymphomas, multiple
myeloma, and breast cancer. Corticosteroids exhibit an antitumor effect by binding with corticosteroid receptors that exist in many cancerous lymphoma cells, which leads to inhibition
of both glucose transport and phosphorylation, which reduces the amount of energy necessary for mitosis and protein synthesis, which, accordingly, leads to cell lysis.
Indications
A major breakthrough in asthma therapy was the introduction
in the 1970s of aerosol corticosteroids. These
agents maintain much of the impressive
therapeutic efficacy of parenteral and oral corticosteroids,
but by virtue of their local administration and
markedly reduced systemic absorption, they are associated
with a greatly reduced incidence and severity of
side effects. The success of inhaled steroids has led to a
substantial reduction in the use of systemic corticosteroids.
Inhaled corticosteroids, along with β2-adrenoceptor
agonists, are front-line therapy of chronic asthma.
Pharmakologie
All corticosteroids have the same general mechanism of
action; they traverse cell membranes and bind to a specific
cytoplasmic receptor. The steroid-receptor complex
translocates to the cell nucleus, where it attaches to nuclear
binding sites and initiates synthesis of messenger ribonucleic
acid (mRNA). The novel proteins that are
formed may exert a variety of effects on cellular functions.
The precise mechanisms whereby the corticosteroids
exert their therapeutic benefit in asthma remain
unclear, although the benefit is likely to be due to several
actions rather than one specific action and is related to
their ability to inhibit inflammatory processes.At the molecular
level, corticosteroids regulate the transcription of
a number of genes, including those for several cytokines.
The corticosteroids have an array of actions in several
systems that may be relevant to their effectiveness
in asthma. These include inhibition of cytokine and
mediator release, attenuation of mucus secretion, upregulation
of β-adrenoceptor numbers, inhibition of
IgE synthesis, attenuation of eicosanoid generation, decreased
microvascular permeability, and suppression of
inflammatory cell influx and inflammatory processes.
The effects of the steroids take several hours to days to
develop, so they cannot be used for quick relief of acute
episodes of bronchospasm.
Clinical Use
The corticosteroids are effective in most children and
adults with asthma. They are beneficial for the treatment
of both acute and chronic aspects of the disease.
Inhaled corticosteroids, including triamcinolone acetonide
(Azmacort), beclomethasone dipropionate (Beclovent,
Vanceril), flunisolide (AeroBid), and fluticasone
(Flovent), are indicated for maintenance treatment of
asthma as prophylactic therapy. Inhaled corticosteroids
are not effective for relief of acute episodes of severe
bronchospasm. Systemic corticosteroids, including prednisone
and prednisolone, are used for the short-term
treatment of asthma exacerbations that do not respond
to β2-adrenoceptor agonists and aerosol corticosteroids.
Systemic corticosteroids, along with other treatments,
are also used to control status asthmaticus. Because of
the side effects produced by systemically administered
corticosteroids, they should not be used for maintenance
therapy unless all other treatment options have been
exhausted.
A fixed combination of inhaled fluticasone and salmeterol
(Advair) is available for maintenance antiinflammatory
and bronchodilator treatment of asthma.
Nebenwirkungen
The side effects of corticosteroids range from minor to
severe and life threatening. The nature and severity of
side effects depend on the route, dose, and frequency of
administration, as well as the specific agent used. Side
effects are much more prevalent with systemic administration
than with inhalant administration.The potential
consequences of systemic administration of the corticosteroids
include adrenal suppression, cushingoid
changes, growth retardation, cataracts, osteoporosis,
CNS effects and behavioral disturbances, and increased
susceptibility to infection. The severity of all of these
side effects can be reduced markedly by alternate-day
therapy.
Inhaled corticosteroids are generally well tolerated.
In contrast to systemically administered corticosteroids,
inhaled agents are either poorly absorbed or rapidly
metabolized and inactivated and thus have greatly diminished
systemic effects relative to oral agents. The
most frequent side effects are local; they include oral
candidiasis, dysphonia, sore throat and throat irritation,
and coughing. Special delivery systems (e.g., devices
with spacers) can minimize these side effects. Some
studies have associated slowing of growth in children
with the use of high-dose inhaled corticosteroids, although
the results are controversial. Regardless, the
purported effect is small and is likely outweighed by the
benefit of control of the symptoms of asthma.
Corticosteroids Upstream-Materialien And Downstream Produkte
Upstream-Materialien
Downstream Produkte
