Corticosteroids are used in pulmonary medicine in treating acute and chronic
asthma, obstructive pulmonary disease in general and in paintings such as
obstructive lung fibrosis.
The steroid therapy is still considered the most effective anti-inflammatory
therapy in the treatment of asthma, leading to resolution or stabilization of
the less severe forms, especially when associated with beta-2-stimulants. The
injectors are used in the acute forms and exacerbations, which are beneficial
when used for short cycles.
Oral therapy, useful in the treatment of chronic forms, should be implemented
with caution in the elderly, often already suffer from osteoporosis, diabetes,
cataracts, hypertension, myopathy, sexual dysfunction.
The adrenal cortex elaborates two types of steroids: glucocorticoids (hydrocortisone
and cortisone) and mineralocorticoids (aldosterone and deoxycorticosterone). The
daily rate of secretion of corticosteroids and their levels in plasma are
summarized below:
STEROIDS and plasma levels
cortisol 5-20 g
1 g corticosterone
aldosterone 3-15 g
dehydroepiandrosterone 65 g
The activities of corticosteroids are numerous, from the metabolic effects to
those on the blood, heart, on the other endocrine organs. Corticosteroids are
molecules with 21 carbon atoms, which is structurally similar to progesterone
and are differentiated with respect to minor changes in the structure, a group
linked to C-OH-21. With these characteristics, and without replacing the C-11 is
present mineralocorticoid activity, with the C11-OH group is observed
glucocorticoid activity. The structural differences obviously affect output,
duration of action, action corticoid significantly.
In the table below are summarized some of the properties, keeping in mind that
steroids carrying a 1-keto group, such as cortisone and prednisone, should be
converted into a 11-hydroxyl molecule in order to exercise their activity (cortisol
or hydrocortisone and prednisolone ): The half-lives are then related to the
initial compounds.
Steroid
Anti-inflammatory activity
Plasma half-life in hours
Biological half-life in hours
Sodium retention (edema)
Short-acting:
hydrocortisone
cortisone
Synthetic analogs have historically originated when it was discovered that the
Mexican potato could get a steroid, and since then has gained increasing
specificity corticosteroids selective biological effectiveness. Specific changes
include:
insertion of a double bond between C1 and C-2 (which converts cortisol into
cortisone, prednisolone and prednisone);
Adding a group to the 6-methyl prednisolone methylprednisolone from which it
originates;
adding fluorine to the C-9 to give fluorocortisone cortisol (which increases the
affinity for gluco-and mineralocorticoid);
addition of OH-to C-16 to give the fluorocortisone triamncinolone, di-CH3 in
position beta to the C-16 to give betamethasone;
add-F to C-alpha triamciclolone to give fluocinolone
addition of betamethasone to give to the C1-beclomethasone
FARMACOLOCIA of corticosteroids in pulmonary
Corticosteroids are lipophilic substances that are well settled and are
clinically effective when given orally, parenterally or topically. Over 90% of
circulating cortisol and its synthetic analogues are bound to plasma proteins.
For the most part are metabolized in the liver before being eliminated. E 'therefore
evident that liver disease or drugs or xenobiotics that alter liver function can
lead to changes in pharmacokinetics.
The main elimination is via the urine, where they are in the form of glucuronide,
sulfate or unconjugated compounds.
Inhaled corticosteroids
Inhaled corticosteroids, which are metabolized quickly, have made possible an
adequate control of asthma with a low risk of side effects than systemic
corticosteroids.
been observed in patients with severe asthma who were using oral corticosteroids,
the introduction of inhaled compounds caused a significant reduction in oral
corticosteroids.
The risk may be caused by inhalation of oropharyngeal candidiasis, cough and
inspiratory disfonia.-A slow pace, gargle and use of spacers in spray dispensers
or use of the device 'jet', however, much lower that risk.
Among the available inhaled corticosteroids in Italy the most widely used, for
efficacy and tolerability is beclometasone. Other corticosteroids include
flunisolide and, more recently, budesonide and fluticasone, but it does not seem
to deliver substantial benefits to fispetto beclomethasone.
Beclomethasone
The compounds are commercially indication is the treatment of bronchial asthma
and obstructive bronchopathy with asthmatic component, both in allergic and
inflammatory diseases of the nasal cavity and nasopharyngeal tract.
Pharmacokinetics
Absorption. After nasal inhalation, is absorbed mainly through the nasal mucosa
with minimal systemic absorption. After oral inhalation, is rapidly absorbed
from the lung and gastrointestinal tract.
Distribution. Distribution is not known when taken intranasally. There is no
evidence of accumulation in the tissues of either beclomethasone or its
metabolites: 10 to 25% (rising to 7% when using the device 'jet') of a single
inhaled dose is deposited in the respiratory tract, the remainder is found in
the oral cavity or oropharynx. The proportion absorbed, 87% bound to plasma
proteins.
Metabolism. Beclometasone is rapidly metabolized by the liver resulting in
monopropionate beclomethasone and beclomethasone alcohol, which have a low
glucocorticoid activity than the parent compound. The fee is inhaled partially
metabolized after absorption through the systemic circulation.
Elimination. The village of beclometasone absorbed into the circulation, and
metabolized by the liver, is excreted as inactive metabolites in both the faeces,
bile, and urine.
Contraindications and precautions
Active or quiescent pulmonary tuberculosis, Herper simplex and individual
hypersensitivity to corticosteroids. Beclometasone is not effective in asthma
attacks in progress.
E 'need to use the beclomethasone in patients who are not using a contemporary
of systemic corticosteroids, since this practice can increase the risk of
suppression of the hypothalamic-pituitary axis. Care must be taken to replace a
preparation administered systemically with another inhaled, as this may lead to
a return of symptoms.
Beclometasone is to be used with caution in patients with tuberculosis, nasal
ulcerations, results of trauma or surgery to the nose or mouth.
The decision to give the drug should be carefully considered in case of
concomitant bacterial infection, viral or fungal infection because there can be
no decrease in the immune response.
And 'finally, to recommend use of the drug is not discontinued, since it
produces optimal effects after about two weeks.
Side Effects
There was no reported serious side effects after use of the product at the
recommended doses.
Occasionally oropharyngeal infection localized in the cable-type fungal (candidiasis),
which usually regress rapidly after local therapy without discontinuing
treatment with antifungals. A few patients have complained of hoarseness and dry
mouth. Systemic side effects are extremely unlikely at the recommended doses,
and patients are still monitored closely during prolonged treatment in order to
promptly establish the possible occurrence of systemic manifestations (osteoporosis,
peptic ulcer, signs of secondary adrenocortical insufficiency, such as
hypotension and weight loss).
Adverse reaction may be particularly serious adrenal insufficiency, in patients
with asthma who can move from systemic treatment than inhaled.
Use and administration
The recommended dose is about 1000 g per aerosol per day, divided into 2-4 times
that, if necessary, can be increased up to 1500-2000 g / day -4 times.
Commercial preparations -
Form of beclomethasone dipropionate aerosol metered Becotide 10 mg, 50 mg
Becotide strong aerosol dosing, 10 mg nasal spray metered Becotide * Bronchial
Turbinal 10 mg dosed aerosols, aerosol dose Clenil FIAC to 0.04%, 5.15 g Clenil
strong spray aerosol metered, Clenil Forte Jet 15.5 g aerosol dosing, 1 g
aerosol spray Clenil determined, Clenil
Jet 1 aerosol measured g * Inalone-A 0.02% gtt Inalone aer-O 0.01 g metered
aerosols, Inalone 0.01 g R-rino spray * Rino Clenil 0.01 g aerosol metered-rino
* Turbinal 0.01 g aerosol metered.
In combination with albuterol (sulfate form): * Clenil Compositum A (0040 g +
0.0964 g) flac-dose aerosol, Clenil Compositum Jet (0010 g + 0020 g) aerosol
metered, Clenil Compositum spray (0010 g + 0020 g) aerosol determined * Flog
Ventolin (0010 g + 0015 g).
With other information are available:
In combination with chlorphenamine: * Fluororinil aerosol f 1 mL, 10 mL nasal
spray.
In combination with phenylephrine: * Rinojet Valeas aerosol metered endo
Flunisolide
Compounds on the market is indicated for the control of the disease and
asthmatic conditions broncostenosi.
Farrnacocinetica
Approximately 50% absorption of the inhaled dose is absorbed through the
systemically. The peak plasma level is detected after 10-30 minutes. After oral
inhalation, approximately 70% of the dose is absorbed from the lung and
gastrointestinal tract. Only 20% of the dose of drug inhaled through the mouth
reaches the systemic circulation unmetabolized due to the substantial hepatic
biotransformation. The action of the drug is generally attained within a few
days, but some patients need up to 4 weeks.
Distribution. Is not sufficiently well described that the distribution takes
place through the intranasal route of administration. Following oral inhalation,
however, is known as the flunisolide is distributed in the lung for about
10-25%, while the remainder is deposited in the mouth and is then swallowed.
There is no evidence that the flunisolide or its metabolites accumulate in any
tissue. The absorbed dose is bound to plasma proteins for about 50%.
Metabolism. Once swallowed, the drug rapidly reaches a biotransformation by the
liver and the gastrointestinal tract, resulting in various metabolites, one of
which, 6-hydroxy-beta, has properties glucocorticoids. The fiunisolide and its
active metabolite can be partially conjugated in the liver (glucuronide or
sulfate), giving rise to inactive metabolites.
Elimination. The flunisolide metabolites are excreted in approximately equal
parts in faeces and urine. The biological half-life is about -2 hours
Contraindications and precautions
The flunisolide should be withheld in patients with an acute state of asthma
because it can worsen the attacks, nor in patients with known hypersensitivity
to any components of the preparation on the market.
The drug should not be administered to patients with tuberculosis or respiratory
infections caused by viruses, fungi, bacteria and because it can mask the
symptoms, both for the immunosuppressive action.
The flunisolide should be used with caution in patients who are administered a
systemic corticosteroid, as this may increase the risk of suppression of the
hypothalamic-pituitary-adrenal axis.
The drug should be used with caution in patients with ulcers of the nasal
mucosa, with results of surgery or trauma to the nose or mouth.
The caution is a must if you want to replace the administration of inhaled with
oral administration, since this may lead to a worsening of symptoms.
Side Effects
The most common side effects, however minor, are charged to the nose and mouth
in the form of irritation, burning, feeling of thick or punctures.
Infrequent headache, anxiety, restlessness. Even more infrequent nausea,
vomiting, dry mouth, watery eyes, rash, flushing, epistaxis, bloody phlegm,
suppression of immunity response.
Use and administration
The recommended starting dose is 500 micrograms 2-3 times daily, up to 2 mg /
day in cases of severe asthma.
After about 15 minutes after flunisolide may be necessary for selected patients,
including the administration of a bronchodilator.
It 'necessary to recommend the patient to keep clean and unblocking the opening
of the inhaler, which sometimes, especially in the elderly, must be equipped
with a special spacer.
It 'should also make sure that does not coexist frequently for signs of
infection of the mucous membranes of the oral cavity, especially of fungal
origin.
E 'to keep in mind that flunisolide is not indicated in acute exacerbations of
seasonal rhinitis, or in those of asthma, but is indicated as an
anti-inflammatory Prince stimulating the synthesis of enzymes to decrease the
inflammatory response by stabilizing leukocyte lysosomal. The flunisolide is
able to suppress the immune response, stimulating the bone marrow, to influence
the metabolism of proteins, lipids, carbohydrates.
The anti-inflammatory and vasoconstrictor power of flunisolide administered
topically inhaled turns out to be 100 times greater than hydrocortisone, and
about the same, the same weight of triamcinolone. His metabolta active,
6-beta-idrossifiunisolide, has 3 times more activity of hydrocortisone.
Commercial preparations
• Gibiflu 0.025% nasal spray * Lunibron-A 0.1% solution aerosol
• Lunis nasal spray 5 mg nasal spray * Syntaris 0.025% nasal spray.
12:42 Syntaris bronchial aerosol solution g * Nisolid Adults flac-dose aerosol
0.1%, Nisolid Children flac-dose aerosol 0.05%.
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