This document discusses steroidal anti-inflammatory drugs, specifically glucocorticoid hormones. It describes the effects of glucocorticoids on various body systems and metabolic processes, including carbohydrate, protein and lipid metabolism, as well as water and electrolyte balance. It also discusses the anti-inflammatory, anti-allergic, and immunosuppressive mechanisms and effects of glucocorticoids. Finally, it outlines the indications, tactics, complications, contraindications of glucocorticoid therapy.

1. Steroidal anti-inflammatory drugs
LECTURE № 10

2. Steroidal anti-inflammatory drugs - drugs
are glucocorticoid hormones
Biogenic drugs glucocorticoid
hormones have little
mineralocorticoid activity
and, therefore, cause a delay
of salt and water in the body.
Currently, the synthetic
hormones, which have only
glucocorticoid activity:
They are almost completely
devoid of mineralocorticoid
activity.
Glucocorticoids

3. Glucocorticoids are released in response to stress, adapting
organism mobilizing and increasing its resistance.
Therefore, glucocorticoids have diverse effects on all types
of metabolism: protein, carbohydrate, fat.
Glucocorticoid effects on carbohydrate
metabolism:
 in the liver stimulates the synthesis of glucose from
amino acids (gluconeogenesis), protein synthesis in
the liver and kidneys is reduced;
 reduced absorption, assimilation and utilization of
blood glucose (hyperglycemia), decreased
resorption of carbohydrates in the digestive tract.
Effect of glucocorticoids on protein metabolism:
 Glucocorticoids enhance the mobilization of amino
acids from tissues, especially skeletal muscle, and
inhibit protein synthesis, particularly in the bones
(osteoporosis)

4. Glucocorticoid effects on lipid metabolism:
 Glucocorticoids play a "resolution" role in the mobilization
of fat from the depots. With prolonged use of hormones is a
redistribution of fat.
 In some tissues there is a strengthening process of lipolysis
(limbs), while increasing the amount of free fatty acids in
blood plasma
 In other tissues, there is a strengthening process of
lipogenesis (upper torso, his face - "moon face, neck -"
buffalo hump "). In the blood there hypercholesterolemia.
Glucocorticoid effects on water and electrolyte metabolism:
 Natural and the first synthetic glucocorticoids have little
sodium delayed, as well as calcium and potassium deducing
action. Therefore, when assigning a patient large doses (300
mg / day) there is sufficient sodium retention. New synthetic
analogues of natural glucocorticoids do not possess this
activity and even, on the contrary, can cause significant loss
of sodium ions in the urine.
Glucocorticoid effects on the blood system
 Glucocorticoid hormones induce rapid lysis of lymphoid
tissue and lymphopenia in the background of a general
leukocytosis. A reduction in the number of eosinophils.
 Glucocorticoid promotes platelet and red blood cells.

5. Effect of glucocorticoids (GC) on inflammation
The mechanism of anti-inflammatory action
 GC stabilizes cell membranes and lysosomes (membrane
stabilizing effect), thereby limiting the output of these
enzymes, resulting in tissue damage
 GC enhance the synthesis of lipomoduline - endogenous
inhibitor of phospholipase A-2, inhibiting its activity this.
Phospholipase A-2 facilitates the mobilization of arachidonic
acid from phospholipids of cell membranes and the
formation of the acid metabolites (prostaglandins and
leukotrienes), which play a key role in inflammation.
 GC stimulates the synthesis of intercellular substance -
hyaluronic acid, which lowers the permeability of the
vascular wall. The decrease of exudation are also
associated with decreased secretion of histamine, as well as
change the sensitivity of adrenergic receptors to
catecholamines (adrenaline). Vascular tone increases as
permeability decreases.
 Inhibition of glucocorticoid-proliferation associated with a
reduction in protein synthesis and a decrease in revenue of
leukocytes into the tissues. Restriction occurs chemotaxis,
spontaneous migration.
 Thus, corticosteroids have no effect on the cause of
inflammation, so their anti-inflammatory activity is
nonspecific and is observed both at the system, and at the
local to use them.
 In this case, GC inhibit all three phases of inflammation
(alteration, exudation, proliferation).

6. Antiallergic and immunosuppressive
action of glucocorticoids
 GC cause both absolute and relative T-
lymphocytopenia, i.e. inhibit cell-mediated
immunity.
 GC inhibit the reaction of graft rejection as well
as suppress the delayed-type hypersensitivity
reaction.
 At the same hormones in this group do not
alter the production of antibodies of B-
lymphocytes, as well as the formation of
immune complexes.
 GC inhibit the activity of phagocytes and
digestive function microphages and
macrophages.
 Immunosuppressive effect of GC associated
with the action at various stages of the immune
response contributes to the susceptibility of the
organism to a variety of bacterial, fungal, viral
and parasitic infections.

7. Indications for use drugs glucocorticoids:
1. As a means of substitution therapy in
adrenal insufficiency (Addison's disease) in
combination with mineralocorticoids.
2. As a means of anti-inflammatory
therapy:
 at Collagenose (diffuse connective tissue
diseases such as rheumatism, rheumatoid
arthritis, ankylosing spondylitis, systemic
lupus erythematosus);
 - In severe forms of glomerulonephritis;
 - In severe forms of hepatitis;
 - In eye diseases of inflammatory etiology
(interstitial keratitis, conjunctivitis, iritis,
iridocyclitis, sympathetic ophthalmia, etc.);
 - Skin diseases (inflammatory dermatoses,
eczema, psoriasis, etc)
3. As a means of anti-allergic therapies:
- Asthma;
- with autoimmune hemolytic anemia,
thrombocytopenia.
4. In order to reduce the permeability of
vascular walls and membranes in general:
- acute swelling of the brain and lungs;
- at toxic and toxic-septic form of pneumonia
(particularly children);
- toxic, toxic-septic gastrointestinal lesions of
staphylococcal and viral etiology;
- for the treatment of shock (any).
5. With the purpose of influencing the blood
system:
- with anemia, thrombocytopenia;
- with lymphoid leukemia, lymphoma;
- To suppress the reaction of graft rejection in
transplantation of organs and tissues.

8. The tactics of therapy with glucocorticoids
By the time of treatment are two types of therapy, GC:
 Short-term (intensive) glucocorticosteroid therapy.
Drugs are introduced singly or within a few days.
 Use of GC in case of emergency allows us to treat
them as ordinary drugs.
 Long-term (maintenance) glucocorticosteroid
therapy. This type of therapy used in the treatment of
patients with subacute or chronic disease course,
with exacerbation of chronic disease.
Prolonged use of GC is only justified in cases of
severe pathology.
When you assign a tablet dosage forms need to be
considered chronobiological features and regularities.
We must strive to administration of drugs through the
day, which reduces the risk of adrenal suppression
and non-specific resistance to infection.
In the case of inadmissibility of such a method of
administration, it is best to introduce single daily dose
in the morning.

9. Complications, side effects of
glucocorticosteroid therapy
 The phenomenon of hyperglycemia ("steroid diabetes")
 Reduction of protein synthesis, which occurs in the form
- Muscle pain, increased muscle fatigue;
- Osteoporosis;
- Delayed wound healing;
- Teratogenic effects;
- The backlog of children in the development and growth (when
using GC for six months or more);
- Reducing the absorbability (suffers gastric mucosa) of calcium
and phosphorus, which in children leads to rickets;
- Exacerbation or appearance of new expressions of intestinal
mucosa (inhibition of proliferation);
cataract and cataract development.
 Especially with prolonged use GC in children;
increased irritability in children;
AP increase, the delay of salt and fluids, especially among
teenagers;
Redistribution of fat ("moon face", "buffalo hump");
Decrease in immunity, immunosuppressive effect, which occurs
increasing frequency of colds.
May develop a withdrawal syndrome, particularly when abrupt
cancellation of drugs (adrenal insufficiency). Therefore,
after long-term use of glucocorticoids, the dosage should
be reduced very slowly.

10. Contraindications to corticosteroids:
 Diabetes mellitus
 Osteoporosis
 Pregnancy
 Peptic ulcer disease
 The presence of wound healing
 Hypertonic disease
 Epilepsy

11. Thank you for your attention!