Drugs affecting the immune system

to the tissue of a sensitized macroorganism are called allergic

(hypersensitivity) reactions. Such reactions are relatively common.
There are 2 main mechanism of immunogenesis:
Humoral, that occurs due to antibody production;
Cellular one that involves many immunocompetent cells.
Hypersensitivity reactions can be divided into the following types: immediate types and delayed type of hypersensitivity.

after subsequent exposure to the antigen. It occurs due to

the interaction between antigens and antibodies. Antibodies are produced by plasmocytes. They are fixed on the high-affinity receptors on the cells (mast cells, basophils). Interaction between an allergen and antibodies leads to tissue damage. Biologically active substances release from cells.
Among reactions of immediate type there are allergic bronchospasm, rhinitis, conjunctivitis, urticaria, anaphylaxis, drug-dependent thrombocytopenic purpura, serum sickness, Arthus’s phenomenon and others.

the Antigen with 2 JgЕ on the surface of the

mast cell or basophile is accompanied by:
The opening of Ca-channels and entry of Ca++ into the cell;
Activation of phospholipase A2 with increasing of membrane permeability and formation of prostaglandins and leukotrienes;
Degranulation of mast cells (basophils), release of mediators of allergy (histamine, serotonin, bradykinin) into the surrounding tissue;
Tissue damage, development of swelling, bronchospasm, collapse, skin rashes, itching, etc.

later. It is the result of cell immunity and depends

on the presence of sensitizing T-lymphocytes. On the surface of such T-L there are special receptors which recognize antigens, localized on macrophages, and interact with them. Cytokines release from T-L and damage cells.
Tuberculin reactions, contact dermatitis, graft-versus-host reaction and some types of immune pathology are the result of delayed type of hypersensitivity.

origin of the allergen (plant pollen, medical drugs, certain food

products, animal hair). Avoidance of contact with allergen produces the best result.
Specific hyposensitization may be used. Low doses of the identified allergen are introduced and this decreases the specific sensitivity.
Non-specific hyposensitization may be used if antigen is unknown.

He stimulates 4 main types of histamine receptors.

of histamine and other mediators from sensitized mast cells and

basophils:
Adrenergic agonists (epinephrine, salbutamol, fenoterol);
Dimethylxanthine (aminophylline);
M-blockers (ipratropium bromide)
Specific stabilizers of membranes of mast cells (cromoglicici acid, ketotifen);
Glucocorticoids (Prednisolone, Dexamethasone, Beclomethasone)

allergy) with the tissue receptors:
blockers H1-histamine receptors (diphenhydramine, etc.);
blockers

of LT-receptors (montelucast)
3. Drugs eliminating the symptoms of allergic reactions:
anaphylactic shock - epinephrine, phenylephrine, prednisolone
bronchospasm – salbutamol, fenoterol, aminophylline, ipratropium bromide
4. Drugs reducing inflammation and tissue damage – NSAIDs and SAIDS

β2-AR on the membrane of mast cells and increase activity

of adenylyl cyclase
→increase in cAMP levels
→closing of the Ca channels→ decrease in the number of active Ca in the cell
→inhibition of degranulation of mast cells
→decrease in the release of mediators of Allergy

are administered via inhalers for the relief of bronchospasm (effect

in 2-3 min.). Salmeterol, Formoterol are used orally or via inhalers in order to prevent bronchospasm.
Epinephrine is also used in a case of bronchospasm. It stimulates α-AR and increase blood pressure. Epinephrine is used for relief of anaphylactic shock.

mast cells, inhibit IgE landing on mast cells. They increase

the catecholamines‘ levels and reduce the process of degranulation.
They inhibit phosphodiesterase and increased cAMP level, reduce level of Ca and decrease the process of degranulation.
They also increase the level of T-suppressors and decrease excessive allergic reaction. They have myotropic bronchodilator effect.
Indications for use: -relief of an attack of BA (IV) - prevention of bronchial spasm (tabl.)

of the mast cells→ closing the Ca channels→ Stabilization of

the membranes of mast cells and granules, ↓degranulation.
2. ↓ release of mediators of allergy (histamine, SRS-A).
3. Increases the sensitivity of β2-AR to catecholamines
4. Reduces the need for inhaled corticosteroids.

drug is administered via inhaler.
The onset of action develops

after 2 weeks Pronounced effect develops within 4-5 weeks.
It is poorly soluble in water, it is not absorbed in the digestive tract. It can be used for prevention allergic rhinitis (drops) and food allergic reactions.

mast cells. It also blocks H1-histamine receptors. It decreases the

formation of IgE.
K. is administered orally for the prevention of bronchial asthma attacks, hay asthma, rhinitis and other allergic reactions of the immediate type. The drug acts slowly and reaches its maximum effect in 3-4 weeks.
The adverse effects: sedation, thrombocytopenia.

the body).
They block phospholipase A2, inhibit degranulation and release

of histamine, serotonin and other allergy mediators, reduce the formation of leukotrienes. They reduce the synthesis of histamine, reduce the sensitivity of histamine receptors, increases the metabolism of histamine (promotes the synthesis of histaminase in the liver).
They eliminate such manifestations of allergy symptoms as a decreasing of blood pressure and bronchospasm (symptomatic effect).
Glucocorticoids are used in all allergic reactions of immediate type.

dipropionate,
budesonide, fluticasone propionate

manifests as a reduction of vascular permeability, a decrease in

the mucosal edema of the bronchi, suppression of the secretion of viscous sputum. Bronchodilation occurs due to the blockade of LTD4-R.
It is used orally. Its clinical effect develops slowly (over 24 h). It is used for the prophylaxis of bronchial asthma.
Adverse effects: headache, gastritis, skin allergies, myalgia.

histamine. They do not really affect the release of free

histamine or histamine synthesis.
They remove such effects of H. as increase in smooth muscle tone of bronchi, intestine, uterus; decrease in blood pressure, increase in capillary permeability followed by edema; hyperemia and pruritis.

quifenadin, mebhydrolin
2 generation: loratadine, astemizole, cetirizine.
3 generation

(active metabolites of the 2nd ): desloratadine, fexofenadine, levocetirizine, ebastine.

for relief of anaphylactic shock: epinephrine, prednisone, diphenhydramine.

in fats, pass through the BBB, have central effects. Their

action begins during 20-60 minutes, duration of action is on average 4-6 hours (clemastin -12 hours). They are administered orally and parenterally.
But! mebhydrolin does not pass through the BBB, does not have a sedative effect. It acts 24-48 hours.

and do not have a sedative effect.
They are prescribed orally,

the action begins in 1-2 hours, lasts 20-24 hours (astemizol-48 hours).
They're cardiotoxic.
Some drugs of the 3rd generation are the active metabolites of the drugs of the 2nd generation. Their effect does not depend on metabolism.

before anesthesia;
fever with antipyretics;
vestibular disorders (motion sickness)

decrease in speed of psychomotor reactions, discoordination of movements
Diphenhydramine can

cause excitement (in children and the elderly even in a therapeutic dose)
Headache, dizziness, dry mouth (M-blocking effect of promethazine and chloropyramine)
Increase of appetite, increase in the body weight
A decrease in the efficiency of the drugs of I generation

hypesensitivity
Drugs suppressing immunegenesis (Immunosuppressants):
Glucocorticoids (prednisolone, etc.)
Cytotoxic agents

(azathioprine, 6-mercaptopurine, cyclophosphamide,)
Antibiotics (cyclosporine, tacrolimus)
2. Drugs diminishing tissue damage: SAID, NSAID

proliferation (especially T-L). Antigen recognition is also suppressed. Activity of

macrophages is decreased. The production and activity of interferon and a number of interleukins are reduced. Cytotoxicity of some T-L population (T-K) is decreased. The formation of migration inhibitory factors is suppressed. Large doses provide lowing of specific antibody production and anti-body complex formation. Glucocorticoids have anti-inflammatory effect also. They are used for the treatment of collagenosises.

and activity of immune cells, inhibit the immunopathological mechanisms for

the development of connective tissue.
Indications: rheumatoid arthritis; lupus erythematosus and other diseases of connective tissue (reserve drugs).
Complications: hematotoxicity, hepatotoxicity, nephrotoxicity, teratogenicity.

disrupts the metabolism of purines. It inhibits the proliferation of

tumor cells.
It has an immunosuppressive effect in low doses, inhibits the proliferation of t-lymphocytes and their activity.
Indications: Autoimmune diseases, organ transplantation (reserve medicine).
Side effects: inhibition of bone marrow function, leucopenia, anemia, thrombocytopenia, excessive bleeding, nausea, vomiting, diarrhea, jaundice.

reduces the differentiation and activity of T-lymphocytes, inhibits the activity

of T-helpers, but keeps the activity of T-suppressors, promotes natural immunosuppression. It suppresses the rejection of transplanted tissues and organs. The drug reduces production of IL-2 and gamma interferon.
Indications: Organ transplantation; autoimmune diseases (rarely)
Side effects: Hepato-and nephrotoxicity.

It is 100 times more active than Cyclosporine.
Indications: organ transplantation
Side

effects: nephrotoxicity; neurotoxicity; increased blood sugar levels; increased blood pressure

Taktivin
Preparations of interferons (α,β,γ),
Adaptogens: Immunal (preparation of Echinacea), preparations of

Chinese Magnolia vine, Ginseng
Synthetic drugs: Levamizol, Dibazol, Methyluracil, Azoximer bromide (Polyoxidonium)

activity of immunocompetent cells (T-and B-lymphocytes and macrophages); production of

cytokines, antibody formation.
They stimulate non-specific immunity: increase the production of interferon, lysozyme, phagocytosis completeness, complement system activity.

therapy
Leukopenia
Poorly healing wounds and ulcers
Immunodeficiency after the use of antibiotics,

glucocorticoids

of T-and b-lymphocytes,
Normalize the reaction of cellular immunity,
Increase

phagocytosis
Stimulate the production of lymphokines.

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