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Lecture №14
• Pathologically excessive immune
responses to an antigen that cause
damage to the tissues of a sensitized
macroorganism are called allergic
(hypersensitivity) reactions.
• Two mechanisms of immunogenesis
participate in the development of
different types of allergic reactions -
humoral, that occurs due to antibody
production, and the cellular one that
involves many immunocompetent cells.
Hypersensitivity reactions can be
divided into the following types:
• IMMEDIATE TYPE OF
HYPERSENSITIVITY (allergy) is
manifested minutes or
hours after subsequent exposure
to the antigen.
• DELAYED TYPE OF
HYPERSENSITIVITY (becomes
apparent after 2-3 days and
later).
In the development of many
immediate type allergic reactions an
important role is played by the mast
cells and basophils that release such
biologically active substances as
histamine, «slow reacting substance
of anaphylaxis» (SRS-A), bradykinin,
serotonin, prostaglandins, platelet
activating factor (PAF), etc.
Allergic bronchospasm, rhinitis,
conjunctivitis, urticaria, anaphylaxis,
drug-dependent thrombocytopenic
purpura, serum sickness, Arthus's
phenomenon and some other
conditions can develop with
immediate hypersensitivity.
Arthus's phenomenon
• glucocorticosteroids,
• cromolyn sodium and ketotifen,
• substances with β-adrenomimetic
activity (epinephrine, etc)
• aminophylline
Drugs blocking the interaction of the
free histamine with the tissue receptors
sensitive to it. Antihistamine drugs.
Histamine H1-receptor Blockers
Promethazine,
Chlorpheniramine,
Diphenhydramine,
Dimenhydrinate,
etc
SECOND GENERATION
ANTIHISTAMINICS
Fexofenadine,
Loratadine,
Desloratadine,
Cetirizine,
Mizolastine,
Ebastine,
Rupatadine,
etc.
In hypersensitivity reaction
of the delayed type two
groups of preparations are
commonly used:
Drugs suppressing immunogenesis
CALCINEURIN INHIBITORS (Specific T-
cell inhibitors)
Cyclosporine,
Tacrolimus
M-TOR (mammalian target of
rapamycin) INHIBITORS
Sirolimus,
Everolimus
Drugs suppressing immunogenesis ALKYLATING AGENTS
Cyclophosphamide,
Chlorambucil,
Carmustine,
Lomustine,
Dacarbazine,
etc.
Drugs suppressing immunogenesis ANTIMETABOLITES
Azathioprine,
Methotrexate,
6-Mercaptopurine,
Fludarabine,
Cytarabine,
etc.
Drugs suppressing immunogenesis BIOLOGICAL AGENTS
Infliximab,
Adalimumab,
Daclizumab,
Basiliximab,
etc.
Drugs suppressing immunogenesis ANTIBIOTICS
Dactinomycin),
Doxorubicin,
Epirubicin,
Bleomycins,
etc.
Dose: 15 µg/kg
i.v. daily for 5
days.
ADVERSE EFFECTS
• vomiting,
• stomatitis,
• diarrhoea,
• erythema and desquamation of skin,
• alopecia,
• bone marrow depression.
• ANTIHISTAMINES BLOCKING H1-
RECEPTORS remove or lower the
following kinds of histamine effects:
increase in smooth muscle tone of
bronchi, intestine, uterus; decrease
in arterial blood pressure (partially);
increase in capillary permeability
followed by edema; hyperemia and
pruritis in cases of intradermal
histamine introduction or
endogenous histamine release in
the skin.
• These substances do not affect
DIPHENHYDRAMINE was first made by
George Rieveschl and came into
commercial use in 1946.
• DIPHENHYDRAMINE is an antihistamine
mainly used to treat allergies.
• It is also used for insomnia, symptoms
of the common cold, tremor in
parkinsonism, and nausea.
• It is used by mouth, injection into a
vein, and injection into a muscle.
• Maximal effect is typically around two
hours after a dose, and effects can last
for up to seven hours.
These drugs are given orally, subcutaneously,
intramuscularly and intravenously. When
administered for oral use, the substances that have
an irritating effect on the stomach (promethazine,
quifenadine) should be given after meals
• This group of preparations is used
mainly for the treatment of allergic
damage to the skin and mucosal
membrane: urticaria, angioneurotic
edema, hay fever, rhinitis and
conjunctivitis.
• They may occur as a result of the
allergic conditions caused by
antibiotic therapy or other drugs.
They show low efficacy in cases of
bronchial asthma and anaphylactic
shock (in the latter the drug of choice
is epinephrine).
Blockers of histamine H1-receptors
suppressing CNS are sometimes used for
the purpose of hypnotic and sedative
effect (for example, diphenhydramine),
but rarely in parkinsonism, chorea,
vomiting during pregnancy or vestibular
disorders.
It is not recommended that the drugs
with sedative properties be taken during
working hours by people whose
occupation requires a lot of attention or
quick reactions (transport workers, etc).
In this case it is advisable that loratadine.
• As a rule, blockers of histamine H1-
receptors are well tolerated.
• Application of some preparations
possessing M-cholinoceptor blocking
activity may be accompanied by
dryness of the oral mucosa.
• Diphenhydramine, promethazine and
chloropyramine may cause a hypnotic
effect and drowsiness.
DRUGS STIMULATING (NORMALIZING)
IMMUNE REACTIONS are used in the
complex therapy of immunodeficiency
conditions, chronic infections and
malignant tumors.
Biogenic substances (preparations of
thymus, interferon, interleukin-2) and
synthetic compounds (for example,
levamisole) are available as
immunostimulators.
• INTERFERONS, which belong to the group
of cytokines, provide antiviral,
immunostimulating and antiproliferative
effects. They are divided into α-, β- and γ-
interferons, with γ -interferon having the
most apparent influence on the immune
system.
• The immunotropic action of interferons is
manifested by the activation of
macrophages, T-lymphocytes and natural
killer cells.
Preparations of natural interferon
obtained from human donor blood
(interferon , interlock) as well as
recombinant interferons (REAFERON ,
INTRON-A, BETAFERON) are
manufactured.
They are used for the treatment of a
number of viral infections (for instance,
influenza, hepatitis) and in some
neoplastic diseases (myeloma, B-cell
lymphoma).
Indications and Usage for Betaseron
BETASERON (interferon beta-1b) is indicated
for the treatment of relapsing forms of
multiple sclerosis to reduce the frequency of
clinical exacerbations. Patients with multiple
sclerosis in whom efficacy has been
demonstrated include patients who have
experienced a first clinical episode and have
MRI features consistent with multiple
sclerosis.
BCG (bacillus Calmett-Gueren, it is a non-
pathogenic bacillus of tuberculosis that
produces tuberculinis) used for
vaccination against tuberculosis.
Nowadays this preparation is sometimes used
in the complex therapy for a number of
malignant tumors.
BCG (bacillus Calmett-Gueren) stimulates
macrophages and, apparently, T-lymphocytes.
Some favorable effects have been noted in
acute myeloid leukemia, certain types of
lymphoma (those which are not related to
Hodgkin's lymphoma), intestinal and breast
cancer, superficial cancer of the bladder.