AntiAllergy and

Immunosupresive Drug
Ratih Pramuningtyas
 Allergy

Represents a sensitivity
to a specific substance,
called an allergen, that
is contacted through
the skin, inhaled into
the lungs or injected.
 The prevalence of allergic diseases
and asthma is escalating.

• Approximately 30 to 40 percent of the world’s

population suffers from allergic diseases.
• An estimated 300 million individuals worldwide have
asthma, and this is likely to increase to 400 million by
the year 2025.*
• Allergic rhinitis, a risk factor for asthma, affects 400
million people annually, and food allergies affect 200
to 250 million.
• The number of avoidable deaths from asthma
occurring every year is estimated at 250,000.*
 Type of Allergy Reaction
• Tipe 1 • Tipe 2
Humoral
cytotoxic
Anafilaksis
imun
responese

Delayed
Antigen-
tipy
antibody
hipersensi complex
tivity
• Tipe 4 • Tipe 3
General principles of prevention and treatment
of allergic reactions

Avoiding contact with the allergen

Performing specific desensitization

Performing nonspecific desensitization through administration
of drugs which depress immune reactions (immune
depressants).
Using antiallergic drugs which are able to prevent releasing the
mediators of allergic reactions

Symptomatic treatment
 Directions of therapy of hypersensitivity
reactions of immediate type
1. Antiallergic drugs :
– antihistamine drugs – block receptors with which
histamine binds in the tissues
– drugs which stabilize membranes of mast cells
and basophiles and slow down releasing of
mediators of hypersensitivity reactions
2. Drugs which decrease damage of the tissues:
– Glucocorticosteroids.
3. Drugs of symptomatic treatment
– Adrenalin;
– euphyllin.
 Antihistamin
• Histamine is a low-molecular-weight amine derived
from L-histidine that is produced throughout the
body

cellular growth and proliferation

histamine
affects modulates inflammation

as a neurotransmitter
 Reseptor Histamin
• H1 receptors are found on neurons, smooth
muscle, epithelium and endothelium, and
multiple other cell types
• H2 receptors are located in the gastric mucosa
parietal cells, smooth muscle, epithelium and
endothelium, heart, and other cell types as well
• H3 receptors are found primarily on
histaminergic neurons
• H4 receptors are highly expressed in bone
marrow and on peripheral hematopoietic cells
 Efek Histamin

Vaskular Jantung Paru

• Vasodilatasi • ↓ Konduksi AV • bronchoconstriction;

• Vasokonstriksi • Inotropik (+) • increased mucus
koroner viscosity
• ↑permeabilitas  • stimulation of vagal
edema sensory nerve
endings  cough
and bronchospasm
 Efek Histamin

Cutaneous nerve
Gastrointestinal
ending
• acid, fluid and • Pain
pepsin secretion • Itching
• increased
intestinal motility
and secretions
 Antihistamin

Sedating, first-
generation h1
antihistamines
Antihistamin H1
Low-sedating,
Antihistamin second-generation
h1 a antihistamines
Antihistamin H2
 Pharmacological characterization of
antihistamine drugs of the first generation
• Effect occurs within 15-20 min. after administration.
• Penetrate through blood/brain barrier (lipophilicity)
and block H1-receptors of CNS, and as a result, cause
sedation and reduce coordination of attention
(contraindicated in occupations related to
concentration).
• Have short duration of action, as prescribed 3-4 times
per day.
• Prolonged use develops tachyphylaxis (reduced
therapeutic efficiency). Therefore is necessary to
replace one drug of another drug from this group every
7-10 days.
Antihistamin H1
H1 Antihistamin
H1 Antihistamin
Side effects of Н1-histamine receptors blockers
of 1st generation
• Depression of CNS (disorders of coordination,
increased tiredness, dizziness, diplopia,
tremor, euphoria, nervousness, insomnia).
• Disturbance of GI functioning
• dryness of mucous membranes, eye disorders
- blurred vision, impotence, tachycardia,
headache, psychosis.
• tachyphylaxis.
H2 Antihistamin
 Pharmacological characterization of
antihistamine drugs of the second generation

• High specificity and affinity to Н1-receptors.

• Non penetrable through blood/brain barrier in
therapeutic doses (have not sedative action).
• Absence of blockade of other types of receptors ( M-
cholino-, Serotonin-receptors)  That way don’t
increase of appetite and body weight, don’t cased by
dry mouth, blurred vision, constipation, urinary
retention.
• Absence of tachyphylaxis. Can be administered for a
long time (up to 1 year).
 Side effects of Н1-histamine receptors
blockers of the second generation
• Drugs are metabolized by CYP- 450 enzymes
(Terfenadine and Astemisole) .
In patients with liver diseases, in case of higher daily
doses, with administration of drugs that also are
metabolized by CYP- 450 enzymes can cause ventricular
tachycardia.
• Examples of such drugs:
– Macrolides (erythromycin, clarithromycin)
– Antifungal drugs (intraconazole, ketaconazole).
– Drugs are contraindicated during pregnancy and
lactation.
 Mast Cell Stabilizers

• Sodium Cromoglycate (Intal, Nasalcrom)

• Nedocromil (Tilade)
 Mechanism of action
• They block a calcium channel essential for mast
cell degranulation,
• stabilizing the cell and thereby preventing the
release of histamine and related mediators.
• One suspected pharmacodynamic mechanism is
the blocking of IgE-regulated calcium channels.
• Without intracellular calcium, the histamine
vesicles cannot fuse to the cell membrane and
degranulate
 Indications for use
• Treatment of bronchial asthma ( As inhalers to
prevent asthma attack), Allergic rhinitis (as
nasal sprays), Allergic conjunctivitis (as eye
drops).
• Drugs only help prevent them - and they work
best if and only if you use their regularly, and
if you start using it well before (like 2-4 weeks
before) the beginning of the season for your
particular allergens.
GLUCOCORTICOIDS
 Pharmacological Actions
• Direct (Intended) Actions
– Anti-inflammatory
– Anti-allergy
– Anti-immunity
• Permissive Actions
– Lipolytic effects
– Effect on bp
– Effect on bronchial muscles
(e.g.,sympathomimetic amine)
 Pharmacological Actions
• Negative feedback mechanism (HPA Axis)
• Glucocorticoids (e.g., prednisolone) used to
suppress inflammation, allergy and immune
responses.
• Anti-inflammatory therapy is used in many
illnesses (e.g., RA, and skin inflammations).
• Striking improvements can be obtained, but
severe adverse, but highly predictable, effects
are ensue.
 The Mighty Corticosteroids
Perceived threat Infection
Corticosteroids

Tissue injury Adaptive immune Innate immune

system system
Corticosteroids

Leukocyte & endothelial cell activation

Corticosteroids

Corticosteroids Inflammatory mediators

Inflammation (redness, edema,

warmth, pain, tissue destruction)
 Hypothalamopituitary adrenal (HPA) axis: Negative
Feedback Immune
Stress system:
Circadian altered
rhythm Hypothalamus
Muscle:
CRH Net loss of amino
Posterior Acids (glucose)
Anterior Pituitary Gland
Pituitary Gland Liver:
(-) Deamination of
proteins into amino
ACTH acids,
gluconeogenesis
Glucocorticoids,
Adrenals Catecholamines, (glucose)
etc.. Fat Cells:
Free fatty
acid
Kidney mobilization

Heart rate:
Increased
 Some Corticosteroids
Relative Anti- Relative Salt-
Inflammatory Retaining
Agent Forms Available Activity Activity
Cortisol (hydro- Oral, parenteral,
topical
1 1
cortisone)

Cortisone Oral 0.8 0.8

Prednisone Oral 4 0.3

Oral, injectable,
Triamcinolone topical, inhaled
5 0

Oral, injectable,
Dexamethasone topical
30 0

Fludrocortisone
Oral 0 250
(mineralocorticoid)
Efek samping
Immunosupressan
• Imunosupresan adalah kelompok obat yang
digunakan untuk menekan respon imun
• Sebagain dari kelompok ini bersifat sitotokis
dan digunakan sebagai antikanker
• Immunosuppressants are characterized by
1. a low therapeutic index (narrow window
between the therapeutic and toxic range) and
2. intra- and interindividual variation of the
pharmacokinetics of these agents
 1. Mycophenolate mofetil (MMF)
• MMF is commonly used in synergistic and safe
combination with CsA and corticosteroids.
• MMF is a semisynthetic derivative of MPA.
• It is a potent reversible ,selective
• Noncompetitive inhibitor of the enzyme inosine
monophosphate dehydrogenase
• Blocking the de novo formation of GMP
Deprivation of proliferation T and B-cell of nucleic
acid
 Farmakokinetik
• It used orally or I.V but the bioavailability after
oral application in general is rapid .

• It is highly bound to plasma proteins .

• It is mainly metabolized in the liver and

excretion by Kidney
 Kontraindikasi

Hamil Menyusui Riw Alergi

Anak-anak Orang tua

 DRUG INTERACTIONS:
Improves the action Reduced the action
Cyclosporine magnesium hydroxide
voriconazole Aluminium hydroxide
steroids Cholysteramine
calcineurin inhibitors Oral contraceptives
FK506
tacrolimus
Azathioprine
allopurinol
Mechanism of action MMF
 2. Methotrexate
• Antimetabolite agent with antiinflamatory
properties and possibly immunosupressive
effect
• Digunakan sebagai obat tunggal atau
kombinasi dengan siklosporin dalam
mencegah
– penolakan transplantasi.
– penyakit autoimun dan peradangan tertentu.
– psoriasis yang sudah refrakter terhadap obat lain
• Methotrexate is an analog of folate that
competitively and irreversibly inhibits
dihydrofolate reductase
• Mechanism of action  Inhibits DNA
synthesis by competitively and irreversibly
inhibiting enzyme, dihydrofolate reductase
(DHFR) which converts dihydrofolate to
tetrahydrofolate essential for DNA synthesis
 Farmakokinetik
• Oral methotrexate is absorbed rapidly
through the gastrointestinal tract
• Methotrexate is eliminated chiefly by the
kidneys, with 60%–95% excreted unchanged
Monitoring
Kontraindikasi
 3. Azatioprine
• Azathioprine is a synthetic analog of natural
purine bases used in RNA and DNA synthesis
• Azatioprin dalam tubuh diubah menjadi 6-
merkaptopurin (6-MP) yang merupakan
metabolit aktif dan bekerja Menghambat
sintesis de novo purin
• In dermatology, azathioprine is used chiefly
as a steroid-sparing agent for
immunobullous disorders
Mechanism of action
 Pharmacological effects:
• Azathioprine is antiproliferative and
affects predominantly rapidly dividing
cells such as precursor cells in the bone
marrow.
• Azathioprine has strong
antiinflammatory properties. It reduces
the numbers of circulating monocytes
by inhibition of proliferation.
 Interaksi
• Penggunaan bersama allopurinol menyebabkan
hambatan Xantin oksidase yang juga merupakan
enzim penting dalam metabolisme 6-
merkaptopurin,sehingga kombinasi Ini
meningkatkan toksisitas azotioprin dan
merkaptopurin
• Derivatives of benzoic acid can inhibit the TPMT
pathway.
• sulfasalazine and salicylic acid derivatives inhibit
TPMT activity and can therefore augment
azathioprine action.
 Pharmacokinetics:

Absorption : Rapidly absorbed orally

within 1-2 hours after administration
Distribution : Distributed in all tissues
but does not cross the blood–brain
barrier.
TERIMA KASIH