The document summarizes drug treatments for allergies. It discusses how allergies result from an overreaction of the immune system to harmless substances. It then describes the main types of allergies and their symptoms. The document outlines the pathophysiology of allergies and the mechanisms of several classes of anti-allergy drugs, including antihistamines, corticosteroids, leukotriene inhibitors, thromboxane inhibitors, cytokine inhibitors, cromolyn, theophylline, decongestants, and anticholinergics. It concludes by mentioning some novel immunotherapy approaches targeting specific proteins or mediators involved in different types of allergies.
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drug treatment of allergy.pptx
1. BY
MSc. student: Dua'a N. GHazy
Department Of Pharmacology
College Of Medicine
University Of Al-Nahrain
Drug Treatment Of Allergy
2. Allergy
Overreaction of immune system to a harmless substance
(allergen) also called hypersensitivity.
Allergy can be mild like runny nose or sever like difficulty
to breath in asthmatic attack and could be very sever
called anaphylaxis.
The tendency to develop allergy is often hereditary.
3. Manifestation
Depend on body part involved ,severity of reaction and vary
among individuals.
Skin: redness ,itching, swelling, rash, hives.
Lung: cough, shortness of breath.
Nose: stuffy, runny, sneezing.
Eyes; red, itchy ,swollen, watery.
stomach: pain, nausea, vomiting, diarrhea.
Head: swelling of face, neck, eyelids, lips, throat .
Anaphylaxis is Any combination of allergic symptoms that is
rapid or sudden, Life-threatening condition manifestate with
shock.
4. Types of allergy
Respiratory allergies: allergic rhinitis, asthma
Food allergies: also called intolerance like lactose
intolerance.
Skin allergies: contact dermatitis, urticaria
Eye allergies: allergic conjunctivitis.
Drug allergies: penicillin and salicylate allergy.
8. Anti allergic drugs
Anti allergic drug is a general term for drugs that regulate
the release and action of chemical mediators involved in
allergic reaction or inhibit a particular stage of allergic
reaction
Therapeutic approaches have focused either on the
treatment of allergic inflammation which called controller
or rapid relief of sever symptoms called reliever.
Typical controller is topical glucocorticoid and typical
reliever is anti-histamine.
9. Histamine
histamine was the First mediator to be associated with
allergy and first who inhibition proved to be useful in
management of allergic reaction.
Histamine stored in mast cell and basophiles, released
after immunological activation.
Four receptor types of histamine H1,H2,H3,H4.
Anti histamines classified to first, second and third
generation.
11. Anti-histamines
First generation/ non selective H1receptor blocker.
Systemic side effect like sedation and dry mouth
The H1 receptor antagonist are inverse agonist that mean
negative intrinsic activity despite the release of histamine
EX: Chlorpheniramine and diphehydramine .
Second generation /Non competitive antagonist highly
selective H1 receptor ,low affinity for other receptors.
Parental administration of 2nd generation cause local irritation
Non sedating due to water solubility and low penetration
through BBB
EX: Loratidin , cetrizine.
12. Third generation
Or multifunctional antihistamine have number of clinical
effect above the antihistaminic effect by binding to H1
receptor.
Ketotifen,terfenadine,cetrizine,oloptadine and azelastine
Many of them unknown MOA but they thought to act on
mast cell and basophiles by preventing Ca influx or
intracellular Ca release which interferes with activation
and release of potent bioactive mediators.
13. Continue with anti-histamine
Chlorpheniramine only used under 1 year age ,desloratidin
1year< and the rest licensed above 2 year.
Extensive first pass metabolism in liver by cytochrom p450 so
Interact with ketoconazole ,erythromycin, azithromycin and
grapefruit juice.
Fexofenadine eliminated un change in urine.
QT prolongation and torsades de pointes arrhythmia due to
direct block of specific k channel related to heart and not due
to H1 block terfenadine, astemizole and high doses of
diphenhydramine
2nd generation do not lead to the development of
tachyphylaxis and show a wide therapeutic window (e.g.
fexofendine).
14. H3 &H4 Antagonists
H3 antagonists inhibit synthesis and release of histamine,
dopamine and non adrenaline from presynptical neuron
in CNS .
Betahistine act through H3 receptor to treat vertigo.
Selective H3 antagonist is not promising as anti allergic
drug but for neurological disease.
While H4 expressed on immunological cell and selective
antagonist may be available in near future for asthma
and atopic dermatitis.
Thioperamide is research drug antagonist to both H3 and
H4 because they are 35% homologous.
15. Other agent with antihistamine properties
TCA like doxepin have high affinity to H1 receptor and
acceptable alternative to for treatment of chronic
idiopathic urticaria
Caution due to strong anticholinergic effect
16. Clinical use of anti-histamine
Topical eye preparation for allergic conjunctivitis.
Topical preparation for skin condition is available but not
recommended due to contact sensitization
First and second generation for urticaria also mix with H2
antagonist
Dual action prefer in asthma due to bronchodilator and
anti-inflammatory activities.
May serve as bronchoprotective.
Loratidin and cetrizine are preferred in pregnancy and
breast feeding.
17. corticosteroids
Is synthetic analogs of glucorticoid hormones of adrenal
gland also called glucocorticoids GCs.
Anti inflammatory agent with inhibitory effect on
multiple inflammatory gens activated during
inflammatory process by diffusing across cell membrane
to GC receptor in cytoplasm.
Used orally , IM, IV, SC, topically.
Developed for inhalation or topical by increasing
lipophilicity and receptor affinity so improve tissue
retention and fewer systemic side effect
18. Continue with GCs
Therapeutic index of inhaled GCs is measured between
local effect and systemic exposure.
fluticasone,mometasone is preferred over
beclomethasone ,budesonide and triamcinolone
use Lowest possible dose with shortest period and when
maximal dose of alternative has failed.
S/E of systemic use: osteoporosis, cataracts,
hyperglycemia, hypertension, disruption of HPA axis.
S/E of local use: candidiasis, cough
19. Leukotriene(LTs)inhibitors
Derived from membrane constituent arachidonic acid
LTs Induce many allergic symptoms like smooth muscle contraction,
acceleration of antigen presentation, hypersecretion, eosinophilia
and airway remodeling
Two groups: LTs receptor antagonist like montelukast and
zafirlukast / 5-lipoxygenase inhibitors like zileuton
Improvement in base line lung function but not in non asthmatic
patient mean do not have direct relaxing activity of bronchial
smooth muscle ,inhibit aspirin induce bronchospasm.
Low participation of LTs in Other allergic diseases like allergic
rhinitis and dermatitis
Zileuton can cause hepatotoxicity .
Zileton and zafirlukast have many drug interactions with warfarin
and theophylline ,caution with use.
20.
21. Thromboxane A2 (TXA2) inhibitors
TXA2 synthetase inhibitors : ozagrel.
TXA2 receptor antagonist : seratrodust.
The efficacy of these agent in asthma is under discussion
but is worthy in allergic rhinitis due to strong expression
of THA2 receptor in nasal mucosa of allergic patient.
Uses/Allergic bronchial asthma –late asthmatic response,
Allergic rhinitis –sneezing rhinorrhea, stenosis, Atopic
dermatitis and conjunctivis.
22. TH2 cytokines inhibitors
Initiates the suppression of IgE antibody production and
eosinophilia by interfering with T hellper 2 cytokine
production.
EX: suplatat
23. Cromones: cromolyn and nedocromil
The role in asthma is limited but effective in conjunctivitis
and rhinitis.
MOA: block chloride transport channel in air way
epithelial cell and mast cell so inhibit mediator release
,IgE synthesis ,eosinophile chemotaxis ,neutrophil
migration and so anti-inflammatory effect.
Their anti-inflammatory effect is weak, used as
maintenance therapy preventatively mainly available as
intranasal or ocular preparations due to low oral
bioavailability.
Very safe for all ages.
24. Theophylline
Low solubility formulated as aminophylline to enhance
absorption.
MOA:not fully understood but thought to adenosine
receptor antagonist and may account for its sever S/E
like seizures and arrhythmia.
Vey Narrow margin of safety and more drug interactions,
caution with use.
Theophylline is an alternative in low income countries.
25. Sympathomimitic decongestant
treatment of nasal obstruction in both allergic and non-
allergic rhinitis, intranasal decongestants are effective in
the short term.
not improve nasal itching, sneezing or rhinorrhea.
Systemic side effects with oral decongestants can include
dizziness, headache, tremor, insomnia, tachycardia and
hypertension
Phenylephrine weaker α adrenergic and less effect on BP
than pseudoephedrine
26. Anticholinergic
Inhaled preparations with minimal systemic side effect
like ipratropium and tiotropium
MOA: block Ach activity in large and medium sized
airways which is normally stimulated by histamine ,
allergens and other resulted in bronchoconstriction and
mucus hyper secretion.
Clinical uses in rhinorrhea and as adjuvant therapy in
asthma ,
27. Novel immunotherapies
Depend on concept allergy is heterogeneous disease with
different mechanisms ,so designing therapy selectively
target the protein, mediator or what ever involved in
pathophysiological process in this group of patients.
Monoclonal Anti IgE: is a treatment option limited to
patients not respond to GCs with IgE mediated allergy
(omalizumab approved for allergic asthma and urticaria)
anti- interleukin : non atopic or non immunological
allergy (mepolizumab which anti IL-5 approved for
eosinophilic asthma)
