More Related Content


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.
  5. Pathophysiology
  6. 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.
  7. 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.
  8. H4 H3 H2 H1 CHARACTERISTIC immunomodulator Neurotransmitter modulation Gastric acid secretion Acute allergic reaction function Bone marrow, peripheral hematopoitic cells(dendritic cells, mast cell, eosinophils, monocytes, basophiles and T cells) Histaminergic neurons Widespread (gastric, parietal cells, smooth muscle, heart) Widespread (neurons, endothelial, smooth muscle) Receptor expression Gi Gs Gs Gq G-protein coupling <5 <5 >10,000 7.9 Diphenhydramine pki <5 ND ND 6.8 Loratidine pki <5 <5 6.2 <5 Cimetidine pki 7.2 7.3 <5 <5 Thioperamide pki
  9. 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.
  10. 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.
  11. 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).
  12. 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.
  13. 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
  14. 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.
  15. 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
  16. 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
  17. 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.
  18. 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.
  19. TH2 cytokines inhibitors  Initiates the suppression of IgE antibody production and eosinophilia by interfering with T hellper 2 cytokine production.  EX: suplatat
  20. 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.
  21. 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.
  22. 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
  23. 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 ,
  24. 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)