ORGANIC CHEMISTRY

CHEM-412
ANEEZA ARSHAD
19012507-042
UOG

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ANTIALLERGIC
DRUGS

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 CONTENTS
Sr no content Slide no
1 Introduction 4
2 Treatments 5
3 Main classes 6
4 1-Ocular Decongestants 7
5 2.Anti-histamines- ocular 11
6 3.Chronic Care Drugs: Mast cell stabilizers 12
7 4. Anti-histamines combined with Mast cell stabilizers 13
8 5-NSAIDS 14
9 6.Corticosteroids 16
10 references 17

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INTRODUCTION
 used to prevent an allergic response : tending to relieve or control allergic
symptoms (Merium webster)
 Release of histamine, prostaglandins, leukotriene and other less well-
defined mediators from the mast cell during an allergic reaction can cause
a variety of uncomfortable symptoms and sometimes life threatening
complications.
 Type 1 hypersensitivity reactions/anaphylactic/immediate or IgE mediated
reactions.
 First antigen exposure-IgE antibodies produced and attach to mast cells.
 Second exposure to the same-Degranulation of mast cells
 Release of large quantities of inflammatory mediators including histamine

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TREATMENTS:
 Based on the symptoms, severity &
characteristics.
 Begins with eliminating & avoiding the allergen.
 Lubricating drops may wash away the allergen.
 Drug intervention required.

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MAIN CLASSES OF ANTI-ALLERGY DRUGS
 Ocular Decongestants
 Antihistamines

 Mast Cell Stabilizers

 NSAIDS

 Corticosteroids
 Other side ingredients

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1-OCULAR DECONGESTANTS
 Cost effective choice for mild allergies
Use with cold compresses
Artificial tears necessary
 Local vasoconstrictor, temporarily reduces
redness
 Does not treat “itching”
 Four alpha-agonists available

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OCULAR DECONGESTANTS
 Phenylephrine 0.12% and 0.125%
 Naphazoline (0.012%, 0.05%, 0.1%)
 Tetrahydrozoline(0.05%)
 Oxymetazoline(0.025%)
 All constrict superficial conjunctival vessels
within minutes
 Prolonged and excessive use causes rebound
conjunctival hyperemia

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HISTAMINE RECEPTORS

Histamine receptors Based on the chemical

structure of antihistamine that bind to the
receptor & on the type of histamine antagonist.
types:
 H1.
 H2

 H3

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HISTAMINE RECEPTORS
 H1 receptors located mainly on neuronal tissues and results
in itching.
 H2 receptors associated with vascular tissue & results in
redness.
 H3 receptors not clinically significant.

 In ocular therapy, mainly H1 antihistamines are applicable.

 H1 antihistamines prevent histamine-H1 receptor interaction

 Thus providing symptomatic relief from histamine activity.

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2.ANTI-HISTAMINES- OCULAR
 Reduces itching caused from already released histamine
from mast cells and basophils
 Blocks H1 receptors which control

Itching
Capillary dilation
Increase in capillary permeability
 Almost always combined with ocular decongestant

 Chlorpheniramine (does not work as well topically)

 Drugs available
 Levocabastine HCl ophthalmic suspension .05% (Livostin)

 Emedastine difumarate 0.05% (Emadine)

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3.CHRONIC CARE DRUGS: MAST CELL STABILIZERS

 Stabilizes mast cell membranes and inhibits

degranulation of mast cells
 Not effective in acute disease
 Preventive and maintenance therapy
 Must be used regularly for better performance
 VERY, VERY safe
 First generation (older)
 Cromolyn Sodium (Sodium cromoglycate) 4% -BD
 Lodoxaminde 0.1%

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4. ANTI-HISTAMINES COMBINED WITH MAST CELL STABILIZERS

   Stabilizes mast cell membranes and controls

immediate itching
 Used BD
 Very, very successful and effective
 Names are:
Olopatadine hydrochloride 0.1% (Patanol)
Ketotifen fumarate 0.025% (Zaditor)
Azelastine HCl 0.05% (Optivar)
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5.NSAIDS
 Ketorolac tromethamine 0.5% (Acular)- First NSAID
approved for topical ocular use in seasonal allergic reactions
 It affects prostaglandin synthesis by inhibiting the activity
of cyclooxygenase (responsible for the conversion of
arachidonic acid to prostaglandin).
 Pharmacokinetic data shows that it penetrates the cornea &
reaches concentrations that reduces prostaglandin E levels in
the aqueous humor.
 Plasma level usually below detectable limit in oral
administration.

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NSAIDS
  Side effects
 Transient stinging & burning occurs frequently

 Allergic reactions & superficial keratitis rarely

occurs.
 Contraindications
 In patients wearing contact lenses.

 Patient who have previously exhibited sensitivity to

acetylsalicylic acid, phenylacetic acid derivatives &
other NSAIDs.
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6.CORTICOSTEROIDS
 Control of inflammatory and immunologic diseases of
eye.
 Reduction in capillary permeability and cellular
exudation.
 Inhibition of degranulation of mast cells, basophils
and neutrophils.
 “Added” ingredients:
Camphor
Menthol
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SYNTHESIS- SCHEME 1
  General synthesis of loratadine analogues 4a–h. Reagents and conditions: (a)
methyl acrylate, MeOH, 40 °C, 12 h; (b) MeONa/MeOH 30% aq., toluene,
110 °C, 5 h; (c) HCl, 100 °C, 5 h; (d) TiCl4/Zn, THF dry, 70 °C, 17 h

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SCHEME 2
 General synthesis of benzimidazole derivatives 12a–f. Reagents and conditions: (a) K2CO3, DMF,
50 °C, 6 h; (b) Boc2O, 1 mol L−1 NaOH, THF, 25 °C, 2 h; (c) Boc2O, 2 mol L−1 NaHCO3, THF, 25
°C, 6 h; (d) ethyl diethoxyphosphoryl acetate, K2CO3, DMF, 78 °C, 12 h; (e) 1 mol L−1 NaOH,
CH3OH, 25 °C, 30 min; (f) 10% Pd/C, H2, C2H5OH, 25 °C, 7 h; (g) 1 mol L−1 NaOH, CH3OH, 25
°C, 30 min; (h) ethyl chloroformate, Et3N, CH2Cl2, 0 °C, 30 min; (i) AcOH, reflux, 2 h

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SCHEME 3
  General synthesis of 3H-benzo[4,5]thieno[2,3-d][1,2,3]triazin-4-
ones 4a–c. Reagents and conditions: (a) CH3COOH/CH3COONH4,
glacial acetic/cyclohexane, reflux 10 h; (b) NaNO2/HCl, glacial acetic,
0–5 °C.

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REFERENCES:
 pubs.acs.org (25 may at 11:39 pm)
 link.springer.com (26 may at 12:09 am)
 tandfonline.com (26 may at 12:46 am)
 inis.iaea.org (26 may at 1:15 am)
 sciencedirect.com (26 may at 2:00am)
 cabdirect.org (26 may 4:00 am)

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