Dr.

Omar Abdelfattah Ahmed *

Assit. Lecturer & Academic Researcher

Dept. of Clinical Research and Pharmacy Practice
 Allergic rhinitis involves inflammation of nasal mucous
membranes in sensitized individuals when inhaled
allergenic particles contact mucous membranes and
elicit a response mediated by immunoglobulin E (IgE).

♯ It may be:-
A. Seasonal (hay’s fever): that occurs with pollination
or pollen grains season “spring ivy”.

B. Persistent (perennial): which is chronic and is caused

by antigens or allergens “at any time _ year-round”.
 Hairs and leathers of
House-dust mites which domestic animals
live in carpets, mattresses
and furniture

Plant pollen

Dust Food
Pharmacological
of components
agents (enzymes,
book (stabilizers,
antibiotics,
depo- genetically modified
vaccines, drugs)
sitories products, diet rich in
histamines)
Pathophysiology:
The allergic response is divided into
several phases:
A. Sensitization Phase (marking)

B. Early phase

C. Late phase “cellular recruitment"

 Allergens Allergen-specific
IgE or antibody

B-cell

T-cell

 Allergens activate immunocompetent cells.

 As a result, immunocompetent cells produce antibodies of IgE

class (each for which?).
 - Further, these antibodies bind to the surface of mast
cells, basophils, and eosinophils.

- When a new exposure (2nd exposure) to allergen occurs

system, it interacts with IgE-antibodies on the surface of mast
cells, basophils, and eosinophils forming antigen – antibody
complex. (memory cell)

This is a first,
immune phase of
allergic reaction.
• As a result of antigen-antibody reaction,
the degranulation “explosion” of mast cells occurs.

• The membranes of mast cells, basophils and

eosinophils ruptures with output of biologically
active substances (histamine, prostaglandins
leukotrienes, bradykinin) which induce early phase
symptoms of allergic rhinitis within minutes.
Rhinorrhea (no pus)
Sneezing
Itching
Discomfort
 it occurs with 4-24 hrs

 Migration of eosinophils, neutrophils, basophils,

macrophages, and monocytes in the nasal mucosa
(cellular recruitment) leading to:

 Congestion (other consequences …)

Symptoms:
- Symptoms are similar and overlap with those of the
common cold. These symptoms include :
Sneezing
Nasal pruritus
Congestion
Clear rhinorrhea (watery discharge)
Conjunctival or eye erythema and itching,
Ear fullness with buzzing sounds and pressure on the
cheeks and forehead
Feelings of weakness and fatigue without fever
Loss of smell or taste
Dark circles under the eyes caused by increased blood
flow near the sinuses (allergic shiners)
Crease just above the tip of the nose from constant
upward nose wiping
I. Antihistamines
 Antihistamines Overview:

 There are two types of H1 receptor-blocking antihistamines:
- First generation (sedating)
 - Second generation (non-sedating)
Antihistamines are useful for treating the sneezing, rhinorrhea,
pruritus, lacrimation, and irritated itchy eyes (early-phase
symptoms).
 They do NOT work to correct nasal congestion (late-
phase symptoms).
First-generation antihistamines:
1 - Alkylamines as:
a. Chloropheniramine (Analerge®, Allergex®, Allergyl®, Avil ®)
b. Calmistine (Tavist®)
2 - Ethylenediamines x
3 - Ethanolamines x
4 - Piperidines x

 First- generation antihistamines adverse effects:

A. They cross the BBB resulting in drowsiness, sedation, dizziness,
confusion and decrease work , academic performance and higher
accidental risk.
B. These agents also produce anticholinergic action, with dry mouth,
urinary retention, blurred vision, and constipation as additional side
effects.
C. Other side effects of first-generation antihistamines include: N, V,
and GI upset.

 Contraindication of first-generation antihistamines:

1. Glucoma !
2. Prostate hypertrophy !
Second- generation antihistamines:
A. Loratadine (Claritine®, Loratan®)
B. Cetrizine (Allevo®, Allear®, Histazine®, Citrak®)
C. Fexofenadine (Telfast®, Histafree®, Fastel®, Fastofen®)
Second- generation antihistamines are currently available by
Prescription (with the exception of loratadine which is an OTC drug
None of these agents has sedative effect or minimal effect.

 Notes about antihistamines:

Antihistamine therapy should be started 1-2 weeks before a
known allergy season or several hrs before exposure to a known
allergen.
Antihistamines should be taken regularly and uninterrupted
throughout the peak season.
Regular, rather than as needed, dosing of antihistamines is more
effective.
The first and second-generation antihistamines are roughly of
equal efficacy, but the latter (2nd) has good safety and less side
effect profile.
* Azelastine (Zalastin® nasal spray)
Antihistamine nasal spray is approved for
the treatment of seasonal allergic rhinitis.
Side effect: drowsiness and headache.
--------------------
* Olopatadine (Patanase®)
another intranasal antihistamine that may cause
less drowsiness.
--------------------
* Levocabastine (Livostin®), Olopatadine (Patanol®),
and Bepotastine (Bepreve®)
ophthalmic antihistamines that can be used
for conjunctivitis associated with allergic rhinitis.
II. Decongestants
 Antihistamines are less effective in reversing nasal and ocular
congestion. Decongestants counter congestion and help reverse
drowsiness associated with first-generation antihistamines.
 Systemic decongestants are preferred when a decongestant
action is required for longer than 3-5 days.

 Nasal or topical Decongestants:---

intranasal decongestants are sympatomimetic amine.
Intranasal decongestants induce prompt and profound
vasoconstriction with relief of congestion and headache as They
stimulate the α-adrenergic receptors of vascular smooth muscle,
which constrict dilated arterioles
These topical agents have varying durations of action.
Some of these products may not be used in young children.
topical naphazoline has resulted in CNS stimulation in young
children (age less than 12 years).
Beside HTN, The major disadvantage is the potential to develop
rebound congestion.
 The intranasal decongestant include:
Ephedrine (Argerol ephedrine nasal drops),
Naphtazoline (Neozoline ®, Prisoline ® nasal & eye
drops)
Phenylepherine (Deltarhino ® nasal drops)
Xylometazoline (Otrivin ®,Balkis ® nasal drops)
Oxymetazoline (Afrin ®. Nasochrom ® nasal drops)
 Oral decongestants:---
 An oral decongestant may be useful in reaching deep into
the nasopharyngeal and sinus passage where topical
solutions may not be accessible.

 Because oral agents induce less intense vasoconstriction

locally, they have not been associated with rebound
congestion.

 Oral decongestants are contraindicated in patients taking

monoamine oxidase (MAO) inhibitors, HTN, IHD.

 Oral decongestants include:

Phenylephrine ?
Pseudoephedrine (Decongess ®, Clarinase ®, Actifid ®)
III. Cromolyn sodium or sodiuum chromoglycate
(Nasochrom ®, Cholichrom ®, Epichrom® Eye and Nasal drops)

 The proposed mechanism of action is stabilization of mast cells,

interfering with calcium transport and induction of
degranulation.

 This agent is more effective in treating seasonal versus perennial

allergic rhinitis.

 It reduces rhinorrhea, congestion, and sneezing.

 To be maximally effective, it must be started 2-4 weeks before

the exposure of the offending allergens and continued
throughout the contact period.

 Dosed 4-6 times per day in each nostril initially, administration

frequency may be decreased when the symptoms are under
control.

 To be effective, it must be used on a regular basis.

IV. Intranasal Corticosteroids “inhalers”
 Intranasal steroids have emerged as the most effective
treatment of allergic rhinitis, relieving sneezing, nasal pruritus,
congestion, and rhinorrhea associated with the inflammation.

 Intranasal steroids are ineffective in the treatment of

ocular tearing or ocular pruritus.

 Symptom relief is though to be related to the ability of steroids

to inhibit the activity of multiple cell types (e.g., mast cells,
basophils, eosinophils, neutrophils, macrophages,
lymphocytes) and mediators of inflammatory response.

 Decreased capillary permeability and decreased nasal

mucous secretion also contribute to the effectiveness
achieved by intranasal steroids.
 Treatment with these medications should start at the first signs of
clinical symptoms and is usually continued throughout the allergen
season.

 It may take up to 3 weeks for the peak effects to occur.

 Major adverse effects of intranasal steroids are local dryness and

irritation.

 The more recently developed formulations are:

Fluticasone (Flexonase® nasal spray)
Beclomethasone (Beclo®, Beclosone® nasal spray)
Budesonide (Rhinocort aqua® nasal spray)

V. Ipratropium (Atrovent) nasal spray

anticholinergic agent useful in persistent allergic rhinitis. It exhibits
antisecretory properties when applied locallyand provides
symptomatic relief of rhinorrhea.
VI. Montelukast
Montkal ® Kokast®, Ventair ®, Clearair®, Monkast® Singulair ®)
The leukotriene receptor antagonists that has been used for asthma has
now been approved for the relief of symptoms of seasonal allergic rhinitis
in patients over the age of 2 and for treatment of persistent allergic rhinitis
in children as young as 6 months.

It shoulld used 2-4 weeks before allergic season.

The dose is once daily, the same as for asthma (4 - 10 mg daily).

VII. Immunotherapy
 Immunotherapy is usually begun only when the patient does not
show a response to pharmacotherapy or cannot tolerate the
medications.
 Routine injections of the diluted antigen are administered initially,
with the conc. of the antigen increasing over time [De-sensitization].
 Serum IgE levels specific to the antigens given tend to decrease
during the course of immunotherapy. Conversely, there is an
increase in serum IgG levels that binds to mast cell instead of IgE
with subsequent inhibition of mast cell degranulation.
Chief complain
"My nose is stopped up, and I can’t
sleep at night. I wake up with a dry
mouth, and it stays dry all day.
Sometimes, I start sneezing and can’t
stop. When I do stop sneezing, my nose
starts running and then plugs up again.
I am having trouble in school because I am
always tired, and now my eyes are itchy
and watery all the time”.
K. B. is a 19-year-old female who presents
to her physician with complaints of upper
respiratory [Link] symptoms have
occurred off and on since she was a child,
worsening in the fall and lessening in the
spring; however, they have been continuous
for the last 7 months. Additionally, she has
developed itchy, watery eyes that did not
occur with rhinitis symptoms she had in the
past. She has not run a fever and does not
have throat pain, but she does have an
occasional nonproductive cough that gets
worse at night.
 Allergic rhinitis × 14 years
Tonsillectomy and adenoidectomy at
age 8

FH:
Brother age 17, with moderate
persistent asthma, and sister age 14,
with allergic rhinitis.
 Tavist 1 tablet po BID
Oxymetazoline nasal spray PRN at
night (once or twice a week)
All:
Codeine (itching)
Gen:
Young women looks tired with darkened areas
under the eyes; her sound is congested and
continually rubbing her nose and eyes.

VS:
BP 102/62, P 64, T 36.9

HEENT:
Periorbital edema with darkened areas around
the eyes. Nasal mucous membranes are swollen
and pale. There is no tenderness over frontal
and maxillary sinuses. There are no
oropharyngeal lesions, and the throat is non-
erythematous.
1 - What is the diagnosis of the patient's main
medical problem?
Perennial rhinitis with seasonal
exacerbations.
2 - What are the data supporting your
diagnosis?
Sneezing.
Rhinorrhea.
nasal congestion.
pruritic eyes.
Nasal mucous membranes are swollen and
pale.
Periorbital edema with darkened areas
around the eyes.
The goal of treatment is to:
Minimize or prevent symptoms with
minimal or no side effects
Patients should be able to maintain a
normal lifestyle.

4 - What could be the possible cause of

the patients complain of dry mouth?
Tavist "Clemastine'' sedating
antihistaminic with anticholinergic side
effect.
The nasal decongestant
Oxymetazoline (sympathomimetic)
should be used only whenever needed
and not more than 5 days to avoid
rebound congestion “tolerance risk”.
 1 Avoidance the exposure to dust, pollens and
other allergens
2 During seasons of allergy, patient should
keep windows closed and minimize time
spent outdoors
3 Filter masks can be worn.
1 Non sedating antihistaminic such as
loratidine (10 mg once daily)
2 keep using the nasal decongestant
Oxymetazoline (sympathomimetic) only
whenever needed not more than 5 days to
avoid rebound congestion.
3 Corticosteroid nasal spray such as
Beclomethasone (50 µg twice daily), or
Fluticasone (100 µg once daily)
 5 Ipratropium bromide (Atrovent)
nasal spray is an anticholinergic agent
useful in perennial allergic rhinitis
6 Montelukast (Singulair) one 10-mg
tablet daily.