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242 Chapter 9 Rheumatoid arthritis
7c) What monitoring is required for patients treated with sulfasalazine?
Athernextclinicappointment3monthslater,Pamela’ssymptomsandinvestigationsindicate
thatsheisnotrespondingwelltothesulfasalazine.TherheumatologistusesaDiseaseActivity
Score to monitor her response to therapy; this involves assessing the number of swollen and
tender joints, and measuring her erythrocyte sedimentation rate or C-reactive protein level.
Pamela is also asked to assess and rate her sense of well-being.
Herrheumatologiststopsthesulfasalazine,andprescribesmethotrexate.
8) Explain why methotrexate is a good DMARD.
When she goes to collect her tablets, the pharmacist asks if she has been told how often to
take them. The pharmacist explains that the prescription reads ‘Methotrexate 10 mg daily’,
which is not the usual frequency. Pamela is unsure, and the pharmacist rings the doctor to
check.
9) Why did the pharmacist query the dosing? What is the usual frequency of administering methotrexate
in rheumatoid arthritis?
The doctor is extremely apologetic, and asks the pharmacist to change the instructions and
says that he will issue a new prescription.
10a) What is the mechanism of action of methotrexate?
10b) What are the side effects of methotrexate?
10c) What monitoring is required with methotrexate?
After one week, blood tests show that Pamela’s liver function tests are elevated. She is also
suffering from mouth ulcers. The rheumatologist prescribes folic acid.
11a) Why has Pamela been prescribed folic acid?
11b) Explain how folic acid acts when used with methotrexate.
Pamela’s symptoms improve gradually. However, she is upset about the impact of the disease
on her life. She has to regularly request time off work to go to clinic for the blood tests required
with methotrexate treatment. She has read up on rheumatoid arthritis on the National
Rheumatoid Arthritis Society website, and decides to contact her local self-help group.
WORKBOOK 6 Rheumatoid arthritis 243
PART 2
Pamela regularly attends sessions arranged through the National Rheumatoid Arthritis Society
where she meets many other patients with similar experiences. One of them is Gwen. She also
suffers from rheumatoid arthritis, but the disease is more advanced. Gwen is on a drug called
leflunomide, as well as methotrexate.
12a) Explain how leflunomide modifies the disease process in rheumatoid arthritis.
12b) What are the side effects of leflunomide?
Pam reads about leflunomide and finds a reference to a ‘loading dose’ of this drug.
13a) Explain the purpose of a loading dose, and why this may be required at the start of therapy with
leflunomide.
13b) Why is the loading dose often not given in practice?
Gwen tells Pam that she tried a number of other drugs before she was prescribed leflunomide.
These included penicillamine and hydroxychloroquine.
14) What are the advantages and disadvantages of:
a) penicillamine?
b) hydroxychloroquine?
Over the course of the following year, Gwen’s arthritis gets a lot worse. She goes to see her GP.
Pamela has spoken to her about two newer drugs used for more severe rheumatoid arthritis,
etanercept and infliximab, which she has read can be very effective. The doctor has to check
the guidelines to ensure that Gwen fits the criteria for these treatments. He wonders if
azathioprine,ciclosporin,orgoldshouldbeusedrst.
15a) What is the mechanism of action of azathioprine and ciclosporin?
15b) Describe the place of gold in the treatment of rheumatoid arthritis.
The doctor decides that etanercept would be appropriate, but tells Gwen that she will need to
be screened for tuberculosis before the treatment can be started. The leflunomide is
discontinued. She is also seen by the specialist rheumatoid arthritis nurse, who tells her more
about treatment with etanercept and teaches her how to administer the drug. Initially she has to
have her blood tested every 2 weeks, but after 8 weeks she only needs monthly checks.
244 Chapter 9 Rheumatoid arthritis
16a) What is the mechanism of action of etanercept?
16b) How is etanercept administered?
16c) What are the side effects of etanercept?
After 2 years taking etanercept and methotrexate, Gwen is diagnosed with heart failure and told
she must stop taking etanercept. The doctor needs to replace it with another biological
DMARD. He considers infliximab, anakinra, rituximab, and abatacept.
17) Explain how the mechanisms of action of these drugs differ.
The rheumatologist discusses these options with Gwen, who is concerned about regular
injections and wants to know how these drugs are administered.
18a) How does the administration of these four differ?
18b) How should treatment with these drugs be monitored?
Chapter 10
Allergies: rhinitis and urticaria
Useful terms for this topic
Atopy: A genetic disposition to hypersensitivity or
allergic states, characterized by high IgE antibody
levels.
Oedema: Swelling of soft tissue as a result of
accumulation of interstitial uid.
Pruritus: Itching.
Rhinitis: Inammation of the inside of the nose.
Rhinorrhea: Running nose.
Urticaria/hives: Skin condition characterized by
raised red and itchy weals.
Millions of people worldwide suer from allergic rhinitis,
most commonly in response to pollen (hay fever). Our
ctional patient Dorothy, in the workbook at the end of
this chapter, is one such person. She suers the classic
symptoms of hay fever when exposed to pollen; her nose
starts running (rhinorrhea), her nostrils and eyes start
itching (pruritus), and she is unable to do anything
except sneeze. ese symptoms can also be triggered, in
susceptible individuals, by exposure to other common
allergens such as dust mites, animal dander (hair and
dead skin cells), and mould.
Allergic rhinitis is the most common form of chronic
rhinitis. Acute rhinitis, on the other hand, is often
non-allergic, and can be caused by viral infections such as
the common cold, or by exposure to changes in
temperature, strong odours, spicy food, etc.
In order to counsel and treat patients most eectively, a
good understanding of the symptoms of allergic rhinitis is
required. An appreciation of the underlying processes
and how to prevent their initiation is also necessary. In
this chapter we focus on allergic rhinitis, examining its
pathophysiology and pharmacological management. We
shall also consider a related condition of the skin—
urticaria (hives), raised red and itchy weals whose
appearance can be triggered by a specic allergen, for
example certain foodstus or contact with latex, or by
drugs including non-steroidal anti-inammatory drugs
(NSAIDs) and opiates.
10.1 Allergic rhinitis
Allergic rhinitis is very common globally, estimated to
aect 10–25% of the population, although as symptoms
are predominantly self-managed, statistics probably
underestimate the actual prevalence. It has been
identied as one of the top 10 reasons for visits to a GP,
aecting social and family life, school performance, and
work productivity.
Allergic rhinitis, like urticaria (see Section 10.3), arises
from inappropriate activation of the immune system and
the subsequent inammatory response (described in
Section P3.2 in the Introduction to Part 3 of this book).
In essence, the immune system protects the body by
recognizing and defending against disease-causing agents
(pathogens) such as bacteria or viruses by mounting an
inammatory response. is involves an array of immune
cells and a wide variety of mediators, such as histamine,
leukotrienes, prostaglandins, and cytokines (see
Figure P3.2 and Tables P3.1 and P3.2). Activated B-cells
produce immunoglobulins, proteins more commonly
246 Chapter 10 Allergies: rhinitis and urticaria
Turbinate
called antibodies, which are directed against specic parts
of the pathogen, known as antigens. e antigen–antibody
interaction leads, either directly or indirectly, to the
elimination of the pathogen from the body.
is immune response can sometimes be activated
inappropriately. In the case of allergic rhinitis or urticaria,
normally innocuous exogenous substances like pollen or
dust bring about an immune response. (Autoimmune
diseases result when an immune response is generated
against endogenous substances.)
Based on the frequency of symptoms and the responsible
allergen, allergic rhinitis is classied as either intermittent
or persistent. Pollen from grasses and trees is the most
common trigger of intermittent (or seasonal) allergic
rhinitis. Persistent (or perennial) allergic rhinitis occurs
all year round; common allergens include dust mites,
animal dander, and mould. e severity of both
intermittent and persistent allergic rhinitis ranges from
mild to severe. For the correct treatment choice, severity
and type must be determined. Table 10.1 details the
criteria used in the classication of allergic rhinitis.
Like patients with asthma and atopic dermatitis (eczema),
suerers from allergic rhinitis sometimes have an
inherited disposition to hypersensitivity (atopy). It is not
uncommon for an infant to develop atopic dermatitis,
then asthma as a small child, and allergic rhinitis as an
adolescent/adult. ese conditions are known
collectively as the atopic triad.
Table 10.1 Classication of allergic rhinitis
Severity/type Duration of
Mild intermittent
Mild persistent
Moderate–
severe
intermittent
Moderate–
severe persistent
symptoms
<4 days per week
or <4 weeks
>4 days/week or
>4 weeks
<4 days per week
or <4 weeks
>4 days/week or
>4 weeks
Features
Normal sleep and daily
activities
No troublesome
symptoms
Presence of at least
one of the following:
•disruptedsleep
•disturbeddaily
activities
•troublesome
symptoms
10.1.1 The anatomy and physiology of the
nose
e structure of the nose (Figure 10.1) enables it to full
its functions of smell, speech, and the conduction and
conditioning of air. e anterior visible part of the nose,
known as the vestibule, is lined by the same epithelium as
skin, and contains hairs which prevent the entry of dust
and particles in the air. e two nasal cavities,
continuations of the nostrils, are large air-lled spaces
which extend back into the head and connect with the
pharynx. During the process of conditioning, air is
humidied, warmed, and ltered in the nasal cavities as it
makes its way to the lungs. Inside each cavity, air passes
over conchae, or turbinates, three nger-sized projections
Frontal sinus
Nasal bone
Cartilage
Nasal cavity
Lip muscle
Tooth
Figure 10.1 Anatomy of the nose and surrounding structures.
Olfactory bulb
Tongue
Sphenoidal sinus
Pharynx
Pharyngeal
tonsil
10.1 Allergic rhinitis 247
of bone and soft tissue which serve to greatly increase the
surface area for conditioning air as it is breathed in. In
patients with rhinitis, the turbinates can become swollen
and inamed, disrupting the normal movement of air
through the nose.
e entire nasal cavity, including the turbinates, is
covered in respiratory epithelium with a rich blood
supply, critical for warming and humidifying the air.
Interspaced with the epithelial cells are goblet cells that
produce mucus, covering the nasal cavities and septum,
and acting as a lter against irritants and infection. e
epithelial cells themselves possess numerous small
nger-like projections or cilia, which sweep the mucus
into the pharynx to be swallowed. e mucosal lining
provides immunological defence by secreting
immunoglobulin A antibodies, which play a critical role
in mucosal immunity.
e autonomic nervous system assists in the conduction
and conditioning of air. Vascular smooth muscle cells
ofthe blood vessels in the nasal cavities express 1
adrenoceptors. As illustrated in Figure 10.2, activation
ofthe sympathetic nervous system leads to stimulation
of these Gq-coupled receptors (see Chapter 2, Section
2.2.3), increasing Ca2+ concentration inside the cells.
Ca2+ combines with the Ca2+ binding protein calmodulin
to stimulate the enzyme myosin light chain kinase
(MLCK). is enzyme phosphorylates myosin to bring
about contraction of the smooth muscle, causing
vasoconstriction and hence decreased resistance to the
movement of air through the nasal cavities. is
sequence of events is the same as that leading to
vasoconstriction of the pre-capillary arterioles, which
plays a major role in determining blood pressure (see
Chapter 5, Section 5.1.4).
A prominent feature of rhinitis is inammation in the
nasal cavity. is immune response involves local
vasodilatation and increased permeability of the rich
network of blood vessels supplying the nasal mucosal
lining. As a consequence, the mucosal lining becomes
swollen with blood and uid, leading to symptoms of
congestion. Sympathomimetic drugs which mimic the
eects of adrenaline and noradrenaline are commonly
used to relieve congestion by causing local
vasoconstriction in the nasal cavities.
Myosin
MLCK
Myosin-P
CaM CaM-Ca2+
2+
Ca
- α1-adrenoceptor
Figure 10.2 Activation of 1-adrenoceptors on nasal blood vessels leads to
vasoconstriction.
Stimulation of Gq-coupled 1-adrenoceptors on nasal blood vessels leads to production of IP3
and subsequent increase in Ca2+ concentration inside the cell. A complex of Ca2+ and
calmodulin stimulates MLCK, which phosphorylates myosin, causing contraction of the
smooth muscle and hence vasoconstriction. NA/A, noradrenaline/adrenaline; IP3, inositol
1,4,5-trisphosphate; Cam, calmodulin; MLCK, myosin light chain kinase; Myosin-P,
phosphorylated myosin; ⊕, stimulates.
IP
3
Muscle contraction
NA/A
248 Chapter 10 Allergies: rhinitis and urticaria
Stimulation of the parasympathetic nervous system leads
receptors on goblet cells by acetylcholine
3
(ACh). ese receptors are also Gq-coupled, and the
resulting increase in intracellular Ca2+ concentration leads
to enhanced production of mucus. us, anticholinergic
agents are also used to treat simple rhinorrhea associated
with rhinitis.
10.1.2 Development of allergic rhinitis
is can be divided into three phases.
Sensitization phase On rst contact with an antigen
such as pollen, antigen-presenting cells (APCs) ingest the
antigen, process it, and produce an antigen complex
which is presented on the cell surface. is in turn
activates T-cells which proliferate and dierentiate,
yielding T-helper cells. Some of these (the 2 cells)
cooperate in the activation of B-cells to give rise to
memory cells, and to plasma cells which secrete
antibodies targeted against the antigen (see Figure P3.2 in
the Introduction to Part 3). In allergy, it is the production
specically of immunoglobulin E (IgE) type antibodies
that is provoked. Some of these IgE molecules x onto the
surface of mast cells.
Early response When re-exposure to the same antigen
(allergen) occurs, it will interact with the mast cell
attached IgE specically directed against it. is
interaction of antigen and antibody leads to mast cell
degranulation, with release of mediators of inammation,
predominantly histamine (see Figure P3.1 in the
Introduction to Part 3). is phase occurs promptly on
contact with the allergen and is short-lived, usually
lasting around an hour. Symptoms include sneezing and
clear rhinorrhea.
Late response is develops in about half of patients
approximately 3–6 hours after the allergen exposure and
can last for up to 4 hours. e underlying complex
inammatory process involves inltration of the area by
many cell types, including eosinophils and basophils,
with the release of numerous pro-inammatory
leukotrienes, prostaglandins, and cytokines. Nasal
congestion is a key symptom of the late phase. Longer
exposure to the antigen results in an increased duration
of the late response.
ese processes are similar to those seen in asthma,
described in more detail in Chapter 11, Box 11.1. e
similarities have led to the development of the ‘one airway
hypothesis’, in which the two conditions are viewed by
some clinicians as manifestations of the same disease.
Both the patient’s genetic make-up and their environment
are implicated in the development of allergic rhinitis.
Having one or more parents with atopic symptoms (e.g.
asthma, rhinitis, and/or atopic dermatitis) increases the
risk of developing rhinitis (and other diseases associated
with atopy). Excessive hygiene and sterilization of a child’s
environment has also been implicated. is ‘hygiene
hypothesis’ is centred on the dierentiation of activated
T-lymphocytes into either 1 or 2 cells. Bacteria and
viruses in a child’s environment stimulate responses by
1 lymphocytes, with a concomitant decrease in the
2-mediated response. Reduced exposure to such
pathogens could therefore result in a 2-dominated
immune response, as seen in allergic disease.
10.2 Treatment of allergic rhinitis
A number of dierent drug types are used to manage the
symptoms of allergic rhinitis. Antihistamines,
anticholinergics, and decongestants are eective in
modifying the early response, whilst nasal antiinammatory drugs and leukotriene receptor antagonists
modify the late-response reactions. For seasonal allergic
rhinitis (e.g. hay fever), treatment should begin 2–3 weeks
before the season starts. Drugs may need to be continued
for years for persistent allergic rhinitis.
10.2.1 Antihistamines
As noted previously, histamine is the major mediator
released in the early-response phase of rhinitis.
Histamine is a basic amine that acts as an agonist at a
family of G-protein-coupled receptors (GPCRs)
comprising four receptor subtypes (see Table 10.2). e
H1 receptor is the subtype primarily involved in allergic
reactions. Activation of these receptors at the sites shown
in Figure 10.3 gives rise to the symptoms of itching,
rhinorrhea, and sneezing in this early phase.
Antihistamines are a large class of drugs used for a
variety of clinical conditions, including allergic rhinitis,
for which they have been the agent of choice for many
decades. Antihistamines act as inverse agonists, rather
than the classic antagonists described in Chapter 2,
Section 2.1. Inverse agonism depends on the receptor
being constitutively active in the absence of any
ligandbinding. An equilibrium will therefore exist
10.2 Treatment of allergic rhinitis 249
Table 10.2 Effects mediated by the different histamine
receptor subtypes
Physiological effect H1H2H
Stimulation of gastric secretion
Contraction of smooth muscle
(except vascular)
Vasodilatation
Increased vascular permeability
Cardiac stimulation
Central nervous system arousal
and wakefulness
Inhibition of neurotransmitter
release in the central nervous
system
Migration and activation of
mast cells
H
3
4
between receptors in their active and inactive states.
Antihistamines exert their antagonist eect by stabilizing
the receptor in its inactive state, thereby preventing its
activation by histamine.
e drug class can be divided into H1 and H2
antihistamines. Not surprisingly, it is the H1 type which is
used in allergic rhinitis, blocking the eects of histamine
at the locations shown in Figure 10.3. (H2 antihistamines
are used for gastrointestinal hyperacid conditions; see
Chapter 12 for details.) In practice, the term
antihistamine is reserved for agents that modify the eect
of histamine at H1 receptors.
H1 antihistamines are subdivided into sedating and
non-sedating antihistamines, depending on their ability
to cross the blood–brain barrier.
Sedating antihistamines
ese are the oldest members of this drug class, and are
also referred to as rst-generation antihistamines. e
group can be further subdivided into ve classes based on
structure (Table 10.3). Although these drugs are eective
in allergic rhinitis, they easily penetrate the blood–brain
barrier and antagonize H1 receptors in the brain, giving
rise to their most prominent adverse eects which include
sedation, CNS depression, and cognitive impairment.
Whilst the sedative eect is unwanted in treating allergies,
Mast cells
Antihistamines
Histamine
Sensory nerves
Itching/sneezing/pain
Goblet cells
Increased mucus
secretion
Blood vessels
Vasodilatation
Increased vascular
permeability
Figure 10.3 Effects of histamine acting at H1 receptors which are blocked
by antihistamines.
250 Chapter 10 Allergies: rhinitis and urticaria
Table 10.3 First-generation antihistamines used in allergy and other applications
Class Examples Other uses
Sedation Cough, cold, and flu Nausea/vomiting
Ethylenediamines Mepyramine
Antazoline
Ethanolamines Diphenhydramine
Clemastine
Dimenhydrinate
Doxylamine
Alkylamines Pheniramine
Chlorphenamine
Dexchlorpheniramine
Brompheniramine
Triprolidine
Piperazines Cinnarizine
Cyclizine
Hydroxyzine
Meclizine
Tricyclics and tetracyclics Promethazine
Trimeprazine
Cyproheptadine
Azatadine
Ketotifen
+, Indication; + +, major indication with preparations specifically for this.
+ +
+ +
+ +
+
+
+ +
+ +
+
+ +
+ +
+ +
+ +
+ +
+ +
+ +
+ +
+
+
it has been put to advantage in the short-term treatment
of insomnia, and explains the inclusion of such drugs in
several over-the-counter sleep remedies. Antagonism of
H1 receptors in the area of the brain which regulates
motion sickness (chemoreceptor trigger zone (CTZ); see
Chapter 12) underlies the use of some sedating
antihistamines as anti-emetics (e.g. cinnarizine,
cyclizine). Such drugs also interact with other substances
that depress the CNS, such as hypnotics and alcohol, to
produce an additive eect. is interaction is explored
further in Workbook 7 at the end of this chapter.
In addition to acting at H1 receptors, many of these drugs
act non-selectively at a number of other receptors,
including 5-hydroxytryptamine (serotonin) receptors
(e.g. cyproheptadine) and 1-adrenoceptors (e.g.
promethazine), giving rise to additional side eects.
Many exert antagonist eects at muscarinic acetylcholine
receptors (mAChRs), leading most commonly to dry
mouth, but also sometimes to blurred vision, urinary
retention, and constipation. is antimuscarinic eect is
put to advantage in cough and cold preparations,
combining with the antihistamine action to treat
symptoms (see anticholinergic drugs below). Table 10.3
details the uses of the dierent classes of sedating
antihistamines.
Non-sedating antihistamines
e newer classes of H1 antihistamines (second and third
generation) have better receptor selectivity and therefore
reduced side eects compared with the older drugs. is,
combined with reduced ability to cross the blood–brain
barrier, results in a marked reduction in CNS eects,
although some of these drugs can still cause drowsiness.
(ey are sometimes referred to as less-sedating
antihistamines for this reason.) Most guidelines
recommend oral non-sedating antihistamines as rst-line
agents for mild allergic rhinitis.
Two second-generation antihistamines, terfenadine and
astemizole, were shown to cause serious cardiac
arrhythmias and have therefore been withdrawn. is, in
part, led to the development of closely related thirdgeneration agents. For example, fexofenadine is the
active metabolite of terfenadine, but lacks the cardiac
eect of the parent compound. Similarly, desloratadine
is the active metabolite of loratadine. e secondgeneration drug cetirizine is a racemic mixture of - and
10.2 Treatment of allergic rhinitis 251
-isomers. Separation of the active -isomer has yielded
the third -generation drug levocetirizine.
Another advantage of the newer antihistamines is their
prolonged duration of action; most are given once or
twice a day. In contrast, many of the older antihistamines
require dosing up to four times a day, unless taken as a
sustained-release preparation.
Nasal spray preparations of antihistamines, such as
levocabastine and azelastine, are also available, and
have an even lower risk of sedation. However, they have
little eect on the non-nasal symptoms of allergic rhinitis,
such as itchy eyes, although eyedrop preparations are
also available. Ketotifen and emedastine, also available
as eyedrops, have combined actions to block H1 receptors
and to stabilize mast cells (see also cromolyns, Section
10.2.3). Olopatadine and rupatadine, H1 receptor
antagonists which additionally block the actions of other
pro-inammatory cytokines including platelet-activating
factor (PAF) and leukotrienes, are also available as
eyedrops.
10.2.2 Corticosteroids
Evidence indicates that persistent (i.e. >4 weeks)
moderate/severe symptoms of allergic rhinitis are best
managed through use of nasal corticosteroids. Briey,
these lipophilic molecules are able to enter cells, and
bind to receptors in the cytoplasm. e steroid–receptor
complex is then translocated to the nucleus, where it acts
to either induce or repress the transcription of various
genes (see Chapter 9, Section 9.3.2 and Box 9.2, for more
details). e net eect in inammation is reduced
production of inammatory mediators, and suppression
of the recruitment or proliferation of immune cells such
as T-cells and macrophages. Corticosteroids are powerful
anti-inammatory agents but, when taken orally, have
the potential for signicant and potentially serious
adverse events, including thinning of the skin, fat
redistribution, osteoporosis, and increased risk of
infections (see Chapter 9, Section 9.3.2 and Table 9.3, for
further details). Very disabling symptoms of allergic
rhinitis may occasionally justify the use of systemic
corticosteroids, but only for short periods so as to
minimize adverse eects.
Corticosteroids are more usually administered locally at
low dose directly into the nasal passages, either as drops
or a spray. Absorption into the bloodstream is therefore
limited, reducing the occurrence of adverse eects. e
corticosteroids used nasally are the more potent drugs,
and include fluticasone, triamcinolone, budesonide,
beclometasone ciclesonide, and mometasone. Most
can be used once daily, apart from beclometasone and
budesonide which are normally administered twice daily,
although a single dose may be possible with budesonide.
Common adverse eects of nasal corticosteroids are local
irritation, stinging and dryness, and nosebleeds
(epistaxis). Because of the way in which corticosteroids
work their main drawback is slow onset of action, often
requiring use over several days before an eect is seen. A
topical or oral decongestant (see below) can therefore be
useful for the rst few days before the corticosteroid starts
to take eect.
10.2.3 Other treatments for rhinitis
Although antihistamines and nasal corticosteroids are the
principal drugs used to manage allergic rhinitis, other
classes of medication are available for use where they
have not been eective, are contraindicated, or not
tolerated.
Cromolyns
ese are referred to as mast cell stabilizers because of
their ability to inhibit the release of histamine. is action
alone, however, does not fully explain their therapeutic
eect. A number of additional modes of action have been
proposed, including blockade of chloride channels and
reducing sensory nerve activity.
Cromolyns do not interfere with the action of histamine
once released, and so must be used prophylactically;
administration must be started several weeks before the
anticipated allergy season. is limits their usefulness for
suerers of intermittent allergic rhinitis, as onset of
symptoms cannot always be anticipated. Cromolyns
have few side eects and are generally well tolerated.
One disadvantage is their short duration of action; they
must be used four to six times a day, which could lead to
reduced compliance and therefore reduced
eectiveness.
e two cromolyns in use are sodium cromoglicate and
nedocromil. Sodium cromoglicate is used as a nasal
spray prophylactically in persistent allergic rhinitis. It is
also used rst line in children with moderate to severe
symptoms, because unlike steroids it does not present a
risk of growth inhibition. Nedocromil is given as eyedrops
for allergic conjunctivitis.