A-Textbook-of-Clinical-Pharmacology-and-Therapeutics-5th-edition

406 CLINICAL IMMUNOPHARMACOLOGY
antihistaminic actions are similar when used in clinically appropriate
dosage, but their major differences are in duration of
effect, degree of sedation and anti-emetic potential.
Uses
These include the following:
• hypersensitivity reactions;
• urticaria and hay fever;
• bee and wasp stings;
• anti-emetic (e.g. cyclizine).
Mechanism of action
Antihistamines are competitive antagonists of histamine at
H 1 -receptors.
Pharmacokinetics
Antihistamines are rapidly absorbed from the intestine and
are effective within about 30 minutes. They generally undergo
hepatic metabolism. Newer agents, such as fexofenadine, cetirizine
and loratadine have half-lives that permit once or
twice daily dosing. They do not penetrate the blood–brain
barrier and cause less psychomotor impairment than firstgeneration
antihistamines.
Adverse effects
These include the following:
• sedation and psychomotor impairment, especially with
older (first-generation) agents;
• photosensitivity rashes;
• antimuscarinic effects: dry mouth, blurred vision, etc.
(first-generation agents);
• prolongation of the QTc and torsades de pointes.
Key points
Antihistamines and therapy of allergic disorders
• Antagonists at H 1 -receptors; widely available agents,
often without prescription (e.g. chlorpheniramine).
• Used to treat hay fever and urticaria, and also used as
therapy for motion sickness.
• Should not be applied topically for skin irritation, as
they may cause dermatitis.
• Hepatically metabolized (CYP3A – long- and shorteracting
drugs.
• Duration of effects often outlasts their presence in the
blood.
• First-generation agents are shorter acting (e.g.
chlorpheniramine), sedating and anticholinergic, better
anti-emetics, and have some 5HT and α-adrenoceptor
antagonist activity.
• Second-generation agents have few or no sedative or
ancilliary properties, and are longer acting (e.g.
cetirizine).
• Second generation agents (e.g. cetirizine, loratadine)
are safe (i.e. ventricular tachycardia is not a risk) if
co-prescribed with macrolides or azoles.
Contraindications
Antihistamines should be avoided in porphyria and in the
Ward–Romano syndrome (congenital long-QT syndrome).
ADRENALINE (EPINEPHRINE)
Adrenaline (epinephrine) is uniquely valuable therapeutically
in anaphylactic shock. Its rapid action may be life-saving
in general anaphylaxis due to insect venom allergy and reaction
to drugs. The usual dose is 0.5–1.0 mg, repeated after ten
minutes if necessary, given intramuscularly or if necessary
intravenously. It is effective by virtue of its α-agonist activity
which reverses vascular dilatation and oedema, and its
β 2 -agonist activity which produces cardiac stimulation and
bronchodilatation. It also reduces the release of pro-inflammatory
mediators and cytokines.
TREATMENT OF ANAPHYLACTIC SHOCK
1. Stop any drug or blood/blood product that is being
administered intravenously.
2. Adrenaline 0.5–1 mg i.m. or 0.25–0.5 mg i.v.
3. Intravenous fluid (e.g. 0.9% NaCl, normal saline).
4. Oxygen (high concentration FiO 2 28–40% ).
5. Hydrocortisone 100–200 mg intravenously.
6. Antihistamine intravenously (e.g. chlorpheniramine,
12.5 mg).
7. Consider nebulized salbutamol (2.5–5 mg) for residual
bronchospasm.
THERAPY OF ALLERGIC RHINITIS (HAY FEVER)
The patient who presents with symptoms of allergic rhinitis
should be assessed to ensure that infection is not the primary
problem. If infection is the cause, the presence of a foreign body
should be excluded and appropriate antibacterial therapy prescribed.
If the symptoms are due to allergy, the first step in therapy
is allergen avoidance and minimization of exposure (e.g.
to ragweed pollen). However, complete avoidance is difficult
to achieve. For patients with mild intermittent symptoms,
either intranasal antihistamine (e.g. olopatadine or azelastine)
or intranasal cromoglicate or a shorter-acting non-sedating
systemic antihistamine (e.g. acrivastine or fexofenadine) is
effective. Short-term use of a nasal decongestant such as
pseudoephedrine is effective, but if used for longer periods
causes rebound vasomotor rhinitis. Ipratropium bromide
administered intra-nasally may be added if rhinorrhoea is the
predominant symptom. If symptoms are more chronic, the firstline
therapy is intranasal glucocorticosteroids because these are
effective against all symptoms, and are more effective than antihistamines
or cromoglicate. In children, topical cromoglicate
given by insufflator or nasal spray is useful. If rhinorrhoea is the
main problem, ipratropium bromide may be added with or
without a long-acting antihistamine (e.g. cetirizine). If these
measures are ineffective, consider low-dose intranasal steroids,
or immunotherapy or surgery if there is evidence of sinusitis.