A Textbook of Clinical Pharmacology and Therapeutics

antihistaminic actions are similar when used in clinically appro-
priate 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,cet-
irizineandloratadinehave half-lives that permit once or
twice daily dosing. They do not penetrate the blood–brain
barrier and cause less psychomotor impairment than first-
generation 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.

Contraindications

Antihistamines should be avoided in porphyria and in the

Ward–Romano syndrome (congenital long-QT syndrome).

ADRENALINE (EPINEPHRINE)

Adrenaline(epinephrine) is uniquely valuable therapeutic-

ally in anaphylactic shock. Its rapid action may be life-saving

in general anaphylaxis due to insect venom allergy and reac-

tion 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-inflamma-

tory 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).


2. 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 pre-

scribed. If the symptoms are due to allergy, the first step in ther-

apy 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. olopatadineorazelastine)

or intranasal cromoglicateor a shorter-acting non-sedating

systemic antihistamine (e.g. acrivastineorfexofenadine) is

effective. Short-term use of a nasal decongestant such as

pseudoephedrineis 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 first-

line therapy is intranasal glucocorticosteroids because these are

effective against all symptoms, and are more effective than anti-

histamines or cromoglicate. In children, topical cromoglicate

given by insufflator or nasal spray is useful. If rhinorrhoea is the

main problem, ipratropium bromidemay 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.

406 CLINICAL IMMUNOPHARMACOLOGY

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 shorter-
  acting 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.