ANTIHISTAMINE

Allergy
 Antihistamine
■ A drug that reduces or eliminates the effects mediated by
the chemical histamine.
■ Refers to H1 receptor antagonists (actually inverse agonists)
■ Antihistamines compete with histamine for binding sites at
the receptors. Antihistamine cannot remove the histamine if
it is already bound.
 Antihistamine
■ Histamine is released by the body during an allergic reaction
and acts on a specific histamine receptor.
■ True antihistamines are only the agents that produce a
therapeutic effect that is mediated by negative modulation
of histamine receptors (other agents may have anti-
histaminergic action but are not true antihistamines)
 Allergies
■ are caused by a hypersensitivity reaction of the antibody
class IgE (which are located on mast cells in the tissues and
basophils in the blood)
■ When an allergen is encountered, it binds to IgE, which
excessively activates the mast cells or basophils, leading
them to release massive amounts of histamines.
 Allergy
■ These histamines lead to inflammatory responses ranging
from runny nose to anaphylactic shock
■ If both parents have allergies, the children have a 70% of
having them, if only one parent does, about 48% chance the
children have
 Allergies Structure of Histamine Mast Cells
Mast Cells
■ When it is released, histamine causes inflammation by
increasing vasodilation, capillary permeability, causing smooth
muscle contraction, mucus secretion, and parasympathetic
nerve stimulation
Structure of Histamine
■ Histamine is distributed in Mast Cells in all peripheral tissues of
the body and basophils, which circulate in the blood.
 Clinical Uses of Antihistamines
■ Allergic rhinitis (common cold)
■ Allergic conjunctivitis (pink eye)
■ Allergic dermatological conditions
■ Urticaria (hives)
■ Angioedema (swelling of the skin)
■ Pruritus (atopic dermatitis, insect bites)
■ Anaphylactic reactions (severe allergies)
■ Nausea and vomiting (first generation H1- antihistamines)
■ Sedation (first generation H1-antihistamines)
Role of Histamine in Allergy and Anaphylaxis
■ Histamine causes contraction of airway smooth muscle, stimulation of
secretions, dilation and increased permeability of the capillaries, and
stimulation of sensory nerve endings
■ If the release of histamine is slow enough to permit its inactivation
before it enters the bloodstream, a local allergic reaction results
■ If histamine release is too fast for inactivation, a full-blown
anaphylactic reaction occurs.
 H1-Antihistamine
q Allergic and inflammatory conditions
§ H-1 receptor blockers are useful in treating and preventing allergic reactions
caused by antigens acting on IgE antibody
■ Oral antihistamines are the drugs of choice in controlling the symptoms of
allergic rhinitis and urticaria because histamine is the principal mediator
released by mast cells
■ Ophthalmic antihistamines are useful for the treatment of allergic
conjunctivitis
■ Not implicated in asthma
 Histamine
q Motion sickness and nausea
■ Diphenhydramine, dimenhydrinate, cyclizine, meclizine and promethazine are
effective for prevention of the symptoms of motion sickness
■ Not effective if symptoms are already present
■ Taken prior to expected travel
■ Antihistamines prevent or diminish nausea and vomiting mediated by the
chemoreceptor and vestibular pathways
■ The antiemetic action is due to blockade of central H1 and M1 muscarinic receptors
■ Meclizine is useful for the treatment of vertigo associated with vestibular disorders
 H-1 Antihistamine
Somnifacients
q Many first-generation antihistamines, such as diphenhydramine and doxylamine
have strong sedative properties
q Used in the treatment of insomnia
q Available OTC without a prescription
q Use is contraindicated in individuals working in jobs in which wakefulness is critical
q Antihistamines are not the medications of choice especially for those job who is
operating a machinery
 Pharmacokinetics
■ H1-receptor blockers are well absorbed after oral administration, with maximum
serum levels occurring at 1 to 2 hours
■ Average: ½ tab is 4 to 6 hours, except for that of meclizine and the second
generation agents which is 12 to 24 hours
■ First-generation H1- receptor blockers are distributed in all tissues, including CNS
■ Most are metabolized by the hepatic system
■ Cetirizine and levocetirizine are excreted largely unchanged in urine
■ Fexofenadine is excreted largely unchanged in feces
■ Some are available as ophthalmic or intranasal formulations
 Classification of H-1 Receptors Blockers
■ The H1-receptor blockers can be divided into:
■ First generation drugs:
1. Penetrate the CNS and cause sedation
2. Interact with other receptors, producing a variety of unwanted adverse effects
■ Second generation drugs/agents:
1. Specific for peripheral H1 receptors
2. Do not penetrate the BBB causing less CNS depression than the first generation drugs
■ Desloratadine, fexofenadine and loratadine show the least sedation
■ Cetirizine and levocetirizine are partially sedating
 Samples of the First Generation Drugs
■ Diphenhydramine
■ Dimenhydrinate
■ Doxylamine
■ Promethazine
■ Hydroxyzine
■ Pheniramine
■ Cyroheptadine
■ Meclizine
■ Chlorpheniramine
■ Dexchlorpheniramine
 Samples of the Second Generation Agents
■ Cetirizine
■ Levocetirizine
■ Fexofenadine
■ Loratidine
■ Desloratidine
■ Ebastine
■ Astemizole
■ Acrivastine
 Conditions That Release Histamine 1
■ Tissue injury: Any physical or chemical agent that injures tissue, skin or mucosa are
particularly sensitive to injury and will cause the immediate release of histamine
from mast cells.
■ Allergic reactions: exposure of an antigen to a previously sensitized (exposed)
subject can immediately trigger allergic reactions. If sensitized by IgE antibodies
attached to their surface membranes will degranulate when exposed to the
appropriate antigen and release histamine, ATP and other mediators.
■ Drugs and other foreign compounds: morphine, dextran, antimalarial drugs, dyes,
antibiotic bases, alkaloids, amides, quaternary ammonium compounds, enzymes
(phospholipase C). Penicillins, Tetracyclines, Basic drugs- amides, amidines,
diamidines, Toxins, venoms, Proteolytic enzymes, Bradykinin,
 3 Types of Histamine Receptors
■ H1 receptors: mediate effects on smooth muscle leading to
vasodilation, increased vascular permeability, and contraction of
nonvascular smooth muscle.
■ H2 receptors: mediate histamine stimulation of gastric acid secretion
and may be involved in cardiac stimulation.
■ H3 receptors: feedback inhibitors in CNS, gastrointestinal tract, lung,
heart.
Pharmacological Effects of Histamine 1.
■ Cardiovascular system
a) triple effect on terminal vasculature (itching & pain):
b) reddening at injection site due to vasodilation
c) wheal or disk of edema within 1 to 2 min iii. a large, bright crimson flare or
halo surrounding the wheal
d) I.V. histamine: fall in blood pressure, cutaneous flushing, over the face and
upper trunk, rise in skin temperature, intense headache. system: itching
and pain
■ Smooth muscle of bronchioles; causes contraction of nonvascular
smooth muscle. Asthmatics may experience marked bronchial
constriction compared with normal subjects.
■ Exocrine glands: potent stimulator of gastric secretion (HCl & pepsin),
enhances salivary and lacrimal gland secretion (minimal unless large
doses are given), stimulates chromaffin cells in adrenal medulla to
secrete catecholamines.
■ Peripheral Nervous system: itching and pain
 Contraindications and Cautions
■ Pregnancy and lactation. Antihistamines are contraindicated during pregnancy and
lactation unless the benefit to the mother clearly outweighs the potential risk to the
fetus or baby.
■ Renal or hepatic impairment. They should be used with caution in renal or hepatic
impairment, which could alter the metabolism and excretion of the drug.
■ Arrhythmias. Special care should be taken when these drugs are used by any patient
with a history of arrhythmias or prolonged QT intervals because fatal cardiac
arrhythmias have been associated with the use of certain antihistamines and drugs
that increase QT intervals, including erythromycin.
 Adverse Effects of Antihistamines
■ CNS: Drowsiness and sedation.
■ GI: Drying of the GI mucous membranes, GI upset, nausea.
■ GU: Dysuria, urinary hesitancy.
■ Skin: Skin eruption and itching.
Interactions
■ Monoamine inhibitor (MAOI). Anticholinergic effects may be prolonged if
diphenhydramine is taken with a monoamine inhibitor.
■ Ketoconazole/erythromycin. Interaction of fexofenadine with ketoconazole or
erythromycin may raise fexofenadine concentrations to toxic levels.
 Nursing Assessment
■ Assess for possible contraindications or cautions: any history of allergy to
antihistamines; pregnancy and lactation; and prolonged QT interval, which are
contraindications to the use of the drug; and renal or hepatic impairment, which requires
cautious use of the drug.
■ Perform a physical examination to establish baseline data for assessing the
effectiveness of the drug and the occurrence of any adverse effects associated with the
drug therapy.
■ Assess the skin color, texture, and lesions to monitor for anticholinergic effects or allergy.
■ Evaluate orientation, affect, and reflexes to monitor for changes due to CNS effects.
■ Assess respirations and adventitious sounds to monitor drug effects.
■ Evaluate renal and liver function tests to monitor for factors that could affect the
metabolism or excretion of the drug.
 Nursing Implementation
with Rationale
■ Proper administration. Administer drug on an empty stomach, 1 hour before or 2
hours after meals, to increase the absorption.
■ Drug effectiveness. Note that the patient may have a poor response to one of these
agents but a very effective response to another; the prescriber may need to try
several different agents to find the one that is most effective.
■ Relief from dry mouth. Because of the drying nature of antihistamines, patients
often experience dry mouth, which may lead to nausea and anorexia; suggest
sugarless candies or lozenges to relieve some of the discomforts.
■ Safety measures. Provide safety measures as appropriate if CNS effects occur to prevent
patient injury.
■ Increase fluid intake. Increase humidity and push fluids to decrease the problem of
thickened secretions and dry nasal mucosa.
■ Ensure voiding. Have patient void before each dose to decrease urinary retention if this
is a problem.
■ Skin care. Provide skin care as needed if skin dryness and lesions become a problem to
prevent skin breakdown.
■ Avoid alcohol. Caution the patient to avoid alcohol while taking these drugs because
serious sedation can occur.
■ Avoid OTC drugs. Caution the patient to avoid excessive dose and to check OTC drugs for
the presence of antihistamines, which are found in many OTC preparations and could
cause toxicity.
■ Health teaching. Provide thorough patient teaching, including the drug name and
prescribed dosage measure to help avoid adverse effects, warning signs that may
indicate problems, and the need for periodic monitoring and evaluation, to enhance
patient knowledge about the drug therapy and promote compliance.
■ Encourage patient support. Offer support and encouragement to help the patient cope
with the disease and the drug regimen.
 Evaluation
■ Monitor patient response to the drug (relief of the symptoms of allergic rhinitis).
■ Monitor for adverse effects (skin dryness, GI upset, sedation and drowsiness,
urinary retention, thickened secretions, glaucoma).
■ Evaluate the effectiveness of the teaching plan (patient can name drug, dosage,
adverse effects to watch for, specific measures to avoid them, and measures to take
to increase the effectiveness of the drug.
■ Monitor the effectiveness of comfort and safety measures and compliance with the
regimen.