Chapter 66 Antihistamine (Do Not Erase)

7/31/2019 Chapter 66 Antihistamine (Do Not Erase)

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Chapter 66Antihistamines

Pharmacology forNursing Care 5 th Edition

Pages 734-740


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Objectives

Define Histamine;

Enumerate two types of Antihistamines;H1 Antagonist I: Basic Pharmacology;H1 Antagonist II: Preparations.


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HISTAMINE


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Histamine

An endogenous compound found in

specialized cells throughout the bodyPlays an important role in allergic reactionsand gastric acid secretions(Antihistamines) Blocks histamines

actionHistamine is still of great interest because ofits involvement in two pathologic states:allergies and peptic ulcer


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DISTRIBUTION,SYNTHESIS,

STORAGE AND

RELEASE


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Distribution

Histamine: present in practically ALL its

tissues

Levels of histamine are high in the skin,lungs, and GI tract


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Synthesis and Storage

histamine: synthesized and stores in two

types of cells: Mast cells : present in the skin and soft tissues Basophils : present in the blood

In both, mast cells and basophils, histamine

is stored in structures called secretorygranules. Secretory granules: contain other substances that are

mediators to allergic reactions.


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Release

Allergic Release: initial requirement for

allergic release of histamine is theproduction of IgEThese antibodies are generated in response to exposureto specific allergens .The antibodies become attached to the outer surface ofthe mast cells and basophils.


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ReleaseWhen the subject is re-exposed to the allergen, theallergen becomes bound by the antibodies

Note: allergic release of histamine requires priorexposure to the allergen; an allergic reaction cannotoccur during initial contact with an allergen

Nonallergic Release: a number of agents canact directly on mast cells to cause histaminerelease. With these agents, no priorsensitization is needed. Cell injury can alsocause direct release of histamine


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PHYSIOLOGIC ANDPHARMACOLOGIC

EFFFECTS

(H1 and H 2 Receptors)


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Effects of H 1 Stimulation

Vasodilation H1 causes dilation of small bloodvessels.prominent in the skin of the face

and upper body causing the area to becomewarm and flushed.

Increased capillary permeability histamine 1 causes capillary endothelial cells to contract,which creates openings between these cellsthrough which fluid, protein and platelets canescape.


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Bronchoconstriction H1 stimulation causesconstriction of the bronchi

exogenous histaminecan stimulate bronchial constriction,*histamine is not the cause of bronchoconstriction during spontaneous asthma attacks.

Other effects: itching, pain, secretion ofmucus, sedation (CNS)


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Response to activation of H 2 stimulation is

secretion of gastric acidAlthough acetylcholine and gastrin also helpregulate acid release, histamine has adominant role.


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Role of Histamine in Allergic Response

Mild Allergy : symptoms of mild allergy arecaused by histamine,. As a result, mild allergicconditions are generally responsive toantihistamine therapy.Sever Allergic Reactions (Anaphylaxis): severe allergic reactions manifest anaphylacticshock. Although histamine is involved inanaphylaxis, it plays a minor role; othersubstance* are principal causative agents.


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Since histamine has little to do with

producing anaphylaxis, it follows thatantihistamines are of little help as treatment.(drug choice for anaphylactic shock:epinephrine )


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THE TWO TYPES OFANTIHISTAMINES(H1 Antagonist and H 2

Antagonist)


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Two Types of Antihistamines

2 basic categories: H1- Receptor

Antagonist and H2- Receptor AntagonistH1 Antagonist : produce selective blockadeof H1 receptorsH2 Antagonist: Produce selective blockadeof H2 receptors


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Two Types of Antihistamines

H1 Blockers: for treatment of mild allergic

disordersH2 Blockers: for treatment of gastric andduodenal ulcers

*because H 2 antagonist do not block H 1receptors, these drugs are no use for treating allergies


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H1 ANTAGONIST I:BASICPHARMACOLOGY


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H1 Antagonist I: Basic Pharmacology

H1 antagonist are the classic antihistamine.

These agents were in use longer before H2blockers were developed.*Although all H1 antagonist available havesimilar antihistaminic actions, these drugs

differ significantly in side effects. Because ofthese differences, selection of a prototype torepresent the group is not possible.


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Classification of H1 Antagonist

2 Major Groups :

First Generation H1 Antagonist : highlysedating

Second Generation H1 Antagonist : nonsedating


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Mechanism of ActionH1 blockers bind selectively to H1-histaminereceptors, thereby blocking the action of histaminesat these sites. H1 antagonist do not block H2receptors. Also, they do not block release ofhistamine from mast cells or basophils**It should be noted that, although interaction of the

classic antihistamines with histaminic receptorsubtype, these drugs can also bind to nonhistaminic receptors.


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Of particular significance is the ability ofcertain antihistamines to bind to and blockmuscarinic receptors. This action underliesseveral important side effects.


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Pharmacologic Effects

Peripheral Effects : prevents action of

histamine at H1 receptors.Effects on the CNS : cause both excitationand depression of the CNS. At therapeuticdoses, antihistamines produces CNS

depression. *With second-generationantihistamines, CNS depression isinsignificant.


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Over dosage : can produce CNS stimulation.Convulsions frequently result.Other pharmacologic effects:anticholinergic responses (due to the

blockade of muscarinic receptors byhistamine)


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Therapeutic Uses

All H1 antagonist are useful in treating allergic disorders. Some drugs are also indicated for other conditions (e.g. motion sickness, insomnia)Mild Allergy

Seasonal allergic rhinitis (aka hay fever/ rosefever): H1 blockers can reduce sneezing,rhinorhrrea, and itching of the eyes, nose adthroat.


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Acute urticaria: reduce redness, itching, andedema

The antihistamines can also reduce symptoms ofallergic conjunctivitis and urticaria assoc. withmild transfusion reactions.

Severe Allergy As noted, the major symptoms of anaphylaxis are

caused by mediators other than histamine.Although antihistamines may be employed asadjuncts in patient with anaphylaxis, their benefits

are minimal.


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Motion sickness

Benefits derive from blockade of H1 receptorsand murcarinic receptors in the neuronal pathwayleading form the vestibular apparatus of theinnner ear to the vomiting center of the medula.

InsomniaCommon cold These drugs neither prevent cold nor shorten their

duration. Moreover, since histamine does not

mediate symptoms of colds.


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Adverse EffectsSedation

Common undesired effect of antihistamines If a preparation with a long half-life is being used,

daytime sedation can be minimized byadministering the entire daily dose at night.

Advise patients to avoid driving or any hazardous

activities if alertness is impaired. Advise patient to avoid alcohol and other CNS

depressants: because these agents willintensify the depressant effects of H1antagonist


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Second-generation antihistamines: exert littleeffect or no sedative effect. (recall: second-

generation H1antagonist are nonsedating) . Theseagents are unable to cross the blood-brain barrier,and therefore cannot alter CNS function.

For patients who experience disabling sedation

with H1 antagonist, therapy with secondgeneration antihistamine is likely to help.


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GI effects

GI disturbances: include nausea, vomiting, loss ofappetite, diarrhea, constipation. These reactions can be minimized by

administering antihistamines with meals.


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Anticholinergic effects Antimuscarinic actions can produce drying of

mucous membranes in the mouth, nasalpassages, and throt.

Cholinergic blockade: urinary hesitancy,constipation and palpitations

Dry mouth discomfort can be minimized bysucking on hard CANDY and by taking frequentsips of fluidPatients with asthma this should be used withcaution because this thickening of bronchialsecretions may impair breathing


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Care should also be exercised in patients with

other conditions that may be exacerbated bymuscarinic blockade (e.g. urinary retention,hypertension, prostatic Hypertrophy).

Second-generation antihistamines are LEAST

anticholinergic


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Drug Interactions

CNS depressants Alcohol and other CNS deppresants can intensify

the depressant effects of H1 antagonist. if medications with CNS-depressant properties

are combines with H1 blockers, dosage of thedepressants may need to be LOWERED.


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Use in Pregnancy and Lactation

Pregnancy Safety of antihistamines in pregnancy is unknown there have been reports of fetal malformation, but

direct involvement of H1 antagonist is has notbeen proved.

It is recommended that antihistamines should beused only when clearly necessary, and onlybenefits of treatment outweigh the potential risk ofthe fetus.


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Antihistamines should avoided late in the thirdtrimester, because newborns are particularlysensitive to the adverse reactions of these drugs(recall: adverse effects sedation, nonsedativeeffects, GI effects, anticholinergic Effects)


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Lactation H1 antagonist can be excreted in the breast milk,

thereby posing a risk to the infant. Since infants and newborns are sensitive to

antihistamines, these drugs should be not usedby women who are breast-feeding


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Acute Toxicity

Although antihistamines have a large marginof safety, acute poisoning is nonethelesscommon, owing to the widespread availabilityof these drugs.CNS effects are prominent, especially

anticholinergic reactions.


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Symptoms and TreatmentSymptoms

Anticholinergic actions of H1blockers produce symptoms

resembling those of atropinepoisoning (dilated pupils, flushedface, hyperpyrexia, tachycardia,dry mouth, urinary retention

In children: excitation,hallucination, incoordination,ataxia, convulsions

Treatment No specific antidote for

antihistamine poisoning. Hence,

treatment is directed at drugremoval and managingsymptoms.

Emesis should be induced toexpel the drug from the stomach(activated charcoal + cathartic isgiven to minimize absorption ofthe drug)

Convulsion treated with IVphenytoin ( avoidanticonvulsants with CNSdepressants)

hyperthermia can be reduced byapplication of icepacks or by


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H1 ANTAGONIST II:PREPARATIONS


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First-Generation H 1 Antagonists(sedating)

5 major categories Alkylamines Ethanolamines Ethylenediamines Phenothiazines Piperidines

These groups differ in antihistaminic efficacyand the ability to cause sedation andmuscarinic blockade.


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Second-Generation H 1 Antagonist(nonsedating)

Fexofenadine (Allegra): oral therapy for seasonalallergic rhinitis and for chronic idiopathic urticaria.

Fexofenadine appears to offer the best combinationof efficacy and safety.Cetirizine (Zyrtec): indicated for chronic idiopathicurticaria and for seasonal and perennial allergicrhinitis. Cetirizine is eliminated by a combination ofhepatic meatbolism and renal exceretion.Loratadine (Claritin): indicated for chronicidiopathic urticaria and seasonal allergic rhinitis.


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Desloratadine (Clarinex): major activemetabolite of loratadine (Claritin). Indicatedfor idiopathic urticaria and seasonal allergicrhinitis.Azelastine (Astelin): unique among the 2 nd generation agents. (1) azelastine isadministered by nasal spray, (2) azelastineblocks the release of histamine and othermediator form mast cells.


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END

Prepared byNorjetalexis M

Cabrera

ADZU BSN 2

Chemistry 209

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Chapter 66 Antihistamine (Do Not Erase)