Chapter 18 - Pharm

7/27/2019 Chapter 18 - Pharm

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Chapter 18:

Autocoids and Antihistamines

Copyright 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.


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2Copyright 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.

Chapter 18 Outline

Autocoids and antihistamines

Histamine (H1 or H2)

Antihistamines (H1-receptor antagonists)

Peripheral (nonsedating) H1-receptor antagonists

Other autocoids


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Autocoids and Antihistamines

Haveles (p. 234)

Autocoids all occur naturally in the body, are

produced by many tissues, and are formed by

the tissues on which they actAgonists or antagonists include H1- and H2-

receptor antagonists (H-RAs) or blockers, the

eicosanoids (prostaglandins [PGs], thromboxanes

[TXs], and leukotrienes [LTs]), serotonin agonists,angiotensin inhibitors, and cytokinins


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Histamine

Haveles (pp. 234-235)

Pharmacologic effects

Adverse reactions

Uses

contd


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Histamine

Haveles (pp. 234-235) (Fig. 18-1)

A ubiquitous biogenic amine

Almost all mammalian tissues contain or can

synthesize histamine

In humans, histamine is stored in mast cells,

intestinal mucosa, and in the central nervous

system (CNS) (mast cell in tissue = basophil

in the bloodstream)

During an allergic reaction, mast cells degranulate

and histamine is released


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Pharmacologic Effects of

Histamine

Haveles (p. 234)

H1-agonist effects: vasodilation, increased

capillary permeability, bronchoconstriction,

and pain or itching in cutaneous nerveendings

H2-agonist effects: increased gastric acid

secretion

contd


7/357Copyright 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.


Histamine


Agents that block or antagonize the effects of

histamine at the H1-receptors are known as

H1-blockers orH1-RAs, and at the H2-receptors they are H

2-blockers orH

2-RAs



Adverse Reactions of Histamine

Haveles (p. 235)

When an allergic reaction occurs, an antibody-antigen reaction causes release of histamineand other autocoids

Anaphylaxis is a serious and sometimes fatalreaction to a foreign protein or drug introducedinto the body

Anaphylaxis may involve difficulty in breathing due tobronchoconstriction, convulsions, lapses intounconsciousness, and death

The predominant feature is bronchoconstrictioncontd




Other effects involve vasodilation and

increased capillary permeability, both of

which lead to decreased blood pressure

followed by shock and cardiovascularcollapse

contd




The drug of choice for anaphylaxis is

parenteral epinephrine

A physiologic antagonist that dilates bronchioles

via 2-receptors rather than an antihistamine An antihistamine is a pharmacologic antagonist that

blocks bronchoconstriction produced by histamine at the

same H1-receptor

Antihistamines antagonize only some of the effects of

histamine, and they work competitively, whereasepinephrine acts as a direct 2-agonist



Uses of Histamine

Haveles (p. 235)

No clinical uses of histamine have been

established



Antihistamines

(H1-Receptor Antagonists)


Pharmacologic effects

Adverse reactions

Toxicity

Uses

contd



Antihistamines

(H1-Receptor Antagonists)

Haveles (p. 235)

Antihistamine refers to agents that areH1-RAs or H1-receptor blockers

Many patients have seasonal allergic reactions

A mild allergic reaction to a drug may be treated

with antihistamines

Patients taking antihistamines may experience side

effects such as xerostomia

Antihistamines interact with many other drug groups

and are additive with other CNS depressants




Antihistamines

Haveles (pp. 235-236) (Fig. 18-2; Table 18-1)

Older H1-RAs have several pharmacologic

effects, including antihistaminic,

anticholinergic, antiserotonergic, and sedativeeffects

Effects can be divided into those caused by

blocking histamine at the H1-receptor and those

independent of this effect



H1-Receptor Blocking Effects of

Antihistamines

Haveles (p. 235)

Drugs that are H1-antagonists competitively block orantagonize histamines effect at the following sites

Capillary permeability: blocking capillary permeability

produced by histamine reduces tissue edema Vascular smooth muscle (vessels): antihistamines

block dilation

Nonvascular (bronchial) smooth muscle: because otherautocoids are also released in an anaphylactic reaction,antihistamines are not effective in counteracting all thebronchoconstriction present

Nerve endings: antihistamines can suppress itchingand pain associated with histamine-mediated reaction

at cutaneous nerve endings



Other Effects (Unrelated to H1-Blocking

Effects) of Antihistamines


CNS: antihistamines produce varying degrees ofCNS depression (may be used to induce sleep)

Anticholinergic: can be used to dry up secretions Antiemetic: some antihistamines, such as

meclizine (Dramamine, Bonine), havepronounced antiemetic or antimotion sicknessactivityAlso effective in controlling dizziness, nausea, and

vomiting with Mnires syndrome

Local anesthesia: may be used to provide somelocal anesthesia



Adverse Reactions of

Antihistamines Haveles (pp. 236-237) (Fig. 18-2)

Vary in relative amounts among the differentagents

CNS depression: can be a pharmacologic effect

or adverse reaction Sedation is the most common side effect associated

with older antihistamines; may be accompanied bydizziness, tinnitus, incoordination, blurred vision, andfatigue

When antihistamines are combined withdecongestants, CNS depression of the antihistamineis counteracted by CNS stimulation of thedecongestant

contd



Adverse Reactions of

Antihistamines

Gastrointestinal (GI) complaints associated

with antihistamines include anorexia, nausea,

vomiting, and constipation

Anticholinergic: H1-RAs have varyinganticholinergic effects

Anticholinergic effects lead to xerostomia



Toxicity of Antihistamines

Haveles (p. 237)

Antihistamine poisoning has become more

common in recent years

Excitation predominates in small children, andsedation can occur in adults

Death usually results from coma with cardiovascular

and respiratory collapse



Uses of Antihistamines


Allergic reactions: allergic rhinitis and

seasonal hay fever can be controlled by

antihistaminesAcute urticarial attacks can be treated

Nausea and vomiting: used to prevent and

treat motion sickness and to control

postoperative vomiting and vomiting induced

by radiation therapy

contd



Uses of Antihistamines


Preoperative sedation: because of their

sedative effects

Over-the-counter sleep aids: diphenhydramine(Nytol) is used in over-the-counter sleep aids

Local anesthesia: diphenhydramine (Benadryl)

can be used by injection to provide some localanesthesia



Examples of Antihistamines

Haveles (p. 236) (Table 18-1)

Ethanolamines

diphenhydramine (Benadryl)

carbinoxamine (Clistin) clemastine (Tavist)

Ethylenediamines

tripelennamine (PBZ)

pyrilamine (various)

contd


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Alkylamines

chlorpheniramine (Chlor-Trimeton)

dexchlorpheniramine (Polaramine) brompheniramine (Dimetane)

Phenothiazines

promethazine (Phenergan)

contd


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Piperadines

cyproheptadine (Periactin)

azatadine (Optimine) phenindamine (Nolahist)

Piperazines

hydroxyzine (Vistaril, Atarax)


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Peripheral (Nonsedating) H1-

Receptor Antagonists

Haveles (pp. 226, 238) (Table 18-1)

No common chemical denominator, they are

different in origin, chemical structure,

solubility, and metabolic effectsAll block peripheral H1-receptors

Do not cross the blood-brain barrier, do not

produce sedation

contd


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Peripheral (Nonsedating) H1-

Receptor Antagonists

Haveles (p. 236)

fexofenadine (Allegra): an active metabolite of

terfenadine (Seldane)

Side effects include drowsiness and viral infections

loratadine (Claritin)

desloratadine (Clarinex)

cetirizine (Zyrtec) acrivastine (Semprex)

azelastine (Astelin)


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Other Autocoids


PGs and TXs

LTs

Kinins

Substance P


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Prostaglandins and

Thromboxanes


Members of a group of biologically active agents

termed eicosanoids

Produced in the body in response to many differentstimuli and small quantities produce a large spectrum

of effects on many different body systems


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Prostaglandins Haveles (pp. 238-239)

Not only is there a wide spectrum of action, butalso different PGs have different activities indifferent tissues Smooth-muscle effects: vascular smooth muscle may be

relaxed or stimulated, depending on the specific PGs

Platelets: TX stimulates platelet aggregation and is avasoconstrictor; PGI inhibits platelet aggregation and isa vasodilator

Effects on reproductive organs: both PGE and PGF haveoxytocic action

CNS: PGs increase body temperature by releasinginterleukin-1

Other effects: increased heart rate and cardiac output


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Dental Implications

Haveles (p. 239)

PGs have been implicated in periodontal

disease

At least two stages of periodontal disease mayinvolve PGs

The first is inflammation of the gingiva with erythema,edema, and increase in gingival exudate

The second is the resorption of alveolar bone with toothloss


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Uses of Prostaglandins

Haveles (p. 239)

PGs may be used for inducing midtrimester

abortions

A PG agonist (misoprostol [Cytotec]) isavailable for prevention of nonsteroidal

antiinflammatory agentinduced ulcers

PGs are being studied in treatment of

bronchial asthma and hypertension


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Prostaglandin Antagonists

Haveles (p. 239)

Administration of PG antagonists may prove

useful in the treatment of certain pathologic

conditionsAspirin can inhibit platelet aggregation by blocking

TX

Indomethacin blocks the effects of PGs on ductus

arteriosus


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Leukotrienes

Haveles (p. 239)

Another complex group of autocoids that are

also derived from arachidonic acid

Cause strong bronchoconstriction in humans They also contract other smooth muscle such as

the uterus and GI tract


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Kinins


Polypeptides that are distributed in a great

variety of body tissues

Kallidin and bradykinin are found in plasma andmay play a role in dental diseases

Plasma kinins may be involved in shock and

acute or chronic allergic or inflammatory

conditions such as anaphylaxis and arthritis


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Substance P

Haveles (p. 240)

A peptide thought to function as a

neurotransmitter in the CNS and a local

hormone in the GI tractsA vasodilator and produces hypotension

Increases the action of the intestinal and bronchial

smooth muscle

Causes secretion in the salivary glands

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