Download Chapter 18 outline

Chapter 18:
Autocoids and Antihistamines
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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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2
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 act

Agonists or antagonists include H1- and H2receptor antagonists (H-RAs) or blockers, the
eicosanoids (prostaglandins [PGs], thromboxanes
[TXs], and leukotrienes [LTs]), serotonin agonists,
angiotensin inhibitors, and cytokinins
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3
Histamine




Haveles (pp. 234-235)
Pharmacologic effects
Adverse reactions
Uses
cont’d…
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4
Histamine


A ubiquitous biogenic amine


Haveles (pp. 234-235) (Fig. 18-1)
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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5
Pharmacologic Effects of
Histamine



Haveles (p. 234)
H1-agonist effects: vasodilation, increased
capillary permeability, bronchoconstriction,
and pain or itching in cutaneous nerve
endings
H2-agonist effects: increased gastric acid
secretion
cont’d…
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6
Pharmacologic Effects of
Histamine


Haveles (pp. 234-235)
Agents that block or antagonize the effects of
histamine at the H1-receptors are known as
H1-blockers or H1-RAs, and at the H2receptors they are H2-blockers or H2-RAs
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7
Adverse Reactions of Histamine



Haveles (p. 235)
When an allergic reaction occurs, an antibodyantigen reaction causes release of histamine
and other autocoids
Anaphylaxis is a serious and sometimes fatal
reaction to a foreign protein or drug introduced
into the body


Anaphylaxis may involve difficulty in breathing due to
bronchoconstriction, convulsions, lapses into
unconsciousness, and death
The predominant feature is bronchoconstriction
cont’d…
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8
Adverse Reactions of Histamine

Other effects involve vasodilation and
increased capillary permeability, both of which
lead to decreased blood pressure followed by
shock and cardiovascular collapse
cont’d…
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9
Adverse Reactions of Histamine

The drug of choice for anaphylaxis is
parenteral epinephrine

A physiologic antagonist that dilates bronchioles
via β2-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, whereas
epinephrine acts as a direct β2-agonist
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10
Uses of Histamine


Haveles (p. 235)
No clinical uses of histamine have been
established
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11
Antihistamines
(H1-Receptor Antagonists)





Haveles (pp. 235-238)
Pharmacologic effects
Adverse reactions
Toxicity
Uses
cont’d…
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12
Antihistamines
(H1-Receptor Antagonists)


Haveles (p. 235)
Antihistamine refers to agents that are
H1-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
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13
Pharmacologic Effects of
Antihistamines


Haveles (pp. 235-236) (Fig. 18-2; Table 18-1)
Older H1-RAs have several pharmacologic
effects, including antihistaminic,
anticholinergic, antiserotonergic, and sedative
effects

Effects can be divided into those caused by
blocking histamine at the H1-receptor and those
independent of this effect
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14
H1-Receptor Blocking Effects of
Antihistamines


Haveles (p. 235)
Drugs that are H1-antagonists competitively block or
antagonize histamine’s 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 other
autocoids are also released in an anaphylactic reaction,
antihistamines are not effective in counteracting all the
bronchoconstriction present
 Nerve endings: antihistamines can suppress itching
and pain associated with histamine-mediated reaction
at cutaneous nerve endings
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15
Other Effects (Unrelated to H1-Blocking
Effects) of Antihistamines



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CNS: antihistamines produce varying degrees of
CNS depression (may be used to induce sleep)
Anticholinergic: can be used to dry up secretions
Antiemetic: some antihistamines, such as
meclizine (Dramamine, Bonine), have
pronounced antiemetic or antimotion sickness
activity


Haveles (pp. 235-236)
Also effective in controlling dizziness, nausea, and
vomiting with Ménière’s syndrome
Local anesthesia: may be used to provide some
local anesthesia
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16
Adverse Reactions of
Antihistamines



Haveles (pp. 236-237) (Fig. 18-2)
Vary in relative amounts among the different
agents
CNS depression: can be a pharmacologic effect
or adverse reaction


Sedation is the most common side effect associated
with older antihistamines; may be accompanied by
dizziness, tinnitus, incoordination, blurred vision, and
fatigue
When antihistamines are combined with
decongestants, CNS depression of the antihistamine
is counteracted by CNS stimulation of the
decongestant
cont’d…
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17
Adverse Reactions of
Antihistamines


Gastrointestinal (GI) complaints associated
with antihistamines include anorexia, nausea,
vomiting, and constipation
Anticholinergic: H1-RAs have varying
anticholinergic effects

Anticholinergic effects lead to xerostomia
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18
Toxicity of Antihistamines


Haveles (p. 237)
Antihistamine poisoning has become more
common in recent years


Excitation predominates in small children, and
sedation can occur in adults
Death usually results from coma with cardiovascular
and respiratory collapse
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19
Uses of Antihistamines


Allergic reactions: allergic rhinitis and
seasonal hay fever can be controlled by
antihistamines


Haveles (pp. 237-238)
Acute 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
cont’d…
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20
Uses of Antihistamines




Haveles (pp. 237-238)
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 local
anesthesia
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21
Examples of Antihistamines


Ethanolamines




Haveles (p. 236) (Table 18-1)
diphenhydramine (Benadryl)
carbinoxamine (Clistin)
clemastine (Tavist)
Ethylenediamines


tripelennamine (PBZ)
pyrilamine (various)
cont’d…
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22
Examples of Antihistamines


Alkylamines




Haveles (p. 236) (Table 18-1)
chlorpheniramine (Chlor-Trimeton)
dexchlorpheniramine (Polaramine)
brompheniramine (Dimetane)
Phenothiazines

promethazine (Phenergan)
cont’d…
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23
Examples of Antihistamines


Piperadines
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


Haveles (p. 236) (Table 18-1)
cyproheptadine (Periactin)
azatadine (Optimine)
phenindamine (Nolahist)
Piperazines

hydroxyzine (Vistaril, Atarax)
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24
Peripheral (Nonsedating) H1Receptor Antagonists


No common chemical denominator, they are
different in origin, chemical structure,
solubility, and metabolic effects


Haveles (pp. 226, 238) (Table 18-1)
All block peripheral H1-receptors
Do not cross the blood-brain barrier, do not
produce sedation
cont’d…
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25
Peripheral (Nonsedating) H1Receptor Antagonists


fexofenadine (Allegra): an active metabolite of
terfenadine (Seldane)






Haveles (p. 236)
Side effects include drowsiness and viral infections
loratadine (Claritin)
desloratadine (Clarinex)
cetirizine (Zyrtec)
acrivastine (Semprex)
azelastine (Astelin)
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26
Other Autocoids





Haveles (pp. 238-240)
PGs and TXs
LTs
Kinins
Substance P
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27
Prostaglandins and
Thromboxanes


Haveles (pp. 238-239)
Members of a group of biologically active agents
termed eicosanoids

Produced in the body in response to many different
stimuli and small quantities produce a large spectrum
of effects on many different body systems
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28
Pharmacologic Effects of
Prostaglandins


Haveles (pp. 238-239)
Not only is there a wide spectrum of action, but
also different PGs have different activities in
different tissues





Smooth-muscle effects: vascular smooth muscle may be
relaxed or stimulated, depending on the specific PGs
Platelets: TX stimulates platelet aggregation and is a
vasoconstrictor; PGI inhibits platelet aggregation and is
a vasodilator
Effects on reproductive organs: both PGE and PGF have
oxytocic action
CNS: PGs increase body temperature by releasing
interleukin-1
Other effects: increased heart rate and cardiac output
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29
Dental Implications


Haveles (p. 239)
PGs have been implicated in periodontal
disease

At least two stages of periodontal disease may
involve 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 tooth
loss
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30
Uses of Prostaglandins




Haveles (p. 239)
PGs may be used for inducing midtrimester
abortions
A PG agonist (misoprostol [Cytotec]) is
available for prevention of nonsteroidal
antiinflammatory agent–induced ulcers
PGs are being studied in treatment of
bronchial asthma and hypertension
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31
Prostaglandin Antagonists


Haveles (p. 239)
Administration of PG antagonists may prove
useful in the treatment of certain pathologic
conditions

Aspirin can inhibit platelet aggregation by blocking
TX
 Indomethacin blocks the effects of PGs on ductus
arteriosus
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32
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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33
Kinins


Polypeptides that are distributed in a great
variety of body tissues


Haveles (pp. 239-240)
Kallidin and bradykinin are found in plasma and
may 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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34
Substance P


Haveles (p. 240)
A peptide thought to function as a
neurotransmitter in the CNS and a local
hormone in the GI tracts



A vasodilator and produces hypotension
Increases the action of the intestinal and bronchial
smooth muscle
Causes secretion in the salivary glands
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35