1. Chapter 18: Autocoids and Antihistamines
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.

2. Chapter 18 Outline Autocoids and antihistamines Histamine (H1 or H2)
Antihistamines (H1-receptor antagonists)
Peripheral (nonsedating) H1-receptor antagonists
Other autocoids

3. 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 H2-receptor antagonists (H-RAs) or blockers, the eicosanoids (prostaglandins [PGs], thromboxanes [TXs], and leukotrienes [LTs]), serotonin agonists, angiotensin inhibitors, and cytokinins

4. Histamine Pharmacologic effects Adverse reactions Uses
Haveles (pp )
Pharmacologic effects
Adverse reactions
Uses
cont’d…

5. Histamine A ubiquitous biogenic amine
Haveles (pp ) (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

6. 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…

7. Pharmacologic Effects of Histamine
Haveles (pp )
Agents that block or antagonize the effects of histamine at the H1-receptors are known as H1-blockers or H1-RAs, and at the H2-receptors they are H2-blockers or H2-RAs

8. Adverse Reactions of Histamine
Haveles (p. 235)
When an allergic reaction occurs, an antibody-antigen 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…

9. 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…

10. 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

11. Uses of Histamine No clinical uses of histamine have been established
Haveles (p. 235)
No clinical uses of histamine have been established

12. Antihistamines (H1-Receptor Antagonists)
Haveles (pp )
Pharmacologic effects
Adverse reactions
Toxicity
Uses
cont’d…

13. 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

14. Pharmacologic Effects of Antihistamines
Haveles (pp ) (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

15. 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

16. Other Effects (Unrelated to H1-Blocking Effects) of Antihistamines
Haveles (pp )
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
Also effective in controlling dizziness, nausea, and vomiting with Ménière’s syndrome
Local anesthesia: may be used to provide some local anesthesia

17. Adverse Reactions of Antihistamines
Haveles (pp ) (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…

18. 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

19. 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

20. Uses of Antihistamines
Haveles (pp )
Allergic reactions: allergic rhinitis and seasonal hay fever can be controlled by antihistamines
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…

21. Uses of Antihistamines
Haveles (pp )
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

22. Examples of Antihistamines
Haveles (p. 236) (Table 18-1)
Ethanolamines
diphenhydramine (Benadryl)
carbinoxamine (Clistin)
clemastine (Tavist)
Ethylenediamines
tripelennamine (PBZ)
pyrilamine (various)
cont’d…

23. Examples of Antihistamines
Haveles (p. 236) (Table 18-1)
Alkylamines
chlorpheniramine (Chlor-Trimeton)
dexchlorpheniramine (Polaramine)
brompheniramine (Dimetane)
Phenothiazines
promethazine (Phenergan)
cont’d…

24. Examples of Antihistamines
Haveles (p. 236) (Table 18-1)
Piperadines
cyproheptadine (Periactin)
azatadine (Optimine)
phenindamine (Nolahist)
Piperazines
hydroxyzine (Vistaril, Atarax)

25. 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 effects
All block peripheral H1-receptors
Do not cross the blood-brain barrier, do not produce sedation
cont’d…

26. 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)

27. Other Autocoids PGs and TXs LTs Kinins Substance P
Haveles (pp )
PGs and TXs
LTs
Kinins
Substance P

28. Prostaglandins and Thromboxanes
Haveles (pp )
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

29. Pharmacologic Effects of Prostaglandins
Haveles (pp )
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

30. Dental Implications PGs have been implicated in periodontal disease
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

31. 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

32. 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

33. 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

34. Kinins
Haveles (pp )
Polypeptides that are distributed in a great variety of body tissues
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

35. 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