1. Autacoids and Antihistamines
L.O. 18
Chapter18
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Definitions
Autacoids: autos ( self), akos ( remedy)
Naturally occurring agents, produced by many tissues, act locally
Examples: histamine, prostaglandins, leukotrienes, serotonin agonists, thromboxanes
Antihistamines: H1-RA, H2-RA
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Histamine
Released from the tissue as a normal reaction, abnormal reaction or after administration of certain drugs.
Stored in the mast cells in the skin, intestinal mucosa and in the CNS
Effects: peripheral and CNS / function of the amount of histamine released
Peripheral effects are well understood, CNS effects under study
2 types of receptors for histamine: H1, H2
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Histamine
Effects on histamine receptors (agonists):
H1 :
vasodilation,
increased capillary permeability
bronchoconstriction,
pain and itching at cutaneous nerve endings
H2 :
increased gastric acid secretion
Histamine antagonists/blockers: H1-blockers,H2-blockers or H1-receptor antagonists, H2-receptor antagonists (H1-RA, H2-RA)
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Histamine
Uses: diagnosis of achlorhydria
diagnosis of pheochromocytoma ( a tumor of the suprarenal gland )
Adverse reactions:
Anaphylaxis ( bronchoconstriction, vasodilation, increased capillary permeability)
Treat: epinephrine: im
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Antihistamine=H1-RA
Sedating
Nonsedating
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7. Sedating antihistamines=H1-RA
older, also called H1-blockers.
Chemical structure similar to histamine
Pharmacologic effects:
Antihistaminic: Block the action of histamine on H1 receptors: block capillary permeability (reduce edema), block the dilation of blood vessels, suppress itching and pain at cutaneous nerve endings
Anticholinergic: decongestive, dry mouth
Antiemetic, anti-motion sickness: meclizamine
CNS: depression manifested by sedation: diphenhydramine
L.A.: topical or injection: diphenhydramine
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Antihistamines = H1- RA
Widely used drugs, o.t.c.:
Treatment of seasonal allergies
Urticarial attacks
Topical treatm of painful oral lesions: diphenhydramine
Prevent /treatm of motion sickness,
Control of vomiting postop and after chemo. treat of dizziness and nausea in Menier syndrome
Preop. Sedation: older H1-RA: hydroxyzine, promethazine
Otc sleeping aids: diphenhydramine (Nytol)
Local anesthesia: Benadryl 1:
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9. H1-RA Adverse reactions
CNS depression
sedation;
wanted or adverse effect.
Dizziness, tinnitus, blurred vision, fatigue.
Counsel re: driving, signing important documents.
Additive with other CNS depressants.
Newer nonsedating H1-blockers: loratadine (Claritin) do not penetrate the brain barrier as easier, so less sedation
Decongestants (adrenergic drugs) counteract the sedation produced by H1-RA, and this combination is common in cold remedies, otc or prescription.
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10. H1-RA adverse reactions
Gastrointestinal:
Anorexia, nausea, vomiting, constipation
Anticholinergic:
Xerostomia: with chronic use of sedating H1-blockers. Counsel patient, caries control.
Non sedating H1-blockers have much less of an anticholinergic effect, so less likely to produce xerostomia.
Toxicity: possible because otc allergy and sleep aids. Manifests in excitation in children, sedation in adults. Treatment is conservative and symptomatic, death by cardiovascular and respiratory collapse.
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11. Peripheral (nonsedating ) H1-RA
Do not produce/are less likely to produce sedation, as they do not cross the blood-brain barrier at usual therapeutic doses
fexofenadine ( Allegra )
loratidine ( Claritin )
cetirizine (Zyrtec )
Will most likely replace the older, sedating H1-blockers in treatment of seasonal allergies, and urticaria.
In dentistry will continue to use the sedation ones because sedation is the desired effect, also nausea treatment postop. and l.a. effect.
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H2-RA
Inhibit the action of histamine at H2 receptors level, thus reducing the amount of HCl acid secreted.
Used in treatment of GERD,
gastric ulcer
cimetidine (Tagamet)
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13. Prostaglandins and Thromboxanes
Eicosanoids: PGs, TXs, and others
Found in most tissues
Produced as a response to different stimuli
Small quantities produce a large spectrum of effects on many body systems
PGs: 6 groups: A-F. Groups E and F are the most predominant.
TXs: produced by platelets, stimulate platelet aggregation, also vasoconstrictors
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Prostaglandins
Currently known effects:
Smooth muscle:
contraction (vasoconstriction, uterine contractions, abdominal cramping)
relaxation (vasodilation)
Platelets: inhibit platelet aggregation
CNS: elevated body temperature, increased secretion of certain hormones
Other effects: increased heart rate and cardiac output, sedation, stimulation of pain fibers, role in chronic inflammation (perio. disease), increased capillary permeability
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15. Prostaglandins and periodontal disease
At least 2 stages of perio disease may involve PGS:
Inflammation of gingival tissues leading to erythema, edema, exudate.
Resorption of alveolar bone leading to tooth loss
Inhibition of new bone synthesis by inhibition of osteoblasts
NSAIDs role in treatment of perio. disease is being explored
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Prostaglandin uses
Inducing uterine contractions to produce abortions or birth.
Possible uses in treatment of hypertension, asthma
A PG agonist is available to prevent NSAIDs – induced peptic ulcer.
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17. Prostaglandin antagonists
Could be useful in treatment of certain conditions like:
inflammation,
other conditions
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Other autacoids
Leukotrienes: powerful bronchoconstriction ( stronger than histamine ) , contraction of uterine and gi tract muscles. Antagonists are possible treatment of asthma.8u
Kinins: plasma kinins may be involved in shock, allergy, anaphylaxis, arthritis, role in pulpal pain, control the synthesis of endogenous analgesics during caries formation. Kinins antagonists or inhibitors could be useful dental therapeutic aids in dental disease
Substance P: neurotransmitter in CNS and a local hormone in gi tract. Vasodilator, hypotensor, increases salivary secretion, increases water and Na retention
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