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How is histamine synthesize? How is it metabolized?
- Sythesis: From histadine via decarboxylation reaction
- Metabolism: Via diamine oxidase or MAO to prodice imidazole acetic acid
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How can you measure overproduction of histamine?
By measuring the amount of imidazole acetic acid in urine
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What are some chemicals released upon degranulation of a mast cell?
- Histamine
- Kinin
- Serotonin
- Slow Reacting Substance of Anaphylaxis
- Prostaglandins
- PAG
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Describe G protein linkage and mechanism of action of H1-H4 reaceptors:
- H1 - Gq - increase IP3/DAG and Calcium
- H2 - Gs - increase cAMP
- H3 - Gi - decrease cAMP, Calcium; N-Type Calcium Channel
- H3 - Gi - decrease cAMP and Calcium
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Describe function of H1 receptors on vascular smM, endothelium, non-vascular smM, sensory nerves, exocrine glands and CNS
- Vascular SmM: Vasodilate - anaphylaxis, edema
- Endothelium: Cause it to release EDRF (NO) - vasodilate
- Non-vascular SmM: Constriction - bronchoconstriction and GI Tract constriction
- Sensory Nerves: Pruritis and cough reflex
- Exocrine Glands: Increase nasal/bronchiole mucus
- CNS: Wakefulness
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Describe function of H2 receptors on gastric mucosa and heart?
- Gastric Mucosa: Increase secretion of gastric acid at parietal cells
- Heart: Increase HR, contractility (HR is due to reflex activation)
- Other - reduces further release of histamine from mast cells
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Describe function of H3 and H4 receptors?
- H3: Acts at presynaptic nerve terminals in CNS and myenetic plexus to reduce NT release
- H4: Acts on leukocytes (CD4 TCells) and mast cells
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Describe therapeutic uses of H1 antagonists?
- Allergic Reactions: Rhinitis, urticaria, conjunctivitis, pruritis
- Motion Sickness, Vascular Disturbance: Sleep aid, Meniere's Disease
- Nausea/Vomiting (pregnancy): NOT piperazines
- Parkinsonism
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Describe adverse effects of H1 antagonists?
- Hyperexcitability in children
- Sedation
- Dry mouth
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What are some drug interactions of H1 antagonists?
- Drugs that are metabolized by CYP3A4
- Drugs that also affect cardiac K channels - may cause long QT syndrome
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What are the major classes of H1 antagonists?
- Ethanolamines
- Alkylamines
- Ethylaminediamines
- Phenothiazines
- Intranasal
- Piperazines
- Piperdines
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Describe ethanolamines - sedative/antiemetic/anticholinergic effects, duration, use, examples and any exceptions:
- Effects: Large sedative, antiemetic and anticholinergic effects
- Duration: Last 4-6 hours
- Use: Motion sickness, insomnia, morning sickness
- Examples: Dimenhydrinate, diphenhydramine, doxylamine (morning sickness)
- Exception: Clemastine lasts for 12 hours; no antiemetic effects
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Describe alkylamines - sedative/antiemetic/anticholinergic effects, duration, use, examples and any exceptions:
- Effects: Large sedative/anticholinergic effects, NO antiemetic effects
- Duration: 4-8 hours
- Use: Not currently used; was used for OTC cold remedy
- Example: Chlorpheniramine
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Describe ethylaminediamines - sedative/antiemetic/anticholinergic effects, duration, use, examples and any exceptions:
- Effects: Only anticholinergic effect - no antiemetic or sedative
- Duration: 4-6 hours
- Use: Not currently used
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Describe phenothiazines - sedative/antiemetic/anticholinergic effects, duration, use, examples and any exceptions:
- Effects: Very large sedative, antiemetic, anticholinergic effects
- Duration: 4-6 hours
- Use: Antiemetic
- Example: Promethazine (phenergan)
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Describe Intranasals - sedative/antiemetic/anticholinergic effects, duration, use, examples and any exceptions:
- Effects: Minimal sedative effects; no antiemetic/anticholinergic
- Duration: Lasts 12 hours
- Use: INTRANASAL - only one that is
- Example: Azelastine
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Describe Piperzines - first and second generation:
- First: Very strong sedative, antiemetic, anticholinergic
- Lasts 8-24 hours
- Used for vertigo, motion sickness, antiemetic, anxiety
- Meclizine (bonidine), Cyclizine
- Second: Minimal sedative, no antiemetic/anticholinergic
- Lasts 12-24 hours
- Citirizine (Zyrtec)
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Describe Piperdines - first and second generation:
- First: No antiemetic effects; sedetive/anticholinergic effects
- Lasts 4-8 hours; significant 5-HT antagonist
- Cyproheptadine
- Second: Minimal sedative/anticholinergic; no antiemetic
- Lasts 4-6 hours
- Loratidine (claritin), fexofenadrine (allegra)
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Describe therapeutic effects of H2 receptor antagonists:
- Peptic duodenal ulcers
- Gastric ulcers
- GERD - gastroesophageal reflux disorder
- Hypersecretory conditions
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Describe side effects of H2 receptor antagonists:
- CNS: Confusion, slurred speech, paradoxical excitement (children, elderly)
- Blood Dyscrasias
- Reversible Hepatitis: Ranitidne
- Liver Enzyme Abnormalities: Famotidine, nizatidine
- Adronergic Effects (cimetidine): Gynecomastic in males, galactorrhea in females, reduces sperm count, impotence
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What are the 4 H2 receptor antagonists?
- Cimetidine
- Ranitidine
- Famotidine
- Nizatidine
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What are some potential uses for H3 antagonists?
Sleep disorder, narcolepsy, obsesity, cognitive disorders, psychiatric disorders
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What are some potential uses for H4 antagonists?
Chronic inflammatory conditions (asthma)
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