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
How can you measure overproduction of histamine?
By measuring the amount of imidazole acetic acid in urine
What are some chemicals released upon degranulation of a mast cell?
- Slow Reacting Substance of Anaphylaxis
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
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
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
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
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
Describe adverse effects of H1 antagonists?
- Hyperexcitability in children
- Dry mouth
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
What are the major classes of H1 antagonists?
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
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
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
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)
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
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)
Describe Piperdines - first and second generation:
- First: No antiemetic effects; sedetive/anticholinergic effects
- Lasts 4-8 hours; significant 5-HT antagonist
- Second: Minimal sedative/anticholinergic; no antiemetic
- Lasts 4-6 hours
- Loratidine (claritin), fexofenadrine (allegra)
Describe therapeutic effects of H2 receptor antagonists:
- Peptic duodenal ulcers
- Gastric ulcers
- GERD - gastroesophageal reflux disorder
- Hypersecretory conditions
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
What are the 4 H2 receptor antagonists?
What are some potential uses for H3 antagonists?
Sleep disorder, narcolepsy, obsesity, cognitive disorders, psychiatric disorders
What are some potential uses for H4 antagonists?
Chronic inflammatory conditions (asthma)