E2: Antihistamines Flashcards
(31 cards)
What cells are histamines found in?
Mast cells and basophils
What is histamine normally complexed to?
Protease, heparin, or chondroitin sulfate proteoglycans
How does an allergic response occur?
- Antibody (IgE) generated. IgE binds to receptors on the surface of mast cells and basophils.
- The antigen bridges IgE on the mast cells and activates protein kinases to increase IP3 and Ca. This activates Phospholipase A2, which increases platelet activating factor, leukotrienes
- This all leads to mast cell degranulation and histamine release
Where is the H1 receptor found?
- Smooth muscle
- Endothelium
- Brain
What does H1 receptor activation do the endothelium?
Activates NO and vasodilation
What does H1 receptor Activation do in the brain?
Wakefulness and appetite control
Where are H2 receptors found and what are the main effects of H2 receptor activation?
- Heart, brain, and mast cells
- Gastric acid secretion and vasodilation
Where is the H3 receptor found and what does it do?
- Presynaptic in the brain
- Inhibits release of NTs, including histamine. May promote sleep
Where are H4 receptors found and what do they do?
- On leukocytes, eosinophils, and neutrophils
- may stimulate chemotaxis in inflammation and allergic reactions
Which histamine receptor can cause bronchospasm and can be a problem in asthmatics?
H1
What are the symptoms associated with histamine release?
- Burning and itching
- intense warmth
- BP drops, HR increases, skin reddens
- HA
- BP recovers, edema, and hives
- Colic, nausea, acid secretion
- Bronchospasm
- Anaphylaxis
What is the general mechanism of antihistamines?
- Inverse agonist (Bascially antagonists)
- Decreases normal histamine activity and blocks the effects of released histamine
Do first generation H1 antagonist enter the Brain?
Yes, so they are very sedating
What are the 5 first generation H1 antagonists
- Diphenhydramine
- Doxylamine
- Hydroxyzine
- Dramamine
- Promethazine
What two H1 antagonists are used for motion sickness because they also have muscarinic blockade?
- Diphenhydramine
- Dimenhydrinate (Dramamine)
- Promethazine
What first generation H1 antagonists are used as an antiemetic and for motion sickness?
Promethazine (phenergan)
Do 2nd generation H1 antagonists enter the brain? Do they have anticholinergic effects?
- They do not enter the brain well so sedation is not common
- No anticholinergic effects so not useful for motion sickness
How are 2nd generation H1 antagonists metabolized?
CYP450
What are the 3 second generation H1 antagonists?
- Cetirizine
- Loratidine
- Fexofenidine
Who should second generation H1 antagonists be avoided in?
They are excreted directly by the kidney so avoid if kidney function is poor. Good for liver disease
What are the uses of second generation H1 antagonists?
- Allergic rhinitis (Best when used prophylactically)
- seasonal itching
- Itching and hives
- Conjunctivitis
What are the CNS side effects of 1st generation H1 antagonists?
- Sedation (worse when combined with other CNS depressants)
- decreased seizure threshold
- dizziness, blurred vision, excitement, insomnia
What are the drug interactions with 2nd generation H1 antagonists?
- Erythromycin
- Ketoconazole
- Grapefruit juice
- Cimetidine (Inhibits metabolism)
What is the presentation of a 1st generation H1 antagonist overdose?
- Similar to atropine poisoning
- sedation
