- How is Histamine Released?
- IgE Receptors stimulated –> PLP A2 turned on –> Increased Platelet Factor, Leukotrienes, Kinins –> Mast Cell Degranulation –> Histamine Release
H1 Histamine Receptor
- Used in what?
- Allergic response; Sm Muscle, Endothelium (turns on NO and causes Vasodilation); Brain (wakefulness and appetite control); Acts thru Gq
H2 Histamine Receptors
- What G-Protein?
- Secretes what?
- Gs (increased cAMP)
- Gastric ACID SECRETION
(found in heart, brain and mast cells)
H3/H4 Receptors
- Linked to what G protein
- H3?
- H4?
- Gi (decrease cAMP)
- Presynaptic in Brain; Inhibits release of NT and can promote sleep
- on Leukocytes, Eosinophils, and Neutrophils…can stimulate Chemotaxis in Inflammation and Allergic Reactions.
- Histamine NT: in CNS (what receptors)?
2. Regulation of Gastric ACID? (what receptor)
- H1 and H3 RECEPTORS
2. H2 RECEPTOR
Effects of Histamine
- Cardiovascular: What receptor increases production of NO from endothelium?
a. At higher concentrations? - Smooth Muscle: BRONCHOSPASM: what receptor?
- GI?
- H1
a. H2 is activated –> Direct Vasodilation - H1: Problem in ASTHMATICS
- Increased GASTRIC ACID SECRETION (H2)
Effects of Histamine
- TRIPLE RESPONSE?
- Localized Red Spot in a few seconds (due to vasodilation)
Followed by BRIGHTER FLUSH (FLARE) (Due to Axon Reflexes)
then WHEAL Appears in 2-3 minutes (Increased Capillary Permeability)
Effects of Antihistamines
- What do they Inhibit?
- Smooth Muscle response (NOT BRONCHOSPASM); Inhibit VASODILATION due to H1 stimulation; Inhibit Flare, itch, and Wheal, salivary and lacrimal gland secretion
* COUNTER MOTION SICKNESS (ANTICHOLINERGIC)
First Gen Antihistamines
- What about them?
- Enter Brain. VERY SEDATING
First Gen H1 Anatagonists
- What 2 are SEDATING ONLY?
- 2 for Motion Sickness?
- What is an Antiemetic and also used for Motion Sickness?
- Benadryl/Tylenol PM and VISTARIL
- Benadryl and DRAMAMINE
- PHENERGAN (also VERY SEDATING)
Second Gen H1 Antagonists
- What about them
- Don’t enter Brain well. (PERIPHERY mainly). NOT ANTICHOLINERGIC. NON-SEDATING. FEWER SIDE EFFECTS
Dont help with Motion Sickness
*CYP450
What 2 Second gen H1 Antagonists are EXCRETED DIRECTLY by the KIDNEY?
ZYRTEC and ZYXAL
What drug might INHIBIT RELEASE of HISTAMINE from MAST CELLS?
ZYRTEC!
Clinical Applications
- Best used for what?
Allergic Rhinitis, Seasonal Itching/Conjunctivits, Itching and Hives
*Motion Sickness (PROPHYLACTIC…usually VERY SEDATING AS WELL (so 1st Gen for this)
Sedation: safe for occasional use (1st gen…long-term TOLERANCE can develop.. DRY up secretions (1st gen))
First Gen Side Effects?
SEDATION! (worse if used with CNS depressants. ANTICHOLINERGIC (DRY MOUTH))
Side Effects on ALL?
GI: Nausea, Anorexia, Increased appetite and weight gain. Maybe Teratogenic.
Allergic Reactions (Topical)
Decrease Seizure Threshold (TCAs, Phenothiazines)
Interactions
- 1st Gen
- 2nd Gen
- CNS Depressants
2. Erythromycin, Ketoconazole, Grapefruit Juice, Cimetidine (Inhibit their Metabolism)
Overdose
- 1st Gen
- 2nd Gen
- Like ATROPINE POISONING; Sedation
2. Cardiac Arrhythmias occurred w/older drugs but not newer ones. Sinus Tachycardia w/newer drugs
Topical Drugs
- AZELASTINE
- KETOTIFEN and EPINASTINE
- decrease Histamine Release AND BLOCKS RECEPTORS (H1 Blocker)
- EYE drops for allergies in the eye