Anti-histamines Flashcards
What are the 1st generation H1 antagonists?
Chlorpheniramine (Chlortrimeton)
Diphenhydramine (Benadryl)
Dimenhydrinate (Dramamine)
What are the 2nd generation H1 antagonists?
Loratadine (Claritin)
Cetirizine (Zyrtec)
Fexofenadine (Allegra)
How is histamine synthesized?
Decarboxylation of L-histidine by histidine decarboxylase
What is an autacoid?
Compounds that are released and act locally in periphery
Includes histamine, serotonin, prostaglandins, leukotrienes and kinins
What are the roles of histamine?
Immune response
Control stomach acid
Neurotransmitter
What is the distribution of histamine in the body?
Periphery: widespread (esp skin, lungs), most synthesized and stored in mast cells and basophils
Gastric Mucosa: In enterochromaffin-like cells (ECL) of stomach fundus
CNS: NTs in cell bodies of histaminergic neurons in ventral posterior hypothalamus
Histamine receptors are what kind of receptors?
G-protein coupled
Histamine in the smooth muscle, endothelium and CNS are received by what receptor subtype?
H1
Postreceptor response is Increase in…IP3, DAG, Ca2+, NO, cCMP (Gq)
Histamine in the gastric mucosa, cardiac muscle, vascular smooth muscle, mast cells and CNS is received by what receptor subtype?
H2
Postreceptor response is increase in cAMP (Gs)
Allergic reactions are what type of immune response?
Type I Hypersensitivity
via IgE: antigen crosslinking
Complement system activation releasing histamine from mast cells at a specific site causes what?
Inflammation
What kind of histamine release is caused by physical or chemical injury to skin or mucosa?
Mechanical release
What effect on histamine release does opioids have?
Opioids stimulate histamine release
What effect on histamine release does epinephrine/cromolyn have?
Blocks release
Does histamine action on smooth vessels (contraction) or endothelial cells (relaxation) win out in overall effect in the lungs?
Endothelial so overall action is relaxation in the lungs
What is felt upon stimulation of primary afferent nerve endings by endogenous histamine?
Itch
Pain
Histamine as a NT in the ventral posterior hypothalamus helps regulate what functions?
Arousal (wakefulness)
Appetite
Body Temperature
What spoiled food can cause histamine toxicity and what can suppress it?
Scombroid fish
Bacteria in fish metabolize histadine to histamine
Suppressed by H1 receptor blockers
Are anaphylaxis symptoms caused primarily by histamine?
No
Are local allergic reaction symptoms caused primarlily by histamine?
Yes
Urticaria
Allergic rhinitis
What drug for allergies acts by directly inhibiting mast cell degranulation?
Cromolyn sodium
Available as nasal spray, inhaler or eye drops
Do 1st gen or 2nd gen H1 antihistamines penetrate the blood brain barrier?
1st gen
What is a common side effect of 1st gen H1 antihistamines?
Sedation
In allergic rhinitis, 2nd gen antihistamines are least effective for:
- itching
- nasal congestion
- rhinitis
- sneezing
- nasal congestion
Can H1 antihistamines be used in event of anaphylactic reactions?
No
Are 1st gen or 2nd gen H1 antihistamines longer lasting?
2nd gen
Where are H1 antihistamines metabolized and then cleared?
Metabolized in liver
Renal clearance
Which H1 antihistamine is inhibited by grapefruit/orange/apple juice due to being transposted by intestinal OATP1A2?
Fexofenadine
1st gen H1 antihistamines can have what cardiac adverse effects?
Dose related sinus tachycardia, reflex tachycardia
What are contraindications for 1st gen H1 antihistamines?
Glaucoma, prostatic hypertrophy
