B - 24. Histamine and antihistamines

Question 1

Histamine release

Answer 1

• immunogenic stimuli: allergen/antibody attaches to IgE of histamine and basophile cells -> degranulation

Negative feedback: Histamine loops back to H2 receptors of origin cells and decreases release

Morphine can also induce histamine release

Question 2

H1 receptor

Answer 2

Gq -> IP3 and DAG up -> Ca++ up.

- found on smooth muscle, endothelium and brain (postsynaptic)

Question 3

H2 receptor

Answer 3

Gs -> cAMP up -> Ca++ up

- found in stomach, cardiac muscle, mast cells and brain

Question 4

H3 receptor

Answer 4

Gi -> cAMP down -> Ca++ down
- Found in presynaptic membranes in nerves of brain and myenteric plexus

Decreases release of histamine, DA, NE and 5-HT

Question 5

H4 receptor

Answer 5

Chemotaxis for mast cells. Not very important.

Question 6

Histamine acts on what organs?

Answer 6

1. CNS - itching and pain H1, NT inhibition H3
2. Vessels - Vasodialation - reflex tachycardia. Flushing
3. Bronchial smooth muscle - constriction
4. GI smooth muscle - contraction. Large dose - diarrhea (H1)
5. Uterine - can cause contraction and abortion in hypersensitive pregnant women
6. Secretory tissue - enhances gastric secretion

Question 7

What is the triple response?

Answer 7

Intradermal injection -> wheal and flare response from stimulating nerves, vessels and smooth muscle

Question 8

Clinical use for histamine

Answer 8

1. Pulmonary function testing
2. Gastric acid secretion testing (Pentagastrin used)
3. Diagnosis of pheochromocytoma - increases catecholamine secretion in affected patients

Question 9

Contraindications of histamine

Answer 9

• Asthma
• CF
• Ulcers and GI bleeding

Question 10

Antihistamines - first and second generation

Answer 10

1st - strong sedation due to BBB crossing, can block autonomic receptors
2nd - less BBB crossing - lower sedation

All agents taken orally, peaks after 1-2 hours

Question 11

First generation AH names

Answer 11

diphenhydramine
promethazine
dimetindene

Question 12

Second generation AH names

Answer 12

(levo)cetirizine
(des)loratadine
fexofenadin

Question 13

H1-receptor blockade

Answer 13

reversible competitive blockade

These drugs are indicated for allergic reactions → to prevent or treat allergic symptoms in which histamine is the primary mediator, e.g:

• allergic rhinitis
• urticaria

Question 14

Other uses

Answer 14

• Sedation
• Antinausea
• Anti-parkinson
• Anti muscarinic
• a1 receptor blockade
• 5-HT blockage
• Local anesthesia
• Decrease mast cell degranulation (cetirizine does this not via H2, but by unknown mechanism)

Question 15

Drug interactions

Answer 15

Don’t combine gen2 drugs with ketoconazole, itraconazole & erythromycin, since these drugs inhibit the liver enzyme that metabolizes the antihistamines (CYP3A4)