Histamine and Antihistamines

HISTAMINE

• Histamine is an autacoid present at high levels in the lungs, skin, and the

gastrointestinal tract and is released from mast cells and basophils by type

I hypersensitivity reactions, drugs, venoms, and trauma.

• Histamine receptors are of the serpentine family, with seven transmembrane-

spanning domains with G-protein-coupled second messenger

effectors.

- H1 activation

+ ↑ capillary dilation (via NO) -→ ↓ BP

+ ↑ capillary permeability -→ ↑ edema

+ ↑ bronchiolar smooth muscle contraction (via IP 3 and

DAG release)

+ ↑ activation of peripheral nociceptive receptors -→ ↑  pain and

pruritus

+ ↓, AV nodal conduction

- H2 activation

+ ↑ gastric acid secretion → ↑  gastrointestinal ulcers

+ ↑ SA nodal rate, positive inotropism, and automaticity

H1 ANTAGONISTS

• Mechanism of action:

- H1 antagonists act as competitive antagonists of histamine and therefore

may be ineffective at high levels of histamine.

- Vary in terms of both pharmacologic and kinetic properties, but all

require hepatic metabolism and most cross the placental barrier.

Properties o f Major Antihistamines

Drug	M block	Sedation	Antimotion	Other Characteristic
Dyphenhydramine	+++	+++	+++	Widely used OTC drugs
Promethazine	+++	+++	++	Some alpha Block and local anesthetic action
Chlorpheniramine	++	++	++	Possible CNS stimulation
Meclizin	++	++	++++	Highly effective in motion sickness
Cetirizine	+/-	+	0
Loratadine	+/-	0	0	No CNS entry
Fexofenadine	+/-	0	0	No CNS entry

• Uses:

- Allergic reactions: hay fever, rhinitis, urticaria

- Motion sickness, vertigo

- Nausea and vomiting with pregnancy

- Preoperative sedation

- OTC: sleep aids and cold medications

- Parkinson disease

- Acute EPSs

• Side effects:

- Extensions of M block and sedation (additive with other CNS

depressants)

Chapter Summary

• Histamine is an autacoid released from mast cells and baso phils by type I

hypersensitivity reactions or under the i nfluence of d rugs, venoms, or trauma.

H istamine receptors a re the G-protein-coupled, seven-transmembrane type.

Three different receptors are recognized: the well-characterized H 1 and H 2

types and an H 3 variant.

• The sequence of reactions leading to H 1 and H 2 activation is presented.

•  H1 antagonists are competitive inhibitors with varying pharmacologic and kinetic

properties. All require hepatic metabolism and cross the placental barrier.

•  The H 1 antagonists are used to treat a llergic reactions, motion sickness,

vertigo, nausea and vom iting in pregnancy, and p reoperative sedation, and

are in over-the-counter sleeping pills.

•  The adverse effects a re excess M block and sedation. Table Vl-1-1

summarizes the properties of some of the m ajor type 1 antih istamines.

KAPLAN medical USMLE step 1- Pharmacology- Lecture Notes (2013)