10.01.3 Drugs that Modify the Actions of Histamine
Theoretically, the effects of histamine (and any other chemical mediator) can be modified at every level of the system; i.e. at the level of synthesis, release, receptors, cell signaling and breakdown. With histamine we have important drugs that modify at the level of release and receptors. The release of histamine from mast cells is inhibited by cromoglycate, which is occasionally used to prevent allergic rhinitis. Cromoglycate is only effective if the histamine is still in the mast cells. After the histamine has been released, it is too late for cromoglycate to have an effect.
Another level at which the effects of histamine is at the receptors. Antagonists at H1-receptors are commonly used in the treatment of allergic rhinitis, conjunctivitis (allergy of the eye), and chronic urticaria (skin allergy). The first generation (older) H1-receptor antagonists crossed the blood brain barrier and caused sedation. Examples of first generation H1-receptor antagonists include dexchlorpheniramine and diphenyhydramine. Dexchlorpheniramine is still used in the treatment of allergic rhinitis, conjunctivitis, and chronic urticaria, whereas diphenyhydramine is no longer used for hypersensitivity reactions, but is used as a mild sedative in insomnia. The second generation H1-receptor antagonists are less able to cross the blood brain barrier and cause less sedation. An examples of a second generation H1-receptor antagonists is fexofenadine.
Antagonists at H2-receptors revolutionized the treatment of peptic acidity conditions such as peptic ulcer disease, gastro-oesphogus reflux disease (GORD), and dyspepsia, as there had been no good treatments previously. An example of an H2-receptor antagonist is ranitidine (Ranitic). Ranitidine is a relatively safe drug and is available over-the-counter (OTC) without a prescription in low doses.
As histamine acting at the H2-receptor is only one of the stimulants of acid secretion, H2-receptor antagonists are only effective against the histamine component. There are other stimulants of gastric secretion such as gastrin and acetylcholine, and H2-receptor antagonists do not inhibit this stimulation of acid secretion whereas proton pump inhibitors do. Thus proton pump inhibitors are often preferred to the H2-receptor antagonists in peptic acidity conditions, as they are more effective.