Are antihistamines safe to take permanently? Why/why not, regarding how histamines work?

Antihistamines are generally safe although they do suppress your immune system somewhat. Most antihistamines are H1 receptor antagonist. This mechanism is achieved by blocking the effect of histamine instead of blocking its production or release. Diphenhydramine is the most common on the market and it inhibits most responses of smooth muscle to histamine and is also a potent vasoconstrictor which counteracts vasodilator effects of histamine.