Calamine works by its counter-irritant effect. After application to the skin the calamine evaporates, which produces a cooling effect that helps distract you from the itch. Calamine cream also contains zinc oxide, which has a soothing effect and also has antiseptic properties that help prevent infection from scratching. Zinc oxide and calamine have similar properties. Calamine has mild astringent (causing the contraction of skin cells), antipruritic(relieve itching) and soothing actions. Zinc oxide is mildly astringent has covering, protective and cooling properties.