**4. Calcium channel blockers and histamine H2-antagonists**

The co-administration of calcium channel blockers and some histamine H2-antagonists, as cimetidine, result in increased concentrations of calcium channel blockers and possible cardiovascular toxicity. This effect happens because of Cytochrome P (CYP) 450 inhibition.

The Cytochrome P (CYP) 450 is a superfamily of hemoproteins that play an important role in the metabolism of steroid hormones, fatty acids and many drugs. Many agents used for management of cardiovascular diseases are substrates, inhibitors or inducers of CYP450 enzymes. When two agents that are substrates, inhibitors or inducers of CYP450 are administered together, drug interactions with significant clinical consequences may occur (Cheng et al., 2009). Monitoring cardiovascular response is necessary when the patient is in use of cimetidine and a calcium channel blocker. Dose reductions of up to 35% to 40% may be needed for diltiazem or nifedipine if co-administered with cimetidine.
