Furthermore, patients with hypertension may sometimes have a co-existing, second medical disease. In such cases, a particular class of anti-hypertensive medication or combination of drugs may be chosen as the first line (initial) approach. The idea in these cases is to control the hypertension while also benefiting the second condition. For example, beta-blockers may treat chronic anxiety or migraine headache as well as the hypertension. Also, the combination of an ACE inhibitor and an ARB drug can be used to treat certain diseases of the heart muscle (called cardiomyopathies) and certain kidney diseases where reduction in proteinuria would be beneficial.

In some other situations, certain classes of anti-hypertensive medications should not be used (are contraindicated). Dihydropyridine calcium channel blockers used alone may cause problems for patients with chronic renal disease by tending to increase proteinuria. However, an ACE inhibitor will decease this effect. Furthermore, the non-dihydropyridine type of calcium channel blockers(Verapamil, Dilteazam) should not be used in patients with heart failure or certain abnormal heart rates or rhythms (arrhythmias). On the other hand, these drugs may be beneficial in treating certain other arrhythmias. Also, some drugs, such as minoxidil, since it is so powerful, usually are reserved for  second or third line choices for treatment. Clonidine is an excellent drug but has side effects such as fatigue, sleepiness, and dry month that make it a second or third line choice. That is, it is used only after all of the first and second line drugs have been tried without success.

Treatment with combinations of drugs for high blood pressure

Most of the times, Doctors have to use combination therapy of Drugs. The use of combination drug therapy for hypertension is not uncommon. At times, using smaller amounts of one or more agents in combination can minimize side effects while maximizing the anti-hypertensive effect. For example, diuretics, which also can be used alone, are more often used in a low dose in combination with another class of anti-hypertensive medications. In this way, the diuretic has fewer side effects while it improves the blood pressure-lowering effect of the other drug. Diuretics also are added to other anti-hypertensive medications when a patient with hypertension also has fluid retention and swelling (edema).

The ACE inhibitors or angiotensin receptor blockers may be useful in combination with most other anti-hypertensive medications. ACE inhibitors and angiotensin receptor blockers ARBs  have additive effects in treating patients with cardiomyopathies and proteinuria. Another useful combination is that of a beta-blocker with an alpha-blocker in patients with high blood pressure and enlargement of the prostate gland in order to treat both conditions simultaneously. Caution is necessary, however, when combining two drugs that both lower the heart rate. For example, adding a beta-blocker to a non-dihydropyridine calcium channel blocker (e.g., diltiazem or verapamil) warrants caution. Patients receiving a combination of these two classes of drugs need to be monitored carefully to avoid an excessively slow heart rate (bradycardia). Combining alpha and beta-blockers may be beneficial for cardiomyopathies and hypertension. Carvedilol (Coreg) is useful for cardiomyopathies and labetalol for hypertension patients.