Vasodilator Drugs

• Amlodipine (Norvasc)

• Diltiazem (Cardizem, Tiazac)

• Verapamil (Calan)

• Nitroglycerin (Nitrostat, Nitrobid)

• Isosorbide mononitrate (Ismo)

• Isosorbide dinitrate (Imdur)

• Hydralazine (Apresoline)

• Minoxidil (Loniten)

• Fenoldopam (Cilopam)

• Sodium Nitroprusside (Nipride, Nitropress)

List of ACE inhibitors

• benazepril (Lotensin)
• captopril (Capoten)
• enalapril (Vasotec, Epaned)
• fosinopril (Monopril)
• lisinopril (Prinivil, Zestril)
• moexipril (Univasc)
• perindopril (Aceon)
• quinapril (Accupril)
• ramipril (Altace)
• trandolapril (Mavik)

List of ARBs

• azilsartan (Edarbi)
• candesartan (Atacand)
• eprosartan (Teveten)
• irbesartan (Avapro)
• telmisartan (Micardis)
• valsartan (Diovan)
• losartan (Cozaar)
• olmesartan (Benicar)

List of CCBs

• amlodipine (Norvasc)
• clevidipine (Cleviprex)
• diltiazem (Cardizem)
• felodipine (Cardene, Cardene SR)
• isradipine
• nicardipine
• nimodipine
• nisoldipine (Sular)
• verapamil (Calan)

List of nitrates

• nitroglycerin (Gonitro, Nitrobid, Nitromist, Nitrolingual, Nitrostat, Nitrobid)
• isosorbide mononitrate (Ismo, Moneket)
• isosorbide dinitrate (Imdur, Isordil))
• Hydralazine (apresoline)
• Minoxidil
• Fenoldopam (carlopam)
• Nitroprusside (Nipride, Nitropress)

Mechanism of Action

In general, Vasodilators dilate or prevent constriction of the blood vessels, which allow greater blood flow to various organs in the body.[rx] Many vasodilators bind to receptors on endothelial cells of the blood vessel, which stimulate calcium release. Calcium activates the enzyme nitric oxide synthase (NO synthase) and converts L-arginine into NO. It leaves the endothelial cell via diffusion and enters vascular smooth muscle cells. NO activates GTP and converts it into cGMP. cGMP then stimulates myosin-light chain phosphatase, which removes a single phosphate from myosin and actin filaments. The dephosphorylation of myosin and actin filaments allows vascular smooth muscle relaxation.

Below are the specific mechanisms of action for different classes of vasodilators:

1. ACE Inhibitors: Prevent the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor.[rx]
2. Angiotensin Receptor Blockers: Prevent angiotensin II from binding to its receptor.
3. Nitrates: Increase the amount of NO in vascular smooth muscle cells, causing vasodilation. Nitrates dilate veins more than arteries and decrease preload.
4. Calcium Channel Blockers: Block calcium channels in the cardiac and smooth muscles, causing decreased muscle contractility and vasodilation. There are two classes of CCBs: Dihydropyridines (act on the vascular smooth muscle), and non-dihydropyridines (act on the heart).
5. Minoxidil: Directly relaxes arteriolar smooth muscle, with minimal effect on the vein. Cyclic AMP may mediate its effects.
6. Hydralazine: the exact mechanism is still unknown.
7. Beta-Blockers: Nebivolol and carvedilol are third-generation β-adrenoreceptor antagonists that have additional endothelium-dependent vasodilating properties.

Indications

Vasodilators are useful in treating a variety of medical conditions, most commonly systemic hypertension.[rx] Other diseases include myocardial infarction (both ST-segment elevation and non-ST-segment elevation), angina, heart failure, stroke, chronic kidney disease, preeclampsia, hypertensive emergency. There are different classes of vasodilators used today in the current clinical practice, and each has different actions on the coronary arteries and peripheral vasculature (arteries and veins). Vasodilators most commonly affect the arteries in the human body, but some vasodilators (such as nitroglycerin) can affect the venous system of the body predominantly.

Several different vasodilators have undergone development over the years, as mentioned below.[rx]

1. Direct-acting vasodilators (hydralazine, minoxidil, nitrates, nitroprusside)
2. Calcium channel blockers (verapamil, diltiazem, nifedipine, amlodipine)
3. An antagonist of the renin-angiotensin-aldosterone system (angiotensin receptor blockers, angiotensin-converting-enzyme inhibitors)
4. Beta-2 receptor agonist (salbutamol, terbutaline)
5. Postsynaptic alpha-1 receptor antagonist (prazosin, phenoxybenzamine, phentolamine)
6. Centrally acting alpha-2 receptor agonist (clonidine, α-methyldopa)
7. Endothelin receptor antagonist (bosentan, ambrisentan)
8. Phosphodiesterase inhibitors (sildenafil, tadalafil)

Renin-angiotensin-aldosterone system blockers such as ACE inhibitors and ARBs are first-line of the treatment in patients with heart failure, history of ST-elevation myocardial infarction, diabetes, or proteinuria. Both groups of medications have cardioprotective and renoprotective effects.

Clinicians can use many vasodilators in preeclampsia, which is a condition seen in the pregnancy characterized by severe hypertension and proteinuria. If not treated quickly, patients can develop seizures. ACE Inhibitors and ARBs are contraindicated in pregnancy due to teratogenicity. Hydralazine and calcium channel blockers (amlodipine, nifedipine) are safe to use in these circumstances.

Many vasodilators are used in hypertensive emergencies and urgencies. Hypertensive emergency is defined as an elevation of systolic blood pressure over 180 mmHg and/or diastolic blood pressure exceeding 120 mmHg with the presence of acute target organ damage (such as kidney insult, encephalopathy, retinal hemorrhage, aortic dissection, subarachnoid hemorrhage). Hypertensive urgencies are defined as an elevation of systolic blood pressure greater than 180 mmHg and/or diastolic blood pressure over 120 mmHg without any clinical or laboratory evidence of acute end-organ damage. In hypertensive emergency following drugs are the first choice depending on systemic involvement.

• Aortic dissection: intravenous esmolol, intravenous nitroprusside, or nitroglycerine
• Acute pulmonary edema: intravenous nitroglycerine, nitroprusside, or clevidipine
• Acute myocardial infarction/unstable angina: intravenous esmolol or nitroglycerine
• Acute renal failure: intravenous fenoldopam, clevidipine, or nicardipine
• Eclampsia: intravenous hydralazine, nicardipine, or labetalol
• Pheochromocytoma/hyperadrenergic state secondary to amphetamine or cocaine: intravenous clevidipine, phentolamine, or nicardipine

This review will focus more on direct-acting vasodilators, calcium channel blockers, and renin-angiotensin-aldosterone antagonists as these classes of medications are more commonly used in the current practice

What are the benefits of using vasodilators?

Vasodilators can be very effective for people with certain heart conditions. They are widely used treatments for high blood pressure.

Opening your blood vessels can:

• Improve blood flow through your heart.
• Reduce pressure in your blood vessels or on your heart.
• Send more oxygen to your heart.

What are the risks of using vasodilators?

Direct vasodilators are strong medicines. Typically, healthcare providers only prescribe them when other treatments have failed to control symptoms.

Direct vasodilators may cause more severe side effects than other types of vasodilators. Sometimes, these side effects are severe enough that you need other medicines to treat the side effects. For example, a vasodilator may cause water retention, which can raise pressure and lead to congestive heart failure. You may need to take a diuretic to help your body release the additional fluid.

Some types of vasodilators cause more severe effects, and the effects can vary from person to person. You and your provider may need to try several medicines to find one that works well with the fewest side effects. When you take vasodilators, you may have:

• Dizziness.
• Dry cough (with ACE inhibitors).
• Edema (fluid retention).
• Fatigue.
• Headaches.
• Joint pain.
• Heart palpitations or rapid heartbeat (tachycardia).
• Nausea and vomiting.

Are there natural vasodilators?

Vasodilators are not the only way to open blood vessels. Some other factors that cause vasodilation include:

• Exercise: When you exercise, your blood vessels open so that your muscles can get extra nutrients and oxygen.
• Inflammation: Inflammation is part of your body’s process of repairing the damage. When a part of your body is inflamed, your blood vessels dilate to send more oxygen and nutrients to that area.
• Natural chemicals: Your body releases some chemicals naturally that can encourage vasodilation. Some examples of these chemicals include carbon dioxide, nitric oxide and the hormone prostaglandin.
• Alcohol: Drinking alcohol causes blood vessel dilation. This is why some people get flushed, warm skin after drinking alcohol. It’s especially common with alcohol intolerance.

Some herbs or supplements can also help with vasodilation. Some supplements have adverse medication reactions, so speak with your provider before taking any herb or supplements. Vasodilator supplements may include:

• Cocoa.
• Coenzyme Q10 (CoQ10).
• Garlic.
• L-arginine.
• Magnesium.
• Niacin (vitamin B3).

What medication interactions should I watch for?

Ask your provider about possible food or drug interactions if you are taking vasodilators. It’s important to be honest and thorough when telling your provider what medications or supplements you take.

Some vasodilator interactions to watch for include:

• ACE inhibitors and potassium supplements.
• ACE inhibitors and medications with lithium.
• ARBs and ACE inhibitors.
• CCBs and grapefruit juice.
• CCBs and verapamil (Calan®, Isoptin®) and diltiazem (Cardizem®).
• Nitrates and sildenafil (Viagra®), tadalafil (Cialis®) and vardenafil (Levitra®).

How long should I take vasodilators?

How long you need to take vasodilators depends on what condition the medicine is treating. For example, if you take vasodilators to treat preeclampsia, you may stop taking the drug after you give birth. But if you have a chronic condition such as pulmonary hypertension, your provider may keep you on vasodilators long-term.

Sometimes, you can manage chronic conditions through lifestyle changes. For example, you may lower your blood pressure by losing weight and exercising regularly. Your provider will monitor any chronic conditions and guide your treatment options.

Who should not use vasodilators?

Vasodilators are not right for everyone. Ask your cardiologist (heart doctor) if you are a good candidate for vasodilator drugs. Generally, you may not be able to take certain types of vasodilators if you are pregnant or have:

• History of angioedema.
• Mitral valve rheumatic heart disease.
• Right ventricular infarction.
• Severe hypersensitivity or hypotension (low blood pressure).

Are vasodilators the only heart treatment I need?

For most people, vasodilators are one part of an overall heart treatment plan. You can keep your heart healthier by adopting healthy lifestyle habits. You may:

• Achieve and maintain a healthy weight.
• Avoid secondhand smoke or quit smoking.
• Drink alcohol in moderation only.
• Eat a nutrient-dense diet full of vegetables, fruits and whole grains.
• Exercise aerobically for at least 150 minutes per week.
• Manage stress with healthy strategies, such as meditation or talk therapy.