How Drugs Work

Pharmacological Treatments for Hypertension

Quick Introduction to Pharmacology

There are a couple important topics that need to be addressed prior to discussing pharmacology. First, most pharmaceuticals in the U.S. have two names. The first, and often most common, is the brand name. Brand names, such as Tylenol or Prozac, are patented and named by a specific company. Only that company is legally allowed to sell the chemical makeup that is contained in the medication. Once the patent period of a drug has expired (maximum of 20 years), other companies can legally produce and sell that drug in generic forms. The drug's non–proprietary name, or trade name, is then used by other companies. Trade names are written in lower case italics, while the brand name is Capitalized.⁶ Examples of trade names are acetaminophen (Tylenol), or fluoxetine (Prozac). It is often debated which drug performs better (trade vs. brand). The answer is usually based on the drug and/or the prescriber's opinion.

Renin–Angiotensin–Aldosterone System Drugs

Due to the complex nature of RAAS, there are different avenues for pharmacological interventions. A well–known RAAS agent is the Angiotensin Converting Enzyme (ACE) inhibitor. These drugs work by blocking the action of ACE, which likewise prevents the conversion of Angiotensin I into Angiotensin II. Without Angiotensin II (which is a strong vasoconstrictor), the body naturally cannot constrict its arteries. This, in turn, causes overall vasodilation. Common ACE inhibitor drug trade names end with the letters –pril (e.g. lisinopril). Common brand names include: Altrace, Accupril, Vasotec, and Capoten. Another way of preventing the effects of Angiotensin II are via Angiotensin receptor blockers (ARB). These work, as described in their title, by blocking Angiotensin II receptors in blood vessels. These are commonly prescribed to patients that cannot take ACE inhibitors. Examples of ARB drugs include Cozaar, Benicar, and Diovan. ^{4 9}

Alpha and Beta Adrenergic Receptor Drugs

There are four main α2 adrenergic agonist drugs that work on hypertension. The oldest of this class, methyldopa, is currently only used for pregnancy induced hypertension. The other three, guanabenz, guanfacine, and clonidine, are still used today as primary treatments. There are many more options when it comes to β–adrenergic receptor drugs. Commonly called "Beta–blockers," beta adrenergic antagonist drugs have become a hallmark for hypertensive drug therapy. Beta–blockers antagonize the actions of β1 receptors. Trade names for these drugs usually end in the letters –olol. Common drugs include atenolol (Tenormin), carvedilol (Coreg), metoprolol (Lopressor or Toprol XL), and propranolol (Inderal). These drugs are also sometimes used with cardiovascular disease, and as antiarrhythmics (to prevent abnormal heart beating). Care must be taken with patients that also suffer from asthma, as the antagonistic features of β–blockers may cause bronchoconstriction (due to antagonism of β2 pathways). ^{4 6 9}

Calcium Channel Blockers (CCBs)

There are a variety of different CCBs on the market that can affect the cardiovascular system in a number of different ways. Four common CCBs on the market, that can be used for hypertension, include nidefipine (Procardia), amlopdipine (Norvasc), diltiazem (Cardizem), and verapamil (Isoptin). As with β–blockers, CCBs are commonly used for other purposes. Specifically, diltiazem is used in emergency situations to treat atrial–fibrillation.⁴

EDRF Agonists

EDRF Agonists are one of the only drugs that have a direct effect on blood pressure. All other drugs discussed in this unit work by activating/deactivating pathways that lead to a balance in blood pressure. EDRF works by directly interacting with vessel endothelium and causing vasodilation. The most common, and widely used, EDRF is nitroglycerine. While this chemical can be used in large quantities for explosives, it is commonly used in emergency medical to cause rapid vasodilation of occluded blood vessels. Patients that are at high risk for heart attacks are often prescribed nitroglycerin (or nitro). In the event they have chest pain (a common sign of heart attack), they are told to administer a nitroglycerin. This nitro acts to dilate coronary blood vessels, which allows much needed oxygenated blood to get to dying tissue. Nitro often gives the patient time to get to the hospital where doctors can administer treatments to clear out blocked blood vessels. ^{4 6 7}

Diuretics

This class of drugs was one of the first oral medications used for the treatment of hypertension.⁵ Diuretics work on the volume of the cardiovascular system in order to correct elevated pressure. These drugs are normally known as "water pills," as they make the patient urinate frequently. There are three main types of diuretics: thiazide diuretics, loop diuretics, and potassium–sparing agents. A fourth type, central antiadrenergic agent, will not be discussed in this unit. Thiazide and Thiazide–like diuretics work on the distal renal tubules by increasing the amount of salt and water that leaves the kidneys and is excreted to the bladder. Examples include chlorothiazed (Diuril), and hydrochlorothiazed (better known as HCTZ). Loop diuretics work on the ascending section of the distal renal tubule, having a similar action to thiazide/thiazide–like drugs but do not last as long. Loop diuretics are usually used with patients that don't have optimal kidneys. Examples of these drugs include bumetanide (Bumex), and furosemide (Lasix). Both of these drug types result in less work on the heart (due to less fluid being pumped), and less SVR. ^{4 9}

One side effect seen in thiazide drugs is the excretion of potassium. Since the potassium atom likes to "follow" the sodium atom, patients can sometimes suffer from hypokalemia (low potassium levels in the blood) due to the kidney excretion of sodium. Hypokalemia can be a very serious problem. To prevent this, patients are often advised to eat a healthy diet including potassium rich foods (such as bananas). One way to prevent the loss of potassium is through potassium–sparing agents, which are usually given concurrently with thiazides. Examples of common potassium–sparing agents include amiloride (Midamor) and triamterene (Dyrenium). ^{4 9} .