In this month's final installment of this series of articles on Western drugs I will discuss cardiovascular drugs, antibiotics, antifungal agents, antiviral agents, anti-inflammatory drugs and immune suppressant drugs (widely used in treating autoimmune diseases such as rheumatoid arthritis).
There are three major conditions that require treatment: hypertension, congestive heart failure, and coronary artery insufficiency with angina.
The first line of defense in treating hypertension is not drugs. Our first approach is lifestyle modifications: stress reduction or better coping skills, weight control, enough exercise, relaxation training in the form of meditation, music therapy, guided imagery, nature walks, or bike riding. There is strong emphasis on nurturing relationships and avoiding conflict (conflict resolution training if needed!) All Western physicians should follow this non-drug approach (most do, but unfortunately not all).
If drugs are needed because of a high risk situation (as with a diabetic patient, or one with heart disease) the first class of drugs we use is the diuretics (so-called water pills). These reduce blood pressure by decreasing blood volume through increased urine production. All these diuretics enhance water and sodium secretion in the urine. Their effect on other ions depends on the drug, but most diuretics lower body potassium and calcium, and the patient is often put on potassium supplements, and often calcium supplements as well (and sometimes magnesium).
The leading diuretic is chlorthiazide (Diuril®), popular for the past 50 years and still widely used. There are also many other drugs in this class with the same actions. They inhibit sodium, chloride and potassium reabsorption in the distal tubules of the kidney nephrons, bringing out water along with the excretion of these ions in the urine. Gentle in their action, mild diuretics are an ideal starting drug for hypertension.
It's always good to avoid pills whenever you can, and make up for the potassium loss with the proper foods. Vegetables (especially beans!) and milk products are high in calcium and potassium, and bananas are high in potassium. Also high in potassium: dried apricots, raisins, prunes, and figs; also walnuts, almonds, and Brazil nuts.
Potassium sparing diuretics are also popular, including spironolactone (Aldactone®) and Dyrenium® (turns urine blue!). More powerful diuretics are used in cases of severe pulmonary edema or fluid retention for other reasons (such as severe congestive heart failure). These include furosemide (Lasix®), bumetanide (Bumex®) and ethnacrinic acid. These stronger diuretics are also used in hypertensive crises, along with alpha blocking agents, as discussed below.
Alpha and beta sympathetic blocking drugs are sometimes used to treat hypertension. Alpha blockers relax the blood vessels and lower pressure. These drugs relax smooth muscles in many parts of the body, also improving urine flow in men with prostate enlargement.
Examples: Minipress® for high blood pressure, and Flomax® for urinary stream blockage.
Beta blockers: this class of drugs slows the heart rate and force of contraction, thereby also reducing blood pressure. Examples include propanolol (Inderal®), metoprolol (Lopressor®), bisoprolol (Zebeta®), and atenolol (Tenormin®). These medicines also reduce the risk of some abnormal heart rhythms (they quiet the irritable heart). Their use has been disappointing, however, and they are mostly used today as add-on agents with another drug for refractory cases of hypertension.
Other agents used to treat hypertension include ACE inhibitors and calcium channel blockers. We will discuss these drugs in more detail in the following section on the treatment of heart failure.
Drugs for Treating Heart Failure
Digitalis has been the 'gold standard' drug for treating heart failure for a very long time. It was first described in the medical literature in 1785 by William Withering. He heard about it from a British village herbalist in Shropshire who told him about an herbal formula that had magical effects for dropsy. Dropsy, meaning heart failure, comes from the Greek hydrops: swelling of the body. Withering reported to the Royal Society on 156 cases of dropsy successfully treated with digitalis leaf. The paper he wrote on this has been considered the beginning of all modern drug therapy.
It is the digitalis plant leaf that is used in treating heart disease (some doctors still prescribe digitalis leaf). Digitalis comes in a variety of preparations in terms of onset of action and length of activity. Digoxin (Lanoxin®) is regular acting digitalis. It is a true miracle drug for the heart. It increases the force of contraction by its effects on increasing calcium and sodium in the heart muscle cells. This causes increased cardiac output in a weakened enlarged heart that is failing from coronary artery disease, myocarditis, or other conditions. This results in decreasing heart size as it becomes more efficient. It also decreases edema in the lungs and lower extremities and abdomen, with increased venous return. Digoxin increases renal perfusion and helps the kidneys get rid of extra fluid that has been building up in the body.
A loading dose of digitalis is gradually given to the patient, followed by a smaller maintenance dose. When needed, there is nothing else quite like digitalis. However the possible side effects of this powerful drug are always of great concern. Unfortunately, these side effects are common, including what is known as digitalis intoxication when too much is on board, with an abnormally slow heart rate (bradycardia), and an irritable heart muscle that is prone to arrhythmias. Fatal ventricular fibrillation can occur. Nausea and vomiting are also common with overdose, which often helps the patient keep the dose in check before something worse happens from taking too much!
Because of the side effects of digitalis and the need to monitor all patients closely who are taking it, particularly when they start taking it, many other drugs are now replacing digitalis as the first line of treatment for heart failure, and also for hypertension. These drugs are considered less dangerous than digitalis. In severe heart failure, however, digitalis may still work the best (and the patient will be closely monitored, often in the hospital).
Classes of drugs to treat heart failure (some are the same drugs we use for hypertension):
- Digitalis (less popular now, as noted above)
- Strong diuretics, such as Lasix
- Beta blockers
- Calcium channel blockers
- Renin-angiotensin system drugs:
- ACE inhibitors (angiotensin converting enzyme inhibitors)
- Angiotensin II receptor blockers
- Renin inhibitors
Strong diuretics include furosemide (Lasix®) and bumetanide (Bumex®). Nothing else is as powerful as these two drugs in getting unwanted fluid out of the body. These drugs also decrease fluid in the lungs, so the patient can breathe more easily. Patients in severe heart failure can lose as much as 15 pounds in three or four days!
Because diuretics make the body lose potassium, calcium and magnesium, the doctor may also prescribe supplements of these minerals. Frequent lab tests must be obtained to check serum potassium levels.
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Potassium-sparing diuretics are also used. These drugs include spironolactone (Aldactone®) and eplerenone (Inspra®). They are primarily potassium-sparing diuretics, but they have additional properties that help the heart work better, may reverse scarring of the heart and may help people with severe heart failure live longer. Unlike other diuretics (which lower potassium), spironolactone can actually raise the level of potassium in the blood; sometimes to dangerous levels. Careful monitoring of potassium is needed. It must not be too high or too low (if it is, it seriously affects the heart).
Calcium Channel Blockers
These drugs also have a role in treating hypertension, but their main usage is in treating heart disease. They block the release of calcium from the muscle cell channels (where it resides when it is inactive), which is an all important step in smooth and cardiac muscle contraction. When these agents are administered to patients the heart becomes more relaxed and is less irritable. It can beat more smoothly and efficiently. Unlike beta blockers, calcium channel blockers do not make the heart less responsive to the sympathetic nervous system, with all its continuous adjustments. This makes things go more smoothly.
Use of calcium channel blockers in other heart conditions: these drugs are especially useful in patients (often young men and women) who suffer from episodes of PAT (also known as SVT: supra-ventricular tachycardia). These episodes feel like a flip-flopping heart to the college student experiencing them and they often last for two or three minnutes, then resolve. The drug of choice for treating PAT is a calcium channel blocker known as verapamil (Isopten®).
Other calcium channel blockers that are widely used include nifedipine (Procardia®) and diltiazem (Cardizem®). There are also many others in use (there is a long list). In many cases a calcium channel blocker may be used in conjunction with a beta blocker in treating heart disease. A cardiologist will individualize such treatment.
The Renin-angiotensin system: This system works to maintain blood pressure at the proper level, even when external conditions would tend to lower it. Examples: dehydration, with reduced fluid volume in the body; blood loss (trauma, GI bleeding, excessive vaginal bleeding, severe nosebleed); severe vomiting or diarrhea; shock with low blood pressure from an anaphylactic reaction (bee sting, allergy to peanuts, strawberries, penicillin, etc.); shock from a severe illness, such as peritonitis or pancreatitis.
Anything causing a reduced blood flow (either low flow rate or reduced pressure) affects the kidneys: Renin is released into the bloodstream from specialized cells near the glomerulus of the kidney (juxtaglomerular cells). This sets in motion a cascade of reactions that combat shock:
- Renin activates angiotensinogen, a protein always circulating in the bloodstream, changing it into angiotensin I.
- Angiotensin I is converted in the lungs to angiotensin II, due to the action of angiotensin-converting- enzyme (ACE)
- Angiotensin II is the most powerful vasoconstrictor known. It constricts the blood vessels throughout the body, raising the blood pressure.
- It also causes the adrenal glands to secrete aldosterone.
- Aldosterone causes the kidneys to retain water and sodium, also raising blood pressure.
- Angiotensin II also activates the sympathetic nervous system, also helping to raise the blood pressure and combat shock.
Angiotensin-converting enzyme (ACE) inhibitors
These drugs block the formation of angiotensin II, so there is less vasoconstriction. This is helpful when the heart is struggling to pump blood against a high pressure in the systemic circulation. ACE inhibitors thus decrease the workload on the heart. Examples include enalapril (Vasotec®), lisinopril (Prinivil®, Zestril®) and captopril (Capoten®). They are widely used to treat high blood pressure.
Angiotensin II receptor blockers:
These drugs block the receptors in the smooth muscle cells that surround the blood vessels, so they do not respond to angiotensin II. Examples are losartan (Cozaar®) and valsartan (Diovan®); they have many of the same benefits as ACE inhibitors. They may be an alternative for people who can't tolerate ACE inhibitors (nausea, diarrhea, skin rashes).
A new class of drugs are now in use that block the action of renin on angiotensinogen so it does not ever get converted to angiotensin I. Examples are aliskirin (Tekturna®), remikirin (brand name not yet available). These are proving to be effective drugs (still being studied). The main side effects are diarrhea or headaches (these are generally well-tolerated, and diminish with time)
The big question: with so many drug choices (drugs that basically do the same thing), which should the practitioner use? There are several answers: physician preference (he/she gets used to using one or two drugs, and gets good at it); side effect issues (the more choices to switch drugs you have, the better for you and the patient); the precise needs of certain patients (i.e., use of a calcium channel blocker and a beta blocker together in certain patients, or an ACE inhibitor in a patient with a weak heart and fluid overload issues).
Several large international longitudinal studies comparing drugs used in treating heart failure and hypertension are in progress, such as the ALLHAT Study. They will take years longer to complete. So far in all these studies no clear winner has emerged, although mild diuretics are strongly holding their own!
Coronary Artery Disease
With narrowing of the coronary arteries there is decreased blood flow to the heart muscle, causing ischemia (decreased oxygen to heart muscle cells). This is what causes angina (severe chest pain). It also causes ECG changes: ST segment depression (the ECG complex is labeled P-Q-R-S-T). Curiously, an actual heart attack often causes ST segment elevation in the leads closest to the area of myocardial cell death.
Anti-angina Coronary Artery Dilators
Nitroglycerin remains the most commonly used agent for angina; usually placed under the tongue for rapid onset of action. Liquid nitroglycerin will explode if shaken, and liquid nitroglycerin mixed with diatomaceous earth makes dynamite! However nitroglycerin has been used since the late 1800's for medical uses. It reaches its peak effect in 1-2 minutes and lasts for about 30 minutes. Isorbide dinitrate (Isordil®) is longer acting and is used to prevent attacks. Because it takes five minutes to become effective it is not used for acute attacks.
Side effects of nitroglycerin are few, but sometimes include hypotension, with the possibility of rebound tachycardia because of falling blood pressure, which can then make the angina worse. Nitroglycerin is far more likely to cause this reaction if the patient is taking Viagra or Cialis!
To understand antibiotics it is important to remember that there are different classes of bacteria. These are often differentiated by their staining qualities, which also correlate with their behavior and their sensitivity to antibiotics. There are gram positive staining bacteria (purple) and gram negative bacteria (pink). There are also acid-fast staining bacteria (the tuberculosis bacteria, for example!)
Gram positive bacteria generally live on the skin: Staphlococcus, Streptococccus, and Pneumococcus. All cause soft tissue infections and pneumonia. Staph also causes infections everywhere else in the body. Staph causes abscesses, strep causes cellulitis (spreading infection).
Gram negative bacteria generally live in the intestinal tract: E. coli, Pseudomonas, Aerobacter, Proteus, Salmonella, Campylobac-ter, and Shigella. These bacteria often cause intestinal or urinary tract infections.
Acid-fast bacteria: Mycobacterium tuberculosum is the best known. It causes Tuberculosis, with nodular infections in the lungs and other areas of the body. These infections are slow-growing and require a long time for treatment (usually a year). Prior to antibiotics tuberculosis was one of the greatest killers on earth. Leprosy is also an acid-fast bacteria (very slow growing and causing slow destruc-tion).
Treatment of gram positive bacteria: Once sensitive to penicillin, these bacteria have become quite resistant to it in recent years. Most staph skin infections do respond well to oral first generation cephalosporins (there are four generations) such as cephalexin (Keflex®) and cephazolin (Ancef®). These antibiotics are a backbone of medical practice, as such infections affect all of us at one time or another. More serious gram positive infections such as pneumonia or osteomylitis: IV Nafcillin® and oral dicloxacillin.
Amoxacillin or Augmentin (amoxicillin plus clavulinic acid) are used to treat otitis media and sinus infections, which if unchecked may lead to brain abscesses, especially in diabetic patients or the elderly.
Methacillin resistant staph infections (MRSA): Vancomycin® and Rocephin® are given together, IV. Sulfa is also sometimes used (it's curious this would work!) These infections require aggressive treatment, often in the hospital, as they can be life-threatening.
Treatment of Gram Negative Bacteria:
Pathogenic gram negative bacteria are common in serious intestinal tract infections (such as peritonitis from a ruptured appendix) or upper urinary tract infections (pyelonephritis). For serious infections of this sort third generation cephalosporins such as ceftriaxone are used IV, and have saved many lives. Aminoglycosides such as gentamycin are also very effective.
Tuberculosis responds well to isoniazid and rifampin, taken over six to twelve months, depending on the severity of the infection.
These infections are common in the mouth or vagina. They respond well to various anti-fungal agents such as mycostatin or ketaconazole. For more serious systemic fungal infections, such as fungal myocarditis (seen in AIDS patients), AmphotericinB is used. Those who take it often call it amphoterrible because of the nausea, vomiting, dizziness, and other side effects, but they continue to take it because it works well when needed.
Relenza and Tamiflu moderate the severity of influenza and the bird flu virus. The government has stockpiled huge quantities of these agents in case there is a bird flu epidemic, as happened in 1918 with the death of at least 50 million people. Hopefully they will not be needed on a mass basis, but these agents are also used to treat the elderly and children who develop severe seasonal influenza that requires hospitalization. Amantadine (Symmetryl®) is also used to treat regular seasonal influenza in the elderly.
Herpes genitalis and oralis are among the most common viral infections in this country. Acyclovir (Zovirax®) is still widely used, and is inexpensive, but it has to be taken five times a day! For this reason Valcyclovir (Valtrex®) has become the drug of choice, as it needs only a twice a day dose. Famcyclivir (Famvir®) is also available.
The treatment of HIV and AIDS should be covered in a separate article, but I will mention three of the most popular drugs: zidovudine (Retrovir®), lamivudine (Epivir®) and abacavir: (Ziagen®). There are about twenty other drugs, usually combined together into a three-agent cocktail, to diminish the development of drug resistance.
Parasite infections are everywhere in the tropics and throughout third world countries, due to hot weather plus poor sanitary conditions. Malaria still kills over a million people worldwide every year. Amebiasis is a scourge that kills hundreds of thousands. Other parasites also abound in these other countries and parts of the world.
Parasite infections in the US:
Giardia, an intestinal infection, and Trichomonas vaginalis which causes vaginitis, are the two most common parasites here. Both are treated with metronidazole (Flagyl®). Pinworms are common in school children, and can then infect the whole family. They are treated with mebenazole (Vermox®), taken by mouth by the entire family if one child shows up with pinworms, which crawl out of the anus at night and lay their eggs, causing intense anal itching.
easy to see with the naked eye. Scabies are microscopic and burrow under the skin: cause red lines that are intensely itchy (can be almost maddening). Proper attention to personal hygiene and sanitation is essential to avoid these infestations, along with thoughtful selection of potential romantic partners in the case of scabies and pubic lice!
Anti-inflammatory and Immunosuppressant Drugs
Infectious agents provoke inflammatory responses, and pharmacologists have developed many anti-inflammatory agents over the years, which are very helpful in reducing inflammation. A true wonder drug in this regard is aspirin, because it has so many beneficial effects. It lowers fever, reduces inflammation, combats pain, and helps prevent blood clots, all at the same time.
Aspirin manages to do this because it blocks the enzyme cyclooxygenase. This enzyme catalyzes the formation of a group of chemicals known as prostaglandins that travel throughout the body in times of infection. These prostaglandins have a role in producing fever, encouraging platelet aggregation, provoking the inflammatory response (redness, heat, swelling) and then facilitating the perception of pain. These reactions are all intended to protect us and help us cope with whatever is infecting or otherwise assaulting us. However, when we have redness, heat, and swelling of the nose, sinuses, and throat, we would rather block those reactions if possible!
Other non-steroidal anti-inflammatory drugs (NSAIDs): acetoaminophen (Tylenol®), ibuprofen (Motrin®, Advil®), naproxen (Naprosyn®, Aleve®), Celebrex® (fewer GI side effects than the others above, but possible cardiac toxicity in some people).
Side effects for all NSAIDs include GI upset and bleeding, especially with prolonged use or overdose. NSAIDs are among the most widely used drugs and are over-the-counter and are thus very easy to obtain. GI bleeding as a side effect of these agents takes a heavy toll of American lives each year.
Corticosteroids are even more potent anti-inflammatory agents than NSAIDs and are a mainstay of treating autoimmune disorders: cortisone, prednisone, Aristocort®, Medrol®, etc. The long-term use of steroids leads to Cushing's syndrome, with diabetes, hypertension, fluid retention, osteoporosis and stomach ulcers along with many other unpleasant features. They are nonetheless miracle drugs because of their powerful beneficial effects in reducing inflammation and swelling. Steroids save the lives of many individuals with closed head trauma from auto accidents and falls who might otherwise die from increased swelling of the brain.
Drugs which suppress the activity of the immune system have been developed which are also widely used in autoimmune disorders: methotrexate, azathioprine (Imuran®), cyclophosphamide (Cytoxan®). Newer agents that block the actions of TNF, the tumor necrosis factor: inflixamab (Remicaid®), and etanercept (Enbrel®). These are expensive drugs that work wonders in helping those with severe rheumatoid arthritis, Lupus, or any of the other less well-known autoimmune disorders. Insurance companies are now starting to recognize the dramatic value of these drugs in severe illness and are now paying for their use.
We have covered most of the drug categories that are most commonly used in Western medicine, with the notable exception of chemotherapy agents for cancer, which is an entire subject on its own. I cover this important topic in my textbooks and also my seminars for acupuncturists on Biomedicine, which will soon be available online.
Click here for previous articles by Bruce H. Robinson, MD, FACS, MSOM (Hon).