NPTA

Understanding Cholesterol

noemail@pharmacytechnician.org — Wed, 06 Aug 2008 13:00:00 GMT

Objectives:

Learning Objectives

1. To relate the effect of high cholesterol to heart disease risk

2. To state the purpose of cholesterol in the body

3. To list beneficial lifestyle changes which lower risk of heart disease

4. To explain the benefits and risks of statins

5. To describe high-risk conditions due to high cholesterol

6. To recognize components of the Western diet

7. To compare non-pharmaceutical options for lowering cholesterol

8. To distinguish between LDL, HDL, triglycerides and cholesterol ratio

Instructor: Jada Fehn, CPhT

Release Date: 6-Aug-08 8:00 AM
Expiration Date: 6-Aug-11 8:00 AM

Introduction
In 1955, President Dwight D. Eisenhower had a heart attack while he was on vacation in Denver, Colorado. He instructed his press secretary to inform the public of his condition every step of the way; however, his personal physician delayed the announcement. These two beliefs and actions of Eisenhower and the physician could easily mirror public sentiment towards heart disease when it happens to them. Some choose to seek treatment and enlist the support of their family and friends, while others deny the condition. When the American public did discover what happened to the president, they were awakened to the fact that heart disease can affect anyone.

Today, more than 80 million Americans have cardiovascular disease. It is estimated that over 17 million people will die this year from heart attack and stroke making heart disease the number one killer worldwide. Some cholesterol is necessary for the body to function, but high cholesterol levels increase the risk of heart disease and stroke.

A well-known study in Framingham, Massachusetts demonstrated that high blood cholesterol is a risk factor for cardiovascular disease. <4> This is only one of many studies linking high cholesterol levels to heart disease. Many studies point to the high cholesterol, high fat Western diet, rich in burgers, fried foods and sodas as contributing to the heart disease epidemic in the United States. Our understanding of cholesterol and how it works has increased significantly since then but its association with heart problems and stroke is still strong.

In today’s healthcare industry, cholesterol has a negative connotation. But the very first thing to know about the substance is that it is a necessary element in the human body. Cholesterol’s waxy ring structure is part of the membrane of every cell. Without cholesterol, our bodies would be unable to build cells or produce important hormones.

The Basics
Cholesterol is necessary in the body for a variety of reasons. It is required to build and maintain cell membranes. It regulates membrane fluidity over a range of temperatures. It aids in the manufacture of bile. It is important for the metabolism of fat-soluble vitamins. It is the major precursor for the synthesis of vitamin D and of the various steroid hormones.

Cholesterol comes from two sources: dietary intake and liver production. About 80 percent of the cholesterol level in the body’s blood is created in the liver and intestines. Most of the cholesterol that the liver creates is stored in the gall bladder as bile salts and released after meals to aid in the digestion of fats. Some cholesterol is released with other body waste but the rest is reabsorbed by the liver to be recycled for future meals.

The other 20 percent of cholesterol makeup is absorbed from diet. Dietary cholesterol sources are mainly from meat, poultry, fish and dairy products. Organ meats, such as liver, are especially high in cholesterol content, while foods of plant origin contain no cholesterol.

To have the ability to travel in the bloodstream, cholesterol made in the liver is combined with protein, forming a lipoprotein. Lipoproteins are a biochemical assembly of protein and lipids that carry fats around the body. The bulkiness of the lipoproteins affects how they work in the body. This lipoprotein then carries the cholesterol through the bloodstream. Because cholesterol is a fatty acid, it is not soluble in water and cannot move around in the bloodstream on its own. Similar to oil and water, cholesterol, which is fatty and blood, which is watery, do not mix. As Mason Freeman writes, “They would congeal into unusable globs.” <2> Lipoproteins wrap around cholesterol to move it around through the body.

Lipid Panel
A lipid panel cholesterol test measures several values. Total cholesterol is the overall number associated with a person’s blood serum levels and then there are the numbers for lipoproteins. The first is low-density lipoproteins (LDL), also known as “bad” cholesterol. This type of transport deposits cholesterol into body tissues. The LDLs transport cholesterol to the arteries and can be retained there starting the formation of plaques.

There are also VLDL particles. These very low-density lipoproteins carry small lipid loads similar to LDL and deliver them to tissues. LDL cholesterol also has a variation called Lp(a) which is another factor that plays a part in prematurely blocked arteries and is considered to be a valuable marker for heart disease risk. Genetic makeup is responsible for levels of Lp(a) but the substance’s role in the system is not yet fully understood.

The “good” kinds of lipoproteins are high-density lipoproteins (HDL) and they take cholesterol back to the liver to be disposed or recycled.

The last measure most cholesterol tests include is triglycerides, another fatty substance. These are the storage forms of fat that the body uses as energy. Each triglyceride has a glycerol base and three fatty acids attached. In the past these were only considered to be a problem for the pancreas but now it has been proven that the risk of developing heart disease increases with high levels of triglycerides.

Total normal levels of cholesterol should be under 200 mg/dl whereas 240 mg/dl and above is considered high (mg/dl stands for milligrams of cholesterol per deciliter of blood). LDL normal levels of cholesterol, or "bad" cholesterol, should be under 130 mg/dl. Between 160 mg/dl and 189 mg/dl is considered high and above 190 mg/dl or more is very high. HDL normal levels of cholesterol should be over 40 mg/dl, and the higher the level, the better, because it helps protect against clogging of the arteries. Optimum levels range around 60 mg/dl. Triglycerides are too high if they are over 150 mg/dl.

The liver manufactures and secretes LDL cholesterol into the blood. It also removes LDL cholesterol from the blood. Active LDL receptors on the liver surfaces are associated with the rapid removal of LDL cholesterol from the blood, helping to exhibit low blood LDL cholesterol levels. A deficiency of LDL receptors is associated with high LDL cholesterol blood levels. Heredity and diet are known factors to have a significant influence on a person's LDL, HDL and total cholesterol levels. High cholesterol, high saturated fat diets also raise the levels of LDL cholesterol in the blood.

An important factor to consider for normal levels of cholesterol is the cholesterol ratio, which is used as a predictor of heart disease risk. This number indicates whether more cholesterol is being stored in cells or is being broken down and removed from the body. To determine this ratio, divide the total cholesterol numbers by your HDL cholesterol number.

The result should be below four. The lower this number, the better with an optimum level hovering around 2.5 for the lowest indicator of heart disease. High ratios indicate a higher risk of heart attack; therefore, a high total cholesterol or a low HDL cholesterol increases the ratio.

The Risk of High Cholesterol
One of the prime dangers associated with cholesterol is plaque. Arteries are usually a smooth track with blood flowing at different speeds as the heartbeats. When damage occurs to an artery wall, platelets and white blood cells are attracted to the inner lining. White blood cells get under that first layer and into the middle of the artery wall and turn into macrophages. These macrophages gather up cholesterol and multiply, causing a fatty bump in the artery lining at that point. This fatty bump becomes a plaque that is in danger of rupturing. If the cap of one of these plaques breaks, a gruel including cholesterol is released into the bloodstream, leading to clots in the body.

Stroke occurs when a branch of the vasculature in the brain - a small artery - becomes blocked due to a clump of platelets: a piece of plaque debris or a blood clot blocks blood flow to the area. The area then fails to get oxygen or glucose to feed the cells and permanent damage may occur.

Heart attacks occur when large clots get lodged in narrow arteries blocking blood supply to the heart. This myocardial infarction can cause cardiac arrest when the muscle stops beating.

Non-pharmaceutical Options
The goal is to lower LDL cholesterol levels to decrease the risk of heart disease. A lifestyle change such as a modified diet, a weight management plan and the addition of physical activity is often the first line non-pharmaceutical treatment suggested. Generally practitioners start to address high cholesterol in their patients by suggesting lifestyle changes such as these. Nancy Ross-Flanigan and Teresa Odle write in the Gale Encyclopedia of Medicine, “By losing weight, stopping smoking, exercising more and reducing the amount of fat and cholesterol in the diet, many people can bring their cholesterol levels down.” <5> Robert E Kowalski gives very specific diet advice in his book, The New 8-Week Cholesterol Cure. The advice focuses on eating a large variety of fruits and vegetables, replacing saturated and trans fats with “good fats” like canola and olive oil, eating fish more often, choosing low fat or non-fat dairy products and including nuts in your diet. <1> The book Love in the Time of Cholesterol is an endearing memoir by food writer Cecily Ross. It is the story of her husband’s heart attack, which also includes many heart healthy recipes for others to try. <6>

Omega-3 fatty acids are moving to the forefront of health research. Some scientists believe that these acids improve cholesterol and triglyceride levels, and, in turn reduce one’s risk of coronary heart disease. Studies are ongoing. Omega-3 fatty acid, a polyunsaturated fat, must be obtained from food because it cannot be manufactured by the body. In her book The Queen of Fats, Susan Allport records the research history that led scientists to find the value of Omega-3’s in the diet. <3> The account makes a good case of why these essential fats are out of balance in the Western diet, deemed extremely poor from a nutritional standpoint, and why a change in eating may be the next approach to heart disease treatment.

Niacin, or nicotinic acid, in small doses is used as the vitamin B-3. At higher doses (500 mg or more), it is also effective at lowering cholesterol. To help reduce high cholesterol, patients are typically started on low doses and gradually increased up to 1.5 – 3 grams per day. Niacin raises HDL cholesterol and lowers triglycerides. Ross-Flanigan and Odle write, “Niacin probably helps reduce cholesterol by inhibiting very low density lipoprotein (VLDL) secretion in the blood stream.” <5> Because of the possible side effects, this treatment should always be done under a doctor’s care. Flushing, a warm sensation in the face or neck is the main complaint for patients due to the widening of blood vessels. It can also lead to uncomfortable redness and itching in some patients. Generally, slow-release Niacin (Niaspan<r>) can alleviate these side effects.

A Pharmacological Approach
Statins are the most common cholesterol lowering drugs on the market. They work by reducing the production of cholesterol in the liver by blocking the enzyme that is responsible for making cholesterol. Two potentially serious side effects of statins are liver damage and muscle problems; however, most patients experience only mild side effects that subside over time.

Considered “tried and true” by most physicians, these statin drugs work by blocking the HMG-CoA enzyme and keeping fat from being converted to cholesterol. Atorvastatin (Lipitor<r>) is one of the most widely prescribed drugs in the United States.<5> Simvastatin (Zocor<r>), rosuvastatin (Crestor<r>), pravastatin (Pravachol<r>), lovastatin (Mevacor<r>) and fluvastatin (Lescol<r>) are all in this same class of medications.

Not everyone agrees that treating cholesterol with statin drugs is the way to go. Duane Graveline is the author of a book titled, Lipitor, Thief of Memory. < 7> He chronicles his own battle with Transient Global Amnesia (TGA), a condition when patients experience short time periods without the ability to form new memories. Graveline attributes the condition to starting Lipitor<r>, but more research is needed to link cognitive side effects to statins.

To lower LDL and triglycerides and raise HDL, fibrates are another drug group that physicians use to treat cholesterol. <5> Although gemfibrozil (Lopid<r>) and fenofibrate (TriCor<r>) do not generally reduce total cholesterol they can be very effective in particular patients.

The bile produced by the liver helps with absorbing fats. If this digestion is blocked by a drug known as a bile acid sequestrant,, cholesterol cannot be formed. Cholestyramine (Questran<r>) and colesevelam (Welchol<r>) are in this class of drugs. <5>

The drug family including ezetimibe (Zetia<r>) and Vytorin<r>(ezetimibe/simvastatin) has come under recent scrutiny. These drugs are supposed to limit the absorption process and prevent the plaque buildup on artery walls. A study of Vytorin<r> presented at the American College of Cardiology and published by the New England Journal of Medicine, showed no effect above and beyond simvastatin alone. <8>

There have been proposals to market Mevacor<r> (lovastatin) as an over-the-counter (OTC) medication available to the general public. Much controversy has risen over this. On one hand, some feel that they would be improving public health by making the medication readily available. On the other hand, OTC medications have typically been reserved for short-term conditions, whereas Mevacor<r> is used for treatment over a long period of time. In addition, there may or may not be any monitoring of the patient when they decide for themselves when to take the medicine, when to stop and how much to take. So for now, Mevacor<r> remains a prescription.

Conclusion
Cholesterol is a necessary building block for every cell in our body. Health care is facing an epidemic of heart disease. The Western diet, with an excess of cholesterol may be the main contributor to or cause of clogged arteries. Patient responsibilities include research, controlling cholesterol through diet, lifestyle changes or pharmaceutical therapy to help prevent heart attack or stroke. Pharmacy professionals are poised as an informational resource to help these patients make the best choices for their health.

References

1. Kowalski, Robert. The New 8-Week Cholesterol Cure. New York: HarperCollins Publishers,
      2002.
2. Freeman, Mason. What to do about High Cholesterol (Harvard Special Report). Harvard
      Health Publications Group, 2006.
3. Allport, Susan. The Queen of Fats, Why Omega-3s Were Removed from the Western Diet
      and What We Can Do to Replace Them. Los Angeles: University of California Press, 2006.
4. Spence, J. David. How to Prevent Your Stroke. Nashville: Vanderbilt University Press, 2006.
5. Ross-Flannigan, Nancy and Odle, Teresa G. “Cholesterol-reducing Drugs.” The Gale
       Encyclopedia of Medicine.   Detroit: Gale, 2006.
6. Ross, Cecily. Love in the Time of Cholesterol. New York: McGraw-Hill, 2006.
7. Graveline, Duane. Lipitor Thief of Memory. Hartford: Infinity Publishing, 2004.
8. Jackevicius, Cynthia, Tu, Jack, et al. “Use of Ezetimibe in the United States and Canada.”
       New England Journal of Medicine. Available at
       http://content.nejm.org/cgi/content/short/NEJMsa0801461

Warafin Drug Information: What Technicians Need to Know

noemail@pharmacytechnician.org — Wed, 02 Apr 2008 13:00:00 GMT

Objectives:

At the program conclusion, participants should be able:
• to explain the effect of warfarin on vitamin K and list some foods that contain vitamin K which
may interact with warfarin
• to list factors to be considered when dosing warfarin
• to differentiate between coagulation tests PT and INR and state the normal ranges for each
• to explain the importance of ongoing warfarin dose monitoring
• to identify severe side effects which may be associated with warfarin
• to define some medications known to interact negatively with warfarin
• to state what pharmacy technicians can do in the safe processing of warfarin prescriptions
• to deduce the safety of warfarin use in pregnant women

Instructor: Christen A. Freeman, PharmD, MBA, BCPS

Release Date: 2-Apr-08 8:00 AM
Expiration Date: 2-Apr-11 8:00 AM

Warfarin is widely prescribed for the treatment and prevention of thromboembolic events. In fact, warfarin (brand name Coumadin) is the most commonly prescribed medication for this condition. Although there are many benefits to warfarin use, there can also be severe effects when not dosed correctly or taken as prescribed. Inadequate warfarin dosing can place patients at an increased risk of life-threatening conditions such as toxicity, excess bleeding, thromboembolic events or inadequate response.

Warfarin sodium is an oral anticoagulant used for the prevention and treatment of blood clotting disorders.1-3 It is given to patients to help prevent blood clots from forming or to help prevent the growth of an existing blood clot which could lead to severe life-threatening conditions such as thromboembolic events. Warfarin was approved by the Food and Drug Administration in 19541. Although highly effective, warfarin carries significant safety risks related to its adverse effect profile and the potential to interact with various foods and medications.1-3 Awareness of warfarin’s unique pharmacological properties, side effects, and the potential impact of dispensing-related medication errors enable pharmacists and pharmacy technicians to play an integral role in the safe and effective utilization of this medication.

Mechanism of Action
Warfarin exerts its therapeutic effects by inhibiting the production of vitamin K-dependent blood clotting factors II, VII, IX, and X. Specifically, it inhibits the ability of vitamin K to aid in the synthesis of these factors. Warfarin also inhibits the production of the body’s natural anticoagulant proteins C and S. The ultimate effect of warfarin administration is anticoagulation, the extent of which is dependent upon the dose administered. Warfarin is used in the prevention and treatment of blood clotting abnormalities such as deep vein thrombosis (DVT) and pulmonary embolism, as well as clotting complications associated with atrial fibrillation, mechanical heart valves, and myocardial infarction.1,3 Warfarin is effective in these disease states because it makes the blood thinner, or less likely to clot.

Dosing and Therapeutic Monitoring
The typical daily dose of warfarin is highly patient-specific and depends on several factors including age, diet, comorbid disease states, and concurrent medication therapy.1-3 The starting dose for warfarin generally ranges from 2.5 mg to 5 mg;3 however, it is not unusual for physicians to prescribe higher or lower doses in certain patient populations such as the elderly, debilitated, or patients with liver disease. Warfarin is commercially available in the United States as the brand name drug, Coumadin® (manufactured by Bristol-Myers Squibb), as well as in the generic form available from various manufacturers. It is available in a variety of strengths to facilitate convenient dosage adjustments.1 Some warfarin regimens require patients to take different strengths of the drug on different days of the week in order to achieve a target weekly dose.

Physicians monitor the effects of warfarin on the blood with two laboratory tests, the prothrombin time (PT) and International Normalized Ratio (INR).1-3 Both tests measure the tendency of the blood to clot. The PT Is typically measured in seconds; the normal range in healthy individuals is 12 to 15 seconds, but may vary slightly depending on the laboratory.4 The INR is a standardized way of expressing the prothrombin time that does not vary depending on the laboratory. The typical INR in young, healthy adults is approximately 1.0. The therapeutic goal for patients on warfarin is anticoagulation, or blood that is less likely to clot. Therefore, warfarin will be dosed to obtain a higher INR. The particular therapeutic goal will depend on the patient’s disease state;1-3 in general, 2.5 (range: 2-3) is the goal INR for most patients.1,2 A goal INR greater than 4 is rarely indicated and places the patient at risk for serious bleeding consequences,3 while patients with a subtherapeutic INR may be more likely to experience a blood clot.

Because of the many factors that may affect the INR (e.g., diet, drug interactions, and illness), patients anticoagulated with warfarin must be monitored closely and regularly.1,3 The PT and INR are usually obtained every four to six weeks in stable patients,2 but may be monitored more frequently in patients who are clinically unstable, undergoing dosing changes, or have recently been initiated on warfarin therapy.1,3 These blood tests may be obtained in physicians’ offices, hospital outpatient clinics, or in special pharmacotherapy or “Coumadin® clinics,” depending on the local resources available. Patients are encouraged to keep a monitoring log to record various warfarin doses and corresponding PT/INR values.

Activity
Arrange a visit to an anticoagulation clinic. Interview pharmacy technicians and inquire as to their responsibilities in the clinic. How did they prepare for the position? What is their previous pharmacy experience and their ongoing education? Ask specifically about details within their scope and how they relate to patients. Do you feel the pharmacy technician is a valuable member of the anticoagulation team? What contribution do you feel they have made in this pharmacy practice area?

Precautions and Adverse Effects
Although warfarin is a commonly prescribed and very effective anticoagulant, it carries the risk of significant adverse effects. The drug carries a “Black Box Warning” regarding the risk of serious bleeding complications, specifically in the elderly (age over 65 years), and those with a history of gastrointestinal bleeding, hypertension, cerebrovascular disease, serious heart disease, anemia, cancer, trauma, and/or renal insufficiency. In addition, patients who are currently on therapy with interacting drugs or have been on warfarin for a long duration of time are more likely to experience a serious adverse event.1,3 The most potentially serious consequence of warfarin therapy is severe hemorrhage from any tissue or organ, such as the brain or gastrointestinal tract.1,3 Other reported adverse effects include bleeding of the gums, easy bruising, blood in the stool or urine, and/or persistent bleeding from a superficial cut or injury.1 Although not all of these adverse effects will be clinically significant, unexpected bleeding often causes significant distress for patients and/or caretakers. Adverse effects are more likely to occur with an INR above the therapeutic range, but may occur even when the INR is therapeutic.1,3

Warfarin is contraindicated in women who are pregnant, because it can cause serious harm and even death to the fetus.1,3 All women of childbearing potential who are on warfarin therapy should be counseled by their physician and pharmacist regarding appropriate birth control options or alternative anticoagulation options if pregnancy is desired.

In patients with excessively high INR values (greater than 9), severe bleeding, or who are undergoing invasive procedures that require reversal of anticoagulation, vitamin K (phytonadione) may be prescribed to counteract the effects of warfarin. Vitamin K may be administered orally or by slow intravenous (IV) infusion.2 Reversal of warfarin anticoagulation generally occurs in the inpatient setting where patients can be closely monitored and managed acutely; however, oral vitamin K may be prescribed to reverse warfarin anticoagulation on a limited basis in the outpatient setting.

Food and Drug Interactions
Warfarin inhibits the ability of vitamin K to be involved in the synthesis of clotting factors; therefore, dietary intake of vitamin K will affect the efficacy of warfarin.1,3 Ultimately, a patient’s daily dose of warfarin will be dependent at least in part on his or her regular diet. Foods that contain significant amounts of vitamin K include kale, collard greens, spinach, broccoli, brussel sprouts, parsley, asparagus, cabbage (including sauerkraut and coleslaw), and mayonnaise.1-3 Patients often believe that because they are on warfarin they must avoid vitamin K-containing foods; however, this is not the case. In fact, a patient initiated on warfarin therapy should be encouraged to keep his or her diet consistent on a day-to-day basis. Significant dietary or appetite changes should promptly be reported to the patient’s physician.

Perhaps one of the most significant considerations when managing patients on warfarin therapy is the potential for serious drug interactions. Warfarin interacts with numerous medications; patients may experience reduced efficacy (more likely to clot) or increased toxicity (more likely to bleed) depending upon the nature of the interaction. One of the most clinically significant interactions occurs between warfarin and amiodarone,1-3 a drug used to treat cardiac arrhythmias. If amiodarone is prescribed to a patient who is stable on warfarin, the patient's INR will almost certainly become elevated, potentially leading to serious bleeding consequences. This effect may persist for weeks to months after amiodarone is discontinued.2 Table 1 lists some of the most common drug interactions with warfarin. Although the consequences of drug interactions with warfarin therapy can be severe, it does not mean that interacting agents can never be used together. The highest chance for a drug interactions occur when interacting medications are initiated or discontinued in a patient who is stable on warfarin therapy. Close monitoring is often warranted in this situation.1,3

Over-the-counter medications such as ibuprofen, acetaminophen, cimetidine, and aspirin also have the potential to interact significantly with warfarin. Herbal products and vitamins that may affect coagulation in a patient on warfarin therapy include: garlic, Ginkgo biloba, coenzyme Q10, St. John’s Wort, green tea, vitamin E, vitamin K, and ginseng.1,3 Refer to the package insert for a more extensive listing of interacting medications and herbal products.

One major contributing factor to drug interactions is polypharmacy, or the use of multiple medications. In addition, patients often see more than one physician, use more than one pharmacy, and may not adequately communicate current medication use to each provider. It is essential that patients notify each healthcare provider if he or she is on warfarin therapy; this communication may require prompting from physicians, nurses, pharmacists, or pharmacy technicians.

Special Considerations for Pharmacy Technicians
Pharmacy technicians play an integral role in the care of patients on warfarin in both the inpatient and outpatient settings. In many practice settings, technicians are involved in nearly every aspect of the dispensing process, including obtaining medication histories, filling prescriptions, and performing the duties of order entry. Pharmacy technicians are often the first, and sometimes the only pharmacy employee a patient may directly encounter while visiting the pharmacy. Therefore, technicians have the responsibility to be aware of and help manage potential safety issues related to warfarin therapy. The following tips may be useful to pharmacy technicians when filling prescriptions for patients on warfarin therapy:

• Always double-check the prescription during order entry. If the dose is illegible, ask for help from the pharmacist before interpreting it. Ensure that the information on the label matches the information on the prescription. Dosing errors due to mistakes at order entry can have potentially significant effects for patients on warfarin therapy.

• When entering orders or prescriptions electronically into the computer, never override a drug interaction alert or warning without notifying the pharmacist first.

• Always double-check that the correct drug strength has been selected after removing it from the shelf.

• If a patient presents a new prescription for warfarin, ensure that his or her medication profile accurately reflects all current medication therapy, including over-the-counter medications, herbal products, and vitamins.

• Notify the pharmacist when a patient presents with a prescription for warfarin for the first time: this is an excellent opportunity for patient counseling.

Awareness of potential patient safety issues related to warfarin therapy is the first step in proactively managing risks associated with this drug. Although warfarin is an effective and commonly prescribed anticoagulant, the potential for clinically significant and sometimes fatal adverse events require pharmacists and technicians to be particularly vigilant when dispensing these prescriptions. Technicians should never hesitate to ask the pharmacist for help interpreting warfarin prescriptions or express concern over potential drug interaction alerts encountered during order entry. Education, awareness, and a sense of responsibility for safe medication usage can help prevent medication errors associated with warfarin.

Resources
1. Facts & Comparisons. Facts & Comparisons web site. http://www.online.factsandcomparisons. com.ezproxy.samford.edu/ . Accessed June 23, 2007.
2. Horton JD, Bushwick BM. Warfarin therapy: evolving strategies in anticoagulation. American Family Physician.1999;59:635-46.
3. Coumadin® [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2006.
4. Prothrombin Time (PT) Medline Plus Medical Encyclopedia Web site. http://www.nlm.nih.gov/ medlineplus/ency/article/003652.htm. Accessed June 22, 2007.

Author Bio:
Christen earned a Bachelor’s Degree in Biology from Tennessee Wesleyan College in 2002, a Pharm.D. from Samford University McWhorter School of Pharmacy in 2006 and an M.B.A. from Samford University School of Business in 2007. She completed a Drug Information Residency at DCH Regional Medical Center in Tuscaloosa, AL, where she currently practices as a Drug Information and Staff Pharmacist.

Pharmacy Technicians & Legal Liability

noemail@pharmacytechnician.org — Wed, 02 Apr 2008 13:00:00 GMT

Objectives:

At the program conclusion, participants should be able to:

• to give examples of legal consequences pharmacy technicians may have imposed on them for misconduct
• to explain why legal regulations are beneficial for pharmacy technicians
• to list and differentiate between criminal, civil and administrative law
• to realize the relationship between liability and patient care and safety
• to relate media influences which have reported on pharmacy technicians and medication errors
• to understand the significance of the responsibility inherent to the practicing pharmacy
technician

Instructor: Christen A. Freeman

Release Date: 2-Apr-08 8:00 AM
Expiration Date: 2-Apr-11 8:00 AM

Introduction
The profession of pharmacy has advanced considerably over the past several decades, bringing about exciting changes in the delivery of pharmaceutical care. Pharmacists and technicians have likely experienced the effects of these changes with an increasing number of available jobs, additional educational opportunities, new legal requirements, expanding roles and responsibilities and higher pay rates.

Pharmacy technicians, in particular, have gained respect and recognition by professional pharmacy organizations as healthcare professionals for their unique knowledge and skill set. However, as the job responsibilities of pharmacy technicians expand, legal liability is becoming an increasingly important consideration. It is necessary for all pharmacy professionals, including technicians to be familiar the laws governing pharmacy practice and fully appreciate the potential legal implications of daily activities and on-the-job decisions.

The intent of this article is to provide basic information about legal liability as it relates to pharmacy and is not meant to be a comprehensive review of the subject. In addition, the information presented in this article should not be interpreted as legal advice. For more information, please see the references at the end of the article or consult an attorney.

Legal Requirements & Personal Responsibility
Many states have already implemented pharmacy technician regulations. Others are still discussing or have deadlines established for the implementation of such regulations as licensing, registration, background checks, education and/or training criteria, mandatory testing and assessment requirements. With each regulation comes a set of rules or responsibilities as to how to maintain that legal status: break the rules, lose the status.

As the role of pharmacy technicians evolves, along with the good, come some bad. For example, a case where a pharmacy technician has diverted medication from the pharmacy or worse. If state regulations do not recognize a class of personnel (through registration or licensure), it is difficult to discipline such personnel in the event of misconduct. In this particular scenario, once a pharmacy technician is terminated from one site, he or she may easily become employed at another site without being held accountable.

In addition to the professional requirements the pharmacy technician will need to adhere to, along comes heightened legal responsibilities. Indeed, a pharmacy technician is under the supervision of a pharmacist, however, through education, training and other legal requirements comes an inherent professional duty to be conscious of the work they perform because they are dealing with patient care and safety. As a member of the healthcare team providing services to patients, they too, are personally responsible for the medication preparation, the prevention of medication errors, quality assurance and following stringent policies and procedures. Pharmacy is one of the most highly regulated health care areas around. Shouldn’t the same expectations be made for the pharmacy personnel?

Types of Law
Various regulations put upon us are meant to protect others as well as ourselves. Throughout our careers, we encounter just as many complex and diversified types of people as we do situations. When people feel they have been harmed, they have a variety of laws to use to seek remedies from the responsible entities.

When approaching the subject of pharmacy liability, it may be beneficial to first differentiate between civil criminal and administrative law. Criminal law is perhaps the most familiar when thinking of the legal system. Criminal law involves the relationship between individuals and society as a whole. In these cases, the state takes action against an individual for crimes committed, attempting to punish the wrongdoer for misconduct. Such cases may result in a police investigation and punishments including imprisonment, probation and fines. Examples of criminal liability cases relating to pharmacy practice could include selling medications without a prescription, intentionally misfilling a patient’s prescription in order to worsen disease or hasten death and falsification of medical information or prescriptions.

Civil law pertains to cases where society holds individuals responsible for their behavior towards each other. In a civil lawsuit, a private party sues another party for damages that occurred as the result of wrongdoing. The goal of the civil lawsuit is compensation for the injured party. In most situations, this compensation is money.

One example of a civil liability suit as it relates to pharmacy may include a lawsuit against a pharmacist or technician for misfilling a prescription that ultimately results in patient harm. For instance, the technician enters the prescription in the computer correctly, but inadvertently puts the wrong medication or wrong strength in the bottle and the pharmacist fails to catch the technician’s error. The medication is dispensed and taken by the patient, who doesn’t know what the original medication was supposed to look like. When an adverse drug reaction occurs and the patient is harmed, the patient sues the pharmacy, the pharmacist, and the pharmacy technician.

As it relates to pharmacy practice, administrative law involves an administrative body, such as the State Board of Pharmacy, which protects the public from licensed individuals. The administrative body is responsible for setting certain professional standards and ensuring such standards are enforced. When violation of a statute or regulation occurs, the professional’s license may be suspended or revoked in order to protect the public from the potential harm he or she may have inflicted as a result of this misconduct. In the previous example, the pharmacist charged with selling medications without a prescription would likely be subject to administrative action. Other forms of administrative action may include warnings, fines, and probation. It is important to note that one single event may violate civil, criminal, and administrative law

Cases
In March 2007, ABC ran a series of programs specifically highlighting pharmacy technicians who had committed grave medication errors. As pharmacy technicians become positively recognized for their accomplishments, some will also become more recognized for their negative actions.

At this point it may appear easy to see how pharmacists may be held liable, but not pharmacy technicians. However, the fact remains that pharmacy technicians are often involved in lawsuits and do not always escape culpability. Consider the following cases that were highly publicized by the media:

• In 1997, a pharmacist, pharmacy supervisor and technician were sued by parents of a child who received a medication overdose while a patient at a children’s hospital. The error occurred when the pharmacy technician did not dilute a dose of enalapril that had been prescribed to control the infant’s blood pressure. The technician’s error was missed by the pharmacist and dispensed. Ultimately, the infant received a 750 mcg dose rather than the 6 mcg dose that was prescribed. The family claimed that the error caused the infant to suffer neurological damage, although the hospital maintains that the infant was born with the condition. The jury initially awarded the family $7.1 million in damages. Due to post trial motions filed by the hospital’s insurer, the final outcome of the lawsuit is unknown.
(http://www.ashp.org/s_ashp/article_news.asp?CID=167&DID=2024&id=2944)

• A pharmacy technician misfilled a prescription of a blood thinner with a strength 10 times what was prescribed. When the patient experienced a cerebral hemorrhage, her cancer treatments were interrupted and she eventually died. The family filed a lawsuit against the chain drugstore and was awarded $25.8 million dollars.
(http://www.usatoday.com/money/economy/2007-08-18-2786864803_x.htm)

• A lawsuit was filed against a major retail pharmacy chain, a pharmacy technician, and the technician’s daughter for a confidentiality breach. The pharmacy technician allegedly shared information with her daughter regarding a classmate’s prescription. The plaintiff’s attorney maintained that the technician’s daughter shared the information with many other classmates, causing tremendous distress for his client.
(http://abclocal.go.com/wls/story?section=local&id=4016186)

These are only a few examples of cases filed against pharmacy technicians. These cases are not meant to frighten, but to highlight the tremendous importance of the job responsibilities of a pharmacy technician. An internet search for “pharmacy lawsuits” will provide numerous examples of cases that involve both pharmacists and technicians.

Activity
Research and discover any case involving a pharmacy technician(s) who may have been embroiled in a legal matter related to their profession. Research from beginning to end, compose a summation and if possible present it to other pharmacy technicians either at your place of study or work. Before revealing how your case turned out, ask your audience if they can guess the outcome. Compare the true outcome with what was stated. Promote discussion as to why everyone felt it should have turned out a certain way. What laws were at play, if any? What future regulations could be developed to change or improve the outcome? What ethical dilemmas were presented?

Liability
It is important to note that although the pharmacist supervising the technician may be sued, along with the employer and even an entire institution, the pharmacy technician shares liability and may be subject to substantial fines and administrative action, depending upon the regulations in that state. It cannot be overlooked that regardless of the verdict, such lawsuits often have a substantial impact on a pharmacy professional’s life. A medication error that results in death, disability or significant patient harm is often a life-altering event for the responsible individuals, regardless of whether the patient or family decides to take legal action.

As the profession of pharmacy evolves and expands, so do the roles and responsibilities of pharmacists and technicians. This article has illustrated various ways in which pharmacy professionals may be subject to civil, criminal, and administrative liabilities, including cases that have been publicized in the media. It is essential for pharmacists and technicians to be aware of national and state pharmacy practice laws, as they are held to the standards set forth in these laws even if they are not familiar with them. Membership in professional organizations and participation in continuing education seminars are two excellent ways to keep up with the changes in pharmacy practice and pharmacy law.

Further Reading
In order to find information regarding pharmacy law in your particular state, contact your State Board of Pharmacy or access their website on the internet. In addition to numerous pharmacy law textbooks, the following online resources may be helpful for obtaining information on a variety of pharmacy topics, including pharmacy law:

• The National Association of Boards of Pharmacy: http://www.nabp.net. This website contains important information pertaining to pharmacy law, in addition to links to the various state boards of pharmacy.
• U.S. Food and Drug Administration: http://www.fda.gov
• Institute for Safe Medication Practices: http://www.ismp.org/
• American Pharmaceutical Association: http://www.aphanet.org
• American Society for Pharmacy Law: http://www.aspl.org/
• American Society of Health-System Pharmacists: http://www.ashp.org/s_ashp/index.asp
• National Association of Chain Drug Stores: http://www.nacds.org/
• National Community Pharmacists Association: http://www.ncpanet.org/
• National Pharmacy Technician Association: http://www.pharmacytechnician.org/

Drug Research & Development: A Glimpse Into the World of Clinical Trials

noemail@pharmacytechnician.org — Fri, 15 Feb 2008 14:00:00 GMT

Objectives:

At the conclusion of this program, participants should be able to:

• to describe how the FDA determines the expiration date of drugs
• to explain the process by which research is conducted
• to list and differentiate between the phases of a clinical trial
• to specify why drugs are not deemed safe beyond their expiration date
• to provide examples of why drugs are developed
• to be able to define the term Serious Adverse Event (SAE)
• to list some agencies involved in drug research and development
• to realize how newly released drugs are monitored

Instructor: Liora Gelbart, CPhT, CCRP

Release Date: 15-Feb-08 8:00 AM
Expiration Date: 15-Feb-11 8:00 AM

Thousands of drugs prescribed daily to millions of people are safe and effective. The world of clinical research is complex and assures that the drug development process in the U.S. is one of the safest in the world.

A drug must be safe and effective for which it is prescribed, not be misbranded and be pure in its form. The Food and Drug Administration (FDA) regulates drugs, biologics and medical devices, as well as food, cosmetics and “natural” products. Laws governing these are known as the Code of Federal Regulations (CFR). The FDA does not in itself conduct clinical trials. The Center for Drug Evaluation and Research (CDER), a branch of the FDA, evaluates data presented to it from research institutions such as universities or the pharmaceutical industry. Drugs go through a rigorous process of research before they are presented for approval. The process may take several years.

An Idea Whose Time Has Come
So where does the clinical trial begin? At first, there is a concept. Research may identify a need for a certain medication or an idea presents itself in the laboratory. Most ideas remain just that: they never take off. Some proceed into further steps of research and only a minute few, about onepercent, will become drugs approved for human or veterinary use. Like many ideas, they originate with necessity. The need to cure or mitigate disease, the quest to improve quality of life and a desire to achieve what has not been achieved thus far are all catalysts for inventions. Before any compound is introduced to humans, it will go through lengthy research in vitro or in an artificial environment outside the living organism.

A compound must first be determined safe enough in the laboratory to be introduced initially to animals. Animal studies take into consideration the compound’s pharmacokinetics: its absorption, distribution, metabolism and excretion (ADME). It is crucial to know how the compound “moves” in the body. Bioavailability is the compound’s concentration in plasma both in peak and trough levels. From these studies, the drug’s half-life data are derived. Toxicity and teratogenicity, the ability of the compound to cause birth anomalies, are the most important factors in the development of any new compound.

The research methods must not only protect study subjects, but also produce no harm to the environment or animals. The FDA inspects all animal studies to ensure that animals are treated humanely. Animal safety data must be obtained on at least two species of mammals before a compound can be given to humans. Most drugs that undergo preclinical (animal) testing never even make it to human testing and review by the FDA.

The Declaration of Helsinki
The principles of ethical research in human subjects originated with the Declaration of Helsinki<1>. After World War II, the world was shocked by the Nazi atrocities. Brutal and heinous experimentations on humans were revealed during the Nuremberg Trials<2>. The medical community vowed never to forget and in 1964, the World Medical Assembly affirmed its stance in a meeting in Helsinki, Finland, that “a physician shall act only in the patient's interest” and that “the voluntary consent of the human subject is absolutely essential.” The declaration is the fundamental law in the ethical conduct of research, ensuring the rights and safety of subjects.

The Clinical Trial
There are three phases of clinical trials: Phase I is the introduction of the compound to humans, enrolls a limited number of healthy subjects, typically 20-80 subjects, and mainly looks at the most frequent side effects and how the drug is metabolized and excreted. Phase II is larger and begins if Phase 1 studies do not reveal unacceptable toxicity. This phase may involve a few dozen to 300 participants and the primary objective is to determine initial efficacy and short term side effects. Phase III, the largest and the most expanded phase, may involve several hundred to 3000 people. The FDA and sponsors of the study try to come to an agreement on how the large-scale studies in Phase III should be done. These studies may last for years and can enroll thousands of subjects with the diseases that are given specific doses of the research drug at specific intervals.

Before conducting any study on humans, the researchers, whether a pharmaceutical company or an academic entity, must apply to the FDA for an approval to conduct the study, which is called an Investigational New Drug application (IND). In order to receive IND approval, preliminary animal safety data must be presented to the FDA. If approved, the research on humans can proceed, but not before a decision by an Institutional Review Board (IRB) is granted.

The IRB
An IRB is comprised of at least five members with the mandate to protect the human subject in research. It examines the research strategy, grants or refuses a research, requests modifications and even puts the research on hold or terminates it as they see fit. Every academic institution that conducts research within its medical facility has an IRB. There are also community-based IRBs, which a pharmaceutical company or other researcher not affiliated with a university may utilize. IRB members come from diverse backgrounds: at least one must be a physician knowledgeable in the particular area of research, while others can be persons representing the community’s values. IRBs must look at the ethical and moral questions regarding the proposed study and determine whether they can cause harm or potentially open legal or moral dilemmas. First and foremost, every study on human subjects must start with an Informed Consent<3>. The FDA is mandated by law to ensure the protection of rights, safety, and welfare of human subjects who participate in clinical trials<4>.

The IRB is an added layer of protection. Its sole responsibility is to safeguard human subjects and ensure that their rights are not violated. Particular attention is focused on the protection of children and a vulnerable population, such as one with mentally or economically disadvantaged people.

The Members
A potential subject must be informed of all risks and benefits, so they can make a decision whether or not to participate in a trial. The Informed Consent must state clearly and in lay terms what the subject can expect in the course of the study and how it may affect his or her health<5>. This vital document is an assurance that research will not violate the rights of subjects. The IRB ensures that the Informed Consent is not written in such a way as to “trick” someone into enrolling and that privacy and confidentiality of the subject will be protected.

The researcher that actually conducts the study is called an investigator. This is a physician who the FDA has deemed to be qualified in a particular research area, one that has the academic credentials, expertise and experience necessary for the study. The research can be done under the auspices of a university hospital, pharmaceutical company or other facility accepted by the FDA. The facility that conducts the research is called the sponsor.

A Research Plan
A sound research proposal starts with a well-written protocol. This is a document outlining the study design, the methods that will be used for analysis and the endpoint, which is the goal and desired outcome of the study. A study may have two or three groups of subjects, called cohorts.

Typically, one cohort will receive the trial drug while the other receives a placebo, which is a look-alike pill with no therapeutic value. A third cohort may receive a different drug that is already on the market and has been approved for that particular disease or condition. That way, the investigational drug is not only compared to a placebo but also to a marketed drug.

In a double blind study, neither the investigator nor the subject knows which pill the subject is taking. This prevents bias from influencing the final analysis. A single blind trial is one where only the investigator knows what the subject receives, while the subject does not. Subjects are assigned to a particular cohort by chance. The computerized process of this assignment is called randomization. A randomized, double blind, placebo-controlled trial is the gold standard of clinical research.

Meticulous records are kept of all tests, lab results, adverse reactions and serious adverse effects. These are recorded on Case Report Forms specifically designed for the study. A Serious Adverse Event (SAE) is defined as any unexpected adverse drug experience occurring at any dose that results in one or more of the following outcomes: death, life-threatening condition, hospitalization or prolongation of hospitalization, congenital anomaly, persistent or significant disability/incapacity or an event that requires intervention to prevent permanent impairment/damage. All serious adverse reactions are reported to the FDA and IRB promptly. Sometimes the SAE will be severe enough to warrant a halt to further research, either temporary or permanent. Certainly death or life-threatening condition could have a catastrophic effect on research. One of the most critical roles of any investigator is the moral obligation to stop a study that clearly demonstrates unacceptable risk to human subjects.

Special Circumstances
Certain investigational drugs show immensely favorable potential while the study is still ongoing, usually in Phase III. It may become clear early on that one cohort is doing by far better than the other and it would be unethical to delay potentially life-saving treatment to desperate patients until the scheduled end of the study.

Another scenario in using an investigational product may arise in an emergency hospital setting. If all treatments have been exhausted and without further intervention a patient will likely die, an investigational drug may provide the only hope to save this patient’s life<6>.

Try This
Choose any drug of your choice that you feel is quite popular, perhaps something in the top 20. Design a timeline for that drug from the pre-clinical phase to clinical studies in support and against that particular drug. From where are the ingredients derived and what are the components of the monograph? Has the drug ever been close to a recall? How long was there a patent on the brand name drug when it came out? Can you find the cost of bringing that drug to market?

Inspections and Audits
The FDA inspects every aspect of the clinical trial and ensures that investigators, sponsors and staff follow guidelines established for the “Good Clinical Practice” (GCP)<7> for the conduct of clinical research. All records are meticulously inspected and violations are addressed quickly. The FDA has the legal authority to stop a clinical trial and disregard its findings if fraud is suspected. Disgraced investigators are barred from conducting research again and their names are made public in the FDA Register. The FDA may bring charges against anyone who acts unethically, which can result in fines or even imprisonment. IRBs are also inspected to ensure compliance with regulations. All this is designed to protect the public and instill confidence in the process of drug development.

The Analysis
A continuous stream of reports must be filed with the FDA for the duration of the research. Every change in plan, every new phase and any modification to the proposed drug must be registered with the FDA in a timely fashion. At the completion of Phase III, the sponsor is ready for the statistical analysis of the data that have poured in for the past several years.

Ideally, a clinically significant, definitive endpoint is achieved, which is the main objective of the study. A phenomenon known as the surrogate endpoint is a marker that may predict other important outcomes or substitute an endpoint. The National Institutes of Health (NIH) define surrogate endpoints as: "a biomarker intended to substitute for a clinical endpoint.” While the endpoint may take more time to establish as further data are analyzed and become available, the surrogate endpoint is an important secondary conclusion.

Request to Market a Drug
When all data are analyzed and ready, the sponsor prepares an application to the FDA to market the drug. This is called the New Drug Application (NDA). After comprehensive hearings, the FDA may request modifications, additional analysis or other corroborating evidence in order to reject or approve the application. Sometimes, the approval may be conditional upon certain factors, such as the sponsor conducting Phase IV, post marketing trials, or that pediatric studies be completed by a certain date. Approved drugs are listed in the FDA’s Orange Book, which can be searched by active ingredient, proprietary name, patent holder or application number.

The process does not end here. Drugs are evaluated continuously by CDER’s drug surveillance office and the FDA’s MedWatch reports adverse effects through inspections and audits of facilities and laboratories. FDA can recall drugs and demand anything from label modifications to complete market withdrawal. It is an extremely tight safety net that ensures a reliable process and protects the public.

In spite of all the stringent criteria and complex research procedures, certain individuals may experience an adverse drug reaction. As clinical trials may, at best, observe only a few thousand subjects, once the drug reaches millions of people, its true impact is determined. Unfortunately, the implications of a drug that “falls from grace” and the publicity this generates are always very influential. A media circus surrounds every such event, and though these are few and far between, the impression is that unsafe drugs are reaching the market. It is hardly newsworthy that thousands of drugs are never recalled and have been safe and effective for very many years.

Expiration Date
Safety is one of the most important aspects of drug research. CDER examines all data presented from a clinical trial and determines the expiration date of each medication based on stringent clinical analysis. Drugs, being chemical compounds, all degrade with time, even under ideal storage conditions. Some drugs, however, are safe and effective, even if the amount of drug falls below 90 percent. Others must have the precise dosage to be effective, or certain drugs may even deteriorate into a toxic substance. For these, the expiration date is a crucial factor. Most expired drugs simply do not deliver the effective therapeutic dose required to treat or cure the condition for which they are prescribed.

The U.S. Pharmacopeia (USP) issues monographs on drug storage, expiration and the variance of drug substance (active ingredient) which is allowed. By law, pharmacies may not dispense a drug beyond its expiration date. Pharmacy technicians must encourage patients to dispose of drugs safely.

Thoughts
Exciting new research activities are ongoing and promising. The importance of ongoing research and its benefits to humankind should be realized. This article should provide a glimpse into the complex world of the clinical studies that are necessary to drug research and development. The different agencies involved, their roles and the series of checks and balances each entity provides are all important components to the process of bringing a potential drug to market for patient use. Perhaps the next drug will be the miracle cure for an obscure disease. One never knows. New drugs, biologics and devices have the potential of helping millions of people live better lives.

About the Author

Liora Gelbart, CPhT, CCRP is a Certified Clinical Research Professional and works as a Clincial Trials Assistant at the Candaian HIV Trials Network in St. Paul's Hospital, located in Vancouver, Canada. She has worked in that capacity for the past eleven years. Canadian HIV Trials Network is funded by Health Canada and is dedicated to research into treatment for HIV/AIDS.

References

1. 18th World Medical Assembly, Helsinki, Finland, June 1964, amended by the 29th World Medical Assembly, Tokyo, Japan, October 1975, and the 35th World Medical Assembly, Venice, Italy, October 1983
2. The Nuremberg Doctor’s Trial (United States of America v. Karl Brandt, et al.): 1946-1947
3. FDA 21CFR 50.20
4. FDA’s Department of Health and Human Services (HHS): 3014 - NIH Human Research Protection Program Issuing Office: OIR/OHSR (301) 402-3444 : May 10, 2005
5. The Eight Mandatory Elements of Informed Consent – FDA 21CFR 50.20
6. FDA 21 CFR 56.104(c) Emergency Use of an Investigation Drug or Biologic
7. ICH (International Conference on Harmonization) GCP Guidelines for Clinical Trials: April 1996

Developing Solutions for an Epidemic Problem: HIV/AIDS

noemail@pharmacytechnician.org — Fri, 30 Nov 2007 14:00:00 GMT

Objectives:

Upon completion of this program, the participant should be able to:
• define HIV/AIDS in the context of its transmission, progression, and global impact.
• provide an overview of medications available within HAART for the treatment of HIV/AIDS.
• address challenges associated with the cost and accessibility of these medications.
• reinforce the role of the pharmacy technician in the successful administration of HAART.

Instructor: Dominic P. Decker, CPhT

Release Date: 30-Nov-07 8:00 AM
Expiration Date: 30-Nov-10 8:00 AM

With 39.5 million people living with HIV/AIDS in the year 2006, the virus is an epidemic problem that demands a solution. Although no known cure currently exists for those with HIV/AIDS, several medications are available to slow the progression of the virus, prolonging the lives of and giving hope to HIV-positive individuals.

This article presents medications from the four classes of Highly Active Antiretroviral Therapy (HAART), providing the pharmacy technician with an overview of the progression of HIV/AIDS and how the medications work to slow this progression. The classes and medications discussed within the article include: Combivir, a Nucleoside Reverse Transcriptase Inhibitor (NRTI); Sustiva, a Nonnucleoside Reverse Transcriptase Inhibitor (NNRTI); Norvir, a Protease Inhibitor; and Fuzeon, a Fusion Inhibitor.

Together with the physician, pharmacist, and patient, the pharmacy technician plays an essential role in the successful administration of HAART. With an increased understanding of HIV/AIDS and the medications available for its treatment, the pharmacy technician will be better able to support the patient to ensure that the therapy is consistent and effective.

The Facts
Recent studies conducted by the Joint United Nations Programme on HIV/AIDS (UNAIDS), a group of ten organizations united to respond to the AIDS epidemic, estimate that an overwhelming 39.5 million people are HIV-positive in the world today. Of those infected with HIV, 2.9 million people died in the year 2006 alone. See Table 1.

With no cure available for the millions of people infected with the virus, HIV/AIDS is an epidemic problem that demands a solution. Fortunately, even with no known cure, people have benefited from a number of medications currently available to treat HIV/AIDS.

In order to understand the effectiveness of these medications, it is critical first to understand HIV/AIDS on the cellular level, as a virus that damages and leads to the eventual failure of the human immune system. HIV is a retrovirus, one which produces DNA from an existing RNA strand through the action of an enzyme known as reverse transcriptase. HIV, which stands for human immunodeficiency virus, is the virus that results in AIDS, or acquired immunodeficiency syndrome.

When a person first becomes infected with HIV, the symptoms are limited and often confused with those of other viruses, such as influenza. However, as the virus progresses to its most advanced stages, the symptoms of HIV worsen to include persistent fever, headache, nausea, weight loss, and fatigue. It is at this point that HIV becomes diagnosed as AIDS.

Mode of Transmission
While there has been extensive research on the transmission of HIV and its development into AIDS, much remains unclear about how the virus is passed on from person to person. What is known is that transmission of HIV/AIDS occurs most often through unprotected vaginal and anal sexual intercourse with an HIV-positive individual. Another known mode of transmission is the sharing of needles for drug injection with a person infected with HIV. Transmission also can occur between a mother and her child during pregnancy, childbirth, or in infancy. The National Institutes of Health estimate that between 25% to 33% of untreated, HIV-positive women will pass the virus on to their child. The most effective way to avoid becoming infected with HIV/AIDS is to become educated about these known modes of transmission and to avoid them if and when possible.

It is important to note that HIV/AIDS is not transmitted through casual contact with an HIV-positive individual. Casual contact includes everyday activities, such as sharing a pen or pencil, and even a fork or a spoon, for example. Additionally, the National Institutes of Health affirm that HIV/AIDS is not transmitted through contact with the saliva, tears, sweat, feces, or urine of a person infected with HIV.

Medications
In response to the unique structure of this virus, medications have been developed to slow the progression of HIV, providing HIV-positive individuals with an increased lifespan and the hope of living to see a cure for HIV/AIDS.

According to the Food and Drug Administration (FDA), all medications that treat HIV/AIDS are classified as Highly Active Antiretroviral Therapy, or HAART. Four classes of medications exist within HAART, including Nucleoside Reverse Transcriptase Inhibitors (NRTIs), Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs), Protease Inhibitors, and Fusion Inhibitors.

An analysis of one medication from each of these four classes will provide an overview of the many dimensions of HAART and its effectiveness in the fight against HIV/AIDS.

NRTIs
Combivir, a Nucleoside Reverse Transcriptase Inhibitor, is a combination drug made of Epivir (lamivudine) and Retrovir (zidovudine), two medications that have been proven to be successful in the treatment of HIV/AIDS. Combivir tablets contain 150mg of lamivudine and 300mg of zidovudine. Both medications work by inhibiting the action of the reverse transcriptase enzyme and thus are classified as NRTIs. FDA studies have shown the advantages of using a combination of the two medications, as lamivudine and zidovudine have “synergistic antiretroviral activity,” or more simply, the two medications are more effective when administered together than when administered separately. An example of this synergistic activity is shown by the fact that when taken together, the two medications of Combivir help delay the development of resistance against lamivudine, a common problem for antiretroviral medications.

Combivir is typically administered as one tablet twice daily and may be taken with or without food. The most common side effects include headache, fatigue, and nausea. Because the medication has a fixed dosage of lamivudine and zidovudine, it should not be administered to patients who require more specialized therapy, such as children or the elderly.

NNRTIs
Sustiva (efavirenz) is a Nonnucleoside Reverse Transcriptase Inhibitor. As an NNRTI, the medication specifically inhibits HIV-1 reverse transcriptase, lowering the viral load (the amount of HIV in the blood) and increasing the number of CD4 immune system cells in the blood system, the same cells that are destroyed by HIV/AIDS. The FDA states that NNRTIs are more susceptible to rapid development of antiretroviral resistance. Because of this, Sustiva and all NNRTIs are not to be administered alone for the treatment of HIV/AIDS, but rather in conjunction with HIV/AIDS medications from the other three classes of HAART.

Sustiva is available in 50mg, 100mg, and 200mg capsules and 600mg tablets. The recommended dose of the medication for children varies from 200mg to 600mg once daily according to weight; the recommended dose for adults is 600mg once daily.

Sustiva should be taken at bedtime on an empty stomach, as food can negatively interfere with the absorption levels of the medication. Side effects of Sustiva include adverse symptoms in the central nervous system, such as drowsiness, dizziness, and insomnia. In FDA trials, a limited number of people reported adverse psychiatric symptoms in addition to the symptoms of the central nervous system. These psychiatric symptoms include depression, suicidal thoughts, and aggressive behavior. Another common, but less serious, side effect is the emergence of a mild to moderate rash, which typically resolves itself within one month of beginning therapy.

Protease Inhibitors
As a Protease Inhibitor, Norvir (ritonavir) inhibits the action of HIV protease, an enzyme which enables the maturation of viral proteins, moving from immature polyproteins to functional protein products.

Norvir is available for administration in a 100mg soft gelatin capsule or an 80mg/mL oral solution in either a caramel or peppermint flavor. In adults, Norvir is most often administered in a dose of 600mg twice daily, in the morning and in the evening. The FDA states that the use of a dose titration schedule may be helpful to reduce adverse events in patients beginning therapy with Norvir, starting with a dose of 300mg twice daily and increasing in increments of 100mg twice daily every 2-3 days. The recommended dose for children varies, according to weight and height, from 50mg twice daily to not exceeding 600mg twice daily.

The soft gelatin capsules should be stored in a refrigerator in the pharmacy prior to dispensing. It is recommended that patients store the capsules in a refrigerator, though it is not required if the capsules are used within 30 days. The oral solution should not be refrigerated, either in the pharmacy or by the patient. Norvir should be taken with food when possible. The taste of the oral solution may be improved by mixing it with chocolate milk or liquids such as Ensure or Advera.

The most common side effects of Norvir are fatigue, headache, dizziness, nausea, and vomiting, among others. As with all medications within HAART, administration should be consistent, according to a dose schedule established by the physician and patient.

Fusion Inhibitors
Fuzeon (enfuvirtide), the only Fusion Inhibitor currently available within HAART, is a subcutaneously administered injection. Fuzeon works to prevent the fusion of viral and cellular membranes, which, in turn, prevents the virus from entering into and infecting the cell.

Fuzeon is available in a single-use vial containing 108mg of the medication in powder form, which provides approximately 90mg/mL when reconstituted with 1.1mL of sterile water. A Convenience Kit is also available for distribution to patients; the kit includes 60 single-use vials of the medication, 60 vials of sterile water for reconstitution, 60 3cc reconstitution syringes, 60 1cc administration syringes, alcohol wipes, and patient information guides. Before reconstitution, Fuzeon should be stored a room temperature; after reconstitution, it should be refrigerated and administered in 24 hours.

Fuzeon is injected subcutaneously into the arm, leg, or stomach twice daily, with or without food. Before administration of the medication in the home, the patient or caregiver should be trained to use Fuzeon by a healthcare professional. All used injection syringes must be properly disposed of in a sharps container and should not be put in the trash.

According to the FDA, most people using Fuzeon will experience injection site reactions, which are usually mild to moderate in intensity, but occasionally can be severe. Injection site reactions occur on the skin and include redness, tenderness, itching, and swelling, among other symptoms. In addition to these injection site reactions, the most common side effects of Fuzeon include allergic reactions, made evident by skin rash, fever, vomiting, troubled breathing, swelling of the feet, and blood in the urine. The FDA states that patients on Fuzeon have an increased susceptibility to bacterial pneumonia, a potentially life-threatening condition for an HIV-positive individual, but a direct connection between Fuzeon and bacterial pneumonia has not yet been established.

Coping With Costs
A number of problems involving the cost and accessibility of HIV/AIDS medications exists, often preventing the medications from reaching the HIV-positive individuals who need them most. Although HIV/AIDS medications are more readily available in the United States than in developing countries, more can be done to improve access to them. Considering the high costs of these medications, the United States government has developed several programs with the goal of providing the medications within HAART to as many people as possible. The largest of these programs in the United States is the AIDS Drug Assistance Program (ADAP), which covers the cost of HIV/AIDS medications for people who are unable to afford them, with neither a private health insurance plan nor the qualifications necessary for coverage under Medicaid. According to AVERT, an international HIV/AIDS charity, state-sponsored ADAPs currently provide medication coverage for 25% of HIV-positive individuals in the United States each year.

Conclusion
With more infections being discovered through HIV testing initiatives and an increased lifespan for people with HIV/AIDS due to the medications within HAART, the amount of HIV-positive individuals continues to rise, forcing more people onto waiting lists for the coverage provided by ADAPs. Reports from the Kaiser Family Foundation presented by AVERT estimate that in February 2006, nine states had a total of 791 HIV-positive individuals on waiting lists for ADAPs. The elimination of these waiting lists requires increased support from the United States government by way of financial contributions. On a larger scale, the elimination of HIV/AIDS demands the realization that this epidemic problem for both the United States and the world can no longer be ignored.

As with all medication regimens, the strength, dosage, and administration should be under the direct supervision of a physician with the support of the pharmacist and pharmacy technician. Together with the physician, pharmacist, and patient, the pharmacy technician plays an essential role in the successful administration of HAART. With an increased understanding of HIV/AIDS and the medications available for its treatment, the pharmacy technician will be better able to support the patient to ensure that the therapy is consistent and effective.

Statistics on the number of people living with HIV/AIDS worldwide are from published reports of the Joint United Nations Programme on HIV/AIDS (UNAIDS). Information regarding the transmission and progression of HIV/AIDS is from the Centers for Disease Control and Prevention (CDC) and the National Institutes of Health (NIH). Information on the medications available within HAART is from the Food and Drug Administration (FDA) with additional information on Protease Inhibitors from the Biology Department at California Lutheran University.

Author Biography
Dominic P. Decker is a sophomore at The Catholic University of America in Washington, DC, where he is studying English and Spanish with a concentration in pre-medicine. He is employed as a certified pharmacy technician with Snyders Drug Stores, Inc. in Little Canada, MN, and lives in Roseville, MN, both suburbs of the Minneapolis-St. Paul metropolitan area.

Resources
Basic information: CDC HIV/AIDS. 6 Apr. 2007. Centers for Disease Control and Prevention. 2
July 2007 .

HIV Infection and AIDS: An Overview. 30 Nov. 2006. National Institutes of Health. 2 July 2007

Combivir Prescribing Information. Aug. 2002. Food and Drug Administration. 2 July 2007

Sustiva Prescribing Information. Jan. 2002. Food and Drug Administration. 2 July 2007
< http://www.fda.gov/cder/foi/label/2002/21360lbl.pdf>.

HIV-1 Protease. 2001. California Lutheran University Biology Department. 2 July 2007
hiv_protease/molmast.htm>.

Norvir Prescribing Information. 3 Oct. 2005. Food and Drug Administration. 2 July 2007
< http://www.fda.gov/cder/foi/label/2005/020659s034,020945s017lbl.pdf>.

Fuzeon Prescribing Information. 2004. Food and Drug Administration. 2 July 2007
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