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Zestril

Lisinopril (lye-SIH-no-pril, ATC code C09AA is a drug of the angiotensin converting enzyme (ACE) inhibitor class that is primarily used in treatment of hypertension, congestive heart failure and heart attacks.
Historically, lisinopril was the third ACE inhibitor, after captopril and enalapril that was introduced into therapy in early 1990s . Lisinopril has a number of properties that distinguish it from other ACE inhibitors: it is hydrophilic, has long half life and tissue penetration and is not metabolized by the liver. more...

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Pharmacology

Chemistry

Lisinopril is chemically described as (S)-1--L-proline dihydrate. Its empirical formula is C21H31N3O5•2H2O. Lisinopril is the lysine-analog of enalapril. Unlike other ACE inhibitors lisinopril is not a prodrug and tablets contain pharamacologically active substance.

Absorption

After oral dosing peak blood levels are reached within ca. 7 hours. The oral bioavailability is approximately 25% according to measurements of the unchanged drug in urine. The interindividual variability is 6 to 60% within the full dose range of 5 to 80 mg. Emptiness of stomach does obviously not influence the extent of gastrointestinal resorption.

Half life

The halflife of Lisinopril under steady-state conditions is 12.6 hours. The terminal phase shows a prolonged terminal phase, but no cumulation of the drug is seen under normal circumstances.

Metabolism

Lisinopril is not metabolized.

Elimination

Lisinopril is solely excreted in urine in the unchanged form. Elimination of the drug depends on glomerular filtration and tubular excretion. Rate of lisinopril elimination decreases with old age and kindney or heart failure. There is a relation between creatinine and lisinopril clearance. With prolonged therapy dose reduction can be necessary to avoid cumulation.

Lisinopril can be removed from circulation by dialysis.

Mode of action

Lisinopril acts by competitive inhibition of Angiotensin Converting Enzyme (ACE), a key enzyme in the renin-angiotensin system (RAS) which plays a crucial role in controlling of blood pressure. Diminished formation of a potent vasocontrictor - Angiotensin II from Angiotensin I leads to lowering of hypertension. Besides it limits degradation of a vasodilator - bradykinin by ACE. Angiotensin II also increases blood pressure by stimulation the production of aldosterone, which promotes sodium and water retention in the body. So the complete action consists of

  • diminished production of angiotensin II
  • diminished degradation of bradykinin
  • diminished production of aldosterone

Indications

  • hypertension
  • congestive heart failure alone or with diuretics
  • acute myocardial infarction
  • renal and retinal complications of diabetes.

Contraindications and Precautions

As with all angiotensin converting enzyme (ACE) inhibitors

Pregnancy

Category D

When lisinopril therapy in women of child-bearing age is started pregnancy must be excluded and effective contraceptive methods used.

Read more at Wikipedia.org


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When patients cannot afford their medications
From American Family Physician, 8/1/04 by Chien-Wen Tseng

The editors of AFP welcome submissions for Curbside Consultation. Please send scenario to Caroline Wellbery, M.D., Department of Family and Community Medicine, Georgetown University Medical Center, 212 Kober Cogan Hall, 3800 Reservoir Rd. NW, Washington, DC 20007. Materials are edited to retain confidentiality.

Case Scenario

Many physicians are frustrated at sending many patients out the door with a handful of drug samples because they cannot afford their prescriptions. Medicare provides health insurance for persons 65 years of age and older and persons with disabilities. There also is a new Medicare drug discount card program available in which beneficiaries can obtain lower drug prices for an annual fee. However, Medicare does not currently cover outpatient prescription drugs for most beneficiaries. (1) Approximately 10 million (about one in four) Medicare beneficiaries are without prescription drug coverage, (1) and more than one in 10 seniors report using less of their medications because of cost. (2)

Even if a person has coverage, prescription copayments can be expensive. For example, if a patient has hypertension, hypercholesterolemia, diabetes, and heartburn, and takes four brand-name medications at $25 per prescription, he or she will pay $100 per month, or $1,200 per year in copayments. For patients without coverage, the pharmacy bill can total more than $400 per month. It is no wonder that patients are turning to their physicians who prescribe these medications for help in managing drug costs. What can physicians do when patients cannot afford their prescriptions? What is the physician's role?

Commentary

For physicians who realize that drug costs can be a problem, we offer some practical solutions and discussion about how to help these patients.

Is There an Ethical Dilemma in Choosing Medications Because of Cost? When patients ask their physician to select medications based on cost, it raises the ethical question of whether a physician can do this and still "practice the best medicine" for patients. Traditionally, practicing the best medicine often has meant prescribing the newest drug on the market. However, no medication can be the best treatment for a patient if it costs so much that the patient cannot fill the prescription. Therefore, it is necessary to redefine the practice of "best medicine" to include helping patients balance their drug costs with benefits.

While new, expensive drugs may offer greater benefits for some patients, they may not offer those improved benefits for all patients. By helping patients use medications cost-effectively, physicians can help keep medications affordable for everyone.

How Can a Physician Know How Much a Drug Will Cost the Patient? Physicians often underestimate retail prescription costs and are as surprised as patients by prices. The retail prices of commonly prescribed drugs such as certain COX-2 inhibitors, statins, and proton pump inhibitors, can cost more than $1,000 per year. A quick way to compare retail prices for different drugs is to check online (e.g., at http://www.drugstore.com) or to call local pharmacies. Even if the patient has prescription drug insurance, the physician may consider it a daunting task to take time out of a busy practice to find out the patient's exact benefits. Patients need to take the responsibility of finding out their generic and brand-name copayments and share this information with their physicians.

Physicians Should Ask Patients if They Have a Yearly "Cap" on Their Drug Benefits. For example, many seniors enrolled in managed care plans have drug benefits that limit coverage to a certain dollar amount per year (e.g., an annual cap of $500). These patients pay a prescription copayment initially, but if their expenses exceed the benefit cap, they must pay the full cost of their medications for the remainder of the year. Physicians need to help these patients find the best way to spend these limited dollars.

Do Pharmacy Assistance Programs Really Work? Pharmacy assistance programs and state prescription assistance programs can work for many lower income persons. In fact, half of the most commonly prescribed drugs are available through a pharmacy assistance program. An estimated 5.5 million people were enrolled in these programs in 2002. (3) There is no denying that it requires paperwork, but it might not take any more paperwork or time than filling out a referral to a specialist.

There are several excellent nonprofit Web sites (e.g., http://www.rxassist.org and http://www.needymeds.com) that let you find out quickly and efficiently which drugs are covered, who is eligible, and how to download the correct forms. Many forms can be filled out in only a few minutes and faxed to the drug company. Information that typically is needed from the physician includes name and address, insurance and financial status, and signature. Generally, a three-month supply is provided; after this time period, a new request is needed just as a new prescription is needed when refills are exhausted. Medications are shipped directly to the patient or physician in as little as two weeks, but some programs request up to a six-week lead time.

Another great source of information on pharmacy assistance programs is in the article titled, "How to Help Your Low-Income Patients Get Prescription Drugs," published in the November/December 2002 issue of Family Practice Management. This article is accessible online at http://www.aafp.org.

Some Other Options for Patients-Available Generics. Another option for physicians who want to help patients lower drug costs is to help patients take advantage of generic versions of medications. Granted, generic medications can be relatively expensive, and there are many medications still without generic equivalents. However, when available, generic equivalents can make the difference between a prescription that is affordable and one that is difficult to pay for.

There are now generic equivalents of fluoxetine (Prozac), lovastatin (Mevacor), lisinopril (Zestril), bupropion (Wellbutrin), and metformin (Glucophage); and loratadine (Claritin), and omeprazole (Prilosec) are available without a prescription. Other medications such as alendronate (Fosamax) are expected also to have generic versions available soon. For patients with insurance, copayments for generic versions are lower than those for brand-name medications. For example, a patient with a $10 generic copayment and a $25 brand-name copayment could save $180 each year by switching just one brand-name drug to a generic equivalent.

Evidence-Based Resources to Help Physicians Help Their Patients. If no generic equivalent is available for a desired drug, cutting costs can mean giving a patient a different drug. For patients with pain or inflammation, physicians might have to choose between a nonsteroidal anti-inflammatory drug (NSAID) and a COX-2 inhibitor, which can cost substantially more.

Physicians need an easy-to-understand, evidence-based summary of when a more expensive drug will benefit a particular patient. The Oregon Health and Science University's Evidence-based Practice Center provides excellent guidelines that are available at http://www.ohppr.state.or.us/hrc/PMPD_hrc.htm#drugclass1. The Web site briefly summarizes evidence-based findings on the advantages of one drug or class of drugs over another, and it also includes sample drug prices. Currently, guides for many drug classes such as statins, angio-tensin-converting enzyme inhibitors, angio-tensin-II receptor blockers, proton pump inhibitors, NSAIDs, and opioids are available, and other categories are to be added.

Can Patients Buy Their Medications Through Mail Order or Online? Many patients are looking for lower prices on prescriptions from mail-order and online pharmacies. These pharmacies work best for chronic-illness medications with stable dosages that can be ordered two to three weeks ahead of time. Patients usually are required to mail in the original prescription, fax a copy of the prescription, or have their physician call in the prescription. The process can be initiated by telephone or on the Internet. Some sites do not require membership, while others charge a nominal fee (e.g., about $20 per year) for their service. Prices are usually lower than retail pharmacy prices, but they require a shipping fee (e.g., a flat rate of $15), and narcotics or controlled substances cannot be mailed. For patients who are not comfortable using the Internet, many of the Web-based pharmacies also provide telephone numbers that allow the registration and prescription submission process to take place by telephone or postal mail. These services likely can provide cost savings for at least some patients.

Patients also need to exercise caution in ordering from credible mail-order or online pharmacies. For instance, a recent service (PharmacyChecker) checked Web-based pharmacies for licensing, privacy policy, secure online transactions, whether documentation of an original prescription was required, and if the Web site provided a company address. In a check of 12 popular sites, only five received top marks. (4)

Similarly, although many patients have considered buying from companies located in countries other than the United States, the reimportation of drugs from overseas is currently under intense debate, and such drugs are not approved by the U.S. Food and Drug Administration. Physicians may not know which mail-order or Internet pharmacies to recommend to their patients. One option is for patients to find out whether their health plan has a mail-order service that can provide access to discounted drug prices negotiated by the plan for their members, even if the health plan itself offers no drug benefits.

The New Medicare-Approved Drug Discount Card. Physicians are wondering whether the new Medicare drug discount card can help their senior patients. (5) Enrollees pay an annual fee (maximum $30), and choose one of the 70-plus discount-card programs. To be eligible, seniors must be a member of Medicare but not have outpatient drug coverage through Medicaid. The cards are required to give discounts in some 200 categories of medications; they offer 11 to 17 percent off the average retail prices (and greater discounts for mail-order and generic drugs).

Many people have difficulty determining which card to choose because of the large number of discount cards available and the fact that drug prices may be changed as often as weekly. However, physicians should encourage their low-income Medicare patients who are paying out-of-pocket for their prescriptions to look into this program. Persons may qualify for a $600 credit toward medications if their annual income is no more than $12,569 ($1,047 per month) for singles and $16,862 ($1,404 per month) for couples.

What Is in Store for the Future? The need to provide adequate drug benefits for all Medicare beneficiaries is great. The newly passed national Medicare drug benefit is set to begin in 2006. However, it is estimated that the program will cost $400 to $500 billion or more over the next 10 years. Any drug benefit will require most seniors to pay for at least some part of their prescription costs out of pocket. Therefore there is no doubt that, more than ever, physicians need to have the skills and knowledge to help patients balance their medication costs and effectively make the most of their drug benefits.

REFERENCES

(1.) Congressional Budget Office. Prescription drug coverage and Medicare's fiscal challenges. April 9, 2003. Accessed online June 10, 2004, at: http://www.cbo.gov/showdoc.cfm?index=4159&sequence=0.

(2.) The Henry J. Kaiser Family Foundation, The Commonwealth Fund, and Tufts-New England Medical Center. Seniors and prescription drugs: an 8-state survey. Accessed online June 10, 2004, at: http://www.kff.org/medicare/6049-index.cfm.

(3.) Pharmaceutical Research and Manufacturers of America. Private and public-sector pharmaceutical financing in the United States. http://www.phrma.org/publications/publications/profile02/ 2003%20CHAPTER%204.pdf.

(4.) Reuters Health. Many Rx Web sites lack proper licensing: analysis. April 7, 2003. Accessed online July 13, 2004, at: http://www.laurushealth.com/HealthNews/reuters/NewsStory0407200327.htm.

(5.) Department of Health and Human Services. Centers for Medicare and Medicaid Services. Facts you need to know about Medicare-approved drug discount cards. April 7, 2003. Accessed online June 10, 2004, at: http://www.medicare.gov/medicarereform/maddc_facts_3steps.asp.

CHIEN-WEN TSENG, M.D., M.P.H. University of Hawaii, John A. Burns School of Medicine, Dept. of Family Medicine and Community Health, Mililani, Hawaii, and the Pacific Health Research Institute, Honolulu.

COPYRIGHT 2004 American Academy of Family Physicians
COPYRIGHT 2004 Gale Group

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