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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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A talk with Dr. Jonathan Sackner Bernstein
From Townsend Letter for Doctors and Patients, 8/1/04 by Jonathan Sackner Bernstein

Before It Happens to You: A Breakthrough Program for Reversing or Preventing Heart Disease

by Jonathan Sackner Bernstein, MD

2004, Da Capo Press, Persus Books Group, 11 Cambridge Center, Cambridge, Massachusetts 02141 USA Hardback, 261 pp., $26

Most doctors "prescribe" lifestyle changes--diet, exercise, reduction of stress--as the first defense against heart disease. In Before It Happens to You, you advocate prescription medications first in many cases. How come?

Recommending lifestyle modification poses two problems. First, few--if any--people can change and keep up those changes. Second, the impact of lifestyle modification is minimal compared to the benefit from certain medicines which are proven to be safe. These medicines reduce risk more than any lifestyle program.

That said, I do believe that an optimal lifestyle helps reduce risk, and try to persuade patients that it is important. If someone can actually do it, it will help. But almost no one can. And even if they can, it's not enough protection.

What medications do you recommend?

I recommend four types of medicines that have been around for awhile. They are: Statins (this includes cholesterol lowering drugs like Lipitor and Zocor), ACE Inhibitors (these guard against high blood pressure, heart attack, and heart failure; Altace and Zestril are two examples), Beta-Blockers (these also guard against blood pressure, heart attack, and heart failure; examples include Coreg and Toprol XL), and Aspirin (for heart attack and stroke prevention). All of them have been proven safe over decades of use.

Do you think that doctors will balk when their heretofore "healthy" patients ask to be put on these medications?

Studies performed by the pharmaceutical industry over the past decade predicted that doctors would prescribe medicines that patients request. Since direct to consumer advertising started, this concept has been proven.

Will people really want to take these medications? What are the side effects?

No one wants to take medication, but when people recognize they have a problem, they do whatever is necessary. Before It Happens to You quickly establishes the harsh reality that we all have heart disease. And in this case, all that's necessary is taking a few pills a day.

When CNN conducted a poll, 94% of the respondents said they would take such treatments to reduce their risk of dying from a heart attack or stroke. As for side effects, all drugs have them. But this program rests on medicines with such proven safety that even with the risk of side effects, taking the medicines puts you at lower risk than if you decided not to take them.

Why do you think most doctors don't yet prescribe these medications for people whom you would determine to be at risk and therefore in need of them?

The system has duped doctors into believing that the recommendations in the guidelines represent optimal treatment. The guidelines represent a strict interpretation of the scientific evidence with a goal of establishing the best care at a reasonable cost for society. They do not represent the optimal care for individual people.

Why haven't the pharmaceutical companies studied the Before It Happens to You program? I would think they'd be falling all over each other to get to you.

It wouldn't be a good use of their money since these are old medicines with limited patent protection. Some are already generic.

Since you raised the issue of money, what is the expense to insurance companies in the short run?

Insurance companies will bear relatively little cost in terms of initial evaluation, since the testing that I advocate is not markedly different from clinical practice. However, the costs of the medications would be significant, based on the prices of the medications. I would estimate that at least 80% of those costs would be paid by an insurance company.

Would insurance companies save money in the long run?

Probably not. The people who save insurance companies money are those who die of sudden death. The Before It Happens to You plan will prevent companies from saving money this way.

For someone without prescription payment coverage, can you estimate the average out-of-pocket expense of a year's worth of these medications?

The medicines in this plan aren't cheap. If a person were to require all four, the cost would range from $1,200 to $3,100 per year, total. The range is due to the difference in price between different drugs, especially based on the lower prices of generic drugs.

Millions of Americans have prescription drug coverage, meaning they would pay a fraction of these costs, perhaps as little as $300 to $400 per year out of pocket. And many pharmaceutical companies have programs to reduce the costs of prescription medications for those in need.

How does your plan compare to the Atkins Diet?

People love Atkins because they can do exactly what they want and ignore the usual advice about exercise and eating soy and grains. The Before It Happens to You plan is similar in that it's counterintuitive (according to standard medical practice) and easy, but it's different in that scientific studies have proven it works.

Talk with us about blood pressure. At what level do you start to get concerned for a patient's heart health?

The newest guidelines acknowledge that the lowest risk of a heart attack or stroke is when your pressure is less than 115/75. Yet this is not the recommendation, because it would be too costly for society to justify. As a compromise, a target of 135/80 is advocated. At that level, the risk to your life can be twice as high as it would be if the target were 115/75.

These new blood pressure treatment guidelines serve the same purpose as those before them. They define treatment targets that are good for society. Your best interest is not the primary focus. You should be concerned when your blood pressure reaches a level that puts you at risk of a heart attack, stroke, or premature death. That happens when your pressure is above 115/75. That's when you want your doctor to treat you with safe medicines to reduce your risk.

What about cholesterol levels? At what level do you start to worry?

The targets for cholesterol depend on your level of risk, with lower targets for those at the highest risk.

Consider an adult who never smoked and is doing things right--exercising, eating a healthy diet, etc. If high cholesterol is the only problem--in other words, the person was never diagnosed with high blood pressure or diabetes and has no relatives who had heart disease at a young age--the target for LDL-cholesterol (a.k.a. the "bad cholesterol") is less than 160, which would correspond to a total cholesterol of under 240.

If this person were a 56 year-old man, he would have a 1 in 100 chance of suffering a heart attack in the next year. Twenty-five percent of male heart attack victims die within the following year. A 56 year-old woman would have a 1 in 500 chance of a heart attack in the next year. Thirty-eight percent of women die within a year of their heart attack.

Treating with a statin would reduce their risk in half. Statins are so safe that the UK authorities are moving them to over-the-counter status. And the side effects of statins are similar to placebo. With such a safe way to reduce risk, I'd be concerned for your safety even if you meet the recommended standards.

In addition to high blood pressure and cholesterol, what are the other "markers" or contributing factors that would make you concerned for a patient's heart health?

Contributing factors to your risk include cigarette smoking (even in the past), being 10% or more above your ideal body weight, and a family history of heart disease.

Having diabetes would also raise concern: this is specifically addressed with components of the Before It Happens to You program.

When should people start with the Before it Happens to You program?

If you are fifty, or getting close, the scientific evidence says that it's time to get started on these medications. You may not need all of them, but more likely than not, you will be safer if you are taking at least some of them. Find out by reading my book, then talking with your doctor.

Author of Before It Happens to You

COPYRIGHT 2004 The Townsend Letter Group
COPYRIGHT 2004 Gale Group

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