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Lines of Therapy – Drugs in Hypertension

by Pravin Shukle, MD
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      Slides Hypertension CardiovascularPharma.pdf
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      JNC 8 Hypertension Guideline.pdf
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    00:01 Let's move on to special considerations in blood pressure management, and I'm going to talk to you about mixing drugs now.

    00:08 Current guidelines, where ever you are in the world, do not choose a first line agent.

    00:15 They determine first line set of choices based on the disease state. So, let's take diabetes for example.

    00:22 In general, diabetics, we like to use ACEi's or ARBs as a first line agent, and then go on to a calcium channel blocker, and then to a diuretic, and then to spironolactone, and then to a beta blocker.

    00:36 Beta blockers, we try to avoid in diabetes, because it can mask the symptoms of hypoglycemia.

    00:42 The reason why ACEi's and ARBs are first line therapy choices, is because they also have vascular protection effects, in the eye, in the brain, in the kidney, and we believe also in the peripheral vasculature.

    00:57 That's why they are first line in this class.

    01:01 Proteinuria. ACEi's or ARBs? Actually ARBs are first line, and ACEi's are a little bit behind them.

    01:09 That's because one study looking at ACEi's versus ARBs showed that the ARBs were a bit superior.

    01:15 So, that kind of put it ahead in the race, and so a lot of people are suggesting that we should use ARBs first in proteinuria.

    01:23 The next class of drugs that we would like to use in this disease state are the non-dihydropyridine calcium channel blockers.

    01:30 I won't get into the details or the argument as to whether or not adding it to an ARB or an ACE inhibitor is better, but just remember that ARB first, ACE inhibitor second, and non-DHP CCBs third.

    01:46 What about choices in acute heart failure? Once again, ARB or ACE inhibitor with a diuretic.

    01:53 So, we often start them with a combination therapy agent.

    01:57 The second line drug would be spironolactone. So, remember that combining an ARB with spironolactone, or combining an ACE inhibitor with spironolactonce can cause high potassium levels.

    02:09 That's why we want that other diuretic on board to prevent that spike in potassium.

    02:14 Although it says number 3, really we're talking about a fourth line agent, the calcium channel blockers, and in this particular case, I tend to recommend the dihydropyridine calcium channel blockers, because they don't have that negative inotropic effect on the heart.

    02:32 Let's look at the next one, beta blocker. This is a special consideration, we only use beta blockers in heart failure once the patient has been stabilized.

    02:41 If the patient has any kind of instability, whether it's difficulty breathing, or shortness of breath, or rales on clinical exam in the lungs, or an elevated JVP, we're not going to use a beta blocker until the patient is stable.

    02:56 Finally, we do use other drugs like hydralazine which are direct vasodilators.

    03:01 Nitrates are excellent in heart failure as well.

    03:06 In terms of the chronic heart failure patient, you can see how the order is changed a little bit.

    03:11 ARB or ACE inhibitor. Diuretic. Spironolactone. Beta blocker. And then others.

    03:18 Let's look at ISH or isolated systolic hypertension.

    03:23 Isolated systolic hypertension has a clear study showing ARBs to be very useful, and ACE inhibitors not so much.

    03:31 So, the first line treatment in isolated systolic hypertension is an angiotensin receptor blocker.

    03:37 Notice that the ACE inhibitor isn't there. The second line choice is a beta blocker or a diuretic.

    03:43 The third line choice after both choices in two have been exhausted is a calcium channel blocker, and then others.

    03:52 In terms of post-MI patients, it's absolutely essential that we get these people on beta blockers.

    03:58 We're not using the beta blocker for hypertension, but I put this list here to reiterate the importance of using a beta blocker post-MI. After that, we'll use either an ACEi or an ARB.

    04:10 Now, on your exam, both ACEi's and ARBs are correct answer. In a cardiologist office, the correct answer is ACE inhibitor.

    04:20 That's because ACE inhibitors have a lot of evidence to support its use.

    04:25 The ARBs also have a lot of evidence to support their use, but they are later drugs, and could only be compared against ACE inhibitors, and they were never shown to be truly superior in class I trials.

    04:38 There is another trial that suggested that ARBs are better, but it was an observational study, it looked at a large group of patients in the province of Ontario in Canada, and it showed that the ARBs did quite well in those patients, but still, you'll often find clinically, people are favouring ACE inhibitors. On your exam, we should treat them equally.

    05:03 I want to talk about the "Pulmonary Edema Special". So, this is something that we use in the intensive care unit, or in the coronary care unit. It's an oral therapy that tends to work quite well when you're trying to get rid of a lot of fluid quickly.

    05:19 What you do is you give metolazone 5 mg first. Remember that metolazone is a thiazide type diuretic.

    05:28 You wait 30 minutes, and then you give intravenous furosemide 40 mg.

    05:35 Now, this combination therapy will give you a massive diuresis.

    05:40 And it would be giving the equivalent of 200 mg of furosemide without the toxic effects.

    05:46 The problem with this, is that it causes a high risk of low potassium or hypokalemia.

    05:51 So, you have to be careful using this combination and be aware of what the potassium is doing, but in an emergency situation, this is a very effective therapy for a person who comes in in florid heart failure.

    06:04 Let's talk about the "Ascites Special". So, sometimes you'll have patients who either have liver cancer or liver failure, or abdominal ascites for some other reason. Giving spironolactone 100 mg in combination with furosemide 40 mg, is quite an effective combination medication regimen. Keep that ratio the same.

    06:28 So, for every 100 mg of spironolactone, you give 40 of furosemide.

    06:34 So you can give 100/40, 200/80, 300/120, or 400/160.

    06:40 400/160 is a mega dose, so you really need to know what you are doing if you're gonna use that dose.

    06:45 But definitely, it works quite well with patients who have ascites.

    06:51 If you're wondering where the source of this is, is if you look at a new England journal of medicine article on the treatment of ascites, it's an old article, but it's a good one, you can look at it and see how the mechanism actually works.


    About the Lecture

    The lecture Lines of Therapy – Drugs in Hypertension by Pravin Shukle, MD is from the course Cardiovascular Pharmacology. It contains the following chapters:

    • Special Drug Mixtures
    • The "Pulmonary Edema Special"
    • The "Ascites Special"

    Included Quiz Questions

    1. ACE inhibitors or ARB's.
    2. Diuretics
    3. Calcium Channel Blockers
    4. Beta Blockers
    1. Valsartan
    2. Metoprolol
    3. Amlodipine
    4. Hydrochlorothiazide
    5. Iisinopril
    1. ACE inhibitor or ARB
    2. Calcium Channel Blocker
    3. Beta Blocker
    4. Alpha Blocker
    5. Diuretic
    1. Diuretic, ACE inhibitor
    2. Diuretic, ACE inhibitor, Beta Blocker
    3. Diuretic, Non dihidryopyridine calcium channel blocker, ACE inhibitor.
    4. Beta Blocker, ARB, ACE inhibitor.
    1. ACE inhibitor, low dose diuretic, spironolactone, beta blocker.
    2. ARB, ACE inhibitor, Renin antagonist, spironolactone
    3. ACE inhibitor, low dose diuretic, spironolactone, calcium channel blocker
    4. ARB, Renin antagonist, Beta Blocker, Calcium Channel Blocker.
    1. Valsartan (an angiotensin receptor blocker)
    2. Enalapril (an angiotensin converting enzyme inhibitor)
    3. Metoprolol (a beta blocker)
    4. Clonidine (an alpha blocker)
    1. ...reply with confidence: "I am going to put you on a beta blocker, an ACE inhibitor (or ARB if you develop cough), aspirin, and a cholesterol lowering agent. I will also add a nitrate pump or tablets in the event that you have chest pain"
    2. ...reply with confidence: "I am going to put you on a beta blocker, an ARB (or ACE inhibitor if you develop cough), aspirin, and a cholesterol lowering agent. I will also add a nitrate pump or tablets in the event that you have chest pain"
    3. ...reply with a shaking voice and downcast eyes: "I am going to put you on a beta blocker, an ACE inhibitor (or ARB if you develop cough), aspirin, and a cholesterol lowering agent. I will also add a nitrate pump or tablets in the event that you have chest pain"
    4. ...reply with confidence: "I am going to put you on a beta blocker, an ACE inhibitor, a diuretic, and a cholesterol lowering agent. I will also add a nitrate pump or tablets in the event that you have chest pain"
    1. metolazone
    2. ethacrynic acid (a loop diuretic)
    3. bisoprolol
    4. amlodipine
    1. Spironolactone 100 mg, furosemide 40 mg daily
    2. Spironolactone 40 mg, furosemide 100 mg daily
    3. Allopurinol 100 mg, furosemide 40 mg daily
    4. Spironolactone 100 mg, enalapril 40 mg daily

    Author of lecture Lines of Therapy – Drugs in Hypertension

     Pravin Shukle, MD

    Pravin Shukle, MD


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