Cardiac Depressants and Vasodilators – Heart Failure and Angina Management

by Pravin Shukle, MD

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    00:01 Welcome to Pharmacology by Lecturio.

    00:04 Today, we're gonna be covering the management of angina.

    00:07 Now, when we take a look at these different types of drugs, really, what we're doing is we're either increasing blood flow to the affected area and therefore, more oxygen for the affected area.

    00:18 Or B, we're reducing the oxygen demand of the affected area.

    00:23 The first category of drugs that we're talking about today are the calcium channel blockers which actually do both.

    00:30 Within the drug class itself, there's different agents and they will act more as a vasodilator and some will act more as a cardiac depressant.

    00:40 The first sub-category of the calcium channel blockers are the dihydropyridine, calcium channel blockers.

    00:48 These include drugs like amlodipidine, or felodipine, or nifedipine, which is the prototypical drug.

    00:55 You don't need to know all of the names, just know, you know, I think nifedipine is probably reasonable.

    01:00 This is usually used as a blood pressure drug so 90% of the time that's why it's being given.

    01:07 But it can be used quite effectively in angina management.

    01:12 It may cause a reflex tachycardia so that can cause an increase in oxygen demand.

    01:19 So obviously a drug like nifedipine is predominantly a vasodilator not necessarily a cardiac depressant.

    01:27 It may worsen proteinuria in some patients with underlying nephropathy so it's important for us to know that clearly.

    01:38 The next category are the nondihydropyridine calcium channel blockers.

    01:44 These are divided into two different categories which you probably don't need to know but for completeness' sake, I put them here.

    01:52 Now, the first one that I wanna talk about is verapamil.

    01:55 Verapamil is sold under very many different names so, I'm just gonna use the generic term.

    02:00 It reduces inotropy and chronotropy, so you can see that unlike say nifedipine which is predominantly a vasodilator, this one is a predominantly a cardiac depressant.

    02:12 It reduces the strength of contraction and it reduces the speed of conduction down certain tissues.

    02:19 So, what happens is the oxygen demand actually goes down.

    02:24 It reduces coronary vasospasm and therefore may help in ischemia.

    02:29 The patient is treated for arrythmia with this particular agent but it is also a really good treatment for patients who have angina.

    02:41 Other categories of drugs within this subclass is diltiazem.

    02:46 Now, diltiazem kind of shares features of both verapamil and nifedipine.

    02:51 It's sort of the halfway drug.

    02:53 So, it does act as a cardiac depressant, it does reduce heart rate, for sure.

    02:57 But it also is a vasodilator.

    02:59 So, the nice thing about using diltiazem is that you sometimes get the benefits of both.

    03:04 The next category of drugs that I wanna talk about are still calcium channel blockers.

    03:11 I've put them in here for completeness' sake but I just want to point out that this particular gabapentinoid class of drug is not necessarily used for angina.

    03:21 But because of the way that it works, it's important for us to know how it works.

    03:25 I've thrown it in here for your for your education.

    03:28 These gabapentinoids will block the alpha 2 delta sub-unit containing voltage-gated calcium channels.

    03:37 This is used in the treatment of neuropathic pain and epilepsy; it's not used in the treatment of angina but the mechanism of action is identical to the other calcium channel blockers, so that's why I wanted to put it in here.

    03:50 I also talk about this drug in greater detail in our seizure lectures and in our pain lectures.

    03:56 Another drug class is ethanol. Ethanol will actually block the L-type calcium channel as well and it causes urinary bladder relaxation.

    04:07 Now, why do I throw this in the angina lecture? The reason why I've put it here is just to emphasize the fact that technically these drugs, the gabapentinoids and ethanol, fall into the same category as the other calcium channel blockers because of the way that they work on the calcium channels and the effect that they have on certain types of smooth muscles and neurological function.

    04:30 These are not being used for the treatment of angina so I just wanna be clear about that and be very, very upfront about it.

    04:38 So, it's really for a mechanistic reason that I'm putting them in here.

    04:41 Now, this painting by the way is by Michelangelo, it's Drunken Noah, it's one of the most beautiful paintings ever created and I highly recommend that you check it out if this painting is being brought to your city.

    04:53 Now, let's get back to talking about all of the calcium channel blockers as a group.

    04:58 The side effects of calcium channel blockers include constipation; you can get pretibial edema, you can get nausea; sometimes, you can get facial flushing so the vasodilation of the capillaries in the face; you can get dizziness sometimes and that dizziness is more often due to low blood pressure than any kind of a direct effect.

    05:19 In terms of the dihydropyridines, like nifedipine and amlodipine, the side effects can include increased proteinuria, a reflex tachycardia, increased ischemia so it's a paradoxical kind of a thing because of the rapid heart rate; and a marked lowering of the blood pressure.

    05:39 In terms of the nondihydropyridines, you get decreased proteinuria, you can have decreased ischemia, and you can have bradycardia and AV blocks, and sinus node depression when you're using these medications.

    05:55 The other category of anti-anginals can be considered the beta-blockers.

    06:00 Now, beta-blockers are often used in angina management, they're often used in post M.I. management too.

    06:06 The prototypical and oldest of the beta-blockers is propranolol, although, ironically we don't really use proplanolol anymore for the treatment of angina.

    06:16 Beta-blockers in general reduce heart rate.

    06:19 They reduce cardiac force and they reduce blood pressure.

    06:23 It is used in the prevention only. It is not really for treating acute episodes of angina.

    06:29 It is not useful against certain types of vasospastic angina, so you have to be careful when you're picking which patients you're going to treat with them.

    06:38 A new category of drugs in the management of angina are the pFOX inhibitors.

    06:44 Now, these drugs are partial fatty acid oxidation inhibitors or pFOX inhibitors.

    06:51 It increases the efficiency of oxygen utilization and it shifts energy production from the fatty acids over to glucose.

    07:00 There may also have -- there may also be an effect on the slow sodium channels within the heart.

    07:07 We're not entirely sure of this but it's certainly one of the potential mechanisms and this ends up causing a reduced heart rate, a reduced automaticity to the atrial tissue, reduced contractile force and generally speaking results in less calcium in the intercellular milieu.

    07:27 These are a new category and I think that they're going to be quite useful going forward.

    07:32 The next category of drugs are what we colloquially refer to as funny channel inhibitors.

    07:38 Ivabradine is at this point in time, one of the few agents that do this.

    07:43 It inhibits the slow sodium potassium channel of the sinoatrial node or the IK current.

    07:50 We call it 'funny channel' because of the appearance of this channel on an electron microscopy and also the behavior of it.

    07:58 So, the scientists that first discovered it called it the funny channel.

    08:02 Now this particular agent has many different trade names in many different countries when you are looking up the drugs in your own country, have a look at my list there and I've got the trade names listed for each of the major countries.

    08:15 What you see with this medication is that it reduces the heart rate because it reduces that pacemaker slowing recurrent.

    08:24 There's no real change in inotropy, it just really reduces the heart rate and is particularly effective.

    08:31 It's used in predominantly in angina and in heart failure.

    08:34 It's also used in inappropriate sinus tachycardia.

    08:38 Now, when we take a look at the effectiveness of this agent in angina versus say a beta-blocker.

    08:43 We found that it was actually more effective than a beta-blocker and as effective as some of our calcium channel blockers.

    08:51 In terms of the adverse event rates of this medication, there's something called luminous phenomena.

    08:58 And it's a very bizarre kind of a description, patients describe walking around in a bright haze.

    09:05 So, they feel that say a light has a more luminous quality to it, it has more of a fuzzy quality to it.

    09:11 And they walk around and they feel like they're in a highly lit up corridor.

    09:18 So, it's strange kind of sensation it's hard to put into words but when your patients come to you and complain about it, it's worthwhile listening to them.

    09:26 I also wanna point out as well that this is something that will be on exams because it's such a unique phenomena related to this drug.

    09:34 Of course, it's gonna cause some patients to have excessive bradycardia.

    09:39 It may cause an AV block, it can cause dizziness due to either low heart rate or low blood pressure, and it can cause a blurred vision that is separate and different from the luminous phenomena that I was talking about.

    09:52 Now we don't want to use this agent in patients who already are excessively bradycardic or have sick sinus syndrome.

    09:59 We don't wanna use this agent, or we wanna use this agent with caution because other agents who are CYP 3A4 inhibitors can interfere with the area under the curve.

    10:11 So, an example of that is, say ketoconazole or macrolides.

    10:15 We want to be aware that it can have an interaction with verapamil or diltiazem as well.

    10:22 Now, remember that we're using this agent in patients who have heart failure as well with cardiac reserve.

    10:31 We also have to be cautious in patients who have underlying tachycardia because you can sometimes can exasturbate an arrythmia and finally, you have to be aware that we don't want to use this medication in atrial fibrillation because the indications are specifically excluding atrial fibrillation in the United States and Canada, so be aware that there are some limitations with using this drug.

    10:53 Okay, that's great. You managed to make it through this lecture.

    10:56 You did really well. I know that you're gonna do really, really well in your exams.

    11:01 Go in there with confidence and show them what you know.

    About the Lecture

    The lecture Cardiac Depressants and Vasodilators – Heart Failure and Angina Management by Pravin Shukle, MD is from the course Cardiovascular Pharmacology. It contains the following chapters:

    • Cardiac Depressants
    • Metabolic Rate Modifiers

    Included Quiz Questions

    1. Verapamil and diltiazem, which cause cardiac depression at the AV node
    2. Nifedipine and felodipine, which cause cardiac depression at the AV node
    3. Metoprolol, which causes cardiac depression at the AV node
    1. ...include nifedipine
    2. ...include diltiazem
    3. ...include verapamil
    4. ...include metoprolol
    1. Verapamil
    2. Diltiazem
    3. Nifedipine
    1. ...shift metabolism from fatty acid oxidation to glucose
    2. ...shift metabolism from glucose to fatty acids
    3. ...shift metabolism from fatty acids to protein (gluconeogenesis)
    4. ...shift metabolism from oxygen to lactic acid
    1. It reduces the heart rate by inhibition of the funny current channels (I-f channels)
    2. It reduces heart rate by blocking the calcium channel.
    3. It reduces heart rate by blocking the slow sodium channel
    4. It reduces heart rate by blocking the potassium channel

    Author of lecture Cardiac Depressants and Vasodilators – Heart Failure and Angina Management

     Pravin Shukle, MD

    Pravin Shukle, MD

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    Excellent lecture!
    By Beate U. on 03. July 2017 for Cardiac Depressants and Vasodilators – Heart Failure and Angina Management

    Everything is clearly explained by the lecturer. In case of student´s questions, the lecturer gives a detailed answer. Thank you!