How Do Nitrates Work? (Nitroglycerin)

Summary

This video explains how nitrates work, focusing on their role in treating angina pectoris, a type of chest pain caused by an imbalance between oxygen supply and demand in the heart. It discusses different types of nitrates, including nitroglycerin, isosorbide mononitrate, and isosorbide dinitrate, their mechanisms, dosing, and when they are used for acute versus chronic angina. The video also covers potential side effects like headaches and dizziness, drug interactions, particularly with PDE5 inhibitors, and the importance of a nitrate-free interval to prevent tolerance build-up.

Takeaways

• 💡 Angina pectoris is chest pain caused by an imbalance between the oxygen supply and demand of the heart.
• 🏃 Running increases the oxygen demand for the heart and the entire body, which can lead to ischemia if the supply can't meet the demand.
• 💊 Nitrates, such as nitroglycerin, isosorbide mononitrate, and isosorbide dinitrate, help alleviate chest pain by increasing the oxygen supply to the heart.
• 🌐 Nitrates work by dilating veins, which allows more blood and oxygen to flow into the heart, reducing the preload.
• 💨 Nitroglycerin is used for acute angina and acts quickly when dissolved under the tongue, providing fast relief.
• 🛡 Chronic angina is managed with longer-acting nitrates like isosorbide mononitrate and dinitrate, which require a 12-hour nitrate-free interval to prevent tolerance.
• 🚨 Patients should call emergency services if chest pain persists after the first dose of nitroglycerin, indicating a severe and ongoing issue.
• 💡 Nitrates release nitric oxide, which aids in the formation of cyclic GMP, leading to the relaxation of smooth muscles and vasodilation.
• 🚫 Nitrates are contraindicated with PDE5 inhibitors due to the risk of severe hypotension caused by the combined vasodilatory effects.
• 🤒 Common side effects of nitrates include headache, flushing, dizziness, and orthostatic hypotension, all related to vasodilation.
• 📚 Dosage for acute angina with nitroglycerin is 0.3 to 0.6 milligrams sublingual every 5 minutes, up to three times, while chronic preventative dosing varies for isosorbide mononitrate and dinitrate.

Q & A

What does 'angina pectoris' refer to?

Angina pectoris refers to chest pain caused by an imbalance between the oxygen supply and demand of the heart.

Why does ischemia occur in the heart?

Ischemia occurs when there is not enough oxygen supply to meet the oxygen demand of the heart, potentially causing damage to the heart muscle.

What is the primary function of nitrates in treating angina?

Nitrates primarily function by dilating the veins leading to the heart, increasing the oxygen supply to the heart and thereby relieving chest pain.

How do nitrates increase the oxygen supply to the heart?

Nitrates increase the oxygen supply to the heart by causing vasodilation, which allows more blood and oxygen to flow into the heart.

What is the role of nitric oxide in the action of nitrates?

Nitric oxide, released by nitrates, facilitates the formation of cyclic GMP, which leads to the relaxation of smooth muscles and results in vasodilation.

What are the two types of angina that nitrates can be used for?

Nitrates can be used for acute angina, which requires immediate relief, and chronic angina, which is a preventative measure.

Which brand name is associated with nitroglycerin for acute angina treatment?

Nitrostat is the brand name associated with nitroglycerin, used for treating acute angina.

What is the importance of a 12-hour nitrate-free interval when using isosorbide mononitrate or dinitrate?

A 12-hour nitrate-free interval is necessary to prevent the development of tolerance, ensuring the effectiveness of these long-acting nitrates.

Why are nitrates contraindicated with PDE5 inhibitors?

Nitrates are contraindicated with PDE5 inhibitors because their combined use can lead to severe hypotension due to the increased vasodilation effect caused by the inhibition of cyclic GMP breakdown.

What are some common side effects associated with nitrate use?

Common side effects of nitrate use include headache, flushing, dizziness, and orthostatic hypotension, all of which are related to vasodilation.

Outlines

00:00

💡 Understanding Nitrates and Angina Pectoris

This paragraph introduces the topic of nitrates and their role in treating angina pectoris, a condition characterized by chest pain due to an imbalance between oxygen supply and demand in the heart. It explains the concept of ischemia, which is the lack of oxygen to the heart, and how it leads to angina. The paragraph also introduces the three common types of nitrates: nitroglycerin, isosorbide mononitrate, and isosorbide dinitrate, and their function in increasing oxygen supply to the heart by dilating veins, thereby reducing the preload.

05:00

🚑 Acute and Chronic Angina Treatment with Nitrates

This section discusses the practical application of nitrates in treating both acute and chronic angina. Acute angina is addressed with nitroglycerin, a fast-acting medication taken sublingually for immediate relief. Chronic angina is managed with longer-acting nitrates, isosorbide mononitrate and isosorbide dinitrate, which require a 12-hour nitrate-free interval to prevent tolerance. The paragraph also covers the dosing for these medications and emphasizes the importance of proper patient counseling on their use.

10:03

💊 Nitrate Side Effects and Drug Interactions

This paragraph delves into the side effects associated with nitrate use, such as headache, flushing, dizziness, and orthostatic hypotension, all of which are linked to vasodilation. It also highlights a critical drug interaction between nitrates and PDE5 inhibitors, commonly used for erectile dysfunction, which can lead to severe hypotension due to the combined vasodilatory effects. The explanation includes a brief overview of the biochemical process involving nitric oxide and cyclic GMP that leads to vasodilation.

📚 Recap and Quiz on Nitrates and Their Applications

The final paragraph provides a summary of the key points discussed in the video script, including the definition of ischemia, the mechanism of action of nitrates, the types of nitrates used for acute and chronic angina, and the importance of a nitrate-free interval. It also outlines the side effects and the significant drug interaction with PDE5 inhibitors. The paragraph concludes with a short quiz to reinforce the viewer's understanding of the material presented.

Keywords

💡Nitrates

Nitrates, as discussed in the video, are a class of drugs used to treat angina by improving blood flow to the heart. They function by dilating veins, which increases the oxygen supply to the heart. This is crucial for patients experiencing chest pain due to an imbalance between oxygen supply and demand. Examples of nitrates mentioned include nitroglycerin, isosorbide mononitrate, and isosorbide dinitrate.

💡Angina Pectoris

Angina pectoris, which translates to 'chest pain,' is a medical condition where the heart muscle doesn't receive enough oxygen, causing pain. The video explains that this occurs due to an imbalance between the oxygen supplied to the heart and the oxygen the heart demands, particularly during activities that increase the heart rate.

💡Ischemia

Ischemia refers to a lack of oxygen to tissues, in this case, the heart. The video describes it as a condition where the oxygen supply is insufficient to meet the oxygen demand, which can lead to damage if not addressed. It is a key concept as it underpins the need for nitrates to improve oxygen delivery to the heart.

💡Vasodilation

Vasodilation is the widening of blood vessels, which is a critical mechanism by which nitrates work. By dilating veins and arteries, nitrates increase blood flow and oxygen supply to the heart. The video explains that nitrates release nitric oxide, leading to the formation of cyclic GMP, which causes smooth muscle relaxation and subsequent vasodilation.

💡Nitroglycerin

Nitroglycerin is a fast-acting nitrate used for acute angina episodes. It is taken sublingually (under the tongue) for rapid relief. The video emphasizes its quick action and the importance of seeking medical help if chest pain persists after its use, highlighting its role in emergency situations.

💡Isosorbide Mononitrate and Isosorbide Dinitrate

These are longer-acting nitrates used for chronic angina management. They are taken orally and provide a sustained release over 12 hours. The video stresses the importance of a 12-hour nitrate-free interval to prevent tolerance. They are used as preventative measures for patients with conditions like coronary artery disease.

💡Cyclic GMP (cGMP)

Cyclic GMP is a molecule that plays a central role in the mechanism of action of nitrates. As explained in the video, nitrates release nitric oxide, which aids in the formation of cyclic GMP. This molecule then leads to the relaxation of smooth muscles in blood vessels, causing vasodilation and increased oxygen supply to the heart.

💡Orthostatic Hypotension

Orthostatic hypotension is a side effect of nitrate use, characterized by a sudden drop in blood pressure upon standing, leading to dizziness or lightheadedness. The video mentions this as a consequence of vasodilation, which is the primary action of nitrates but can have this unintended effect.

💡PDE5 Inhibitors

PDE5 inhibitors are a class of drugs used to treat erectile dysfunction, such as Viagra and Cialis. The video warns against their use in conjunction with nitrates due to a dangerous interaction that can lead to severe hypotension. This is because PDE5 inhibitors prevent the breakdown of cyclic GMP, which would otherwise limit the vasodilatory effects of nitrates.

💡Tolerance

Tolerance refers to the reduced effectiveness of a drug over time due to repeated use. In the context of the video, chronic nitrate use can lead to tolerance if a nitrate-free interval is not observed. This is why a 12-hour break is recommended daily for long-acting nitrates to maintain their efficacy.

Highlights

Introduction to the topic of nitrates and their pharmacological role in treating chest pain.

Definition of angina pectoris as chest pain caused by an imbalance of oxygen supply and demand in the heart.

Explanation of ischemia as a condition of insufficient oxygen supply to the heart, leading to potential damage.

Overview of the three common nitrates: nitroglycerin, isosorbide mononitrate, and isosorbide dinitrate.

Mechanism of action of nitrates in dilating veins to increase oxygen supply to the heart.

Description of nitroglycerin's role in treating acute angina by providing rapid relief.

The importance of a 12-hour nitrate-free interval for chronic nitrate medications to prevent tolerance.

Brand names and dosing information for nitroglycerin (Nitrostat) and isosorbide mononitrate/ dinitrate.

Instructions for patients on using nitroglycerin sublingually and the necessity to call emergency services if chest pain persists.

Side effects of nitrates including headache, flushing, dizziness, and orthostatic hypotension.

Contraindication of nitrates with PDE5 inhibitors due to the risk of severe hypotension.

Explanation of the biochemical process involving nitric oxide and cyclic GMP leading to vasodilation.

Importance of proper administration of chronic nitrate medications to avoid improper dosing and potential health risks.

Differentiation between acute and chronic angina treatment approaches and their respective nitrate medications.

Summary of the video's key points on nitrates, their use in treating angina, and associated side effects and drug interactions.

Introduction of a short quiz to test viewers' understanding of the presented information on nitrates.

Transcripts

hello and welcome to another drug drug

episode and today we'll talk about

nitrates and how they work

plus some pharmacology let's get right

into it

so here's a breakdown of everything in

this video there will be time stamps

down below

and a short quiz at the end to see what

we retained

so to understand how nitrates work we

need a quick overview

and to do that we kind of need to look

at the heart

so the first thing we need to know is

something called

angina pectoris which literally means

chest pain and here we could see a

patient holding their heart

and they're having that chest pain and

that's actually caused by the heart

so let's take a look how so here we have

the heart

and essentially there's a balance

between the oxygen supplied

and the oxygen demanded by the heart

because remember

the heart is a muscle so as it keeps

pumping

and if it pumps harder and faster it's

going to need more and more

oxygen so the issue with angina pectoris

is there is a imbalance

of oxygen supply and oxygen demand

meaning the heart is demanding more

oxygen

than it can actually pump to itself

so let's take running for example you

know if we run obviously our heart rate

goes up

and the demand for oxygen for not only

the heart but essentially the whole body

will go up so the issue

is that the oxygen supply isn't getting

to the heart

fast enough or efficiently enough

and when this happens when there is less

oxygen supply and more oxygen

demand right then we have something

called

ischemia which literally means not

enough oxygen and that could damage our

heart

but the heart knows that it's not having

enough oxygen

and then that's when we'll see patients

have angina pectoris because the heart

is literally hurting because of the lack

of oxygen

and they feel that chest pain so now

that we know a little bit about the back

story of

having chest pains let's talk about

nitrates

and how they work so here we have our

first three nitrates these are the most

common

we have something called nitroglycerin

which is the most common

and then we have longer acting nitrates

which we'll talk about in detail later

called isosorbide mononitrate and

isosorbide dinitrate so since we said

the

issue with angina that chest pain

was the lack of oxygen supply

to oxygen demand what we need to do

is increase the oxygen supply right

if we need more oxygen we got to figure

out a way

to allow the heart to have more oxygen

and in a nutshell

that's what nitrates do they allow more

oxygen to go to the heart so here we see

we have

veins and arteries that lead

to and from the heart and remember

oxygen is carried

through blood cells right your blood

and your hemoglobin inside the actual

blood cell

holds oxygen so the way nitrates work is

they actually

dilate the veins leading to the heart

and this is also called preload meaning

before

the blood supply and if we increase the

preload

if we dilate those veins

we allow more blood to easily flow in

with

oxygen so now we know that nitrates

dilate the veins allowing

more blood and more oxygen to reach the

heart

so how does that actually happen right

so if we have a patient like this one

here

and we give them nitroglycerin

essentially what happens is

that medication gets absorbed and

nitric oxide which is part of the

medication

is released so that nitric oxide

in our body will allow the formation of

something called

cyclic gmp or abbreviated as

c gmp and cyclic gmp in our body

allows for smooth muscles to relax

and smooth muscles are like our veins

and arteries now when the smooth muscles

relax we get that

vasodilation and because of that

we see an improved blood supply

and we have an increased oxygen supply

to meet the demand

so essentially again we're just

increasing that

supply to the heart so that it has

efficient

oxygen so when do we actually use these

nitrates

well there's two realistic possibilities

in our patients

so we have something called acute angina

meaning they have

severe chest pain and we need to treat

their chest pain right now

and we use the nitroglycerin for that

it's very quick acting

it dissolves under the tongue and it

gives very fast relief

and on the other side we have chronic

angina

and here we use our other preventative

measures

we use the isosorbide mononitrate or

dinitrate

and again this is more of a preventative

cause these last a lot longer

these last for 12 hours and the reason a

patient may need these drugs

is that their blood vessels may narrow

for example a patient can have coronary

artery disease we could have plaque

buildup in the veins leading less and

less blood flow

to the heart which could lead to the

ischemia

and the chest pain so let's dive a

little bit deeper into the actual drugs

and the dosing

so to treat the acute angina we said we

used nitroglycerin

the brand name is nitrostat meaning

immediate use right so nitrostat

and here we have the dosing of 0.3

to 0.6 milligrams sublingual

every 5 minutes again we're using this

to treat

and it's very quick acting so

a patient can actually use this up to

three times

and the way we want to counsel them is

first we want them to sit down

we want them to dissolve under their

tongue

and then they have to call 911

if their angina persists after the first

five minutes

so after the first dose if they don't

feel well

and they're still having chest pain they

need to call 9-1-1

so that the paramedics can come assuming

that the second or third dose doesn't

work

because it is an emergency now for the

chronic

preventative nitrates we have

isoscorbide

mono nitrate brand name is emder

der because of duration they last a long

time

the dosing is anywhere from 30 to 240

milligrams

by mouth daily now it is extended

release

it does work for 12 hours but it also

requires

a 12 hour nitrate free interval

if you don't take a 12 hour break every

day

then these medications stop working you

build up essentially a taller

and the second medication is the

isosorbide

dinitrate or eyesore dill

and the dosing is 40 to 160 milligrams

by mouth daily

this is also extended release and this

one also requires

that 12 hour nitrate free interval

now one thing from the chronic side

versus the acute side

these chronic medications have to be

swallowed whole

right they're not sublingual they don't

dissolve

they need to swallow it whole you can't

chew break or crush these

extended release capsules and tablets

all right so let's talk about some side

effects and drug interactions

so the big things here is patients

taking these nitrates can have

headache we could see them having

flushing

so redness they could become dizzy

or they could have something called

orthostatic hypotension

which basically means low blood pressure

when they get up too

quickly so they get very light-headed

now

all of these side effects have to do

with vasodilation

right so as we dilate those veins we get

these very distinct side effects

now we do need to talk about drug

interactions

and there is one that you need to know

you cannot

use nitrates with pde5 inhibitors

these are erectile dysfunction drugs so

think of

viagra the dalaphil which is cialis

and essentially when both of these drugs

are used at the same time

it could cause severe hypotension

so a dramatic drop in blood pressure

and a quick overview on how it causes

this severe hypotension

remember when we take nitrates it has

nitric

oxide which help with the formation of

cyclic gmp which then cause

vasodilation now the cyclic gmp

that causes the vasodilation is broken

down by

pde5 right so

if we take a pde5 inhibitor

we stop the breakdown of cyclic gmp

which increases the vasodilation effect

even more to the point where it could be

potentially harmful

for our patients all right so we made it

to the end so let's have a real quick

summary of everything we learned

so we know ischemia which means not

enough oxygen for a tissue like the

heart

is due because of an imbalance of oxygen

supply

and oxygen demand this imbalance can

cause something called

angina pectoris which is that chest pain

so then we talked about nitrates and how

they work

so we know it they released nitric oxide

which helped with the formation of

cyclic gmp

causing vasodilation which actually

improved

the oxygen supply to the heart and then

we talked about three major drugs we

talked about nitroglycerin

which is our nitrostat and then our two

chronic medications

isosorbide mono nitrate and isosorbide

dinitrate so these two here remember

they need a 12 hour nitrate free

interval to prevent that tolerance

buildup

and then we also had our acute angina so

the nitrostat

and then the chronic agents that we just

talked about

then we went into the side effects

remember everything that had to do with

vasodilation

so we had headache flushing dizziness

orthostatic hypotension and then we had

our

big drug interaction and remember we

can't use those nitrates with any

pde5 inhibitor because of the severe

hypotension

so that's everything so let's jump into

the short quiz to see what we retained

question 1 which of the following is

approved for acute angina

question 2 nitrates increase which

molecule to allow

vasodilation

question 3 nitrates are contraindicated

with

which of the following

question 4 how long should the

nitrate-free interval be

for isosorbide dinitrate

and thanks for watching guys i hope you

learned something and a special shout

out to my supporters

[Music]

[Music]

you