Let’s say there are three of the following ways to treat angina, which one would you choose? Which one of these is the primary mechanism of action to treat angina?
- Coronary artery vasodilation
- Peripheral artery dilation
- Peripheral venous dilation
Even though it’s the coronary artery that is having trouble getting oxygen, the treatment for it doesn’t involve dilation of the coronary arteries. The proper mechanism of action is on dilating the peripheral veins (#3).
How does dilating the peripheral veins alleviate angina? It decreases preload, so we have blood pooling in the venous side. That means we have less blood returning to the heart. If we have less blood going to the heart, that decreases the amount of blood the heart needs to pump, decreasing the work load, and reducing the oxygen demand. Dilating just the coronary arteries doesn’t provide a significant change. It’s more effective if we dilate all the other veins in the rest of the body.
Nitrate uses
- Acute angina: Provides relief of symptom of pain.
- Prophylactic: Medication we give everyday that decreases the incident of anginal pain.
Nitrate cautions
Tolerance
Individuals get tolerant to the therapeutic properties of nitrates. When a person takes nitrates everyday, it stops working. We first especially noticed this problem when the nitroglycerine patch came out on the market. This was the very first patch medication, ever. It would release nitrogylcerine (NTG) out at a constant rate, all the time. If we drew a time-graph showing the NTG blood levels, it would be a perfectly horizontal straight line. This turned out to be a problem.
The nitroglycerine patches came in different strengths. People would start using the small patches and after a while they wouldn’t work so people went to the larger patches and kept stepping up to the largest patches until they were eventually putting on two of the largest patches. Patients were developing tolerance to the constantly steady blood levels. We found out that if drop the blood levels temporarily and then get them back up, that the drug will work again. So now the order is to discontinue the use at bed time. If we make the blood levels drop overnight and get the patch back on in the morning then the drug continues to work.
Is the patient in danger of angina at night? Not really because the oxygen demand of someone lying down is at its lowest. If they are having anginal pain while sleeping in bed at night, then that’s a heart attack.
Increased Intraocular Pressure: A warning to glaucoma patients.
Side effects:
- headache (because all the blood vessels are dilating)
- syncope (blood vessels are dilating)
- cutaneous flushing (blood vessels are dilating)
Nitrate Comparison Chart
| Acute | Onset | Duration |
|---|---|---|
| NTG Sublingual | 3 min | 10 min |
| ISDN Dinitrate | 2-5min | 1 hr |
| Prophylactic | Onset | Duration |
|---|---|---|
| NTG Ointment | 1 hour | 4-6 hrs |
| Isosorbide Tab | 1/2 hour | 6 hrs |
| NTG Patch | 24 hr | 24 hr |
Understand the concept here. The drugs are either acute or prophylactic based on the onset and duration time. If you were to use the NTG sublingual drug prophylactically, you’d have to take it every 10 minutes throughout the day. The prophylactic drugs take a long time to kick in, so they don’t make sense for acute pain, but make sense prophylactically because they last a long time.
NTG Sublingual
This can be administered as a sublingual tablet or as a spray. Both give the same dose and in general, we want to use the lowest dose possible. The problem with the spray is, how do you know if you just used the last dose? There’s no counter on it to know absolutely.
The instructions: 1 dose every 5 minutes for 3 doses maximum. If 3 doses were administered in 15 minutes and the chest pain is still there, they should call 911 because it’s possibly a heart attack.
There’s a few other possibilities for why the drug may not be working:
Acid Reflux: Heart burn could have every symptom of a heart attack but it has nothing to do with their heart. But you can’t take the chance though and assume it might be heart burn because you can’t tell the difference.
Expiration: Another reason why it doesn’t work is because it’s possible the nitroglycerin tablets may be expired. Another reason is that it must be stored appropriately. Typically a good nitroglycerine tablet will leave a stinging sensation. If there is no stinging/burning sensation under the tongue, it’s possible it’s no good.
Storage: The nitroglycerin must be stored in a glass bottle with a metal cap. Most of the ones you pick up from a pharmacy are in a plastic bottle with a plastic cap and the pharmacy. The plastic absorbs the nitroglycerine. Some people transfer their pills to a glass bottle and store them in a cool non-humid place. Most people store it in a bathroom cabinet where it gets hot and humid. Another problem is with men. They tend to store their nitroglycerine in a pocket. How many men have a cool, non humid pocket?
NTG Ointment
We normally dose medications using the metric system (milligrams, micrograms, etc), except this ointment is dosed by the inch. This tube of ointment comes with a 3 inch pad of paper with markings. You squeeze the ointment onto the paper and then apply it onto the patients body. The primary mechanism of action of nitrates is peripheral venous dilation and it will work if you apply it anywhere that has good blood supply, usually the upper body. You always want to alternate where you want to put it so the skin has a chance to breath.
Use gloves when applying otherwise it will go through your fingers and hands. You can get hypotension and faint and eventually build up tolerance from absorbing nitroglycerine day in and day out.
Nitrate Patch
This has a 24 hour onset. To prevent tolerance, remove at bed-time.
Nitrate Injection
Use
- Unstable angina.
- Post-cardiac surgery to take the most stress off the heart.
This is an IV infusion. It’s a ready made bottle (not a bag because it must not be mixed with plastic). It needs a tube to get to the veins, though, and that tube is normally made of plastic. There’s a special non-plastic tubing especially made for this and usually the pharmacy sends up the IV bottle to you with this special (non-phthalate) tubing that you must use.
