Anti-anginal Drugs

Question 1

The underlying pathology of severe angina is…

Answer 1

…severe atherosclerotic affliction of larger coronary arteries

Question 2

Unstable/variant angina is caused by

Answer 2

recurrent localized coronary vasospasms which maybe superimposed on coronary artery disease.

Question 3

Drugs useful in treatment of stable angina work to

Answer 3

primarily reduce cardiac work by directly acting on the heart or reducing preload to cause a redistribution of blood to ischemic areas.

Question 4

Drugs useful in treatment of unstable angina work to

Answer 4

primarily relieve the causative coronary spasms.

Question 5

The symptoms of angina include

Answer 5

Chest pain
Referred pain

breathlessness, sweating, and nausea , vomiting and pallor in some cases.
“Autonomic symptoms” could present as increased the pulse rate and the blood pressure, pallor ,vomiting.

Question 6

Typical locations for referred pain in angina are

Answer 6

arms (often inner left arm), shoulders, and neck into the jaw.

Question 7

Major risk factors for angina include:

Answer 7

cigarette smoking
diabetes
high cholesterol
high blood pressure
sedentary lifestyle etc

Question 8

Tests used to detect angina:

Answer 8

ECG, Cardiac enzymes e.g troponin, coronary angiogram

Question 9

Classes of antiangina drugs

Answer 9

Nitrates
Beta blockers
Calcium channel blockers
K channel openers

Question 10

Short-acting nitrates:

Answer 10

Glycerol trinitrate (GTN)
nitroglycerine.

Question 11

Long-acting nitrates

Answer 11

Isosorbide dinitrate (short acting)
Isosorbide mononitrate
Erythrityl tetranitrate
Penta erythritol tetranitrate

Question 12

The mechanism of relief of angina is by

Answer 12

1. vasodilatory effect on larger coronary vessels to counteract coronary spasm in variant angina
2. reduction of cardiac work in classical angina by action on peripheral vasculature through increase in blood supply to ischemic areas are the focus of nitrates.

Question 13

Uses of nitrates

Answer 13

• Congestive heart failure- Causes venous pooling of blood to reduce the preload , decrease end diastolic volume and thus improve left ventricular function.
• Myocardial infarction
• Interventional cardiac procedures like percutaneous coronary angioplasty to dilate coronaries
  Biliary Colic
• Esophageal spasm- relives pain, taken before a meal to facilitate feeding in esophageal achalasia

Question 14

RODA for GTN

Answer 14

• Transdermal patch for steady delivery for 24hrs, starts working within 60mins and has a high bioavailability.
• Intravenous route is rapid, steady, a titratable infusion.
• Sublingual spray or tablet : Sublingual route us useful for aborting an imminent attack. It may be crushed under the teeth and spread over the buccal mucosa. Acts within 1-2mins as it bypasses hepatic circulation where 90% is metabolized.
• Sustained release oral capsules for chronic prophylaxis.

Question 15

Adverse effects of nitrates

Answer 15

• Headache and head fullness. Tolerance occurs after continued use
• Flushing, weakness, sweating, palpitation, dizziness and fainting
• Methemoglobinemia
• Rashes- rare more common with pentaerythritol tetranitrate

Question 16

Drug interactions of nitrates

Answer 16

• Sildenafil causes a dangerous potentiation of nitrate – hypotension
• Additive effect when nitrates are administered with other vasodilators.

Question 17

MOA of beta blockers in angina

Answer 17

They do not dilate coronary arteries or affect total coronary flow. They act by reducing cardiac work and O2 consumption via decrease in heart rate, inotropic state and blood pressure, thereby reducing the myocardial oxygen demand below the level that would provoke an angina attack.

Question 18

How to use beta blockers for prophylaxis

Answer 18

Not to be used alone but with CCB±Nitrates that take care of vasospasm.

Question 19

CCB MOA

Answer 19

• It dilates arterioles and has some α-adrenergic blocking property, decreasing the total peripheral resistance and blood pressure.
• It has cardiodepressant effect, slows AV conduction but cardiac output is maintained by reflex sympathetic stimulation.

Question 20

Adverse effects of CCB

Answer 20

Nausea
Constipation
Hypotension
Bradycardia
Flushing
Headache

Question 21

DI of CCB

Answer 21

It should not be administered with beta blockers due to additive sinus depression and conduction defects.

Question 22

Pharmacological action of nifedipine

Answer 22

It has minimal effects on direct cardiac depression

Question 23

Side effects of nifedipine

Answer 23

• Palpitation
• Flushing
• Ankle edema
• Hypotension
• Headache
• Drowsiness
• Nausea.
• It has relaxant effect on the bladder and thus increase voiding difficulty in elderly males.

Question 24

Effects of CCBs on vascular smooth muscle

Answer 24

• Vasodilation of systemic arterial smooth muscle, reducing systemic BP
• Vasodilation of coronary arteries smooth muscle, increasing blood supply to heart

Question 25

MOA of K-channel blockers

Answer 25

• It acts by activating the ATP sensitive K+ channels thus hyperpolarizing vascular smooth muscle.
• It also acts as an nitric oxide donor like nitrates causing relaxation of blood vessels by increasing cGMP.
• There is a combined arterial dilation coupled with venodilation.

Question 26

Which class of anti angina drugs are associated with pharmacological pre-conditioning?

Answer 26

K-channel openers

Question 27

What is pharmacological preconditioning?

Answer 27

When certain drugs mimic the protective effects of ischemic preconditioning. Here, Ischemia followed by reperfusion protects the tissues against subsequent prolonged ischemic events.

Question 28

Explain the pharmacological conditioning of nicorandil

Answer 28

Nicorandil among other drugs protect the heart against acute myocardial infarction when used before the onset of acute myocardial infarction.

Question 29

Examples of K channel openers

Answer 29

Nicorandil
Pinacidil
Cromakalim

Question 30

MOA of pharmacological conditioning by nicorandil

Answer 30

It shows its beneficial effects of myocardial protection through the mechanism of ischemic preconditioning by opening of mitochondrial adenosine 5′-triphosphate-sensitive K+channels.

Question 31

Other anti angina drugs

Answer 31

Dipyridamole
Trimetazidine
Oxyphedrine
Ranolazine
Ivabradine

Question 32

MOA of nitrates

Answer 32

• Organic nitrates are rapidly denitrated enzymatically by glutathione S-transferase in the smooth muscle to release the reactive free radical nitric oxide (NO).
• NO activates cytosolic guanylyl cyclase which acts on converting GTP to cGMP.
• cGMP activates the cyclic GMP- dependent protein kinase (or PKG) that activates the myosin light chain phosphatase causing a dephosphorylation of myosin light chain kinase (MLCK).
• The contraction of smooth muscles is dependent on phosphorylated/ active MLCK and so in the dephosphorylated state, there is relaxation.