Pharmacology Of CVS

Question 1

What is angina name

Answer 1

The full name of the angina (chest pain) is angina pectoris that translates as choking of the chest
(from Latin).

Question 2

Where does angina pain originate from

Answer 2

Angina pain originates from the heart muscle and is caused by the lactic acid produced
during anaerobic respiration. This irritates myocardial pain receptors and stimulates them to send
messages via cardiac nerves and upper posterior nerve roots to the brain.

Question 3

What are the symptoms of angina

Answer 3

The symptoms of angina
are the feeling of cramp and sever constriction of the chest, referred pain at the jaw and shoulders,
as well as associations with shortness of breath, sweating, nausea and increased heart rate.

Question 4

What is the aim of treatment of angina

Answer 4

The aims of treatment of angina would be to improve quality of life by reducing symptoms, improve
prognosis and prevent complications (e.g. MI and premature death), and for the treatment to cause
minimal side effects.

Question 5

Typical cause of angina symptoms

Answer 5

Typical angina is substernal chest discomfort provoked by stress or exertion and relived by rest or
nitrates within minutes.

Question 6

Atypical causes of angina symptoms

Answer 6

Atypical angina presents two of the characteristics of typical angina. Chest
pain without presentation of the characteristics of typical angina is termed non-anginal chest pain.
This classification however is outdated.

Question 7

What is the new classification of angina

Answer 7

Newer classification describes the first type of angina as being stable angina. This is pain that follows
a set pattern and is very predictable in terms of onset, duration and intensity. There is short duration
radiation to the left arm, neck, jaw or back that builds to a peak and lasts 2-5 minutes. It is
precipitated by exertion and increased oxygen demand (e.g. walking uphill, climbing stairs and
emotional stress). It is not life-threatening but can be a warning for something more fatal like a heart
attack or stroke.

Question 8

How can stable angina be relieved

Answer 8

Stable angina can be relieved by rest or taking medications.

Question 9

What can stable angina attribute

Answer 9

Symptoms of it are

attributed to myocardial ischaemia.

Question 10

What is the main cause of stable angina

Answer 10

Stable angina is mainly caused by the build-up of atherosclerotic plaques on both sides of cardiac
arteries that causes them to narrow as well as stenosis (elasticity of artery reduced).

Question 11

What are the triggers and symptoms of unstable angina

Answer 11

The second type of angina is unstable angina. This angina is unpredictable and pain symptoms are
more severe that can persist and last longer. This type of angina can also happen at rest with little
exertion as it does not necessarily have a trigger.

Question 12

What is used to treat unstable angina

Answer 12

Medication will also not usually treat it because of
its aetiology (cause). This type of angina is usually a progression of stable angina however, it is not
possible to predict who will develop it. Unstable angina is also quite serious and regarded as an
emergency.

Question 13

What does the pathosphysiology of unstable angina indicate

Answer 13

The pathophysiology of unstable angina indicates that one of the main causes of it is the
break off of atherosclerotic plaques. This exposes the subendotheliam that causes the formation of a
blood clot. This will further reduce blood flow through this already narrow blood vessel. This means
that the oxygen supply is inadequate even at rest. This clot however does not completely occlude the
blood vessel such that MI occurs however, it is still considered an emergency as there is high risk of
this developing into MI.

Question 14

Describe symptoms of prinzmetal angina

Answer 14

The final type of angina is prinzmetal angina (variant angina). This type of angina can again occur at
rest and during the night and early hours of morning. Episodes can last between 5 and 15 minutes. It
is a very rare type of angina (1 in 100 cases of angina) and mainly effects younger patients. Attacks
are also very severe and painful with the pain potentially spreading from the chest to the head,
shoulder or arm. Associated symptoms include heart burn, nausea, sweating, dizziness, palpitation
migraines and Raynaud’s phenomenon.

Question 15

What usually initiates symptoms of prinzmetal angina

Answer 15

It is usually initiated by coronary spasm (tightening of muscle
surrounding heart arteries) and tends to come in cycles. This type of angina can be relieved by
medication.

Question 16

What is the pathophysiology of prinzmetal angina

Answer 16

There may also be a genetic cause to prinzmetal angina. The pathophysiology of this
type of angina indicates that the cause of this angina is the vasoconstriction of blood vessels. The
coronary vessel constricts and therefore reduces blood flow to the heart such that oxygen supply is
inadequate. The response of the heart is to send a sensation of pain.

Question 17

Which patients tend to suffer from prinzmetal angina

Answer 17

Drugs abusers tend to present

with this kind of angina (e.g. cocaine)

Question 18

In general what causes angina

Answer 18

In general, angina is caused by decreased blood flow caused by vasospasms or blockage (e.g.
thrombus).

Question 19

What does vasospasms or blockage to thrombus cause

Answer 19

This causes supply ischaemia leading to angina (chest pain).

Question 20

What is stenosis

Answer 20

Stenosis, which means narrowing, can cause pressure on your spinal cord or the nerves that go from your spinal cord to your muscles. Spinal stenosis can happen in any part of your spine but is most common in the lower back. This part of your spine is called your lumbar area.

Question 21

What does fixed stenosis lead to and why

Answer 21

Fixed stenosis leads to
increased oxygen requirement. This is because the body responds to

increased oxygen demand by
vasodilating blood vessels however, due to the stiffening of the coronary arteries, these cannot
vasodilate much. They are required to supply more blood to the heart that now has a higher demand
for oxygen due to the heart pumping harder.

Question 22

What does lack of oxygen supply to the heart cause

Answer 22

The lack of oxygen supply causes the heart to respire

anaerobically causing a build-up of lactic acid.

Question 23

What causes the sense of pain in the heart

Answer 23

The lactic acid is what causes the sensation of pain.

Question 24

What are the precipitating factors of angina

Answer 24

The precipitating factors of angina include increased sympathetic activity including increased heart
rate that reduces diastolic time and therefore less coronary artery perfusion which only occurs in
systole. Exercise, emotion and stress that cause an increase in contractility increase oxygen demand
to the heart. Vasoconstriction of blood supply to the heart including during cold weather and after a
large meal also causes angina.

Question 25

What is angina treatment designed to do

Answer 25

Angina treatment is designed to improve perfusion to the heart. This is in order to increase oxygen
delivery by improving coronary blood flow.

Question 26

What is the target for treatment

Answer 26

The way this is achieved is through coronary vasodilators.

Question 27

What is also an aim for treatment to reduce ……….

Answer 27

Angina treatment is also done to reduce metabolic demand. This is to decrease oxygen demand by
the heart by decreasing cardiac work. In this case, not only are vasodilators used (reduce afterload
and preload), but cardiac depressants are also used (reduce heart rate and contractility.

Question 28

How is angina treatment designed to reduce episodes

Answer 28

Angina
treatment is also designed to prevent angina and reduce the risk of subsequent episodes. These
include lipid lowering drugs, anti-coagulants, fibrinolytic and anti-platelet drugs.

Question 29

What are nitrates used for and what affect do they have

Answer 29

Nitrates (e.g. glyceryltrinitrate or GNT and isosorbide mononitrate) are mainly used in venodilation.
This decreases blood flow into the heart (decrease intraventricular pressure) reducing workload on
the heart (preload reduced). They can also cause modest arterial dilation that decrease TPR and
therefore reduce afterload.

Question 30

What do nitrates have limited affect on

Answer 30

Nitrates however have limited effect on coronary vessels that are
affected by atherosclerosis as the endothelial cells have been damaged and may not be able to
produce nitric oxide for relaxation.

Question 31

What are the side effects of nitrates

Answer 31

Nitrates have some side effects including throbbing headache
(due to more blood pumping into the brain and compressing on pain fibres in the head), flushing
(increased blood flow near skin causing redness) and syncope (temporary loss in consciousness
caused by a fall in blood flow). There can also be postural hypotension caused by venodilation and
reflex tachycardia that is triggered in response to low blood pressure.

Question 32

What does organic nitrate mimic the effects of

Answer 32

Organic nitrates mimic the

effects of endogenous nitric oxide.

Question 33

Where is nitric oxide produced and in response to what

Answer 33

Nitric oxide is produced by endothelium NO synthase that
produces it from arginine. The NO is produced in the endothelium in response to acetylcholine,
stress, histamine and bradykinin.

Question 34

Where does the NO diffuse

Answer 34

The NO then diffuses vascular smooth muscle where it

stimulate guanylate cyclase to convert GTP to cGMP that stimulates protein kinase G.

Question 35

What does protein kinase g do

Answer 35

PKG reduces
muscular tone by dephosphorylating MLC, increases uptake of calcium ions by the SR reducing
cytoplasmic levels, and activates potassium channels causing hyperpolarisation and the closing of
voltage gated calcium channels.

Question 36

What are organic nitrates specifically important to

Answer 36

Organic nitrates are especially important for acting on arteries that
have damaged endothelium (cannot produce NO).
Beta-blockers (atenolol or bisoprolol) can be used in treating angina.

Question 37

What do beta blockers mimic

Answer 37

Beta-blockers mimic the effects

of adrenaline and noradrenaline on beta adrenoreceptors.

Question 38

What happens when AV conduction is prevented

Answer 38

This has
the effect of decreasing heart rate that lengthens diastole and therefore gives more time for
coronary perfusion and improve myocardial oxygen supply).

Question 39

How do beta blockers improve exercise tolerance

Answer 39

Beta-blockers also reduce the force of
cardiac contractions that improves exercise tolerance. The effect of beta-blockers is reduced cardiac
output and therefore lower BP.

Question 40

What are the adverse effects of beta-blockers

Answer 40

Adverse effects of beta-blockers include fatigue, postural hypotension
and bronchospasms.

Question 41

What would a patient with asthma experience when out on beta blockers

Answer 41

If the patient is suffering from asthma, the beta-blockers would block the beta-2
receptors that leads to constriction of the airways and therefore bronchospasms so beta-blockers are
not used in this case.

Question 42

When are beta blockers also avoided

Answer 42

A second case where beta-blockers are avoided is in patients suffering from heart block where atrial-ventricular conduction is poor.

Question 43

What are another class of drugs to treat angina - examples

Answer 43

Calcium channel blockers are also another set of drugs that can be used to treat angina. Examples
include amlodipine and nifedipine that are both dihydropyridines that target calcium channels in
smooth muscle.

Question 44

What does benzothiazepine and diphenylalkylamine target

Answer 44

Benzothiazepine verapamil targets cardiac calcium channels, and the
diphenylalkyamine diltiazem can target both cardiac and vascular smooth muscle calcium channels.

Question 45

What is the overall effect of calcium blockers

Answer 45

They have the effect of reducing calcium entry into cardiac myocytes and vascular smooth muscle
cells reducing contractility. One of the effects of this is direct coronary vasodilation that improves
coronary blood flow. TPR, BP and afterload are also all reduced that lowers the workload on the
heart. The force with which the heart contracts also reduces which reduces oxygen consumption.

Question 46

What are the side effects of calcium blockers

Answer 46

Some side effects include lower limb oedema caused by increased capillary pressure in the lower
limbs, flushing, headache and reflex tachycardia (increased sympathetic activity caused by the
baroreflex). Calcium channel blockers in the heart my also alter electrical conduction and contractility
which can be very dangerous.

Question 47

What is nicorandil

Answer 47

Nicorandil is a
potassium channel activator that causes hyperpolarisation. This decreases the number of VGCCs that
are stimulated reducing calcium entry into the cell leading to coronary vasodilation. It also partly
mimics the effects of nitrates in stimulating the production of NO. Ivabradine is a specific inhibitor of
the funny current in the SAN. It has the effect of slowing the sinus heart rate and thus decreasing the
pacemaker potential frequency.

Question 48

What happens when the SAN is inhibited

Answer 48

This decreases heart rate resulting in the reduction in demand for
oxygen by the myocardium. This drug does not affect myocardial contractility.