Pharmacology Of CVS Flashcards
What is angina name
The full name of the angina (chest pain) is angina pectoris that translates as choking of the chest
(from Latin).
Where does angina pain originate from
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.
What are the symptoms of angina
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.
What is the aim of treatment of angina
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.
Typical cause of angina symptoms
Typical angina is substernal chest discomfort provoked by stress or exertion and relived by rest or
nitrates within minutes.
Atypical causes of angina symptoms
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This classification however is outdated.
What is the new classification of angina
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.
How can stable angina be relieved
Stable angina can be relieved by rest or taking medications.
What can stable angina attribute
Symptoms of it are
attributed to myocardial ischaemia.
What is the main cause of stable angina
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).
What are the triggers and symptoms of unstable angina
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.
What is used to treat unstable angina
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.
What does the pathosphysiology of unstable angina indicate
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.
Describe symptoms of prinzmetal angina
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.
What usually initiates symptoms of prinzmetal angina
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.
What is the pathophysiology of prinzmetal angina
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.
Which patients tend to suffer from prinzmetal angina
Drugs abusers tend to present
with this kind of angina (e.g. cocaine)
In general what causes angina
In general, angina is caused by decreased blood flow caused by vasospasms or blockage (e.g.
thrombus).
What does vasospasms or blockage to thrombus cause
This causes supply ischaemia leading to angina (chest pain).
What is stenosis
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.
What does fixed stenosis lead to and why
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.
What does lack of oxygen supply to the heart cause
The lack of oxygen supply causes the heart to respire
anaerobically causing a build-up of lactic acid.
What causes the sense of pain in the heart
The lactic acid is what causes the sensation of pain.
What are the precipitating factors of angina
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.
What is angina treatment designed to do
Angina treatment is designed to improve perfusion to the heart. This is in order to increase oxygen
delivery by improving coronary blood flow.
What is the target for treatment
The way this is achieved is through coronary vasodilators.
What is also an aim for treatment to reduce ……….
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.
How is angina treatment designed to reduce episodes
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.
What are nitrates used for and what affect do they have
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.
What do nitrates have limited affect on
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.
What are the side effects of nitrates
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.
What does organic nitrate mimic the effects of
Organic nitrates mimic the
effects of endogenous nitric oxide.
Where is nitric oxide produced and in response to what
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.
Where does the NO diffuse
The NO then diffuses vascular smooth muscle where it
stimulate guanylate cyclase to convert GTP to cGMP that stimulates protein kinase G.
What does protein kinase g do
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.
What are organic nitrates specifically important to
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.
What do beta blockers mimic
Beta-blockers mimic the effects
of adrenaline and noradrenaline on beta adrenoreceptors.
What happens when AV conduction is prevented
This has
the effect of decreasing heart rate that lengthens diastole and therefore gives more time for
coronary perfusion and improve myocardial oxygen supply).
How do beta blockers improve exercise tolerance
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.
What are the adverse effects of beta-blockers
Adverse effects of beta-blockers include fatigue, postural hypotension
and bronchospasms.
What would a patient with asthma experience when out on beta blockers
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.
When are beta blockers also avoided
A second case where beta-blockers are avoided is in patients suffering from heart block where atrial-ventricular conduction is poor.
What are another class of drugs to treat angina - examples
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.
What does benzothiazepine and diphenylalkylamine target
Benzothiazepine verapamil targets cardiac calcium channels, and the
diphenylalkyamine diltiazem can target both cardiac and vascular smooth muscle calcium channels.
What is the overall effect of calcium blockers
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.
What are the side effects of calcium blockers
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.
What is nicorandil
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.
What happens when the SAN is inhibited
This decreases heart rate resulting in the reduction in demand for
oxygen by the myocardium. This drug does not affect myocardial contractility.
