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122 Chapter 6 Atherosclerosis and ischaemic heart disease
(a) Stable angina
Atherosclerotic plaque causes
narrowing of coronary artery and
reduces ability of vessel to dilate
(b) Unstable angina
Plaque ruptures providing
thrombogenic surface
Arterial thrombus forms,
and occludes coronary artery
(c) Variant angina (rare)
Intense vasospasm causes
narrowing of coronary artery
Figure 6.8 Processes underlying the three types of angina: stable,
unstable, and variant.
(a) Stable angina is caused by an atherosclerotic plaque narrowing the lumen of a
coronary artery. Pain occurs on exertion, for instance, when the compromised vessel is
unable to supply blood to meet the increased demand. (b) Unstable angina is caused
when an atherosclerotic plaque ruptures, and gives rise to a thrombogenic surface. A
platelet plug may develop, which disrupts or potentially halts the flow of blood through
the artery. (c) In variant angina, reduced blood flow through the coronary artery is the
result of vascular spasm, temporarily narrowing the coronary artery.
Box 6.2
Resistance
How arterial and venous vasoconstriction affect coronary blood flow
Venous capacitance
vessels
Left ventricle Coronary
vessels
arterioles
Preload Afterload
Aorta
Vasoconstriction Vasoconstriction
Blood volume
Central venous
pressure
Figure e Relationship between venous and arterial vasoconstriction and coronary blood flow.
Venous vasoconstriction, or increased blood
volume, will both result in higher central venous
pressure, increased preload, and increased enddiastolic volume (EDV). As a result of this (and
following Starling’s law), the ventricular muscle cells
will be more stretched and so will subsequently
contract with greater force (Chapter 5, Figure 5.5),
generating greater pressures within the ventricle wall
(intramural pressure).
Arterial vasoconstriction raises arterial blood
pressure and so increases afterload. is necessitates
raised ventricular pressure to achieve a given ejection
of blood, again leading to increased pressures within
the ventricle walls. With both arterial and venous
vasoconstriction (Figure e) the consequence is
increased compression of coronary arterioles, and so
reduced blood ow to the myocardium. In both cases
this restriction in oxygen supply occurs when demand
EDV
Muscle stretch
in late diastole
Force of
contraction
is increased, since the increased force of contraction
requires more oxygen. is leads to supply not
meeting demand (ischaemia). Increased sympathetic
activity (e.g. as seen with exercise and stress) will yield
vasoconstriction on both the venous and arterial sides.
Drugs used to treat angina include those that
reduce venous and/or arterial blood
pressures, thereby reversing the eects described
above. is will facilitate blood ow to the
myocardium (as well as reducing work), helping to
restore oxygen supply suciently to meet oxygen
demand. Drugs which reduce vasoconstriction
include organic nitrates, calcium channel blockers,
and potassium channel activators. In addition, drugs
such as ACE inhibitors can be used in the long-term
management of angina patients, because of their
ability to reduce vasoconstriction and decrease plasma
volume (see Chapter 5, Section 5.2.1).
Aortic
pressure
Ventricular pressure
Ventricle intramural pressure
Coronary blood flow
124 Chapter 6 Atherosclerosis and ischaemic heart disease
Most of the drugs described below act to reduce the
workload of the heart, or to increase coronary perfusion.
ese drugs therefore do not modify the progression of
the underlying disease—they treat and prevent
symptoms, and some may reduce the probability of
progression to MI. Here we have divided the drugs into
those where the therapeutic eect is largely due to direct
action on either the heart or the peripheral vasculature. In
addition, the role of antiplatelet drugs in the management
of angina is briey covered.
6.4.4 Drugs with action mainly at the heart
-adrenoceptor antagonists are the main class of drugs
in this group. We have encountered these drugs before—
they are perhaps best known as antihypertensive agents,
and their cardiovascular actions have been reviewed in
that context in Chapter 5. Here we are concerned with
blocking the direct action of noradrenaline (and
adrenaline) on the heart through action at 1adrenoceptors. Activation of these receptors on both the
sinoatrial node and ventricular muscle cells leads to a
decrease in oxygen supply to the heart muscle by
restricting coronary blood ow, whilst simultaneously
increasing its oxygen demand. is is summarized in
Figure 6.9.
If a patient with partially blocked coronary arteries is
subject to stress or exercise, the 1-adrenoceptormediated changes in oxygen supply and demand
illustrated in Figure 6.9 may lead to ischaemia and
angina. (In reality, of course, the changes illustrated in
heart function in Figure 6.9, and in vascular function in
Box 6.2, will be occurring together.) ese events will be
reduced by -adrenoceptor antagonists (-blockers), and
the onset of angina may be averted or its intensity
reduced. -adrenoceptor antagonists are, then, a rst-line
option for improving symptoms and prognosis of both
stable and unstable angina. ey are particularly eective
in stable angina where pain is brought on by exertion.
ere is no evidence to suggest that any particular drug is
most eective, although some patients may respond
better to one -blocker than another. Sudden withdrawal
should be avoided as this may cause a worsening of
angina. -Blockers are not used in variant angina, as
blocking the 2-mediated vasodilatation of coronary
arteries can worsen coronary vasospasm. eir adverse
eects and other considerations are covered in Chapter 5
(Section 5.2.5). It is worth noting that the benets of
taking -blockers in the treatment of angina may well be
deemed sucient to outweigh their associated risks, and
Stress or exercise
↓
Release of noradrenaline/adrenaline
↑
↓
Stimulation of cardiac β
Heart rate
↑
Figure 6.9 Effect of sympathetic stimulation of the heart
on its oxygen balance.
Note that increased heart rate reduces oxygen supply to the
cardiac muscle by reducing the time between the peaks of
systole. This reduces the time in a given cardiac cycle when
blood can flow freely through the coronary vessels to perfuse the
muscle of the heart. Similarly, an increased force of contraction
means the reduction in blood flow at the peak of systole is more
profound. Both these factors therefore reduce oxygen supply at
the same time as they are increasing the work of the heart
muscle, thus increasing its oxygen demand. -Adrenoceptor
antagonists will reduce both these effects, increasing oxygen
supply and decreasing oxygen demand.
↓Oxygen
supply
↑Oxygen
demand
-adrenoceptors
1
↑Force of
myocardial
contraction
so they are frequently prescribed in patients for whom
they would normally be avoided (e.g. diabetics). eir use
is, though, contraindicated in asthma, as explored in
Chapter 5.
A reduction in heart rate will result in lengthened
diastole, increasing the time during which heart muscle
can be perfused and improving oxygen supply. Reduction
in heart rate may be seen as a cornerstone in the
treatment of angina, and the second class of anti-angina
drugs that primarily act at the heart, the If current
inhibitors, directly target heart rate. e inward current
carried by the sinoatrial If channels contributes to the
pacemaker slope, which is the sole determinant of heart
rate (Chapter 5, Figure 5.3). Inhibiting this channel will
reduce the slope’s gradient, increasing the time between
heart beats. e If channel inhibitor ivabradine has
recently become available, and has a role to play in the
treatment of angina in combination with -blockers, or
where these drugs are not tolerated or are inappropriate
(e.g. asthmatics, or some diabetic patients). is
interesting drug class reduces heart rate while
contractility and atrioventricular conduction remain
unaected. Ivabradine has a short half-life of about
6.4 Ischaemic heart disease: angina 125
2 hours and must be taken twice daily. It is generally well
tolerated; the most common side eect is luminous visual
disturbances which most likely arise from interaction
with retinal channels close in structure to those carrying
the If current. Ivabradine is not used in the treatment of
unstable angina.
Ranolazine is another recently introduced drug used as
adjunctive therapy in the treatment of stable angina. Its
mechanism of action is not fully resolved, but includes
blocking late inward Na+ currents into cardiac myocytes,
which in turn decreases intracellular Ca2+ concentration
through reduced Na+–Ca2+ exchange. is modulates
ventricular repolarization and contractility. It is possible
that additional mechanisms contribute to the antianginal benets of ranolazine. It is available for patients
with chronic stable angina who are inadequately
controlled by rst-line drugs. Side eects can include
constipation, nausea, vomiting, and dizziness, but the
drug is generally well tolerated.
6.4.5 Action mainly at the peripheral
vasculature
Drugs discussed in this section are not necessarily free
from a direct eect on heart, but have a major
contribution through their action at the vasculature. ey
have in common the eect of reducing vasoconstriction
on the arterial and venous side. Box 6.2 explains how this
leads to increased coronary blood ow (and therefore
oxygen supply). Lowering blood pressure on the arterial
side will also reduce the workload of the heart, reducing
oxygen demand. Not surprisingly, we have met many of
these drugs before in the treatment of hypertension
(Chapter 5).
Organic nitrates
e main therapeutic eect of these drugs is derived from
peripheral vasodilatation; there is also a minor
contribution from relaxation of arteries. Benet derives
chiey from dilatation of systemic veins, with consequent
reduction of preload and left ventricular work (Box 6.2).
Additionally, arterial relaxation will lead to some
reduction in afterload. At rst sight it might seem that
coronary artery dilatation underlies the eectiveness of
nitrates. In reality, such dilatation appears to mainly
increase perfusion by non-occluded vessels, where blood
ow is not compromised, and so does not contribute
greatly to reduction in symptoms. However, in variant
angina the direct vasodilatory eect of nitrates on
non-diseased coronary arteries may have a major role in
reducing the arterial spasm which causes pain.
e nitrates act by entering vascular smooth muscle (and
other) cells where they are metabolized to release NO,
which activates the cyclic-GMP-based intracellular
vasodilatation mechanism set out in Chapter 5, Box 5.2.
Nitric oxide from administered organic nitrates also has
antiplatelet and anti-atherosclerotic eects, which may
be benecial.
e NO generated in the cells is very rapidly broken
down, so the duration of the therapeutic eect is
dependent on the kinetics of the organic nitrate chosen.
Glyceryl trinitrate (GTN) is used for fast short-term relief
from pain in stable and unstable angina. It is given
sublingually, providing absorption without rst-pass
metabolism, which would be extensive. (Unlike the gut,
the circulation from the mouth does not pass directly to
the liver.) GTN quickly distributes around the body; when
it is used during an angina attack, pain relief is rapid and
eective for about 30 min. It can also be used
prophylactically when taken immediately before activity
known to precipitate angina. Extended action may be
achieved with a transdermal patch.
Longer-acting organic nitrates are available to prevent an
attack. Isosorbide mononitrate is taken as a tablet and is
absorbed and metabolized more slowly than GTN, being
eective for about 4 hours. It is taken twice a day;
slow-release preparations are available for once-daily
administration.
Tolerance to organic nitrates is rapid and profound, and
must be considered when using longer-acting nitrates,
such as isosorbide mononitrate, or sustained-release
preparations. e generation of NO from the parent drug
depends on the presence of –SH groups on intracellular
proteins. ese become exhausted with exposure to
nitrates; this presumably underlies the reduced
eectiveness seen with prolonged usage. Eectiveness is
rapidly restored following a drug-free period of a few
hours. Tolerance is not a concern in the administration of
short-acting nitrovasodilators. However, longer-term
treatment with isosorbide mononitrate, or transdermal
patches of GTN, must include a drug-free 4–8 hour period
in every 24 hours, to minimize tolerance. is should be
timed to coincide with the patient being at rest and
therefore in least danger of an angina attack. is
irregular dosing to maintain eectiveness is explored in
the workbook at the end of this chapter, when Brian takes
126 Chapter 6 Atherosclerosis and ischaemic heart disease
isosorbide mononitrate tablets to relieve pain from
unstable angina. He is also aected by headaches, the
most common side eect of nitrovasodilators.
Calcium channel blockers
e anti-angina benets of calcium channel blockers are
achieved through eects on both the heart and vascular
smooth muscle, with distinct classes of drugs displaying
dierent selectivity for these sites of action:
dihydropyridines preferentially act on the vasculature;
verapamil is relatively selective for its cardiac eects;
diltiazem is intermediate between the two. At all sites of
action these drugs act by decreasing Ca2+ entry into cells
by blocking L-type voltage-gated calcium channels. e
drugs are described more fully in the context of their
antihypertensive action in Chapter 5.
Vascular eects derive from reduced calcium entry into
vascular smooth muscle cells, favouring vasodilatation.
is leads to decreases in arterial blood pressures
(through reduced total peripheral resistance) and hence
afterload, thereby reducing cardiac work and oxygen
demand.
Cardiac eects which explain their usefulness in angina
are:
1) reduced calcium entry at the sinoatrial node, reducing
pacemaker slope and heart rate
2) reduced atrioventricular node conduction and
increased refractory period
3) reduced calcium entry into ventricular myocytes,
reducing force of contraction, with a net eect of
reduced oxygen demand.
All calcium channel blockers can be used to control
symptoms of stable angina as an alternative to
-adrenoceptor antagonists (for instance, in asthmatic
patients). Verapamil has an important role here due to its
very eective ability to lower heart rate and therefore the
oxygen demand of the myocardium. Examples of
dihydropyridines indicated for prevention of angina
include nicardipine, amlodipine, felodipine, and
long-acting, modied release preparations of nifedipine.
(Short-acting nifedipine formulations are not
recommended for angina as their use is associated with
reex tachycardia.) A combination of a dihydropyridine
and a -blocker can be given where either drug alone
does not adequately control symptoms. e combined
cardio-depressant eects of -blockers and non-
dihydropyridines, and in particular verapamil, can
be dangerous, and these drugs should not be taken
together.
Calcium channel blockers prevent coronary artery spasm,
and are therefore particularly useful in the treatment of
variant angina. ey are not used in the treatment of
unstable angina, but may be continued for symptom
control if the patient is already receiving them for chronic
stable angina. eir side eects are covered in Chapter 5.
As with -blockers, rapid withdrawal may exacerbate
angina.
Potassium channel activator
e only potassium channel activator in clinical use is
nicorandil. is drug combines vasodilatory nitrate
behaviour with activation of ATP-sensitive K+ channels to
enhance K+ eux, leading to hyperpolarization of
vascular smooth muscle cells. As a result, the inux of
Ca2+ through voltage-gated calcium channels is reduced,
thereby decreasing contractility. e combination of its
two actions results in vasodilatation on both the venous
and arterial side, including coronary vessels. Nicorandil is
used in stable angina where -adrenoceptors and/or
calcium channel blockers are insucient, or are not
tolerated. Adverse eects include those associated with
vasodilatation (e.g. ushing, dizziness, hypotension, and
headache) as well as nausea and vomiting.
6.4.6 Antiplatelet drugs in the
management of patients with angina
In stable and unstable angina there is a need for longterm reduction of cardiovascular risk, requiring both
lifestyle changes and medication. Atherosclerotic plaques
provide a focus for the development of arterial thrombi,
the initiating event in unstable angina and MI.
Management of stable and unstable angina should
therefore include drugs which reduce the likelihood of
thrombus formation. Such drugs, and the pathways that
they alter, are discussed in detail in Chapter 4. A daily low
dose of aspirin, which suppresses the activation and
recruitment of platelets, has been shown to greatly reduce
the risk of myocardial infarction in patients with angina,
and should be taken indenitely. Clopidogrel, another
antiplatelet drug, is slightly more eective than aspirin at
reducing events in such patients. Aspirin and clopidogrel
are used in combination for patients with unstable angina
who are at moderate to high risk of having an MI. Most
6.5 Ischaemic heart disease: myocardial infarction (MI) 127
patients with angina will also be advised to take a statin to
reduce LDL-cholesterol levels (see Section 6.2.2), and
may additionally be prescribed an ACE inhibitor
(see Chapter 5, Section 5.2.1), which has been shown to
improve survival in certain patient groups (e.g. those with
diabetes or heart failure).
6.5 Ischaemic heart disease: myocardial infarction (MI)
Myocardial infarction (MI; also called acute MI or AMI),
or heart attack, is caused by a thrombotic event in a
diseased coronary artery (see above) leading to a sudden
decrease in ow of blood. is is almost always initiated
by the rupture of an atherosclerotic plaque. It may have a
rapid onset and progression, leading to the death of
cardiac muscle cells, and so causing disordered
transmission of the electrical impulse around the heart
(see arrhythmias, Chapter 7), and disruption of
coordinated contraction. is can lead to a catastrophic
collapse of cardiac output, leading to sudden death
(Figure 6.10). A signicant number of patients die within a
short time of having an MI.
Sudden ischaemia
↓↓↓ATP, ↑Ca
Triggers
arrhythmias
Sudden
death
Ventricular
brillation
Cardiac
↓↓
output
Release of troponin into bloodstream
Figure 6.10 Sudden profound ischaemia leads to cell
death, myocardial infarction, and risk of sudden or
delayed death of the individual.
The ischaemic event normally occurs when rapid platelet plug
formation on a fragmenting coronary artery atheroma leads to a
thrombus-based sudden occlusion of the artery, shutting off the
oxygen supply to contracting heart muscles. Intracellular events
in these muscle cells (blue box) leads to cell death and the
subsequent life-threatening series of events. In addition, the
dead cells release intracellular contents, such as the musclespecific protein troponin, into the blood, providing a marker for
the prior occurrence of an MI.
↑Proteases
↑DNA fragmentation
→ Necrosis
→ Apoptosis
Myocardial
tissue death
Contractile
dysfunction
2+
In both angina and MI, ischaemia is brought about by
occlusion of coronary arteries. e distinction between
the two conditions is the irreversible nature of the
ischaemia in MI, with death (necrosis) of myocardial
tissue. As a result of cardiac myocytes dying, the
intracellular protein troponin is released into the blood.
is, then, acts as a marker for myocardial cell death. In
addition, the pattern of electrical activity in the heart is
altered, reected in changes in electrocardiography
(see Chapter 7); troponin levels combined with an
electrocardiogram (ECG) can therefore be used
diagnostically to distinguish between angina and
MI in a patient presenting with chest pain. e
characteristics of the ECG can reveal the extent of damage
caused by the ischaemic event, and so are used to
determine the immediate treatment of a patient
admitted with an MI. Two types of MI are distinguished
through ECG.
1. ST-segment Elevation MI (STEMI) represents the most
serious condition, occurring when a thrombus
completely occludes a coronary artery for a signicant
amount of time. is leads to death of heart muscle in
a large area of the myocardium, usually across the full
thickness of the ventricular wall. is is indicated on
the ECG by elevation of the ST segment (see Chapter 7
for more on ECGs). Patients who have suered a
STEMI require immediate thrombolysis and/or
surgical intervention.
2. Non-ST segment Elevation MI (NSTEMI) results from
a lesser level of myocardial ischaemia and necrosis
than STEMI; nevertheless it also represents a medical
emergency. NSTEMI is not treated with thrombolytics,
but patients may receive surgical intervention to
improve blood ow to the aected area.
e distinction between STEMI and NSTEMI is explored
further in Workbook 3.
Survivors of heart attacks have a patch of dead muscle in
the heart. As a result of this, and of the longer-term
formation of scar tissue, these individuals are liable to
long-term heart failure and arrhythmias (Chapter 7).
Importantly, they are also at increased risk of further
128 Chapter 6 Atherosclerosis and ischaemic heart disease
heart attack (secondary). In such patients, preventative
treatment is a more aggressive application of the drug
therapy described above for prevention and treatment of
angina, as the underlying processes are the same.
MI is a medical emergency best treated within cardiac
care units, with the intention of securing immediate and
long-term survival of the patient. Acute management of
such patients is a medical specialty, and with respect to
drugs includes nitrovasodilators to reduce cardiac work
and to relieve pain, thrombolysis with brinolytics, and
antiplatelet and anticoagulant drugs to reduce further
thrombus formation (see Chapter 4). Opiates may be
given for alleviation of pain, and anti-arrhythmia drugs to
Key references and suggested reading
Abrams JMD. Chronic stable angina. New Engl J Med 2005; 352:
2524–33.
Armitage J, Bowman L. Lipid-lowering treatment: today’s
recommended management. Prescriber 2009; 17(10): 33–44.
suppress or prevent arrhythmias (see Chapter 7).
Longer-term management to prevent a further MI
(secondary prevention) involves ACE inhibitors and
-adrenoceptor antagonists (Chapter 5) to reduce cardiac
work and the dysrhythmic eects of excessive
sympathetic stimulation. e aldosterone antagonist
eplerenone, has a role in patients with evidence of heart
failure, post MI. Statins and antiplatelet drugs, including
aspirin, are also given long term. As seen in the case of
Brian in Workbook 3, patients leaving hospital after
suering an MI are often taking a vast array of drugs, for
both control of symptoms and the secondary prevention
of cardiovascular events.
Fox K, Ford I, Steg PG, Tendera M, Ferrari R. Ivabradine for
patients with stable coronary artery disease and leftventricular systolic dysfunction (BEAUTIFUL): a
randomised, double-blind, placebo-controlled trial. Lancet
2008; 372: 807–16.
SUMMARY OF DRUGS USED FOR ISCHAEMIC HEART DISEASE
6.5 Ischaemic heart disease: myocardial infarction (MI) 129
Therapeutic
class
Inhibitors of
cholesterol
synthesis
Inhibitors of
cholesterol
absorption
Fibrates Bezafibrate
Nicotinic acid
group
-adrenoceptor
antagonists and
mixed 1 and
antagonists
Drugs Mechanism of action Common clinical uses Comments Common adverse drug
Statins e.g.
Simvastatin
Atorvastatin
Fluvastatin
Pravastatin
Rosuvastatin
Lovastatin
1. Anion
exchange resins
Colestyramine
Colesevelam
Colestipol
2. Ezetimibe Blocks cholesterol transporter in
Ciprofibrate
Fenofibrate
Gemfibrozil
Nicotinic acid
Acipimox
Propranolol
Atenolol
Bisoprolol
Metoprolol
Nebivolol
Carvedilol
Labetalol
Competitive inhibitors of rate-limiting
enzyme in cholesterol synthesis
Reduce TC and LDL-cholesterol by
decreasing hepatic cholesterol synthesis
and increasing LDL clearance
Prevent reabsorption of bile salts in
the intestine by producing an insoluble
complex that is excreted in the faeces
duodenum, reducing uptake of dietary
cholesterol
Stimulate activity of lipoprotein lipase,
reduce hepatic synthesis of VLDL and
enhance receptor-mediated clearance
of plasma LDL
Mechanism poorly understood
Increases HDL and reduces triglycerides
and LDL-cholesterol
Dyslipidaemia
Primary and secondary
ischaemic heart disease
prevention
Hypercholesterolaemia 1 month required to peak
Dyslipidaemia Adjunct therapy
Hypertriglyceridaemia
Dyslipidaemia (second-line)
Dyslipidaemia Very long elimination half-life
Angina (stable and
unstable)
Secondary prevention of MI
Simvastatin, lovastatin and
atorvastatin metabolized by
hepatic P450 enzymes leading
to interactions
effect
Can aggravate
hypertriglyceridaemia
Very long half-life of
19–30 h
Measurable effect on VLDL
takes 2–5 days, optimum after
4 weeks.
Not combined with statins
owing to increased risk of
serious muscle toxicity
Acipimox is less effective
See Drug summary table in Chapter 5 for adverse drug reactions
NB -adrenoceptor antagonists can worsen coronary vasospasm
and so are not used in variant angina
Not taken with verapamil as cardiodepressant effects combine
reactions
Muscle pain and weakness, can
be severe (rhabdomyolysis)
Mild transient GI symptoms
Headache
Insomnia
Dizziness
Elevated liver enzyme activities,
rarely jaundice and hepatitis
Constipation
Diarrhoea
Nausea
Vomiting
GI disturbance
Headache
Fatigue
Myalgia
GI disturbance
Anorexia
Muscle toxicity (myositis
and myalgia) can be severe
(rhabdomyolysis)
Flushing (very common)
Diarrhoea
Nausea
Vomiting
Rash
130 Chapter 6 Atherosclerosis and ischaemic heart disease
Therapeutic
class
If channel
blockers
Sodium
channel blocker
Nitrates Glyceryl trinitrate Releases nitric oxide, a potent
Drugs Mechanism of action Common
Ivabradine Inhibits If current, which contributes to
pacemaker potential, thereby slowing
heart rate
Ranolazine
Isosorbide
mononitrate
Isosorbide
dinitrate
Blocks late Na+ entry into cardiac
myocytes
Reduces Na+–Ca2+ exchange to
decrease intracellular Ca2+ concentration
and so decrease contractility
Additional actions unclear
vasodilator that acts through increased
cGMP levels to bring about relaxation of
vascular smooth muscle
clinical uses
Stable angina
Heart failure
Stable angina
(adjunct therapy)
Treatment of
acute angina
attack
Heart failure
Angina
prophylaxis
Heart failure
(adjunct therapy)
Comments Common adverse drug reactions
Metabolized by
hepatic P450
enzymes, leading
to interactions
Aerosol spray
and tablets used
sublingually
Tablets should be
discarded 8 weeks
after opening
Transdermal
patches also
available but
tolerance may
develop (see below)
Nitrate-free period
of 4–8 h required to
prevent tolerance
Luminous visual disturbances
Bradycardia
First-degree heart block
Headache
Dizziness
Dizziness
Constipation
Nausea
Vomiting
Headache
Headache
Postural hypotension
Flushing
Tachycardia
6.5 Ischaemic heart disease: myocardial infarction (MI) 131
Calcium
channel
blockers
Dihydropyridines:
e.g.
Amlodipine
See also Drug summary table in Chapter 5
Used in stable and variant angina
Felodipine
Nifedipine
Nondihydropyridines:
Verapamil
Diltiazem
Potassium
channel
activator
Nicorandil Combined nitrate action (vasodilatation)
and K+ channel activation
Increased K+ efflux hyperpolarizes cells
and reduces Ca2+ entry through voltagegated Ca2+ channels
Prophylaxis and
treatment of
stable angina
Treatment
commenced with
low dose to reduce
risk of headaches
Nausea
Vomiting
Rectal bleeding
Flushing
Tachycardia
Headache
Dizziness
ACE inhibitors Examples:
See Drug summary table in Chapter 5
Lisinopril
Ramipril
Captopril
Perindopril
Antiplatelet
drugs
ACE, angiotensin converting enzyme; cAMP, cyclic AMP; GI, gastrointestinal; HDL, high density lipoprotein; LDL, low density lipoprotein; MI, myocardial infarction; TC, total cholesterol; VLDL, very low density lipoprotein.
Aspirin
Clopidogrel
See Drug summary table in Chapter 4