Coronary Artery disease Flashcards
coronary artery diseases (CADs) can be symptomless, true or false
true
ACS(acute coronary syndromes) mostly have symptoms, true or false
true
typically chest pain or discomfort, shortness of breath, nausea, sweating, or dizziness
CADs normally present as?
athelerosclerosis
what is athelerosclerosis
it is a disease of the large and medium sized elastic and muscular arteries, usually affecting the intima and the media. Causes the buildup of fats, cholesterol and other substances in and on the artery walls
the intima is the innermost layer of the arteries, the media is the middle layer. the damage to the media is **secondary **
is the adventitia affected in athelerosclerosis
no it is generally uninvolved
it is the outermost layer of a blood vessel or organ
describe ATHEROSCLEROTIC LESIONS
note they are essentially the same as plaques
they are fibroinflammatory lipid plaques that occur over several decades, continually growing and encroaching the other layers of the arterial wall, thereby narrowing the lumen of the affected vessel
describe the stages of ATHEROSCLEROTIC plaque development
fatty streaks initially identified. note this may deteriorate(get worse) as the process advances .
the fatty streak is followed by the formation of an established plaque(aka intermediate lesion).
then there is a complicated plaque formation
Plaque rupture may occur after the fibrous cap has been weakened by the production of degradative enzymes, and reactive oxygen species, from the inflammatory cellular infiltrate
this exposes highly prothrombotic material, leading to formation of thrombus
this may then result in ACS
fatty streaks in the vessels are the earliest identifiable change in atherosclerosis
the intermediate lesion in ATHEROSCLEROTIC
PLAQUE DEVELOPMENT is characterised by?
characterised by the accumulation of increasing numbers of;
* macrophages
* foam cells
these are local chronic inflammatory infiltrates in CADs
the complicated plaque in ATHEROSCLEROTIC
PLAQUE DEVELOPMENT is characterised by?
smooth muscle cell migration
formation of;
a fibrous cap
a necrotic lipid core
an ever-lasting inflammatory infiltrate
the role of smooth cell migration in ATHEROSCLEROTIC
PLAQUE DEVELOPMENT
initially contributing to the expansion of atherosclerotic lesions by moving into the intima from the media layer of the artery wall, and later by forming a protective fibrous cap that stabilizes the plaque
some signs and symptoms of chronic CAD
asymptomatic in some cases
chest pain
shorteness of breath
heart attack
fatigue…etc
what is angina and how is it experienced ?
it is chest pain or discomfort that occurs when the heart doesn’t get enough blood
it is experienced as squeezing or pressure, or heaviness in the chest.
these signs also radiate and then localise to the shoulders, neck, jaw and back
what is the cause of angina pectoris
note this is the same as angina
it IS DUE TO
MYOCARDIAL OXYGEN DEMAND
EXCEEDING MYOCARDIAL OXYGEN
SUPPLY
state the types of angina
stable
unstable
variant
the most common type is stable angina
how do the various types of angina compare, especially stable and unstable
variant is quite rare
stable angina has a common pattern, occurs during exercise, and decreases at rest. it is also treatable
while
unstable angina has no pattern, is not relieved by rest/medicine , and is a prelude to heart attack. treatable
variant angina is rare, occurs at rest between midnight and early morning, and is relieved by medicine
stable and unstable angina not curable but both treatable
prelude means an action or event serving as an introduction to something more important.
risk factors of angina
Unhealthy eating
Physical inactivity
Smoking
Alcohol
Stress
High blood pressure
High cholesterol
Diabetes
Heart conditions
Inflammation
family history
the goal of treatment in chronic stable angina
To “restore” the balance between myocardial oxygen
supply (coronary blood flow) and myocardial oxygen
demand
what does restoring the balance between myocaridal oxygen supply and myocardial oxygen demand depend on?
the heart rate:The most significant factor, as increasing heart rate directly increases oxygen consumption.
contractility: Higher contractility leads to increased oxygen demand.
afterload(wall tension): Increased afterload, like high blood pressure, increases oxygen demand.
What does ᵦ-adrenoceptor stimulation in the heart do?
- Increased Heart Rate (Positive Chronotropy): β₁-receptor activation in the sinoatrial (SA) node increases firing rate, leading to tachycardia.
- Increased Contractility (Positive Inotropy): β₁-receptor stimulation enhances calcium influx into cardiomyocytes, leading to stronger myocardial contractions.
- Increased Conduction Velocity (Positive Dromotropy): β₁-receptors in the atrioventricular (AV) node increase conduction speed, reducing PR interval and improving impulse propagation.
what does the use of β-ADRENOCEPTOR ANTAGONISTS lead to
leads to decreased:
o heart rate (sinus rate)
o contraction
o conduction velocity through the AV node
o Leads to reduced myocardial oxygen demand
o May also increase coronary blood flow by
prolonging the diastolic filling time
delays the onset of angina
β-ADRENOCEPTOR ANTAGONISTS are used prophalactically, true or false?
are they used in the treatment of acute angina ?
means they are only used in the prevention of diseases
true
it is not used to treat acute angina
the role of beta blockers during exercise
decrease the peak heart rate during exercise
Dose of drug is calibrated to maintain the
* resting HR at approx 50 bpm
* peak HR during exercise ≈ 110-120 bpm
CCBs MoA
Decrease Ca2+ influx through voltage gated L-type Ca2+ channels. As a result, Intracellular Ca2+ conc decreases leads to reduced contraction of:
o cardiac myocytes
o vascular smooth muscle
why are CCBs effective especially in CAD
Effective because they:
o ↓ arteriolar pressure (afterload)
o ↓ myocardial O2 consumption
describe what afterload is in relation to the CV system
Afterload refers to the resistance the heart must work against to pump blood out of the ventricles. It is mainly determined by arterial pressure and vascular resistance.
Higher afterload = heart works harder to eject blood.
Lower afterload = less effort needed for blood ejection.
does a decrease in afterload mean a decrease in myocardial oxygen demand
yes
Afterload = The resistance the heart must overcome to pump blood out of the ventricles.
🔹 When afterload decreases (e.g., with vasodilation from CCBs), the heart pumps more easily → less strain → less O₂ needed.
CCBs are used prophalitically and to also treat acute angina, true or false
false
they are used prophalitically in CAD(including angina), but not to treat acute angina attacks. so they are used long-term to prevent angina
note CCBs are effective in the treatment of vasospastic angina
differences between dihydropyridines(amlodipine…etc) and non-dihydropyridines(Verapamil and diltiazem)
all CCBs
the main target for DHPs are the** vascular smooth muscles(eg arteries)** while that for NDHPs is the** heart** (Verapamil and diltiazem).
DHPs do not affect AV node conduction but NDHPs may affect it at higher doses
DHPs do not reduce cardiac contractility but NDHPs do
DHPs can increase heart rate due to causing vasodilation, which can lead to reflex tachycardia but NDHPs decrease heart rate by directly slowing conduction of the heart
Reflex tachycardia is a rapid heartbeat that occurs as a reflex response to a perceived drop in blood pressure or blood volume, or an unexpected change in blood flow, in an attempt to restore adequate blood flow and pressure.
main counselling points when prescrining CCBs
Excessive alcohol can enhance the BP-lowering effects of CCBs, leading to dizziness or fainting.
For patients on NDHPs, increasing fiber intake may help prevent constipation.
Avoid Grapefruit Juice (especially with certain CCBs like nifedipine and verapamil): It can increase the drug’s concentration in the body, raising the risk of side effects.
Inform patients that CCBs can interact with other medications, including beta-blockers, and drugs that affect heart rhythm or blood pressure.
** It’s important to take the medication regularly and not skip doses. If a dose is missed, usually take it as soon as remembered, unless it’s almost time for the next dose**
Avoid Stopping Abruptly: Non-DHPs (like verapamil and diltiazem) should not be stopped suddenly, as it can cause a rebound increase in heart rate or BP. Always consult a doctor first.
regularly monitor BP
Symptom Awareness: If they feel lightheaded, dizzy, or faint, especially when standing up quickly, they should inform their healthcare provider.
how does hydrazaline work
Acts on the IP3R receptor R on the sarcoplasmic reticulum (SR) preventing the release of calcium from the SR.
it has a direct vasodilator effect on the vessels
which drugs are considered the mainstay for angina treatment
If something is described as the mainstay of treatment for a disease, it means it is the most important, essential, or widely used therapy for managing that condition. It is the foundation or cornerstone of treatment, often providing the greatest benefit based on clinical evidence and guidelines.
organic nitrates
examples of organic nitrates used in angina treatment
glyceryl trinitrate (GTN), isosorbide dinitrate,
isosorbide mononitrate
how do organic nitrates work
they reduce myocardial oxygen demand by relaxing smooth muscles, including ateries and veins
what is the efficacy of organic nitrates depedent on
the underlying cause of the angina or other disease that it’s being used for
in atherosclerosis, the chief benefits of organic nitrates arise from their actions on coronary circulation, true or false?
false
chief benefit arises from
actions on peripheral
circulation (not on the
coronary circulation)
preload description
The load against which the heart must work.
it is a major contributor to the oxygen demands of the heart
the effects of nitrates in CAD
dilation of the venous capacitance vessels
coronary circulating nitrate oxides dilate predominantly the large epicardial arteries
resdistribution of blood to the subendocardial areas of the heart
The subendocardium is the innermost layer of the heart’s myocardium, located between the endocardium and the bulk of the heart muscle, and is particularly vulnerable to injury due to its location and the stresses it experiences.
there’s wayy more to this, so refer to CAD lecture slides to read more
nitric oxide can only dilate veins , true or false
false, NO can dilate both arteries and veins, but venous dilation predominates at therapeutic doses
Glyceryl nitrate is a prodrug, true or false
true
it is DENITRATED to produce active metabolite NO
has a half life of 3 mins
the active metabolite of Glyceryl nitrate
NO
what are longer acting glyceryl nitrates used for
in the treatment of angina. they are more useful in preventing angina attacks than reversing them once they have commenced
what enzyme does Glyceryl nitrate target
The target of glyceryl trinitrate (GTN) is guanylate cyclase, an enzyme found in vascular smooth muscle cells.
what does guanylate cyclase activation lead to
cGMP generation from GTP
cGMP causes cGMP dependent kinase (PKG) to become
activated, phosphorylating voltage gated ion channels on the sarcoplasmic reticulum (SR) reducing Ca2+
This stimulates the SR Ca2+ATPase, so increasing Ca2+
uptake into SR
Activation of myosin light chain (MLC) phosphatase → dephosphorylates MLC-P to MLC, preventing its binding to actin, which reduces muscle contraction
Allows dilation of blood vessels, so increasing blood flow.
myosin light chain= MLC
counselling points on nitrates
alert patient they may build tolerance to nitrates
common side effects may include, Arrhythmias; asthenia; cerebral ischaemia; dizziness; drowsiness; flushing; headache; hypotension; nausea; vomiting
caution in hepatic impairment and renal impairment
avoid abrupt withdrawal
Monitor blood pressure and heart rate during intravenous infusion
contraindicated in nitrate hypersensitivity
can patients build tolerance to nitrates
yes
in which patients does thiocynante accumulation occur in patients using/ on nitrates
In patients with kidney problems after prolonged
nitroprusside infusion
Nitroprusside is a direct acting vasodilator used to treat hypertension, to induce controlled hypotension to reduce postoperative bleeding, and to manage acute heart failure.
some side effects of thiocyanate
causes nausea, disorientation, psychosis and muscle
spasms
the function of PDE5 ( phosphodiesterase type 5)
an enzyme that breaks down cyclic guanosine monophosphate (cGMP) in smooth muscle cells
MoA of cGMP PDE5 INHIBITORS
they inhibit the breakdown of cGMP, leading to increase in cGMP levels in smooth muscle cells and other cells. This causes vasodilation, smooth muscle cell relaxation..etc
they prevent cGMP conversion to GMP
examples of cGMP phosphodiesterase inhibitor drugs
Sildenafil (Viagra)
o Tadalafil (Cialis)
o Vardenafil (Levitra)
are cGMP PDE5 inhibitors used in treating angina
no it is not
what is Ivabradine used for
Used to treat angina in patients in normal sinus rhythm.
it decreases “funny currents” - pacemaker currents in the sinoatrial node in a dose dependent manner.
Funny currents (If) are slow inward Na⁺ currents found in the sinoatrial (SA) node of the heart. They play a key role in spontaneous depolarization and pacemaker activity of cardiac cells.
main differences between cGMP and cAMP
cGMP: Made from GTP by guanylate cyclase, activated by nitric oxide (NO) or natriuretic peptides (ANP, BNP).
cGMP: ↓ Intracellular Ca²⁺ → smooth muscle relaxation.
cGMP: Broken down by phosphodiesterase-5 (PDE-5).
activates protein kinase G(PKG)
while
cAMP: Made from ATP by adenylate cyclase, activated by G-protein-coupled receptors (GPCRs) (e.g., β-adrenergic receptors).
cAMP: ↑ Intracellular Ca²⁺ → muscle contraction in some tissues (e.g., heart).
cAMP: Broken down by phosphodiesterase-3 (PDE-3) and PDE-4
activates PKA
what effect does ivabradine have on heart rate
does it have a negative ionotropic effect ?
it decreases heart rate
but it has no negative ionotropic effect
negative ionotropy= weakened force of contraction in the heart
MoA of nicorandil
works via two mechanisms, activating(opening) ATP-sensitive potassium channels, and the nitric oxide pathway. This Causes hyperpolarization.
it is used in both the treatment and prophalyxis of stable angina
some of the effects of nicorandil
vasodilation, i.e relazes coronary and peripheral arteries
it is cardioprotective as it limits the duration of the APs
nicorandil inhibits calcium channels, true or false
true
it prevents intracellular calcium overload by reducing calcium influx
ranolazine MoA
which condition is it used to treat
inhibiting the late phase of the inward sodium current (INa,L) in cardiac cells, reducing intracellular sodium and calcium overload, which in turn leads to decreased ventricular wall tension and oxygen demand, thus relieving angina. This improves the diastolic tone and coronary blood flow
**Diastolic tone: **During diastole, the heart muscle relaxes and the chambers fill with blood. However, in certain conditions, the heart muscle may not relax completely, leading to a persistent tension or “tone” in the heart chambers during diastole.
what would happen if there is an increase in late phase sodium influx into the cells
there would be a sodium overload in the cells, which would then lead to a calcium overload, causing issues like arrhythmias, decreased contractility…etc
MoA of Aliskiren
A direct renin inhibitor, binds to renin to prevent the production of angiotensn 1.
it may also be used to prevent the progression of athlerosclerosis
the differences between NSTEMI and STEMI
in NSTEMI there is ST elevation while there is none in STEMI
in NSTEMI the atherothrombosis causes partial obstruction to blood flow while it causes total obstruction in STEMI
so in STEMI there is no blood flow but there is REDUCED blood flow in NSTEMI
which biological marker helps distinguish between NSTEMI and unstable angina
elevated cardiac TROPONIN levels. elevated levels of these indicate cardiac damage. Troponin is a protein found in heart muscle cells, and its presence in the blood indicates damage to those cells.
note there are also elevated levels of troponin in STEMI
describe stenosis
refers to the abnormal narrowing of a passage or opening in the body, such as a blood vessel, valve, or canal
acute MI can lead to ?
Death of heart muscle due to a prolonged reduction in the supply of oxygenated blood, relative to demand (i.e.
ischemia), in the region served by an occluded coronary
artery
fibrosis or scarring of the cardiac muscle.
healing after MI involves ?
marked acute inflammation(w inflammatory cells clearing up debris from the dead cardiac cells )
granulation tissue formation(includes new vessels+ fibroblasts lay collagen)
fibrosis(scarring of the heart tissue): the area affected will lose it’s contractile ability, and become permanently non-functional
name some of the ways we treat acute MI
we restore the bloodflow using stents or fibrinolytic drugs(to break down the clots)
use of oxygen
use of agents to prevent blood clotting
Pain relief with intravenous morphine
beta blockers
percutaneuous coronary perfusion with stents keep the arteries open to allow for blood flow
angioplasty description
a minimally invasive procedure used to widen narrowed or blocked arteries, often to treat coronary artery disease, by using a balloon catheter to stretch the artery and, in many cases, inserting a stent to keep it open
MoA of fibrinolytics, and examples of them
Fibrinolytic drugs act as thrombolytics by activating plasminogen to form plasmin, which degrades fibrin and so breaks up thrombi. they directly break up clots
examples are;
streptokinase
o alteplase
o reteplase
o tenecteplase
how does fibrinolysis occur
plasminogen is converted to plasmin by TPA(tissue plasminogen activator) released from vascular endothelial cells
**plasmin(a proteolytic enzyme) dissolves fibrin **
which enzyme conerts fibrinogen tp fibrin
thrombin
name some;
1. fibrin-selective fibrinolytics
2. non fibrin selective fibrinolytics
1.Alteplase (rt-PA)
o Relteplase
o Recombinant prourokinase
- streptokinase
TPA(tissue plasminogen activator) function
activates plasminogen to plasmin, which breaks down fibrin and dissolves blood clots
streptokinase is a protease enzyme, true or false
false, not a protease and
has no enzymatic activity
MoA streptokinase
it acts as a fibrolytic agent, by forming a complex with plasminogen, indirectly activating it. This releases plasmin which breaks down fibrins
it binds equally to circulating and non-circulating plasminogen
when do we use eplerenone in the treatment of MI
used in patients with ventricular dysfunction and evidence of heart failure.
ACE inhibitors and angiotensin receptor antagonists are used in the treatment of acute MI, true or false
yes
ACE inhibitors are considered for all patients if MI, esp those with evidence of left ventricular ejection/ dysfunction
statins are used in the treatment of acute MI, true or false
true
describe the events of clotting after an injury
Injury will expose collagen underlying the endothelial cells.
Platelets bind to the collagen and vWF, thereby activating the platelets. they then change shape and form a monolayer(adhesion)
the activated platelets release ADP and TXA2, which further activates platelets
aggregation of platelets occur
the platelet aggregate becomes stabilised with fibrin, thereby forming a clot
Von Willebrand factor(vWF) is a factor important in clotting and it’s deficiency can lead to bleeding disosrders
some class drugs that fall under antiplatelet drugs
COX inhibitors (aspirin)
ADP antagonists akaThienopyridines(clopidogrel, prasugrel, ticlopidine)
Phosphodiesterase inhibitors (Dipyridamole)
GP IIb/IIa inhibitors (tirofaban, eptifibatide, abciximab)
