Angina Flashcards
Where does most infarct-causing occlusions occur?
small-to-medium plaques (“active plaques”)
how doesmost infarct-causing occlusions occur?
thrombosis
what happens if the endothelium covering of the plaque or the cell layer enclosing the necrotic core of the plaque disrupt?
<ul><li>thrombogenic materials such as collagen are presented to the bloodstream</li><li>causing platelet adhesion</li><li>fibrin deposition</li><li>thrombus formation</li><li>closure of the blood vessel</li></ul>
What doesAtherosclerosis encompass?
<ul><li>increased lipid deposition in the subendothelial space (early plaque)</li><li>endothelial dysfunction with decreased production of NO</li><li>less vasodilation and increased risk of platelet adhesion</li><li>influx of lipid scavenger cells (mainly macrophages)</li><li>necrosis</li><li>sterile inflammation</li><li>proliferation of smooth muscle cells</li><li>calcification and narrowing of the blood vessel by increasing plaque formation<br></br></li></ul>
what are theTriggering factors of Ischemia?
<ul><li>acute inflammation (e.g., influenza)</li><li>blood pressure peaks during physical exercise or emotional stress</li></ul>
thrombus formation is the result of?
balance between thrombosis and thrombolysis by the fibrinolytic system (plasminogen)
What determines the infarct size?
<ul><li>degree and the duration of coronary obstruction</li><li>thereby of the ischemia of downstream myocardium (and its size)<br></br></li></ul>
What are the important factors that determine the progress of CAD?
<ul><li>concentration of lipids in the blood</li><li>endothelial function</li><li>blood pressure (as a mechanical factor predisposing to plaque rupture)</li><li>the activity of the inflammatory system</li><li>the reactivity of pro- and antithrombotic systems<br></br></li></ul>
What is theprimary symptom of ischemic heart disease?
Angina pectoris
Angina pectoris is caused by?
transient episodes of myocardial ischemia that are due to an imbalance in the myocardial oxygen supply-demand relationship
Imbalance in the myocardial oxygen supply-demand relationship is caused by?
<ul><li>increase in myocardial oxygen demand<br></br></li><li>decrease in myocardial oxygen supply<br></br></li></ul>
An increase in myocardial oxygen demand is determined by?
<ul><li>heart rate</li><li>ventricular contractility</li><li>ventricular wall tension<br></br></li></ul>
A decrease in myocardial oxygen supply is caused by?
<ul><li>primarily determined by coronary blood flow</li><li>occasionally modified by the oxygen-carrying capacity of the blood</li></ul>
which is the most prevalent form of angina pectoris?
typical or stable angina
coronary thrombosis occurs in which form of angina?
Unstable angina or ACS (Acute Coronary Syndrome)
localized vasospasm occurs in which form of angina?
Variant or Prinzmetal angina
In which angina, the pathological substrate is usually fixed atherosclerotic narrowing of an epicardial coronary artery, on which exertion or emotional stress superimposes an increase in myocardial O2 demand?
typical stable angina
In which angina, focal or diffuse coronary vasospasm episodically reduces coronary flow?
variant angina
In which angina, rupture of an atherosclerotic plaque, with consequent platelet adhesion and aggregation, decreases coronary blood flow?
unstable angina
Myocardial ischemia also may be {{c1::silent}}, with electrocardiographic, echocardiographic, or radionuclide evidence of ischemia appearing in the absence of symptoms.
silent
What is the principal therapeutic goal in ACSs with unstable angina?
<ul><li>prevent or reduce coronary thrombus formation</li><li>increase myocardial blood flow</li></ul>
The principal therapeutic aim in variant or Prinzmetal angina is to
prevent coronary vasospasm
In patients with typical exercise-induced angina on the basis of CAD, these antianginal agents improve the balance of myocardial O2 supply and O2 demand principally by
reducing myocardial O2 demand by <br></br><ul><li>decreasing heart rate</li><li>myocardial contractility</li><li>ventricular wall stress</li></ul>
What is the major effect of nitrovasodilators and Ca2+ channel blockers in variant angina?
Increased O2 supply by dilating the coronary vasculature
What medication is used routinely in patients with myocardial ischemia?
Aspirin
The optimal dose of Aspirin appears to be between {{c1::75}} and {{c1::150}} mg/d, although most large studies have been done with a {{c2::325}}-mg dose.
75<br></br>150<br></br>325
What medication is advised only as an alternative in patients with aspirin intolerance and advise against the routine use of dual platelet inhibition in patients with stable disease?
Clopidogrel
ACEIs or angiotensin receptor blockers are recommended for subgroups of patients with CAD with
<ul><li>reduced left ventricular systolic function</li><li>hypertension</li><li>diabetes</li><li>chronic kidney disease<br></br></li></ul>
{{c1::Statins}} reduce mortality in patients with CAD.
Statins
The organic nitrate agents are prodrugs that are sources of {{c1::NO}}
NO
NO activates the soluble isoform of {{c1::guanylyl cyclase}}, thereby {{c1::increasing}} intracellular levels of {{c1::cGMP}}
guanylyl cyclase<br></br>increasing<br></br>cGMP
cGMP promotes the {{c1::dephosphorylation}} of the {{c1::myosin light chain}} and the {{c1::reduction}} of {{c1::cytosolic Ca2+}} and leads to the {{c1::relaxation}}of {{c1::smooth muscle cells}}in a broad range of tissues
dephosphorylation<br></br>myosin light chain<br></br>reduction<br></br>cytosolic Ca2+<br></br>relaxation<br></br>smooth muscle cells
The NO-dependent relaxation of vascular smooth muscle leads to {{c1::vasodilation}}
vasodilation
NO-mediated guanylyl cyclase activation also {{c1::inhibits}} {{c2::platelet aggregation}} and {{c1::relaxes}} smooth muscle in the {{c2::bronchi and GIT}}.
inhibits <br></br>platelet aggregation<br></br>relaxes<br></br>bronchi and GIT
What are three distinct mammalian NOS isoforms?
nNOS, eNOS, and iNOS
What processes are the NOS isoforms involved in?
<ul><li>neurotransmission</li><li>vasomotion</li><li>immunomodulation</li></ul>
NO gas also may be administered by {{c1::inhalation}}
inhalation
The NO-stimulated elevation of cGMP {{c1::activates}} {{c3::PKG}} and modulates the activities of {{c2::cyclic nucleotide PDEs (PDEs 2, 3, and 5)}} in a variety of cell types.
activates <br></br>PKG <br></br>cyclic nucleotide PDEs (PDEs 2, 3, and 5)
{{c1::Reduced}} phosphorylation of myosin light chain is the result of {{c2::decreased}} myosin light-chain kinase activity and {{c2::increased}} myosin light-chain phosphatase activity and promotes {{c3::vasorelaxation}} and smooth muscle {{c3::relaxation}} in many tissues.
Reduced<br></br>decreased<br></br>increased<br></br>vasorelaxation<br></br>relaxation
{{c1::cGMP}} is a substrate for {{c2::PDE 5}}, whose {{c3::inhibition}} by {{c3::sildenafil}} and related compounds potentiates the action of nitrovasodilators
cGMP<br></br>PDE 5<br></br>inhibition<br></br>sildenafil
what happens at low doses of Nitrates?
<ul><li>dilate veins and conductance arteries </li><li>leave the tone of the small-to-medium arterioles (that regulate resistance) unaffected</li></ul>
What happens at low-to-medium doses of nitrates?
<ul><li>venodilation decreases venous return</li><li>leading to a fall in left and right ventricular chamber size and end-diastolic pressures</li><li>reduced wall stress</li><li>thereby reduced cardiac O2 demand</li></ul>
{{c1::Systemic vascular resistance}} and {{c1::arterial pressure}} are not or only mildly decreased, leaving coronary perfusion pressure unaffected.
Systemic vascular resistance<br></br>arterial pressure
Heart rate remains {{c1::unchanged}} or may {{c1::increase}} slightly in response to a decrease in blood pressure.
unchanged <br></br>increase
What remains unchanged or may increase slightly in response to a decrease in blood pressure?
Heart rate
Doses of nitroglycerine that do not alter systemic arterial pressure may still produce {{c1::arteriolar dilation}} in the face and neck, resulting in a facial flush, or dilation of meningeal arterial vessels, causing headache.
arteriolar dilation
Doses of GTN (Nitroglycerine) that do not alter systemic arterial pressure may still produce arteriolar dilation in the face and neck, results in?
<ul><li>facial flush</li><li>dilation of meningeal arterial vessels</li><li>causing headache</li></ul>
What does Higher doses of organic nitrates cause?
<ul><li>venous pooling </li><li>decrease arteriolar resistance</li><li>decrease systolic and diastolic blood pressure<br></br></li><li>pallor, weakness, dizziness, and activation of compensatory sympathetic reflexes<br></br></li></ul>
Higher doses of organic nitrates can compromise what?
coronary flow
In Higher doses of organic nitrates,the sympathetic increase in myocardial O2 demand leads to?
ischemia
Sublingual nitroglycerin administration may produce {{c1::bradycardia}} and {{c1::hypotension}}, probably owing to activation of the Bezold-Jarisch reflex.
bradycardia<br></br>hypotension
What causes Bezold-Jarisch reflex?
sublingual nitroglycerin administration
What is tolerance?
Frequently repeated or continuous exposure to high doses of nitrovasodilators lead to tolerance, that is, marked attenuation in the magnitude of most of their pharmacological effects.
Monday disease occurs due to
prolonged exposure with nitrates
Due to Monday disease, there is an increase in the incidence of ACSs during the {{c1::24}} to {{c1::72}} h periods away from the work environment.
24<br></br>72
Due to Monday disease, workers may experience
<ul><li>severe headaches</li><li>dizziness</li><li>postural weakness</li></ul>
High doses of nitrates should be avoided and therapy interrupted for {{c1::8–12}} h daily, which allows the return of efficacy.
8–12
In patients with {{c1::exertional angina}}, it is usually most convenient to omit dosing at {{c1::night}} either by adjusting dosing intervals of oral or buccal preparations or by removing cutaneous GTN
exertional angina<br></br>night
Patients whose anginal pattern suggests its precipitation by increased left ventricular filling pressures (e.g., in association with orthopnea or paroxysmal nocturnal dyspnea) may benefit from continuing nitrates at {{c1::night}} and omitting them during a quiet period of the {{c1::day}}.
night<br></br>day
TOXICITY OF NITRATES
<ul><li>Headache<br></br></li><li>dizziness</li><li>weakness</li><li>postural hypotension<br></br></li><li>occasionally progress to loss of consciousness<br></br></li><li>seen in patients with autonomic dysfunction<br></br></li></ul>
Coomon drugs for Erectile dysfunction
sildenafil and other PDE5 inhibitors with organic nitrate vasodilators
In Erectile dysfunction, antianginal therapy can cause
extreme hypotension
Cells in the {{c1::corpus cavernosum}} produce NO during sexual arousal in response to nonadrenergic, noncholinergic neurotransmission
corpus cavernosum
What drugs inhibit PDE5 and have been demonstrated to improve erectile function in patients with erectile dysfunction?
<ul><li>Sildenafil</li><li>Tadalafil</li><li>Vardenafil</li></ul>
PDE5 inhibitors are contraindicated for patients taking {{c1::organic nitrate vasodilators}}, and the PDE5 inhibitors should be used with caution in patients taking {{c2::α- or β blockers}}.
organic nitrate vasodilators<br></br>α- or β blockers
PDE5 inhibitors and nitrates act synergistically to cause profound {{c1::increases}} in cGMP and dramatic {{c2::reductions}} in blood pressure ({{c2::>25}} mm Hg)
increases<br></br>reductions<br></br>(>25 mm Hg)
PDE5 inhibitor should NOT be used in the {{c1::24}} h prior to initiating nitrate therapy
24
Sildenafil, tadalafil, and vardenafil are metabolized via {{c1::CYP3A4}}
CYP3A4
Short-Acting Nitrates
<ul><li>GTN/NITROGLYCERINE (onset of action is within 1–2 min)</li><li>ISDN (onset of action: 3–4 min)<br></br></li></ul>
FIRST CHOICE OF DRUG against anginal episodes in patients who have more than occasional angina
β blockers
DRUGS FOR Variant (Prinzmetal) Angina
<ol><li>Ca2+ channel blockers (1st line drugs)<br></br></li><li>Long-acting nitrates<br></br></li></ol>
In which angina, Nitrates are considered assecond-line drugs?
Unstable Angina Pectoris
DRUGS FOR Unstable Angina
Ca2+ channel blockers
TYPE OF Voltage-gated Ca2+ channels mediate the entry of extracellular Ca2+ into smooth muscle and cardiac myocytes and SA and AV nodal cells in response to electrical depolarization.
L-type or slow channels
In vascular smooth muscle, {{c1::INHIBTION}} of {{c1::CALCIUM INFLUX}} leads to {{c1::relaxation}}, especially in arterial beds, in cardiac myocytes to {{c2::negative}} inotropic effects.
INHIBTION<br></br>CALCIUM INFLUX<br></br>relaxation<br></br>negative
Ca2+ channel blockers DRUGS
phenylalkylamine: verapamil
benzothiazepine: diltiazem
dihydropyridines:amlodipin,clevidipine,
felodipine, isradipine, lercanidine
Ca2+ is a trigger for
contraction
In contrast to cardiac muscle, smooth muscles typically contract {{c1::tonically}}
tonically
The Ca2+ channel blockers produce their effects by binding to the {{c1::α1}} subunit of the L-type voltage-gated Ca2+ channels and reducing Ca2+ flux through the channel.
α1
Only the {{c1::L-type}} channel is sensitive to the dihydropyridine Ca2+ channel blockers.
L-type
Voltage-gated Ca2+ channels subtypes are?
<ul><li>L</li><li>N</li><li>T</li></ul>
IN CARDIAC CELLS,Ca2+ channel blockers {{c1::reduce}} the peak size of the systolic Ca2+ transient and thereby produce a {{c1::negative}} inotropic effect
reduce<br></br>negative
the greater degree of peripheral vasodilation seen with the {{c1::dihydropyridines}} is accompanied by a baroreceptor reflex–mediated increase in sympathetic tone sufficient to overcome the negative inotropic effect.
dihydropyridines
WHAT DRUG reduces the slow inward current in a dose-dependent manner, it does not affect the rate of recovery of the slow Ca2+ channel?
Nifedipine
nifedipine has clear {{c1::negative}} chronotropic effects in isolated preparations
negative
WHAT DRUG stimulates the heart indirectly by eliciting reflex sympathetic activation in response to a lowering of blood pressure?
Nifedipine
WHAT DRUG reduces the magnitude of the Ca2+ current through the slow channel, also decreases the rate of recovery of the channel?
Verapamil
WHAT DRUG inhibits fast Na+ and repolarizing K+ currents?
Verapamil
{{c1::Verapamil}} and {{c1::diltiazem}} depress the rate of the sinus node pacemaker and slow AV conduction
Verapamil<br></br>diltiazem
WHICH DRUG shows a phenomenon known as frequency dependence or use dependence (channel blockade is enhanced as the frequency of stimulation increases)?
Verapamil
Ca2+ channel blockers show {{c1::first-pass metabolism}}by {{c1::CYP3A4}} enzymes in the intestinal epithelium and the liver.
first-pass metabolism<br></br>CYP3A4
What is a common side effect of verapamil?
Constipation
TOXICITY OF CA CHANNEL BLOCKERS
<ul><li>PULMONARY EDEMA</li><li>gastroesophageal reflux<br></br></li><li>Constipation: Verapamil<br></br></li><li>Urinary retention: rare<br></br></li><li>rash and elevations of liver enzymes: uncommon<br></br></li><li>headache, flushing, and dizziness: Nifedipine<br></br></li></ul>
verapamil and diltiazem are used as antiarrhythmic agents in
supraventricular tachyarrhythmias
Ca2+ channel blockers are contraindicated in patients with
heart failure with reduced ejection fraction
which drugimproves left ventricular outflow obstruction and symptoms in patients with HCM (Hypertrophic Cardiomyopathy)?
Verapamil
WHICH DRUG is used in patients with neurological deficits secondary to cerebral vasospasm after the rupture of a congenital intracranial aneurysm?
Nimodipine
Nimodipine has been approved for use in patients with {{c1::neurological deficits}} secondary to {{c1::cerebral vasospasm}} after the rupture of a {{c2::congenital intracranial aneurysm}}
neurological deficits<br></br>cerebral vasospasm<br></br>congenital intracranial aneurysm
DRUGS used in Raynaud disease
<ul><li>Nifedipine</li><li>diltiazem</li><li>amlodipine</li><li>felodipine</li></ul>
WHAT DRUG causes relaxation of the myometrium in vitro?
Nifedipine
DRUG used in reducing preterm uterine contractions in preterm labor
Nifedipine
only drug class that is effective in reducing the severity and frequency of attacks of exertional angina and in improving survival in patients who have had an MI
β blockers
firstline treatment of patients with stable CAD andunstable angina/ACS
β blockers
DRUG showing reverse steal or Robin Hood phenomenon
β blockers
What is reverse steal or Robin Hood phenomenon?
An increased blood flow toward ischemic regions by increasing coronary collateral resistance and preventing blood from being shunted away from the ischemic myocardium during maximal coronary vasodilation
WHAT DRUG shows steal phenomenon?
Nitrates
What is steal phenomenon?
Dilating the relatively constricted arterioles of the healthy myocardium, leading to redistribution of blood flow away from the ischemic myocardium
the net effect of β blockade usually is to
decrease myocardial O2 consumption
Standard drugs for the treatment of angina are
<ul><li>β1 -selective</li><li>those without intrinsic sympathomimetic activity</li></ul>
β1 -selective drugs are
<ul><li>atenolol</li><li>bisoprolol</li><li>metoprolol</li></ul>
The decrease in myocardial O2 consumption is due to a {{c1::negative}} chronotropic effect (particularly during exercise), a {{c1::negative}}inotropic effect, and a {{c1::reduction}} in arterial blood pressure (particularly systolic pressure) during exercise.
negative<br></br>negative<br></br>reduction
DRUGS represent the cornerstone of therapy for ACS
Antiplatelet agents
