Angina

Question 1

Where does most infarct-causing occlusions occur?

Answer 1

small-to-medium plaques (“active plaques”)

Question 2

how doesmost infarct-causing occlusions occur?

Answer 2

thrombosis

Question 3

what happens if the endothelium covering of the plaque or the cell layer enclosing the necrotic core of the plaque disrupt?

Answer 3

<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>

Question 4

What doesAtherosclerosis encompass?

Answer 4

<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>

Question 5

what are theTriggering factors of Ischemia?

Answer 5

<ul><li>acute inflammation (e.g., influenza)</li><li>blood pressure peaks during physical exercise or emotional stress</li></ul>

Question 6

thrombus formation is the result of?

Answer 6

balance between thrombosis and thrombolysis by the fibrinolytic system (plasminogen)

Question 7

What determines the infarct size?

Answer 7

<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>

Question 8

What are the important factors that determine the progress of CAD?

Answer 8

<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>

Question 9

What is theprimary symptom of ischemic heart disease?

Answer 9

Angina pectoris

Question 10

Angina pectoris is caused by?

Answer 10

transient episodes of myocardial ischemia that are due to an imbalance in the myocardial oxygen supply-demand relationship

Question 11

Imbalance in the myocardial oxygen supply-demand relationship is caused by?

Answer 11

<ul><li>increase in myocardial oxygen demand<br></br></li><li>decrease in myocardial oxygen supply<br></br></li></ul>

Question 12

An increase in myocardial oxygen demand is determined by?

Answer 12

<ul><li>heart rate</li><li>ventricular contractility</li><li>ventricular wall tension<br></br></li></ul>

Question 13

A decrease in myocardial oxygen supply is caused by?

Answer 13

<ul><li>primarily determined by coronary blood flow</li><li>occasionally modified by the oxygen-carrying capacity of the blood</li></ul>

Question 14

which is the most prevalent form of angina pectoris?

Answer 14

typical or stable angina

Question 15

coronary thrombosis occurs in which form of angina?

Answer 15

Unstable angina or ACS (Acute Coronary Syndrome)

Question 16

localized vasospasm occurs in which form of angina?

Answer 16

Variant or Prinzmetal angina

Question 17

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?

Answer 17

typical stable angina

Question 18

In which angina, focal or diffuse coronary vasospasm episodically reduces coronary flow?

Answer 18

variant angina

Question 19

In which angina, rupture of an atherosclerotic plaque, with consequent platelet adhesion and aggregation, decreases coronary blood flow?

Answer 19

unstable angina

Question 20

Myocardial ischemia also may be {{c1::silent}}, with electrocardiographic, echocardiographic, or radionuclide evidence of ischemia appearing in the absence of symptoms.

Answer 20

silent

Question 21

What is the principal therapeutic goal in ACSs with unstable angina?

Answer 21

<ul><li>prevent or reduce coronary thrombus formation</li><li>increase myocardial blood flow</li></ul>

Question 22

The principal therapeutic aim in variant or Prinzmetal angina is to

Answer 22

prevent coronary vasospasm

Question 23

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

Answer 23

reducing myocardial O2 demand by <br></br><ul><li>decreasing heart rate</li><li>myocardial contractility</li><li>ventricular wall stress</li></ul>

Question 24

What is the major effect of nitrovasodilators and Ca2+ channel blockers in variant angina?

Answer 24

Increased O2 supply by dilating the coronary vasculature

Question 25

What medication is used routinely in patients with myocardial ischemia?

Answer 25

Aspirin

Question 26

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.

Answer 26

75 
150 
325

Question 27

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?

Answer 27

Clopidogrel

Question 28

ACEIs or angiotensin receptor blockers are recommended for subgroups of patients with CAD with

Answer 28

• reduced left ventricular systolic function
• hypertension
• diabetes
• chronic kidney disease
  

Question 29

{{c1::Statins}} reduce mortality in patients with CAD.

Answer 29

Statins

Question 30

The organic nitrate agents are prodrugs that are sources of {{c1::NO}}

Answer 30

NO

Question 31

NO activates the soluble isoform of {{c1::guanylyl cyclase}}, thereby {{c1::increasing}} intracellular levels of {{c1::cGMP}}

Answer 31

guanylyl cyclase
increasing
cGMP

Question 32

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

Answer 32

dephosphorylation
myosin light chain
reduction
cytosolic Ca2+
relaxation
smooth muscle cells

Question 33

The NO-dependent relaxation of vascular smooth muscle leads to {{c1::vasodilation}}

Answer 33

vasodilation

Question 34

NO-mediated guanylyl cyclase activation also {{c1::inhibits}} {{c2::platelet aggregation}} and {{c1::relaxes}} smooth muscle in the {{c2::bronchi and GIT}}.

Answer 34

inhibits
platelet aggregation
relaxes
bronchi and GIT

Question 35

What are three distinct mammalian NOS isoforms?

Answer 35

 nNOS, eNOS, and iNOS

Question 36

What processes are the NOS isoforms involved in?

Answer 36

• neurotransmission
• vasomotion
• immunomodulation

Question 37

NO gas also may be administered by {{c1::inhalation}}

Answer 37

inhalation

Question 38

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.

Answer 38

activates
PKG
cyclic nucleotide PDEs (PDEs 2, 3, and 5)

Question 39

{{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.

Answer 39

Reduced
decreased
increased
vasorelaxation
relaxation

Question 40

{{c1::cGMP}} is a substrate for {{c2::PDE 5}}, whose {{c3::inhibition}} by {{c3::sildenafil}} and related compounds potentiates the action of nitrovasodilators

Answer 40

cGMP
PDE 5
inhibition
sildenafil

Question 41

what happens at low doses of Nitrates?

Answer 41

• dilate veins and conductance arteries
• leave the tone of the small-to-medium arterioles (that regulate resistance) unaffected

Question 42

What happens at low-to-medium doses of nitrates?

Answer 42

• venodilation decreases venous return
• leading to a fall in left and right ventricular chamber size and end-diastolic pressures
• reduced wall stress
• thereby reduced cardiac O2 demand

Question 43

{{c1::Systemic vascular resistance}} and {{c1::arterial pressure}} are not or only mildly decreased, leaving coronary perfusion pressure unaffected.

Answer 43

Systemic vascular resistance
arterial pressure

Question 44

Heart rate remains {{c1::unchanged}} or may {{c1::increase}} slightly in response to a decrease in blood pressure.

Answer 44

unchanged
increase

Question 45

What remains unchanged or may increase slightly in response to a decrease in blood pressure?

Answer 45

Heart rate

Question 46

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.

Answer 46

arteriolar dilation

Question 47

Doses of GTN (Nitroglycerine) that do not alter systemic arterial pressure may still produce arteriolar dilation in the face and neck, results in?

Answer 47

• facial flush
• dilation of meningeal arterial vessels
• causing headache

Question 48

What does Higher doses of organic nitrates cause?

Answer 48

• venous pooling
• decrease arteriolar resistance
• decrease systolic and diastolic blood pressure
  
• pallor, weakness, dizziness, and activation of compensatory sympathetic reflexes
  

Question 49

Higher doses of organic nitrates can compromise what?

Answer 49

coronary flow 

Question 50

In Higher doses of organic nitrates, the sympathetic increase in myocardial O2 demand leads to?

Answer 50

ischemia

Question 51

Sublingual nitroglycerin administration may produce {{c1::bradycardia}} and {{c1::hypotension}}, probably owing to activation of the Bezold-Jarisch reflex.

Answer 51

bradycardia 
hypotension

Question 52

What causes Bezold-Jarisch reflex?

Answer 52

sublingual nitroglycerin administration

Question 53

What is tolerance?

Answer 53

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.

Question 54

Monday disease occurs due to

Answer 54

prolonged exposure with nitrates

Question 55

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.

Answer 55

24
72

Question 56

Due to Monday disease, workers may experience

Answer 56

• severe headaches
• dizziness
• postural weakness

Question 57

High doses of nitrates should be avoided and therapy interrupted for {{c1::8–12}} h daily, which allows the return of efficacy.

Answer 57

8–12

Question 58

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

Answer 58

exertional angina
night 

Question 59

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}}.

Answer 59

night
day

Question 60

TOXICITY OF NITRATES

Answer 60

• Headache
  
• dizziness
• weakness
• postural hypotension
  
• occasionally progress to loss of consciousness
  
• seen in patients with autonomic dysfunction
  

Question 61

Coomon drugs for Erectile dysfunction 

Answer 61

sildenafil and other PDE5 inhibitors with organic nitrate vasodilators

Question 62

In Erectile dysfunction, antianginal therapy can cause 

Answer 62

extreme hypotension

Question 63

Cells in the {{c1::corpus cavernosum}} produce NO during sexual arousal in response to nonadrenergic, noncholinergic neurotransmission

Answer 63

corpus cavernosum

Question 64

What drugs inhibit PDE5 and have been demonstrated to improve erectile function in patients with erectile dysfunction?

Answer 64

• Sildenafil
• Tadalafil
• Vardenafil

Question 65

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}}.

Answer 65

organic nitrate vasodilators
α- or β blockers

Question 66

PDE5 inhibitors and nitrates act synergistically to cause profound {{c1::increases}} in cGMP and dramatic {{c2::reductions}} in blood pressure ({{c2::>25}} mm Hg)

Answer 66

increases
reductions
(>25 mm Hg)

Question 67

PDE5 inhibitor should NOT be used in the {{c1::24}} h prior to initiating nitrate therapy

Answer 67

24

Question 68

Sildenafil, tadalafil, and vardenafil are metabolized via {{c1::CYP3A4}}

Answer 68

CYP3A4

Question 69

Short-Acting Nitrates

Answer 69

• GTN/NITROGLYCERINE (onset of action is within 1–2 min)
• ISDN (onset of action: 3–4 min)
  

Question 70

FIRST CHOICE OF DRUG against anginal episodes in patients who have more than occasional angina

Answer 70

β blockers

Question 71

DRUGS FOR Variant (Prinzmetal) Angina

Answer 71

1. Ca2+ channel blockers (1st line drugs)
   
2. Long-acting nitrates
   

Question 72

In which angina, Nitrates are considered as second-line drugs?

Answer 72

Unstable Angina Pectoris

Question 73

DRUGS FOR Unstable Angina

Answer 73

Ca2+ channel blockers

Question 74

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.

Answer 74

L-type or slow channels

Question 75

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.

Answer 75

INHIBTION
CALCIUM INFLUX
relaxation
negative

Question 76

Ca2+ channel blockers DRUGS

Answer 76

phenylalkylamine: verapamil benzothiazepine: diltiazem dihydropyridines:amlodipin,clevidipine, felodipine, isradipine, lercanidine

Question 77

Ca2+ is a trigger for 

Answer 77

contraction

Question 78

In contrast to cardiac muscle, smooth muscles typically contract {{c1::tonically}}

Answer 78

tonically

Question 79

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.

Answer 79

α1 

Question 80

Only the {{c1::L-type}} channel is sensitive to the dihydropyridine Ca2+ channel blockers.

Answer 80

L-type 

Question 81

Voltage-gated Ca2+ channels subtypes are?

Answer 81

• L 
• N
• T 

Question 82

IN CARDIAC CELLS, Ca2+ channel blockers {{c1::reduce}} the peak size of the systolic Ca2+ transient and thereby produce a {{c1::negative}} inotropic effect

Answer 82

reduce
negative

Question 83

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.

Answer 83

dihydropyridines

Question 84

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?

Answer 84

Nifedipine

Question 85

nifedipine has clear {{c1::negative}} chronotropic effects in isolated preparations

Answer 85

negative 

Question 86

WHAT DRUG stimulates the heart indirectly by eliciting reflex sympathetic activation in response to a lowering of blood pressure?

Answer 86

Nifedipine

Question 87

WHAT DRUG reduces the magnitude of the Ca2+ current through the slow channel, also decreases the rate of recovery of the channel?

Answer 87

Verapamil 

Question 88

WHAT DRUG inhibits fast Na+ and repolarizing K+ currents?

Answer 88

Verapamil

Question 89

{{c1::Verapamil}} and {{c1::diltiazem}} depress the rate of the sinus node pacemaker and slow AV conduction

Answer 89

Verapamil 
diltiazem

Question 90

WHICH DRUG shows a phenomenon known as frequency dependence or use dependence (channel blockade is enhanced as the frequency of stimulation increases)?

Answer 90

Verapamil

Question 91

Ca2+ channel blockers show {{c1::first-pass metabolism}} by {{c1::CYP3A4}} enzymes in the intestinal epithelium and the liver.

Answer 91

first-pass metabolism
CYP3A4 

Question 92

What is a common side effect of verapamil?

Answer 92

Constipation

Question 93

TOXICITY OF CA CHANNEL BLOCKERS

Answer 93

• PULMONARY EDEMA
• gastroesophageal reflux
  
• Constipation: Verapamil
  
• Urinary retention: rare
  
• rash and elevations of liver enzymes: uncommon
  
• headache, flushing, and dizziness: Nifedipine
  

Question 94

verapamil and diltiazem are used as antiarrhythmic agents in

Answer 94

supraventricular tachyarrhythmias

Question 95

Ca2+ channel blockers are contraindicated in patients with

Answer 95

heart failure with reduced ejection fraction

Question 96

which drug improves left ventricular outflow obstruction and symptoms in patients with HCM (Hypertrophic Cardiomyopathy)?

Answer 96

Verapamil

Question 97

WHICH DRUG is used in patients with neurological deficits secondary to cerebral vasospasm after the rupture of a congenital intracranial aneurysm?

Answer 97

Nimodipine

Question 98

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}}

Answer 98

neurological deficits
cerebral vasospasm
congenital intracranial aneurysm

Question 99

DRUGS used in Raynaud disease

Answer 99

• Nifedipine
• diltiazem
• amlodipine
• felodipine

Question 100

WHAT DRUG causes relaxation of the myometrium in vitro?

Answer 100

Nifedipine

Question 101

DRUG used in reducing preterm uterine contractions in preterm labor

Answer 101

Nifedipine

Question 102

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

Answer 102

β blockers

Question 103

firstline treatment of patients with stable CAD and unstable angina/ACS

Answer 103

β blockers

Question 104

DRUG showing reverse steal or Robin Hood phenomenon

Answer 104

β blockers

Question 105

What is reverse steal or Robin Hood phenomenon?

Answer 105

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

Question 106

WHAT DRUG shows steal phenomenon?

Answer 106

Nitrates

Question 107

What is steal phenomenon?

Answer 107

Dilating the relatively constricted arterioles of the healthy myocardium, leading to redistribution of blood flow away from the ischemic myocardium

Question 108

the net effect of β blockade usually is to 

Answer 108

decrease myocardial O2 consumption

Question 109

Standard drugs for the treatment of angina are 

Answer 109

• β1 -selective
• those without intrinsic sympathomimetic activity

Question 110

β1 -selective drugs are

Answer 110

• atenolol
• bisoprolol
• metoprolol

Question 111

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.

Answer 111

negative 
negative 
reduction

Question 112

DRUGS represent the cornerstone of therapy for ACS

Answer 112

Antiplatelet agents

Question 113

Which drug inhibits platelet aggregation by irreversibly inactivating the thromboxane-synthesizing COX-1 in platelets, thereby reducing production of TxA2?

Answer 113

Aspirin

Question 114

Antiplatelet agents interfere either which two signaling pathways?

Answer 114

1. TxA2
2. ADP

Question 115

Antiplatelet agents interfere either with two signaling pathways (TxA2 and ADP) that cooperatively {{c1::promote}} platelet aggregation in an auto- and paracrine manner or with a major common pathway of platelet aggregation, the {{c1::GpIIb/IIIa}} fibrinogen receptor.

Answer 115

promote
GpIIb/IIIa

Question 116

Drugs which are ADP receptor (P2Y12 receptor) antagonists that block the proaggregatory effect of ADP

Answer 116

thienopyridines

Question 117

Nonemergency major noncardiac surgeries should therefore be postponed for {{c1::5}} ({{c2::ticagrelor, clopidogrel}}) or {{c1::7}} days ({{c2::prasugrel, aspirin}}) after intake of the last dose of Antiplatelet agents

Answer 117

5 or 7 days
ticagrelor, clopidogrel
prasugrel, aspirin

Question 118

What drugs directed against the platelet integrin GPIIb/IIIa (including abciximab, tirofiban, and eptifibatide) are highly effective by blocking the final effector pathway of platelet aggregation?

Answer 118

Anti-integrin agents

Question 119

Anti-integrin agents directed against the platelet integrin {{c1::GPIIb/IIIa}} (including abciximab, tirofiban, and eptifibatide) are highly effective by {{c1::blocking}} the final effector pathway of platelet aggregation

Answer 119

GPIIb/IIIa 
blocking

Question 120

Heparin is a/an 

Answer 120

Antithrombotic agent

Question 121

a heparinoid pentasaccharide, antithrombin III-dependent Factor Xa inhibitor has the best efficacy-safety profile of all anticoagulants and is therefore currently first choice

Answer 121

Fondaparinux

Question 122

first choice of anticoagulant drugs

Answer 122

Fondaparinux

Question 123

Thrombin inhibitors

Answer 123

• hirudin
• bivalirudin

Question 124

Thrombolytic agents 

Answer 124

 rTPA

Question 125

second-line agent for the treatment of chronic angina

Answer 125

Ranolazine

Question 126

Ranolazine reduces {{c1::cardiac fatty acid oxidation}} and stimulates {{c1::glucose metabolism}} without inhibiting carnitine palmityl transferase 1

Answer 126

cardiac fatty acid oxidation 
glucose metabolism

Question 127

Preferential inhibition of late INa

Answer 127

Ranolazine

Question 128

Ranolazine is metabolized mainly by 

Answer 128

CYP3A4

Question 129

Which drug is approved for treating stable angina and heart failure in patients in whom β blockers are not tolerated or are insufficiently effective in reducing heart rate and FDA-approved only for the treatment of heart failure?

Answer 129

Ivabradine

Question 130

Funny channels 

Answer 130

Ivabradine

Question 131

selective blocker of hyperpolarization-activated HCN ion channels involved in the generation of automaticity in the SA node

Answer 131

Ivabradine

Question 132

nitrate ester of nicotinamide is used for the treatment of stable angina

Answer 132

Nicorandil

Question 133

Which drug has nitrate-like (cGMP-dependent) properties and acts as an agonist at ATPsensitive potassium (KATP) channels

Answer 133

Nicorandil

Question 134

Properties of Nicorandil

Answer 134

• nitrate-like (cGMP-dependent) properties
• agonist at ATPsensitive potassium (KATP) channels

Question 135

Nicorandil's vasodilating action is potentiated by {{c1::PDE5 inhibitors}} and only partially blocked by inhibitors of {{c2::KATP channels}}, such as {{c2::glibenclamide}}

Answer 135

PDE5 inhibitors
KATP channels
glibenclamide

Question 136

Nicorandil {{c1::dilates}} both arterial and venous vascular beds, leading to {{c1::decreases}} in afterload and preload of the heart.

Answer 136

dilates
decreases

Question 137

Adverse Effects of Nicorandil

Answer 137

nitrate-like headache and hypotension
GI ulcerations, perforations

Question 138

Which drug is ussed in the partial shift from FFA to glucose oxidation in the heart, which provides less ATP but requires less O2 and may therefore be beneficial in ischemia?

Answer 138

Trimetazidine

Question 139

Adverse effects of Trimetazidine

Answer 139

• GI upset
• nausea
• vomiting
• rarely
• thrombocytopenia
• agranulocytosis
• liver dysfunction

Question 140

CONTRAINDICATIONS OF Trimetazidine

Answer 140

Parkinson disease
patients with decreased kidney function

Question 141

considered first-line treatment of chronic angina relief

Answer 141

β blockers

Question 142

Drugs considered in patients who do not tolerate β blockers

Answer 142

Dihydropyridines

Question 143

In case of persistent angina, a combination of a {{c1::dihydropyridine}} and a {{c1::β blocker}} should be considered.

Answer 143

dihydropyridine
β blocker

Question 144

Second-Line Treatment of angina

Answer 144

• Longer-acting organic nitrates
• ranolazine
  
• ivabradine
• trimetazidine
• nicorandil

Question 145

Drugs which have a direct effect on the myocardium and likely act independently of hemodynamic effects.

Answer 145

• Ranolazine
• trimetazidine 

Question 146

In severe exertional or vasospastic angina, what drugs are used 

Answer 146

• Ca2+ Channel Blockers
• Nitrates

Question 147

{{c1::Nitrates}} primarily reduce {{c2::preload}}, whereas {{c1::Ca2+ channel blockers}} reduce {{c2::afterload}}

Answer 147

Nitrates
preload
Ca2+ channel blockers
afterload

Question 148

unstable angina pectoris is resistant to 

Answer 148

nitrates

Question 149

Most patients with peripheral vascular disease have 

Answer 149

CAD

Question 150

In the cerebral circulation, arterial disease may be manifest as {{c1::stroke}} or {{c1::transient ischemic attacks}}

Answer 150

stroke or transient ischemic attacks

Question 151

peripheral arterial disease in the lower extremities is called

Answer 151

claudication

Question 152

Drugs used specifically in the treatment of lower extremity claudication

Answer 152

1. pentoxifylline 
2. cilostazol
   

Question 153

A methylxanthine derivative that is called a rheologic modifier for its effects on increasing the deformability of red blood cells

Answer 153

Pentoxifylline

Question 154

an inhibitor of PDE3 and promotes accumulation of intracellular cAMP in many cells, including blood platelets.

Answer 154

Cilostazol

Question 155

Which anti-claudication drug is labeled as being contraindicated in patients with heart failure?

Answer 155

Cilostazol 

Question 156

Atherosclerotic angina

Answer 156

Atherosclerotic angina is also known as angina of effort or classic angina. crushing, strangling chest pain that is precipitated by exertion and relieved by rest

Question 157

Which type of plaques are associated with classic angina?

Answer 157

associated with atheromatous plaques that partially occlude one or more coronary arteries. When cardiac work increases (eg, in exercise), the obstruction of flow and inadequate oxygen delivery result in the accumulation of metabolites, eg, lactic acid, and ischemic changes that stimulate myocardial pain endings. Rest, by reducing cardiac work, usually leads to complete relief of the pain within 15 min

Question 158

This type of angina is associated with 90%of all cases

Answer 158

atherosclerotic angina

Question 159

Vasospastic angina

Answer 159

Vasospastic angina, also known as rest angina, variant angina, or Prinzmetal’s angina, is responsible for less than 10% of angina cases. It involves reversible spasm of coronaries, usually at the site of an atherosclerotic plaque. Spasm may occur at any time, even during sleep. Vasospastic angina may deteriorate into unstable angina

Question 160

Unstable angina

Answer 160

The third type of angina—unstable or crescendo angina, one manifestation of acute coronary syndrome—is characterized by the increased frequency and severity of attacks that result from a combination of atherosclerotic plaques, platelet aggregation at fractured plaques, and vasospasm.

Question 161

“Monday disease

Answer 161

Industrial disease caused by chronic exposure to vasodilating concentrations of organic nitrates in the workplace; characterized by headache, dizziness, and tachycardia on return to work after 2 days absence

Question 162

Nitrate tolerance, tachyphylaxis

Answer 162

Loss of effect of a nitrate vasodilator when exposure is prolonged beyond 10–12 h

Question 163

Preload

Answer 163

Filling pressure of the heart, dependent on venous tone and blood volume; determines end-diastolic fiber length and tension

Question 164

Afterload

Answer 164

Impedance to the ejection of stroke volume; determined by vascular resistance (arterial blood pressure) and arterial stiffness; determines systolic fiber tension

Question 165

Intramyocardial fiber tension

Answer 165

Force exerted by myocardial fibers, especially ventricular fibers at any given time; a primary determinant of myocardial O2 requirement

Question 166

Double product

Answer 166

The product of heart rate and systolic blood pressure; an estimate of cardiac work

Question 167

Myocardial revascularization

Answer 167

Mechanical intervention to improve O2 delivery to the myocardium by angioplasty or bypass grafting

Question 168

A major determinant of Cardiac oxygen requirement

Answer 168

myocardial fiber tension (the higher the tension, the greater the oxygen requirement)

Question 169

Diastolic factors that increase O2 requirement

Answer 169

Blood volume and Venous Tone

Question 170

Systolic factors that increase O2 requirement

Answer 170

TPR, HR, Heart force, Ejection time

Question 171

. Heart rate and systolic blood pressure may be multiplied to yield

Answer 171

double product, a measure of cardiac work and therefore of oxygen requirement. As intensity of exercise (eg, running on a treadmill) increases, demand for cardiac output increases, so the double product also increases

Question 172

In patients with atherosclerotic angina, effective drugs reduce the

Answer 172

double product by reducing cardiac work without reducing exercise capacity.

Question 173

This defect (lack of O2 supply)can be corrected—at present—in 2 ways

Answer 173

increasing oxygen delivery and by reducing oxygen requirement

Question 174

What are the traditional pharmacologic therapies useful for inadequate coronary oxygen delivery?

Answer 174

Nitrates, CCBs and Beta-blocker

Question 175

the newer strategies to improve oxygen delivery

Answer 175

increase the efficiency of oxygen utilization by shifting the energy substrate preference of the heart from fatty acids to glucose. Drugs that may act by this mechanism are termed partial fatty acid oxidation inhibitors (pFOX inhibitors) and include ranolazine and trimetazidine

Question 176

a new group of antianginal drugs selectively reduces heart rate (and O2 requirement) with no other detectable hemodynamic effects

Answer 176

These drugs (ivabradine is the prototype) act by inhibition of the sinoatrial pacemaker current, If

Question 177

drugs that reduce the cardiac oxygen requirement in atherosclerotic angina

Answer 177

nitrates, calcium blockers, and β blockers

Question 178

Drugs that also increase oxygen delivery by reducing spasms in vasospastic angina

Answer 178

Nitrates and calcium channel blockers (but not β blockers)

Question 179

Myocardial revascularization

Answer 179

corrects coronary obstruction either by bypass grafting or by angioplasty (enlargement of the coronary lumen by means of a special catheter)

Question 180

How does unstable angina therapy differ from regular (stable) angina

Answer 180

Therapy of unstable angina differs from that of stable angina in that urgent angioplasty is the treatment of choice in most patients and platelet clotting is the major target of drug therapy. A variety of platelet inhibitors are used in this condition (see Chapter 34). Intravenous nitroglycerin is sometimes of value in unstable angina.

Question 181

Drugs that are platelet inhibitors

Answer 181

Anticoagulants, Thrombolytics Antiplateletdrugs

Question 182

Anticoagulants

Answer 182

Heparins, Direct thrombin inhibitors, Direct factor Xa inhibitors, Warfarin

Question 183

Thrombolytics

Answer 183

t-Pa derivatives, Streptokinase

Question 184

Anti-platelet drugs

Answer 184

Aspirin, GP 2b/3a inhibitors, ADP inhibitors (Clopidogrel)PDE/adenosine uptake inhibitors

Question 185

NITRATES

Answer 185

Nitroglycerin (the active ingredient in dynamite) is the most important of the therapeutic nitrates and is available in forms that provide a range of durations of action from 10–20 min (sublingual for relief of acute attacks) to 8–10 h (transdermal for prophylaxis)

Question 186

Nitroglycerin (glyceryl trinitrate)

Answer 186

rapidly denitrated in the liver and in smooth muscle—first to the 2 dinitrates (glyceryl dinitrate), which retain a significant vasodilating effect; and more slowly to the mononitrates, which are much less active. Because of the high enzyme activity in the liver, the first-pass effect for nitroglycerin is about 90%. The efficacy of oral (swallowed) nitroglycerin probably results from the high levels of glyceryl dinitrate in the blood

Question 187

why are sublingual and transdermal administrations of nitroglycerin better than oral?

Answer 187

they can bypass FPM

Question 188

Isosorbide dinitrate

Answer 188

commonly used nitrate; it is available in sublingual and oral forms. Isosorbide dinitrate is rapidly denitrated in the liver and smooth muscle to isosorbide mononitrate, which is also active. Isosorbide mononitrate is available as a separate drug for oral use.

Question 189

pentaerythritol tetranitrate

Answer 189

Like the oral nitroglycerin preparation, these oral organic nitrates have an intermediate duration of action (4–6 h)

Question 190

Amyl nitrite

Answer 190

is a volatile and rapid-acting vasodilator that was used for angina by the inhalational route but is now rarely prescribed

Question 191

MOA of Nitrates

Answer 191

Nitrates release nitric oxide (NO) within smooth muscle cells, probably through the action of the mitochondrial enzyme aldehyde dehydrogenase-2 (ALDH2). NO stimulates soluble (cytoplasmic) guanylyl cyclase and causes an increase of the second messenger cGMP (cyclic guanosine monophosphate); the latter results in smooth muscle relaxation by stimulating the dephosphorylation of myosin light-chain phosphate. Note that this mechanism is identical to that of nitroprusside

Question 192

Cardiovascular effects of Nitrates

Answer 192

Smooth muscle relaxation by nitrates leads to an important degree of vasodilation, which results in reduced cardiac size and cardiac output through reduced preload. Relaxation of arterial smooth muscle may increase flow through partially occluded epicardial coronary vessels. Reduced afterload, from arteriolar dilation of resistance vessels, may contribute to an increase in ejection and a further decrease in cardiac size

Question 193

Venodilation leads to

Answer 193

decreased diastolic heart size and fiber tension.

Question 194

Arteriolar dilation leads to

Answer 194

reduced peripheral resistance and blood pressure. These changes contribute to an overall reduction in myocardial fiber tension, oxygen consumption, and the double product.

Question 195

the primary mechanism of the therapeutic benefit of nitrates in atherosclerotic angina is

Answer 195

reduction of the oxygen requirement. A secondary mechanism—namely, an increase in coronary flow via collateral vessels in ischemic areas—may also contribute. In vasospastic angina, reversal of coronary spasm and increased flow can be demonstrated.

Question 196

Nitrates have no direct effects on the cardiac muscle, but

Answer 196

significant reflex tachycardia and increased force of contraction are common results when nitroglycerin reduces the blood pressure. These compensatory effects result from the baroreceptor mechanism

Question 197

Nitrates effect on Other organs

Answer 197

Nitrates relax the smooth muscle of the bronchi, gastrointestinal tract, and genitourinary tract, but these effects are too small to be clinically significant. Intravenous nitroglycerin (sometimes used in unstable angina) reduces platelet aggregation. There are no clinically useful effects on other tissues

Question 198

The standard form for treatment of acute anginal pain is the

Answer 198

sublingual tablet or spray, which has a duration of action of 10–20 min. Sublingual isosorbide dinitrate is similar with a duration of 30 min.

Question 199

Oral (swallowed) normal-release formulations of nitroglycerin and isosorbide dinitrate have durations of action of

Answer 199

4-6 hours

Question 200

Transdermal formulations (ointment or patch)

Answer 200

maintain nitrate blood levels for up to 24 h. However, tolerance develops after 8–10 h, with rapidly diminishing effectiveness thereafter. It is therefore recommended that nitroglycerin patches be removed after 10–12 h. A new patch can be applied after 12 h of patch-free recovery.

Question 201

Toxicity of Nitrates and Nitrites

Answer 201

The most common adverse effects of nitrates are the responses evoked by vasodilation. These include tachycardia (from the baroreceptor reflex), orthostatic hypotension (a direct extension of the venodilator effect), and throbbing headache from meningeal artery vasodilation

Question 202

Nitrates interact with sildenafil and similar drugs

Answer 202

hese agents inhibit a phosphodiesterase isoform (PDE5) that metabolizes cGMP in smooth muscle (Figure 12–4). The increased cGMP in erectile smooth muscle relaxes it, allowing for greater inflow of blood and more effective and prolonged erection. This relaxation also occurs in vascular smooth muscle. As a result, the combination of nitrates (through increased production of cGMP) and a PDE5 inhibitor (through the decreased breakdown of cGMP) causes a synergistic relaxation of vascular smooth muscle with potentially dangerous hypotension and inadequate perfusion of critical organs

Question 203

Nitrites toxicity

Answer 203

are of significant toxicologic importance because they cause methemoglobinemia at high blood concentrations. This same effect has a potential antidotal action in cyanide poisoning (see later discussion). The nitrates do not cause methemoglobinemia

Question 204

Nitrites in the Treatment of Cyanide Poisoning

Answer 204

Cyanide ion rapidly complexes with the iron in cytochrome oxidase, resulting in a block of oxidative metabolism and cell death. Fortunately, the iron in methemoglobin has a higher affinity for cyanide than does the iron in cytochrome oxidase. Nitrites convert the ferrous iron in hemoglobin to the ferric form, yielding methemoglobin. Therefore, cyanide poisoning can be treated

Question 205

3 steps to treat CN poisoning

Answer 205

(1) immediate inhalation of amyl nitrite, followed by (2) intravenous administration of sodium nitrite, which rapidly increases the methemoglobin level to the degree necessary to remove a significant amount of cyanide from cytochrome oxidase. This is followed by (3) intravenous sodium thiosulfate, which converts cyanomethemoglobin resulting from step 2 to thiocyanate and methemoglobin. Thiocyanate is much less toxic than cyanide and is excreted by the kidney.

Question 206

hydroxocobalamin,

Answer 206

an alternative to nitrate, a B12 analogue, is preferred for CN

Question 207

CALCIUM CHANNEL-BLOCKING DRUGS

Answer 207

Several types of calcium channel blockers are approved for use in angina; these drugs are typified by nifedipine, a dihydropyridine,several other dihydropyridines, and the nondihydropyridines diltiazemand verapamil. Although calcium channel blockers differ markedly in structure, all are orally active and most have half-lives of 3–6 h

Question 208

Mechanism of Action of CCBs

Answer 208

Calcium channel blockers block voltage-gated L-type calcium channels, the calcium channels most important in cardiac and smooth muscle, and reduce intracellular calcium concentration and muscle contractility (Figure 12–3). None of these channel blockers interferes with calcium-dependent neurotransmission or hormone release because these processes use different calcium channels that are not blocked by L-channel blockers. Nerve ending calcium channels are of the N-, P-, and R-types. Secretory cells use L-type channels, but these channels are less sensitive to the calcium blockers than are cardiac and smooth muscle L-type channels

Question 209

Effects and Clinical Use of CCbs

Answer 209

Calcium blockers relax blood vessels and, to a lesser extent, the uterus, bronchi, and gut. The rate and contractility of the heart are reduced by diltiazem and verapamil. Because they block calcium-dependent conduction in the atrioventricular (AV) node, verapamil and diltiazem may be used to treat AV nodal arrhythmias Nifedipine and other dihydropyridines evoke greater vasodilation, and the resulting sympathetic reflex prevents bradycardia and may actually increase heart rate. All the calcium channel blockers insufficient dosage reduce blood pressure and reduce the double product in patients with angina

Question 210

Calcium blockers are effective as prophylactic therapy in

Answer 210

effort and vasospastic angina;

Question 211

nifedipine

Answer 211

used to abort acute anginal attacks but the use of the prompt-release form is contraindicated (see Skill Keeper)

Question 212

A pair of studies during the 1990s suggested that the use of nifedipine was associated with an increased risk of myocardial infarction. What effects of nifedipine might lead to this result?

Answer 212

Several studies have suggested that patients receiving prompt-release nifedipine may have an increased risk of myocardial infarction. Slow-release formulations do not seem to impose this risk. These observations have been explained as follows: Rapid-acting vasodilators—such as nifedipine in its prompt-release formulation—cause a significant and sudden reduction in blood pressure. The drop in blood pressure evokes increased sympathetic outflow to the cardiovascular system and increases heart rate and force of contraction. These changes can markedly increase cardiac oxygen requirement. If the coronary blood flow does not increase sufficiently to match the increased requirement, ischemia and infarction can result.

Question 213

In severe atherosclerotic angina, CCBs are

Answer 213

particularly valuable when combined with nitrates In addition to well-established uses in angina, hypertension, and supraventricular tachycardia, some of these agents are used in migraine, preterm labor, stroke, and Raynaud’s phenomenon

Question 214

Toxicity if CCBs

Answer 214

The calcium channel blockers may cause constipation, pretibial edema, nausea, flushing, and dizziness. More serious adverse effects include heart failure, AV blockade, and sinus node depression; these are most common with verapamil and least common with dihydropyridines.

Question 215

BETA-BLOCKING DRUGS

Answer 215

Actions include both beneficial antianginal effects (decreased heart rate, cardiac force, blood pressure) and detrimental effects (increased heart size, longer ejection period) Like nitrates and calcium channel blockers, β blockers reduce cardiac work, the double product, and oxygen demand.

Question 216

Are b-blockers helpful in Acute anginal attacks?

Answer 216

Beta-blockers are used only for the prophylactic therapy of angina; they are of no value in an acute attack

Question 217

Beta blockers are effective in ___________ and ineffective in _____________

Answer 217

effective in preventing exercise-induced anginaineffective in- Vasospastic angina

Question 218

The combination of β blockers and nitrates is useful because

Answer 218

adverse undesirable compensatory effects evoked by the nitrates (tachycardia and increased cardiac force) are prevented or reduced by β blockade

Question 219

Nitrates Alone

Answer 219

HR: Reflex increase (undesirable)Arterial P: DecreaseEnd-dia P.- DecreaseContractility- Reflex increase (undesirable)Ejection time- Reflex decreaseNet Myocardial O2 req: Decrease

Question 220

Beta Blockers or Calcium Channel Blockers Alone

Answer 220

HR; DecArt.P: DecEDP: inc (undesireable)EJT: increase (und)Contractility: DecreaseMO2 req: Decrease

Question 221

Combined Nitrates and a Blockers or Calcium Channel Blockers

Answer 221

HR, AP, EDP, Net O2 req:- DecreaseCon, ET- decrease

Question 222

Ranolazine

Answer 222

appears to act mainly by reducing a late, prolonged sodium current in myocardial cells. The decrease in intracellular sodium causes an increase in calcium expulsion via the Na/Ca transporter (see Chapter 13) and a reduction in cardiac force and work. As noted previously, it may also alter cardiac metabolism. Ranolazine is moderately effective in angina prophylaxis.

Question 223

Ivabradine

Answer 223

a drug used in heart failure inhibits the Ifsodium current in the sinoatrial node. The reduction in this hyperpolarization-induced inward pacemaker current results in decreased heart rate and consequently decreased cardiac work. Ivabradine is used off-label with β blockers as prophylaxis in angina.

Question 224

NONPHARMACOLOGIC THERAPY

Answer 224

Myocardial revascularization by coronary artery bypass grafting (CABG) and percutaneous transluminal coronary angioplasty (PTCA) are extremely important in the treatment of severe angina. These are the only methods capable of consistently increasing coronary flow in atherosclerotic angina and increasing the double product.

Question 225

Short-acting nitrates

Answer 225

Nitroglycerin, (sublingual), Isosorbide nitrate (longer acting- 20-30 min)

Question 226

Mechanism of Action of SAN

Answer 226

Releases nitric oxide (NO), increases cGMP (cyclic guanosine monophosphate), and relaxes vascular smooth musle

Question 227

Clinical Applications of SAN

Answer 227

Acute angina pectoris • acute coronary syndrome

Question 228

Pharmacokinetics SAN

Answer 228

Rapid onset (1 min) • short duration (15 min)

Question 229

Toxicities, Interactions SAN

Answer 229

Tachycardia, orthostatic hypotension, headache

Question 230

Intermediate-acting nitrates

Answer 230

Nitroglycerin, oral; Isosorbide dinitrate and mononitrate, oral Pentaerythritol tetranitrate and other oral nitrates

Question 231

MOA IAN

Answer 231

Like nitroglycerin SL • active metabolite dinitroglycerin

Question 232

CA of IAN

Answer 232

Prophylaxis of angina

Question 233

Pharmacokinetics IAN

Answer 233

Slow onset • Duration: 2–4 h

Question 234

Toxicities, Interactions of IAN

Answer 234

Tachycardia, orthostatic hypotension, headache

Question 235

Long-acting nitrate

Answer 235

Transdermal nitroglycerin

Question 236

MOA of LAN

Answer 236

active metabolite dinitroglycerin

Question 237

LAN Applications

Answer 237

Prophylaxis of Angina

Question 238

Pharmacokinetics of LAN

Answer 238

Slow onset • long duration of absorption: 24 h • duration of effect: 10 h (tachyphylaxis)

Question 239

Toxicities, interactions

Answer 239

Tachycardia, orthostatic hypotension, headacheloss of response is common after 10–12 h exposure to drug

Question 240

Ultrashort-acting nitrite

Answer 240

Amyl nitrite

Question 241

MOA of UsAN

Answer 241

Releases nitric oxide (NO), increases cGMP (cyclic guanosine monophosphate), and relaxes vascular smooth muscle

Question 242

CA of UsAN

Answer 242

Obsolete for angina • some recreational use

Question 243

PK of UsAN

Answer 243

Volatile liquid, vapors are inhaled • onset seconds Duration: 1–5 min

Question 244

TOxicities of UsAN

Answer 244

Tachycardia, orthostatic hypotension, headache

Question 245

CCBs that are indicated in Raynauds

Answer 245

Felodipine, Nifedipine, Diltiazem

Question 246

This drug is claimed to be particularly selective for cerebral blood vessels.

Answer 246

Nimodipine, appears to reduce morbidity after a subarachnoid hemorrhage. Nimodipine was approved for use in patients who have had a hemorrhagic stroke. Verapamil is better indicated despite its lack of vasoselectivity in treating strokes

Question 247

This drug is a selective T-type calcium channel blocker that was introduced for antiarrhythmic use but has been withdrawn.

Answer 247

Mibefradil

Question 248

Many vasodilators can be shown to increase coronary flow in theabsence of atherosclerotic disease. These include

Answer 248

dipyridamoleand adenosine. In fact, dipyridamole is an extremely effective coronary dilator, but it is not effective in angina becauseof coronary steal

Question 249

What is FFR and Which drug helps in measuring Fractional flow reserve (FFR)

Answer 249

FFR is the ratio between maximum blood flow in a diseased coronary artery and theoretical maximum flow in that artery. FFR of 1.0 is considered normal. FFR any lower than 0.75-0.8 is considered as MI.Adenosine, acting on A2A receptors causes a very brief but marked dilationof the coronary resistance vessels and has been used as a drugto measure maximum coronary flow (“fractional flow reserve,”FFR) in patients with coronary disease. The drug also markedlyslows or blocks atrioventricular (AV) conduction in the heartand is used to convert AV nodal tachycardias to normal sinusrhythm

Question 250

Regadenoson

Answer 250

a selective A2A agonistand has been developed for use in stress testing in suspectedcoronary artery disease and for imaging the coronary circulation.It appears to have a better benefit-to-risk ratio than adenosine in these applications. Similar A2A agonists (binodenoson, apadenoson)

Question 251

Coronary steal

Answer 251

the term is given to the action of nonselective coronary arteriolar dilators in patients with partial obstruction ofa portion of the coronary vasculature. It results from the fact thatin the absence of drugs, arterioles in ischemic areas of the myocardium are usually maximally dilated as a result of local control factors, whereas the resistance vessels in well-perfused regions are capable of further dilation in response to exercise

Question 252

In patients with unstable angina, transient coronary steal mayprecipitate a

Answer 252

myocardial infarction. Adenosine and regadenoson are labeled with warnings of this effect.

Question 253

This oxytocin antagonist is better indicated in preterm labor than Nifedipine

Answer 253

. Nifedipine has some efficacy in preterm labor but is moretoxic and not as effective as atosiban, an investigational oxytocinantagonist

Question 254

Why is a combination of verapamil and diltiazem worse than Nifedipine on Ventricular depression

Answer 254

Nifedipinedoes not decrease atrioventricular conduction and therefore canbe used more safely than verapamil or diltiazem in the presence ofatrioventricular conduction abnormalities. A combination of verapamil or diltiazem with β blockers may produce atrioventricularblock and depression of ventricular function. In the presence ofovert heart failure, all calcium channel blockers can cause furtherworsening of failure as a result of their negative inotropic effect

Question 255

This drug does not increase mortality in patients with heart failure due to nonischemic left ventricular systolic dysfunction and can be used safely in HF patient

Answer 255

amlodipine

Question 256

Why is a combination of verapamil and diltiazem better than Nifedipine (dihydropyridine) on people with hypotension

Answer 256

dihydropyridinescan cause further deleterious lowering of pressure. Verapamil anddiltiazem appear to produce less hypotension and may be bettertolerated in these circumstances. In patients with a history of atrialtachycardia, flutter, and fibrillation, verapamil and diltiazem provide a distinct advantage because of their antiarrhythmic effects.In the patient receiving digitalis, verapamil should be used withcaution, because it may increase digoxin blood levels through apharmacokinetic interaction

Question 257

Ranolazine

Answer 257

appears to act by reducing a late sodium current (INa) that facilitates calcium entry via the sodium-calciumexchanger (see Chapter 13). The reduction in intracellular calcium concentration that results from ranolazine reduces diastolictension, cardiac contractility, and work. Ranolazine is approvedfor use in angina in the USA. Several studies demonstrate itseffectiveness in stable angina, but it does not reduce the incidenceof death in acute coronary syndromes

Question 258

ECG changes in Ranolazine

Answer 258

prolongs theQT interval in patients with coronary artery disease (but shortensit in patients with long QT syndrome, LQT3). It has not beenassociated with torsades de pointes arrhythmia and may inhibitthe metabolism of digoxin and simvastatin

Question 259

trimetazidine

Answer 259

pFOX inhibitors because they partially inhibit the fatty acidoxidation pathway in myocardium. Because metabolism shifts tooxidation of fatty acids in ischemic myocardium, the oxygenrequirement per unit of ATP produced increases. Partial inhibition of the enzyme required for fatty acid oxidation (long-chain3-ketoacyl thiolase, LC-3KAT) appears to improve the metabolic status of ischemic tissue

Question 260

New drugs or drug groups underinvestigation for use in angina.

Answer 260

AmilorideCapsaicinDirect bradycardic agents, eg, ivabradineInhibitors of slowly inactivating sodium current, eg, ranolazineMetabolic modulators, eg, trimetazidineNitric oxide donors, eg, L-argininePotassium channel activators, eg, nicorandilProtein kinase G facilitators, eg, detanonoateRho-kinase inhibitors, eg, fasudilSulfonylureas, eg, glibenclamideThiazolidinedionesVasopeptidase inhibitorsXanthine oxidase inhibitors, eg, allopurinol

Question 261

Perhexiline

Answer 261

found to benefit some patients with anginadecades ago but was abandoned because of reports of hepatotoxicity and peripheral neuropathy. However, pharmacokinetic studiessuggested that toxicity was due to variable clearance of the drug,with extremely high plasma concentrations in patients with deficient CYP2D6 activity. This drug may shift myocardial metabolism from fatty acid oxidation to more efficient glucose oxidation(compared with trimetazidine). Because it does not involve vasodilation, it may be useful in patients refractory to ordinary medicaltherapy if plasma concentration is carefully controlled.

Question 262

, ivabradine

Answer 262

bradycardic drugs, relatively selective If sodium channel blockers (eg, ivabradine), reduce the cardiac rate by inhibiting thea hyperpolarization-activated sodium channel in the sinoatrial node.No other significant hemodynamic effects have been reported.Ivabradine appears to reduce anginal attacks with an efficacy similar to that of calcium channel blockers and β blockers. The lack of effect on the gastrointestinal and bronchial smooth muscle is an advantage of ivabradine, and it is approved for use in angina and heartfailure outside the USA

Question 263

Rho kinases (ROCK)

Answer 263

family of enzymes thatinhibit vascular relaxation and diverse functions of several othercell types. Excessive activity of these enzymes has been implicatedin coronary spasm, pulmonary hypertension, apoptosis, and otherconditions. Drugs targeting the enzyme have therefore been soughtfor possible clinical applications

Question 264

. Fasudil

Answer 264

an inhibitor of smoothmuscle Rho kinase and reduces coronary vasospasm in experimental animals. In clinical trials in patients with CAD, it has improvedperformance in stress tests. It is investigational in angina.

Question 265

Allopurinol

Answer 265

Studies suggest that high-dose allopurinol (eg, 600 mg/d)prolongs exercise time in patients with atherosclerotic angina.The mechanism is uncertain, but the drug appears to improveendothelium-dependent vasodilation. Allopurinol is not currentlyapproved for use in angina

Question 266

Refractory angina and acute coronary syndromes are best treated with

Answer 266

physical revascularization, ie, percutaneous coronary intervention(PCI), with insertion of stents, or coronary artery bypass grafting(CABG).

Question 267

First-line therapy of CAD depends on

Answer 267

modification of risk factors such as hypertension, hyperlipidemia, obesity, smoking, and clinical depression. Inaddition, antiplatelet drugs are very important.

Question 268

Specific pharmacologic therapy to prevent myocardial infarctionand death consists of

Answer 268

antiplatelet agents (aspirin, ADP receptorblockers, and lipid-lowering agents, especially statins. Aggressive therapy with statins has been shown toreduce the incidence and severity of ischemia in patients duringexercise testing and the incidence of cardiac events (including infarction and death) in a clinical trial

Question 269

Inpatients with unstable angina and non-ST-segment elevation myocardial infarction, aggressive therapy consisting of

Answer 269

coronary stenting, anti-lipid drugs, heparin, and antiplatelet agents are recommended

Question 270

therapeutics Angina of Effort

Answer 270

Many studies have demonstrated that nitrates, calcium channelblockers and β blockers increase the time to onset of angina andST depression during treadmill tests in patients with angina ofeffort. Although exercise tolerance increases, thereis usually no change in the angina threshold, ie, the rate-pressureproduct at which symptoms occur.

Question 271

maintenance therapy of chronic stable angina

Answer 271

β blockers,calcium channel-blocking agents, or long-acting nitrates may bechosen; the drug of choice depends on the individual patient’sresponse.

Question 272

In hypertensive patients

Answer 272

monotherapy with either slow release or long-acting calcium channel blockers or β blockers maybe adequate

Question 273

In normotensive patients,

Answer 273

long-acting nitrates may besuitable. The combination of a β blocker with a calcium channelblocker (eg, propranolol with nifedipine) or two different calciumchannel blockers (eg, nifedipine and verapamil) has been shown tobe more effective than individual drugs used alone. If a dihydropyridine is used, a longer-acting agent should be chosen (amlodipine or felodipine)

Question 274

Some patients may require therapy with all threedrug groups, which include the_____________

Answer 274

Ranolazine or ivabradine (off-label), combined with βblockers, may be effective in some patients refractory to traditionaldrugs. Most experts recommend coronary angiography and revascularization (if not contraindicated) in patients with stable chronicangina refractory to three-drug medical treatment. In the future,agents such as allopurinol or perhexiline may be useful in patientswho are not candidates for revascularization.

Question 275

Vasospastic Angina therapy

Answer 275

Nitrates and the calcium channel blockers, but not β blockers,are effective drugs for relieving and preventing ischemic episodesin patients with variant angina. In approximately 70% of patientstreated with nitrates plus calcium channel blockers, angina attacksare completely abolished; in another 20%, marked reduction offrequency of anginal episodes is observed.

Question 276

Surgical revascularization and angioplasty are notindicated in patients with

Answer 276

variant angina

Question 277

Unstable Angina & Acute CoronarySyndromes

Answer 277

In patients with unstable angina with recurrent ischemic episodesat rest, recurrent platelet-rich nonocclusive thrombus formationis the principal mechanism. Aggressive antiplatelet therapy with acombination of aspirin and clopidogrel is indicated. Intravenousheparin or subcutaneous low-molecular-weight heparin is alsoindicated in most patients.

Question 278

If percutaneous coronary interventionwith stenting is required

Answer 278

glycoprotein IIb/IIIa inhibitors such as abciximab should be added. In addition, therapy with nitroglycerin and βblockers should be considered; calcium channel blockers should beadded in refractory cases for relief of myocardial ischemia. Primarylipid-lowering and ACE-inhibitor therapy should also be initiated

Question 279

TREATMENT OF PERIPHERALARTERY DISEASE & INTERMITTENTCLAUDICATION

Answer 279

Atherosclerosis can result in ischemia of peripheral muscles justas coronary artery disease causes cardiac ischemia. Pain (claudication) occurs in skeletal muscles, especially in the legs, duringexercise and disappears with rest. Although claudication is notimmediately life-threatening, peripheral artery disease (PAD) isassociated with increased mortality, can severely limit exercisetolerance, and may be associated with chronic ischemic ulcers,susceptibility to infection, and the need for amputation

Question 280

Conventional vasodilators are of no benefit because

Answer 280

vessels distal to the obstructive lesions are usually alreadydilated at rest. Antiplatelet drugs such as aspirin or clopidogrel(see Chapter 34) are often used to prevent clotting in the regionof plaques and have documented benefits in reducing the risk ofmyocardial infarction, stroke, and vascular death even thoughthey have little or no effect on claudication

Question 281

Two drugs are usedalmost exclusively for PAD

Answer 281

Cilostazol, a phosphodiesterase type3 (PDE3) inhibitor, may have selective antiplatelet and vasodilating effects. This drug has been shown to increase exercisetolerance in patients with severe claudication. Pentoxifylline, axanthine derivative, is widely promoted for use in this conditionbut is not recommended. It is thought to act by reducing theviscosity of blood and perhaps increasing the deformability of redblood cells, allowing blood to flow more easily through partiallyobstructed areas.

Question 282

Naftidrofuryl

Answer 282

5-HT2 antagonist, is availableoutside the USA and appears to have benefits similar to those ofcilostazol. Percutaneous angioplasty with stenting may be effective in patients with medically intractable signs and symptoms oflower limb ischemia.