Pathophysiology, Pharmacology, Pharmacotherapy of CAD Flashcards
(201 cards)
1
Q
What is chronic coronary disease?
A
Heterogeneous group of conditions that includes:
- obstructive and nonobstructive CAD with or without previous MI or revascularization,
- ischemic heart disease diagnosed only by noninvasive testing,
- and chronic angina syndromes with varying underlying causes
2
Q
What are the types of angina?
A
- Printzmetal’s variant angina (vasospasm)
- Chronic stable angina (fixed stenosis)
- Unstable angina (thrombus)
3
Q
What is printzmetal’s variant angina also known as?
A
Supply ischemia
4
Q
What is chronic stable angina also known as?
A
Demand ischemia
5
Q
What is unstable angina also known as?
A
Supply ischemia
6
Q
Describe printzmetal’s variant angina
A
Artery closes bc of spasm(s)
7
Q
Describe chronic stable angina
A
Plaque blockage that results in ischemia with exertion
8
Q
Describe unstable angina
A
Plaque + thrombus that causes vessel to fully close
9
Q
What causes increased oxygen demand that leads to ischemia?
A
Increased HR, contractility, afterload, preload
10
Q
What causes decreased coronary blood flow that leads to ischemia?
A
Fixed stenosis, vasospasm, thrombus
11
Q
What are the components of ischemia and describe them
A
- Angina -> chest pain
- Anginal equivalents -> Sx like SOB that is normally caused by another disease like HF
12
Q
How does contractility impact myocardial O2 supply/demand ratio?
A
Decrease in contractility will decrease O2 consumption
13
Q
How does HR impact myocardial O2 supply/demand ratio?
A
- Decreased HR will decrease O2 consumption
- Decreased HR will increase coronary perfusion
14
Q
How does preload-LVEDV impact myocardial O2 supply/demand ratio?
A
- Decreased by venodilation
- Decrease leads to decrease in O2 consumption
- Decrease leads to increase in myocardial perfusion
15
Q
How does afterload impact mycardial O2 supply/demand ratio?
A
- Decreased by dilation of arteries
- Decrease leads to decrease in O2 consumption
16
Q
What is stable pectoris usually associated with?
A
Large single to multivessel ASCAD
17
Q
What do approx 85% of pts with angina pectoris have?
A
Significant coronary artery disease (defined as >70-75% atherosclerotic reduction) in a major epicardial coronary vessel
18
Q
What are major epicardial coronary vessels?
A
Vessels that sit and are connected to epicardial surface of the heart
19
Q
What does not usually cause ischemia?
A
Atherosclerotic reductions between 50-70%
20
Q
What is the pathophysiology of myocardial ischemia?
A
- Imbalance between myocardial oxygen supply and demand
- Produces disturbances in myocardial function without causing myocardial necrosis
21
Q
What is the pathophysiology of angina?
A
- Resulting symptoms from ischemia
- Is a clinical syndrome of chest discomfort
22
Q
What is the definition of stable angina pectoris?
A
- Discomfort in the chest and/or adjacent areas
- Caused by myocardial ischemia and associated with a disturbance in myocardial function WITHOUT myocardial necrosis
23
Q
What is the definition of stable in stable angina pectoris?
A
Characteristics of an anginal episode (quality, frequency, severity, duration of Sx, time of day, etc) have not changed recently
24
Q
What is the first P in PPQRST?
A
Precipitating factors
25
Presentations of precipitating factors?
- Exercise/exertion
- Weather factors (cold, warm, and humid)
- Walking against wind
- Large meal
- Emotional factors involved with exercise
- Fright, anger
- Coitus
26
What is the second P in PPQRST?
Palliative measures
27
Presentations of palliative measures?
Rest and/or sublingual nitroglycerin/nitrates
28
What is the Q in PPQRST?
Quality and quantity of pain
29
Presentations of quality and quantity of pain?
Squeezing, heaviness, tightening
30
What is the R in PPQRST?
Region and radiation
31
Presentations of region and radiation?
- Substernal
- Anywhere between epigastrium and pharynx
- Sometimes limited to left shoulder and arm
- Rarely limited to right arm
- Limited to lower jaw
- Lower cervical and upper thoracic spine
- Left interscapular or suprascapular area
32
What is S in PPRQST?
Severity of pain
33
Presentations of severity of pain?
Subjective, >5 out of 10
34
What is the T in PPRQST?
Timing and temporal pattern
35
Presentations in timing and temporal pattern?
Lasts <20 min, usually relieved in 5-10 min
36
What is the classic clinical characteristics of typical angina?
- Substernal
- Duration of 0.5 to 20 min
- Nitroglycerin/rest gives relief
37
What is the typical ECG findings of typical ischemia/angina?
ST segment depression during event
38
What is typical ECG findings during variant angina?
ST segment elevation in variant angina
39
What are the endpoints of exercise tolerance testing
Duration, workload achieved, ECG changes, BP and HR responses, and Sxs
40
What are the diagnostic procedures for CHD?
- Cardiac imaging
- Echocardiography
- Cardiac catheterization and coronary angiography
41
What does cardiac imaging consist of in CHD diagnostic procedures?
- Pharmacologic stress testing
- Nuclear imaging
- Electron beam computerized tomography (calcium score)
42
What does cardiac catheterization and coronary angiography accomplish?
- Definitive assessment of coronary anatomy
- Invasive
43
Where is cardiac catheterization typically inserted?
Radial artery in the wrist
44
What is the desired outcome 1 of CCD tx?
- Risk factor modification
- Prevent ACS and death
45
What is the desired outcome 2 of CCD tx?
- Management of anginal episodes
- Alleviate acute Sxs and prevent recurrent Sxs of ischemia
46
What is the desired outcome 3 of CCD tx?
Avoid/minimize adverse tx effects
47
What is the tx goal of dyslipidemia risk factor?
>= 50% reduction in LDL
48
What is the preferred tx for dyslipidemia risk factor?
- Lifestyle modifications
- Low (<7%) sat fat, low (<200 mg/dL) cholesterol
- Moderate to high intensity statins
49
What is the tx goal for HTN risk factor?
BP <130/80 mmHg
50
What is the preferred tx for HTN risk factor?
- Lifestyle modifications
- BBs, ACEi, ARBs, and others as necessary
51
What is the tx goal for DM risk factor?
A1c <7%
52
What is the preferred tx for DM risk factor?
- Individualize to reach goal
- SGLT2 or GLP-1 for T2DM with ASCVD
53
What is the tx goal for smoking risk factor?
Complete smoking cessation/exposure
54
What is the preferred tx for smoking risk factor?
Systematic strategy, pharmacotherapy
55
What is the tx goal for weight management risk factor?
- BMI 18.5 to 24.9
- Waist circumference of 40 or less in men and 35 or less in women
- Wt loss of 5-10% initially
56
What is the preferred tx for high weight risk factor?
- Diet/lifestyle modifications
- Printed educational materials
- Encouragement
57
What is the tx goal for low physical activity risk factor?
- 30 to 60 min moderate intensity 5 to 7 days a week
- Cardiac rehab/supervised
58
What is the preferred tx for low physical activity risk factor?
- Brisk walking, swimming, cycling
- Increased daily activities in general
59
How can a pt lower their risk for CAD?
- Yearly influenza vaccination
- Lower alcohol consumption
- Lower exposure to air pollution
- Management of psychological factors
60
What is aspirin's MOA?
- Acetylation and irreversible inactivation of platelet COX-1
- Antiplatelet activity by blocking TXA2 synthesis
61
What does aspirin achieve through its MOA?
- Interferes with platelet aggregation
- Prolongs bleeding time
- Blocks arterial thrombi formation
62
What is a downside of aspirin?
It does not treat currently formed thrombus
63
What are effects of COX-1?
- Increases platelet aggregation
- Vasoconstriction
64
What are effects of COX-2?
- Inhibits platelet aggregation
- Vasodilation
65
What is the loading dose of aspirin?
160-325 mg
66
What is the maintenance dose of aspirin?
75-162 mg daily
67
What are the AEs of aspirin?
- GI bleeding
- Hematologic bleeding (intracranial and extracranial)
- Hypersensitivity
- Major bleeding in 2-3% of pts in year 1
68
What is the MOA of P2Y12 inhibitors?
Selectively inhibit adenosine diphosphate induced platelet aggregation with no direct effect on TXA2
69
What is the loading dose of clopidogrel (Plavix)?
300-600 mg
70
What is the maintenance dose of clopidogrel (Plavix)?
75 mg daily
71
What is the loading dose of prasugrel (Effient)?
60 mg
72
What is the maintenance dose of prasugrel (Effient)?
10 mg daily
73
What is the loading dose of ticagrelor (Brilinta)?
180 mg
74
What is the maintenance dose of ticagrelor (Brilinta)?
90 mg BID
75
How is cangrelor (Kengreal) administered that is different from the other P2Y12 inhibitors?
IV only
76
When is prasugrel (Effient) and cangrelor (Kengreal) indicated?
Following ACS
77
When is ticagrelor (Brilinta) indicated?
Following ACS or prior MI
78
Why can 2 or more platelet inhibitors be used together?
Different MOAs
79
What drug class is clopidogrel and prasugrel?
Thienopyridine
80
What is the pharmacology of clopidogrel?
- It is CYP dependent
- Converted to active (prodrug)
81
What is the time to peak inhibition of clopidogrel?
- 4 to 5 hours for 300 mg
- 2 to 3 hours for 600 mg
82
What is the time required for effect dissipation for clopidogrel?
5 days
83
What is the pharmacology of prasugrel?
- "less" CYP dependent (still a prodrug)
- Converted to active
84
What is the time to peak inhibition of prasugrel?
2-4 hours
85
What is the time required for effect dissipation for prasugrel?
7 days
86
What drug class is ticagrelor?
Cyclopentyl-triazole-pyrimidine
87
What is the pharmacology of ticagrelor?
- Direct acting
- Not a prodrug
88
What is the time to peak inhibition for ticagrelor?
2-4 hours
89
What is the time required for effect dissipation of ticagrelor?
5 days
90
What are AEs of clopidogrel?
- Bleeding, diarrhea, rash
- About 1% increase in major bleeding when used with aspirin
91
What are AEs of prasugrel?
- Bleeding, diarrhea, rash
- About 0.6% increase (absolute risk) in major bleeding and about 0.5% increase (vs. clopidogrel) in life-threatening bleeding when used with aspirin
92
What are AEs of ticagrelor?
Bleeding, bradycardia, heart block, dyspnea (SOB)
93
What is the REQUIRED dose of aspirin if it is taken with ticagrelor (Brilinta)?
<= 100 mg
94
Why does aspirin dose need to be <= 100 mg if taken with ticagrelor (Brilinta)?
Increased risk of cerebral hemorrhage and therefore stroke
95
What improvements should pts show before being given ACEi/ARBs?
Stabilized plaque, improved ET function, inhibition of VSM cell growth, decreased macrophage migration, and anti-ox properties
96
What do ACEi and ARBs not do in ischemia?
Does not improve symptomatic ischemia
97
What do ACEi and ARBs do in ischemia?
Lowers CV events in high risk pts with or without LV dysfunction
98
When are ACEi and ARBs considered in ischemia?
- Considered in all pts with CCD
- Esp in pts with LVEF <40%, HTN, DM, CKD
99
What does colchicine do in ischemia?
Heart disease is inflammation and colchicine reduces inflammation
100
How does colchicine reduce inflammation?
Via reduction in IL-1beta and IL-18
101
When is colchicine considered?
When pt presents with elevated levels of hsCRP (>2)
102
What is hsCRP?
An inflammation marker
103
What is the pharmacology of colchicine?
CYP3A and P-gp substrate
104
What is something to watch out for with colchicine?
Caution in concomitant use with strong inhibitors of CYP3A and P-gp
105
When is colchicine CI?
CI in severe renal and hepatic disease
106
What is the pharmacotherapy behind preventing and/or reducing ischemia and angina sx?
- Increase myocardial O2 supply
- But MAINLY by decreasing myocardial O2 demand
107
What is the MOA of organic nitrates?
- Nitric oxide donors/releasers
- Activation of guanylate cyclase
108
What are the effects of organic nitrates?
- Marked venodilation (decreased preload)
- Less arteriole dilation, coronary and peripheral
- Inhibition of platelet aggregation (minor)
109
Where is NO produced?
In the endothelial cells
110
How does NO cause vasodilation?
- It interacts with GC+, making it sGC
- sGC converts GTP to cGMP
111
What are the clinical effects of nitrates?
- Increased myocardial O2 supply
- Decreased myocardial O2 demand
112
Explain how nitrates increase myocardial O2 supply.
Endothelium-dependent vasodilation; dilates epicardial arteries and coronary collateral vessels
113
Explain how nitrates decrease myocardial O2 demand.
Venous vasodilation causes reduced preload and decreased LV volume
114
What do nitrates not tx/reverse?
Nitrates has no effect on the natural progression of the disease; it only tx sxs
115
What is the biggest advantage of a spray NTG over other dosage forms
Spray NTG has a shelf life of about 3 years
116
What are the AEs of nitrates?
- Headache (throbbing, pulsating)
- Hypotension, dizziness, lightheadedness, facial flushing
- Reflex tachycardia
117
What should be done if a pt gets headache while using NTG?
- Use APAP meds like acetaminophen/tylenol
- DO NOT USE NSAIDs
118
Why is there extreme caution exercised when using PDEi + nitrates?
Substantially enhanced vasodilatory effects (hypotension; 25 mmHg drop in SBP)
119
How long should a pt wait to take Avanafil after taking a nitrate?
12 hours
120
How long should a pt wait to take Sildenafil or Vardenafil after taking a nitrate?
24 hours
121
How long should a pt wait to take Tadalafil after taking a nitrate?
48 hours
122
What is the bottom line clinical recommendation for nitrates?
- SL NTG or SL spray should be utilized in all pts with CCD
- Can be taken prior to exertion to prevent acute angina
123
What drugs are used to PREVENT RECURRENT ischemia and angina Sx?
BBs, CCBs, nitrates
124
Explain the action of B-adrenergic receptors in cardiac myocytes.
125
What are the pharmacologic effects on B-adrenergic receptors?
126
Explain the mechanism of B-adrenergic receptors in smooth muscle cells.
127
What is the MOA of BBs?
Competitive, reversible inhibitors of beta-adrenergic stimulation by catecholamines
128
What are the desired effects of BBs on myocardial O2 demand?
- Reduce HR, myocardial contractility, arterial BP
129
What are the undesired effects of BBs on myocardial O2 demand?
- Increase in preload; this negates some positive effects of BBs
130
What is the main reason BBs are used to keep pts alive?
BBs are associated with reduced ventricular arrhythmias and remodeling
131
What are cardiac related AEs of BBs?
Sinus bradycardia (HR <60), sinus arrest, AV block, reduced LVEF
132
How should a BB be initiated?
Initiate at lowest dose and titrate to Sx reduction
133
What is the goal HR of a pt on BBs?
- Rest: 50-60 bpm
- Exercise: <= 100 bpm or 75% of HR that causes angina
134
What is the brand name of atenolol?
Tenormin
135
What is the receptor selectivity of atenolol?
B1
136
What is the ISA (intrinsic sympathomimetic activity) of atenolol?
0
137
What is the lipid solubility of atenolol?
Low
138
What is the primary route of elimination of atenolol?
Renal
139
What is the usual maintenance dose of atenolol?
50-100 mg QD
140
What is the brand name of metoprolol and metoprolol XL?
Lopressor and Toprol XL, respectively
141
What receptor(s) are metoprolol and metoprolol XL selective for?
B1
142
What is the ISA of metoprolol and metoprolol XL?
0
143
What is the lipid solubility of metoprolol and meto XL?
Moderate
144
What is the primary route of elimination of metoprolols?
Hepatic
145
What are the usual daily maintenance doses of metoprolol and meto XL?
- 50-100 mg BID
- 100-200 mg QD
146
What are the brand names of propranolol and propranolol LA?
Inderal and Inderal LA
147
What receptors are propranolol and propranolol LA selective for?
B1, B2
148
What is the ISA of the propranolols?
0
149
What is the lipid solubility of the propranolols?
High
150
What is the primary route of elimination for the propranolols?
Hepatic
151
What is the usual maintenance dose of the propranolols?
- Variable for regular
- 80-160 mg BID for the LA
152
What is MOA of CCBs?
153
What is the pharmacologic characteristics of CCBs?
154
Myocardial selectivity of calcium channel antagonists:
155
Vascular selectivity of calcium channel antagonists:
156
What are the AEs of DHP CCBs?
- Hypotension, flushing, headache, dizziness
- Peripheral edema, likely related to arteriolar vasodilation
- Reduced myocardial contractility
- Reflex adrenergic activation
157
What are the AEs of non-DHP CCBs?
- Reduced myocardial contractility (V>D)
- AV/SA nodal conduction disturbances: bradycardia and atrioventricular block (V>D)
- Hypotension, flushing, headache, dizziness
- Constipation (V>D)
158
How should CCBs be initiated?
Initiate at lowest dose and titrate to Sx reduction
159
Explain nitrate tolerance.
Decreased response in the presence of continuously or frequently administered nitrates
160
How is nitrate tolerance prevented?
- Nitrate free period of at least 10-12 hours
- Biopharmaceutics and PK contribute to the amount of time required to be dosage-free
161
What is the pharmacology of nitrate tolerance?
- Reversible (hours) in absence of drug
- ALDH2 inactivation in mitochondria
- ISMN and ISDN also elicit tolerance but via a slower, less understood process
162
What is the dosing interval of SL NTG tabs/caps?
2-4 times/day
163
What is the dosing interval of NTG ointment?
3-4 times/day
164
What is the dosing interval of NTG patch?
Once daily
165
What is the dosing interval of ISDN tabs?
2-3 times/day
166
What is the dosing interval of ISDN SR caps/tabs?
1-2 times/day
167
What is the dosing interval of ISMN tabs?
2 times/day 7 hours apart
168
What is the dosing interval of ISMN SR tabs?
Once daily
169
What are patient counseling points of nitrate patches?
- Discussion of nitrate free interval
- Apply patch between elbows and knees
- Apply patch to clean, dry, hairless skin
- Choose diff area every day
- Showering is allowed with patch on
- Do not cut patch
- Wash hands before and after
170
What are patient counseling points of NTG ointment?
- Same as patches
- Do not rub or massage ointment
- Do not cover area
171
Describe the cellular events during ischemia.
172
What is the MOA of ranolazine?
- Inhibition of inward Na+ current in ischemic myocytes
- Decreased intracellular Na+ -> decreased Ca2+ influx
- DOES NOT affect HR, BP, inotropy, or perfusion
173
What is the brand name, strength, and dosage form of ranolazine?
Ranexa 500mg ER tabs
174
How is ranolazine administered?
Titration from 500 BID to 1000 BID over 1-2 weeks
175
What is the indication for ranolazine?
Tx of chronic angina
176
What is the EMA's indication for ranolazine?
Add on therapy for sx tx of pts with stable angina pectoris who are inadequately controlled or intolerant to 1st line antianginal therapies
177
How is ranolazine used in combo therapy?
Add to CCBs, BBs, or nitrates when inadequate response to monotherapy
178
When is ranolazine used as monotherapy?
When BP/HR too low with first line agents
179
How is ranolazine metabolized?
- 70-85% by CYP3A4
- 10-15% by CYP2D6
- Substrate for P-gp
180
What should ranolazine not be used with?
Strong 3A inhibitors (KTZ, ITZ, PIs, clarithomycin) or inducers (CBZ, RIF, st. john's wart)
181
What dose should ranolazine be limited to if used with moderate inhibitors (Dilt, Ver, ERY and FLZ)?
500 mg BID
182
What does ranolazine inhibit?
CYP3A and/or P-gp
183
What are the AEs of ranolazine?
- Constipation, nausea, dizziness, headache
- Dose related increase in QT interval; should not be used with other drugs that prolong QT interval
184
How is an agent selected for stable angina?
- BBs, CCBs, and nitrates can be used
- Selection should be based upon pt characteristics and concomitant conditions
185
When should BBs be used in stable angina?
- Compelling indications: stable HF, MI hx
- Esp useful in afib, high resting HR, migraine HAs
- Avoid in vasospastic/printzmetal's angina, conduction disturbances
186
What are the CIs of BBs in stable angina?
- Bradycardia (HR <50 bpm)
- High degree of AV block or sick sinus syndrome (w no pacemaker)
187
When should CCBs be used in stable angina?
Non-DHP CCBs preferred instead of BBs if:
- CIs to BBs
- Unacceptable SEs to BBs
- Potentially useful in chronic lung disease, HTN, DM, and peripheral vascular disease
188
What are the CIs of CCBs in stable angina?
- Non-DHPs: HFrEF, bradycardia (HR <50 bpm), high degree of AV block or sick sinus syndrome (w no pacemaker)
- DHPs: HFrEF (except amlodipine and felodipine)
189
When should nitrates be used in stable angina?
Preferred as:
- Combo with BBs/non-DHPs (to blunt nitrate induced increase in HR)
- Short acting prn nitrates to relieve discomfort or prevent ischemia before exertion
190
Why is nitrate monotherapy challenging?
Due to nitrate free period and tolerance
191
What are the cautions of nitrates in stable angina?
Hypertrophic obstructive cardiomyopathy (HOCM), severe aortic stenosis, PDI use
192
Is ivabradine approved in the US?
No
193
What is ivabradine?
HCN channel inhibitors - reduces diastolic depolarization:
- slows HR
- prolongs diastole and improves ventricular filling
- reduces myocardial o2 consumption
- no hemodynamic or conduction abnormalities (vs BBs and CCBs)
194
What is ivabradine approved for?
Approved for angina in Europe and other countries
195
What is ivabradine indicated for?
Indicated for Sx tx of chronic stable angina pectoris in CAD adults w normal sinus rhythm and HR >= 70 bpm
- adults unable to tolerate/CI to use of BBs
- combo w BBs in pts inadequately controlled w an optimal BBs dose
196
What is ivabradine approved for by the FDA?
HF tx, but not SIHD
197
When does ischemia/angina occur in prinzmetal's angina?
- Usually occurs at rest
- Not precipitated by physical exertion or emotional stress
198
What is the ECG associated with prinzmetal's angina?
ST segment elevation
199
At what time of day do prinzmetal angina ischemic episodes most frequently occur?
In the early morning hours
200
What is prinzmetal's angina not necessarily associated with?
Atherosclerosis
201
How is vasospastic angina managed?
- Acute tx: SL NTG, etc
- Chronic tx: CCBs, nitrates, combo therapy
- NEVER BBs
