CVPR Week 4: Pharmacology of ischemic heart disease Flashcards
1
Q
Objectives
A
2
Q
Strategies to manage ischemic heart disease
2 listed
A
- ↓ Oxygen demand
- ↑ Oxygen delivery to the myocardium
3
Q
Drug classes to treat angina pectoris
3 listed
A
- Vasodilators
- cardiac depressants
- other drugs (metabolic modifiers, rate inhibitors)
4
Q
Examples of vasodilators used to treat angina pectoris
A
- Nitrates
- Ca2+ channel blockers (verapamil)
5
Q
Examples of cardiac depressants used to treat angina pectoris
A
- Ca2+ channel blockers (verapamil)
- Beta blockers (propranolol)
6
Q
Propranolol drug class
A
β blockers
7
Q
Verapamil drug class
A
Ca2+ blockers
8
Q
Explain the balance of myocardial O2 supply and demand
A
9
Q
Explain the factors of myocardial O2 supply
3 listed
A
- Heart rate (reduces supply due to reduced diastolic time)
- O2 content of the blood
- Coronary perfusion
10
Q
Explain the factors of myocardial O2 demand
4 listed
A
- ↑ HR
- ↑ contractility
- ↑ ventricular wall tension (↑ afterload and ↑ preload)
11
Q
O2 supply and demand modifiers
A
12
Q
Epidemiology of Chronic Coronary artery disease
A
13
Q
Coronary atherosclerosis evolves into
A
angina
then
heart failure
14
Q
Angina semantic definition
A
Greek meaning to strangle, throttle or choke
15
Q
Angina pectoris pain characteristics
A
deep visceral pressure or squeezing sensation rather than sharp or stabbing or pinprick-like pain
16
Q
Angina pectoris location
A
- The pain almost always has a substernal component although some patients complain of pain only on the right or left side of the chest, upper back or epigastrum
- The pain may radiate from the thorax to the jaw, neck or arm
17
Q
Angina pectoris precipitating factors
A
Angina is usually precipitated by exertion, emotional upset or other events that obviously increase myocardial oxygen demand such as rapid tachyarrhythmias or extreme elevations in blood pressure
18
Q
Angina pectoris duration
A
- is transient usually lasting between 2 and 30 minutes
- It is relieved by cessation of the precipitating event such as exercise or by the administration of treatment such as sublingual nitroglycerin
19
Q
Types of angina
3 listed
A
- Stable (classic or effort)
- Vasospastic or variant (Prinzmetal)
- Unstable (medical emergency)
20
Q
Prinzmetal angina is what?
A
- Vasospastic or variant angina which has localized spasms associated with atheroma
21
Q
Vasospastic angina AKA
A
Variant
or
Prinzmetal
22
Q
Description of vasospastic angina
A
Localized spasms associated with atheroma
23
Q
Description of unstable angina
A
angina when at rest or when it becomes longer or more frequent
24
Q
Goals of managing stable angina
2 listed
A
- Reduce symptoms and ischemia
- Prevent MI and death
25
Methods of managing stable angina
5 listed
* Treat associated conditions that can increase oxygen demand or limit oxygen supply
* Manage risk factors (obesity, hyperlipidemia, smoking, etc.)
* Utilize antiplatelet agents (aspirin or clopidogrel)
* Coronary revascularization
* USe pharmacological agents
26
Risk factors for angina
* Advancing age
* Smoking
* DM
* Dyslipidemia (statins are very beneficial)
* Hypertension
* Obesity
* Family Hx of premature heart disease
* Physical inactivity
* Psychosocial factors
27
Factors that can aggravate myocardial ischemia: Increasing oxygen demand
6 listed
* Tachycardia
* Hypertension
* Hyperthyroidism
* Heart failure
* Valvular heart disease
* Catecholamine analogs (bronchodialators, TCAs)
28
Factors that can aggravate myocardial ischemia: Reducing oxygen supply
* Tachycardia
* Anemia
* Hypoxia
* Hypotension
29
Explain methods of coronary revascularization
30
Pharmacological agents to treat stable angina
5 listed
* Nitrates
* β blockers
* Ca2+ channel antagonists
* Ranolazine
* Ivabradine
31
Examples of nitrates
4 listed
* Trinitrotoluene (TNT) NOT A MEDICATION
* Nitroglycerine (glyceryl trinitrate)
* Isosorbide dinitrate
* Isosorbide mononitrate
32
Metabolism of nitrates
Organic nitrate reductase in the liver removes nitrate groups in a step-wise fashion which results in a short half-life
33
Oral bioavailability of nitroglycerin
\<10-20%
34
Oral bioavailability of Isosorbide dinitrate
\< 10 - 20%
35
Oral bioavailability of isosorbide mononitrate
100 %
36
Nitroglycerin routes of administration
6 listed
* Sublingual
* Buccal
* Parenteral
* Transdermal
* Topical
* Oral sustained release
37
Isosorbide dinitrate routes of administration
3 listed
* Sublingual
* oral chewable
* oral sustained release
38
Isosorbide mononitrate routes of administration
2 listed
* Oral
* Oral sustained release
39
Nitrovasodilators MOA
Aldehyde dehydrogenase takes NO2- off of nitrates
NO2- is broke ndown into NO
NO activates Guanylyl cyclase to form cGMP
cGMP activates cGMP-dependent kinase (PKG)
cGMP-dependent kinase (PKG) has various effects on vasculature such as
1. Potentiates K+ channels leading to smooth muscle relaxation
2. Decreases cytoplasmic [Ca2+] leading to smooth muscle relaxation
3. Activates myosin-light chain phosphotase (MLCP) leading to smooth muscle relaxation
40
cGMP-dependent kinase (PKG) has various effects on vasculature such as
3 listed
1. Potentiates K+ channels leading to smooth muscle relaxation
2. Decreases cytoplasmic [Ca2+] leading to smooth muscle relaxation
3. Activates myosin-light chain phosphotase (MLCP) leading to smooth muscle relaxation
41
PKG AKA
cGMP-dependent kinase (PKG)
42
Riociguat MOA
activates guanylyl cyclase to produce more cGMP to promote more vasodilation and smooth muscle relaxation
43
Sildenafil AKA
Viagra
44
Sildenafil MOA
Inhibits PDE5 preventing the breakdown of cGMP to GMP thereby increasing smooth muscle relaxation and vasodilation
45
PDE5 AKA
Phosphodiesterase Type 5
46
PDE5 function
Breaks down cGMP into GMP
47
The formation of nitric oxide from nitrates is dependent upon?
ALDH2 (Mitochondrial aldehyde dehydrogenase)
48
ALDH2 AKA
Mitochondrial aldehyde dehydrogenase
49
ALDH2 MOA
takes nitrates into NO2- which can be further processed into NO
50
NO AKA
Nitric oxide
51
NO2- AKA
Nitrite
52
Polymorphisms in ALDH2 can cause
reduced effectiveness for treatment of angina with nitrates
because they can't be broken down into NO
53
Nitrovasodilator organ system effects
7 listed
* Relax veins \> arteries
* Increase venous capacitance
* Decrease preload
* Decrease pulmonary vascular pressure
* Heart size is decreased
* Decreased cardiac output
* Dilate epicardial coronaries
54
Identify
55
Beneficial effects and the result of angina treatment with nitrates
5 listed
56
Describe coronary steal
* if no drug in someone with CAD
* showing how the fully dilated arterioles cant fill
* Dipyridamole well dilate the healthy artery and will steal away blood from the affected side making the ischemia worse (base for pharmacological induction of ischemia in the stress test)
* nitrates dilate the collaterals instead of the main arteries which don't produce the steal effect phenomenon
57
Additional beneficial effects of nitrates
58
Adverse effects of nitrates
Reflex tachycardia - increase mycardial oxygen demand and reduce coronary perfusion
Reflex increase in contractility which will further increase the myocardial oxygen requirements
59
Amyl Nitrite caveat
* induce the conversion of hemoglobin into Methemoglobin (ferric iron-lower O2 affinity)
* so causes methhemoglobinemia
* Treatment is methylene blue
60
Nitrites and cyanide poisoning
The bond between cyanide and cytochrome oxidase is weaker than that between cyanide and methemoglobin which leads to the transfer of cyanide from mitochondria to the circulation
61
The treatment of choice for cyanide poisoning
Hydroxycobalamin (form of vitamin B12) with high cyanide affinity
62
Nitrovasodilators adverse effects List
8 Listed
might have to do some combining of flashcards
* Orthostatic hypotension (due to increased venous capacitance)
* syncope (due to a decrease in arterial pressure)
* reflex tachycardia (due to decreased atrial pressure)
* throbbing headache (due to the dilation of meningeal arteries)
* Increase in intracranial pressure (be careful in patients with trauma)
* Use without interruption will result in tachyphylaxis (tolerance to nitrates)
* Common with long-acting preparations or continuous IV infusions (Monday disease in explosive manufacturing)
* sudden termination from long-acting preparations can have a rebound effect and can worsen angina
63
Monday disease description
Common with long-acting preparations or continuous IV infusions (Monday disease in explosive manufacturing) tolerance to nitrates over week, lose tolerance over the weekend and are sick again on monday
64
Nitrovasodilators drug interactions
* Sildenafil (excessive effect)
* Riociguat (excessive effect)
* Anti-hypertensive meds
* Morphine (decreases sympathetic efferent discharge)
* Anesthetics
* CNS depressants
65
Other uses of nitrovasodilators
2 listed
1. Hypertensive emergencies (Na+ Nitroprusside)
2. Congestive heart failure (Isosorbide dinitrate + hydralazine)
66
Na+ Nitroprusside description
A complex of cyanide, ironn and nitroso moiety
Does not need enzymatic denitration!
67
Na+ Nitroprusside caveat
does not require enzymatic degradation
68
Na+ Nitroprusside uses
used for hypertensive emergencies and severe heart failure
69
Na+ Nitroprusside effects
Dilates both veins and arteries
## Footnote
**Decreases peripheral resistance, or ↓ Cardiac output (RESEARCH THIS IDK WHAT VALENZUELA SAID) the effect on preload sometimes offsets the increase in cardiac output that is normally seen with an arterial vasodilator**
70
Na+ Nitroprusside metabolism
* Rapidly metabolized in the RBCs
* Cyanide is metabolized by rhodanase combined to less toxic thiocyanate in the presence of a sulfur donor (thiosulfate)
* Thiocyanate is slowly eliminated by the kidneys
71
Cyanide is metabolized by?
rhodanase
72
Na+ Nitroprusside side effects
3 listed
* an excessive decrease in blood pressure
* Cyanide toxicity (to decrease risk co-administer sodium thiosulfate or hydroxocobalamin)
* Thiocyanide toxicity in patients with renal failure can cause (Psychosis and seizures)
73
Isosorbide dinitrate + hydralazine AKA
BiDil because Bi = Two and Dil = dilators
74
Hydralazine indications ORAL
2 listed
* Advanced?refractory heart failure (with nitrates), particularly in African-Americans
* Used for severe hypertension NEVER USED ALONE Usually combined with a β blocker to prevent reflex tachycardia, a diuretic must also be used to prevent fluid retention (Triple Therapy)
75
Hydralazine indications IV
Indicated in some cases of eclampsia
76
Hydralazine MOA
* ↑ NO release
* reduction of superoxide
77
Hydralazine adverse effects
4 listed
* Tachycardia
* fluid retention
* aggravation of angina
* lupus-like syndrome
78
Drugs that cause Lupus-like-Syndrome
* **H**ydralazine
* **I**soniazide
* **P**rocainamide
* **P**henytoin
It is not **HIPP** to have lupus
79
β blockers antianginal MOA
↓ Hr and Contractility
↓ CO
Additionally
↓ Renin secretion
80
β blockers antianginal Pros
↓ O2 consumption
↑ Diastolic coronary perfusion time
81
β blockers antianginal Cons
2 listed
↑ End diastolic volume
↑ Ejection time
**These can be mitigated by coadministration with a nitrate**
82
β blockers antianginal selectivity considerations
Avoid non-selective agents to avoid complicated peripheral vascular disease etc. and partial agonists with intrinsic sympathomimetic activity such as Pindolol (non-selective agonist) or Acebutolol (β1 selective agonist)
83
Pindolol drug class
non-selective β agonist
84
Acebutolol drug class
β1 selective agonist
85
How should β blockers be used in angina
recommended that β blockers be used as a first-line therapy in the treatment of chronic stable angina
86
Selectivity in β-blockers for angina
cardioselective β blockers offer the potential advantage of not interfering with bronchodilation or peripheral vasodilation and are equally effective in reducing anginal attacks and increasing exercise capacity
87
β blockers effectiveness for angina
β blockers decrease angina frequency and threshold but have nevere been shownn to decrease mortality, cardiovascular events or improve survival in patients with stable angina
88
β blockers post acute MI
β blockers do reduce short-term complications and improve long-term survival in patients after an acute MI with or without revascularization
89
Ca2+ channel antagonists types for angina
2 Listed
Cardiac \> Vascular
Vascular \> Cardiac
**EXCEPT** for **immediate-release dehydropyridines**
90
Ca2+ channel antagonists for angina with Cardiac \> Vascular
* Verapamil
* Diltiazem
91
Ca2+ channel antagonists for angina with Vascular \> Cardiac
* Dihydropyridines such as Nifedipine except for immediate release
* commonly used Amlodipine
* used in hypertensive emergencies Clevidipine
92
Ca2+ channel antagonists used in emergent situations
Clevidipine
93
Clevidipine drug class
Dihydropyridines: Ca2+ channel antagonist with Vascular \> Cardiac selectivity
94
Ca2+ channel antagonists MOA for antianginal action for Cardiac selective (non-dihydropyridines
↓ contractility (Verapamil-Diltiazem)
↓CO (Verapamil-Diltiazem)
95
Ca2+ channel antagonists MOA for antianginal action for Vascular Selective (Dihydropyridines)
↓ Peripheral resistance (Dihydropyridines)
↓ Coronary tone (Dihydropyridines) (Useful in variant angina)
96
Ca2+ channel antagonists antiangina treatment pros
* ↓O2 consumption
* ↑ Diastolic coronary perfusion time
* Dilate coronaries (only class of drugs that does this and is a particularly helpful action for angina)
97
Amlodipine drug class
Long-acting dihydropyridine
98
Ca2+ channel antagonists antiangina treatment Cons
↑ HR (Dihydropyridines)
↓ BP (Dihydropyridines) (can be massive)
99
Amlodipine benefits
* A slow smooth onset of action
* long half-life (once a day administration)
* Antiatherogenic action (hyperlipidemia increases Ca2+ influx to smooth muscle?)
* Decreased progression of carotid atherosclerosis (but not coronary)
* Reduce the risk of major cardiovascular events
* Minimal negative ionotropic effects (useful in patients with LV dysfunction)
100
Ca2+ channel antagonist that can be used in patients with LV dysfunction
Amlodipine, because of its minimal negative ionotropic effect
101
Effects of nitrates alone and with β-blockers or Ca2+ channel blockers for treating Angina
Know this table
Table 12-1 Katzung Pharm review
102
Nitrates effect on HR
undesirable increase in HR due to reflex tachycardia
103
Nitrates effect on contractility
undesirable increase
104
Nitrates effect on ejection time
Decreases as a result of the baroreceptor reflex
105
Ranolazine MOA
blocks late INa+ which is enhanced in ischemia and facilitates Ca2+ intake via NCX
blocks late sodium currents in the context of lidocaine and perhaps its how lidocaine shortens the action potential duration
Late INa are essentially coupled with Na+ /Ca2+ exchanger
by blocking this channel reducing Ca2+ influx from NCX which decreases diastolic tension, cardiac contractility and improves blood through coronary arteries
106
Ivabradine MOA
blocks the funny current directly reducing HR and O2 consumption
107
Vasospastic angina common causes
3 listed
* Smoking
* excessive alcohol consumption
* stress
108
Know this whole table
109
Vasospastic Treatment of angina
* statins
* low dose aspirin (high dose aspirin will block the production of prostacyclin which has vasodilatory actions)
* Avoid using sumatriptan (a 5-HT1D receptor agonist) for migraines
* Ca2+ channel blockers and nitrates are effective (but not β-blockers, particularly non-selective agents which can aggravate vasospasm due to antagonism of β2 coronary artery dilatory actions
110
Unstable Angina Non-STEMI and normal enzymes: Relief of ischemic pain
5 listed
* O2 if saturation \< 90%
* Nitroglycerin (except with right ventricular infarction
* Severe aortic stenosis
* or Sildenafil use within 24hrs
* morphine only if pain control is unacceptable
111
Unstable Angina Non-STEMI and normal enzymes: Assess hemodynamic status and correction of abnormalities
* Hypertension and tachycardia both of which will markedly increase myocardial oxygen consumption requirements may be managed with β-blockers and IV nitroglycerin
112
Unstable Angina Non-STEMI and normal enzymes: Estimation of risk and choice of a management strategy
* ie an early invasive strategy (percutaneous coronary intervention or coronary artery bypass graft surgery; examples of indications
* hemodynamic instability, sustained ventricular arrhythmias, etc) versus a conservative strategy with medical therapy
113
Unstable Angina STEMI: Relief of ischemic pain
* O2 if saturation \< 90%
* Nitroglycerin (except with right ventricular infarction
* Severe aortic stenosis
* or Sildenafil use within 24hrs
* morphine only if pain control is unacceptable
* same as NON-STEMI
114
Unstable Angina STEMI: Assessment of the patients hemodynamic status and correction of abnormalities
Hypertension and tachycardia both of which will markedly increase myocardial oxygen consumption requirements may be managed with β-blockers and IV nitroglycerin
same as non-STEMI
115
Unstable Angina STEMI: Initiation of reperfusion therapy
Initiation of reperfusion therapy with primary percutaneous coronary intervention (PCl- should be accomplished in \< 90 min from onset)
or if this isn't possible
fibrinolysis (should be accomplished in \< 30 min from onset)
116
Unstable Angina STEMI: Antithrombotic therapy
to prevent rethrombosis or acute stent thrombosis (aspirin and heparin)
117
Unstable Angina STEMI: β-blocker therapy
to prevent recurrent ischemia and life-threatening ventricular arrhythmias (metoprolol or atenolol)
Same as non-STEMI
118
Unstable Angina Non-STEMI and normal enzymes: Initiation of antithrombotic therapy
(including antiplatelet and anticoagulant therapies) to prevent further thrombosis of or embolism from an ulcerated plaque
119
Unstable Angina Non-STEMI and normal enzymes: β-blocker therapy
to prevent recurrent ischemia and life-threatening ventricular arrhythmias (metoprolol or atenolol)
120
Overview of clinical management of unstable angina
121
Long term care of unstable angina
122
READ and Know it
this can also happen with patients that have aortic stenosis
123
MI involving the Right Ventricle
124
inferior myocardial infarctions
β-blockers can trigger bradycardia and AV block
