Sowinski Angina Lectures Flashcards
Clinical syndromes of chronic coronary disease
-Stable angina pectoris: “macrovascular disease”
-Post-ACS; post-revascularization
-Variant or Prinzmetal’s angina: “vasospastic disease”
-Cardiac syndrome X: “microvascular disease”
-Silent myocardial ischemia
Types of angina
-Prinzmetal’s variant angina (vasospasm)
-Chronic stable angina (fixed stenosis)
-Unstable angina (thrombus)
What increases O2 supply?
-Coronary blood flow
-O2 carrying capacity
What increases O2 demand?
-Wall tension
-Contractility
-Heart rate
Pathophysiology of stable angina
-Stable angina pectoris is usually associated with large single to multivessel ASCAD
-Approximately 85% of patients with angina pectoris have significant coronary disease in a major epicardial coronary vessel
Pathophysiology of myocardial ischemia
-Imbalance between myocardial oxygen supply and demand
-Produces disturbances in myocardial function without causing myocardial necrosis
Pathophysiology of angina
Resulting symptoms from ischemia…is a clinical syndrome of chest discomfort
Definition of stable angina pectoris
-Discomfort in the chest and/or adjacent areas
-Caused by myocardial ischemia and associated with a disturbance in myocardial function without myocardial necrosis
-“Stable”: characteristics of an anginal episode have not changed recently
Clinical presentation (PQRST)
-Precipitating factors: Exertion
-Palliative measures: Rest and/or SL NTG
-Quality and quantity of the pain: Squeezing, heaviness, tightening
-Region and radiation: Substernal
-Severity of the pain: ~subjective, > 5 (out of 10)
-Timing and temporal pattern: Lasts <20 min, usually relieved in 5-10 minutes
Classic clinical characteristics of typical angina
-Substernal
-Duration: 0.5-20 min (usually short)
-Relieved by nitroglycerin or rest
-ST-segment depression (during event)
Diagnostic procedures to preform for a patient with angina
-History and physical examination
-Electrocardiogram to look for ST segment depression or elevation
Diagnostic procedures for coronary heart disease
-Cardiac imaging
-Echocardiography
-Cardiac catheritization and coronary angiography
What are the two desired outcomes for the treatment of chronic coronary disease?
-Risk factor modification
-Alleviate acute symptoms
Pharmacotherapy to prevent ACS and death
-Anti-platelet therapy
-Statin therapy: see dyslipidemia lectures
-RAS inhibitors: ACE/ARBs
-Colchicine?
-Beta-blockers
MOA of aspirin
-Acetylation and irreversible inactivation of platelet COX-1
-Blocking of TXA2 synthesis leading to antiplatelet activity
Aspirin loading dose
162-375 mg (typically 375 mg)
Aspirin maintenance dose
75-162 mg daily (typically 81 mg)
Clopidogrel loading dose
300-600 mg
Clopidogrel maintenance dose
75 mg daily
Prasugrel loading dose
60 mg
Prasugrel maintenance dose
10 mg daily
Ticagrelor loading dose
180 mg
Ticagrelor maintenance
90 mg BID
Cangrelor dosing
IV only
Adverse effects of aspirin
-Stomach bleeding
-Bleeding (intracranial and extracranial)
-Hypersensitivity
-Major bleeding: 2-3% in year 1
Which P2Y12 inhibitors are prodrugs?
-Clopidogrel
-Prasugrel
Which P2Y12 inhibitors are not prodrugs?
Ticagrelor
How long does it take the effect of clopidogrel to dissipate?
5 days
How long does it take the effect of prasugrel to dissipate?
7 days
How long does it take the effect of ticagrelor to dissipate?
5 days
Adverse effects of clopidogrel
-Bleeding
-Diarrhea
-Rash
Adverse effects of prasugrel
-Bleeding
-Diarrhea
-Rash
Adverse effects of ticagrelor
-Bleeding
-Bradycardia
-Heart block
-Dyspnea
Pharmacotherapy to treat chronic coronary disease with no history of a stent implantation
-Single-antiplatelet therapy
-Dual-antiplatelet therapy (for certain high-risk patients)
Type of single-antiplatelet therapy
-Aspirin 75-100 mg/day indefinitely (preference for 81 mg)
-Clopidogrel 75 mg/day if contraindicated or intolerant to aspirin
Types of stents
-Bare metal stents
-Drug-eluting stents
Pharmacotherapy for chronic coronary disease before an elective PCI + drug-eluting stent
Aspirin and P2Y12 inhibitor loading dose
Pharmacotherapy for chronic coronary disease after an elective PCI + drug-eluting stent when the patient has a low risk of bleeding
-Dual-antiplatelet therapy for a minimum of 6 months
-Single antiplatelet therapy indefinitely (81 mg aspirin preference)
Pharmacotherapy for chronic coronary disease after an elective PCI + drug-eluting stent when the patient has a high risk of bleeding
-DAPT 1-3 months may be reasonable
-P2Y12 inhibitor for 12 months (Clopidogrel, prasugrel, or ticagrelor do not distinguish choice)
-SAPT indefinitely (preference for 81 mg of aspirin)
Pharmacotherapy following a CABG
Aspirin 81 mg/day indefinitely + clopidogrel 75 mg/day for a year
What must be considered if you choose to use aspirin with ticagrelor?
Aspirin dose MUST BE 100 mg or less
With which patients should an ACEi be considered?
-In all patients with CCD
-Especially in patients with LVEF <40%, HTN, DM or CKD
With which patients should an ARB be considered?
-In those who are intolerant to ACEis due to cough or other adverse effects
-NEVER USE AN ACE AND AN ARB TOGETHER
Mechanism of action of organic nitrates
-Nitric oxide donors and releasers
-Activation of guanylate cyclase
Effects of organic nitrates
-Marked vasodilation which causes a decrease in preload
-Less arteriole dilation, coronary and peripheral
-Minor inhibition of platelet aggregation
Nitroglycerin sublingual tab dosing
0.3-0.6 mg PRN, repeat dose 1-3 times every 5 minutes
Nitroglycerin sublingual spray dosing
0.4 mg/spray PRN, repeat dose 1-3 times every 5 minutes
Counseling points on nitroglycerin sublingual tablets
-Keep in original dark glass container
-No safety cap
-Place under tongue, do not swallow tab
-Remove the cotton plug as soon as you pick up the medication from the pharmacy
-Do not store in humid locations such as your bathroom
-Keep on person at all times
-Teach technique on how to use
-Preventative use instructions
-911 procedures
Counseling points on nitroglycerin sublingual spray
-Spray under tongue, do not inhale
-Do not shake
-Keep on person at all times
-Teach technique on how to use
-Preventative use instructions
-911 procedures
Adverse effects of nitroglycerin
-Headache
-Hypotension
-Dizziness
-Lightheadedness
-Facial flushing
-APAP use, avoid NSAIDs
-Extreme caution with PDEI
Clinical recommendations for nitrates
-Should be utilized in all patients
-Products may also be useful for the prevention of angina, when taken just prior to the initiation of exertion or some other event which precipitates angina
Pharmacotherapy to prevent recurrent ischemia and angina symptoms
-Beta-blockers
-Calcium-channel blockers
-Nitrates
Mechanism of action of beta blockers
Competitive, reversible inhibitors of beta-adrenergic stimulation by catecholamines
Beta blocker desired effects on myocardial oxygen demand
-Reduced HR
-Reduce myocardial contractility
-Reduce arterial BP (afterload)
Beta blocker undesired effect on myocardial oxygen demand
Reduced heart rate leads to an increased diastolic filling time leading to an increased LVEDV resulting in an increased preload
Atenolol receptor selectivity
beta 1
Atenolol maintenance dosage
50-100 mg qd
Metoprolol receptor selectivity
beta 1
Metoprolol IR dosage
50-100 mg bid
Metoprolol XL dosage
100-200 mg qd
Propranolol receptor selectivity
beta 1 and 2
Propranolol dosing
80-160 mg qd
Beta blocker adverse effects
-Sinus bradycardia
-Sinus arrest
-AV block
-Reduced LVEF
-Bronchoconstriction
-Fatigue
-Depression
-Nightmares
-Sexual dysfunction
-Exercise intolerance
-Intensification of insulin-induced hypoglycemia
-Peripheral vascular complication
-Beta blocker withdrawal syndrome
Beta blocker dosage and monitoring parameters
-Initiate at lowest dose and titrate to symptom reduction
-Monitor heart rate
-Monitor amount of painful episodes
Calcium channel blockers mechanism of action
-Decrease influx of trigger calcium in myocytes
-Decreased chronotropy in nodal cells; inotropy in myocytes
-Vasodilation
Dihydropyridine calcium channel blocker adverse effects
-Hypotension
-Flushing
-Headache
-Dizziness
-Reduced myocardial contractility
-Peripheral edema
-Reflex adrenergic activation
Non-dihydropyridine calcium channel blocker adverse effects
-Reduced myocardial contractility (V>D)
-AV/SA nodal conduction disturbances: bradycardia and atrioventricular block (V>D)
-Hypotension
-Flushing
-Headache
-Dizziness
-Constipation (V>D)
Calcium channel blockers dosing
Initiate at lowest dose and titrate to symptom reduction
Monitoring parameters for DHP calcium channel blockers
-Edema
-Blood pressure
Monitoring parameters for non-DHP calcium channel blockers
-Heart rate
What is nitrate tolerance?
Decreased response in the presence of continued or frequently administered nitrates
How long should the nitrate free period?
Nitrate free period of at least 10-12 hours
Pharmacology of nitrate tolerance
-Reversible in absence of drug
-ALDH2 inactivation in mitochondria
-ISMN and ISDN also elicit tolerance but via a slower, less understood process
Nitrate patches patient counseling
-Discussion of nitrate free period
-Apply patches between elbows and knees
-Apply the patch to clean, dry, hairless skin that is not irritated, scarred, burned, broken, or calloused
-Choose a different area each day
-You may shower while wearing patch
-Do not cut the patch
-Wash hands before and after
Ranolazine mechanism of action
Inhibition of late inward Na+ current in ischemic myocytes, decreased intracellular Na+ leads to a decrease in Ca2+ influx
What differentiates ranolazine from other anti-ischemic agents?
DOES NOT affect HR, BP, inotropy, or perfusion like traditional anti-ischemic agents
How to dose ranolazine
Titration from 500 BID to 1000 BID over 1-2 weeks
When do you use ranolazine?
As add-on therapy for the symptomatic treatment of patients with stable angina pectoris who are inadequately controlled or intolerant to first-line antianginal therapies
When can you use ranolazine as a monotherapy for the treatment of chronic angina?
Only when BP/HR too low with first-line agents
Which medications should ranolazine not be used with?
Strong CYP3A inducers or inhibitors
Adverse effects of ranolazine
-Constipation
-Nausea
-Dizziness
-Headache
-Dose related increase in QT-interval
Which drug is the first choice of use when selecting an agent for treatment for ischemic heart disease?
Beta blockers for patients without contraindications
Compelling indications for beta blockers
-Stable heart failure
-History of myocardial infarction
-Angina
Beta blocker contraindications
-Bradycardia
-High degree AV block
-Sick sinus syndrome (with no pacemaker)
When are non-DHP CCBs preferred when treating ischemic heart disease?
-If the patient has contraindications to beta blockers
-Unacceptable side effects to beta blockers
-Potentially useful in chronic lung diseases, HTN, DM and peripheral vascular disease
Contraindications to non-DHP CCBs
-HFrEF
-Bradycardia
-High degree AV block
-Sick sinus syndrome
Contraindications to DHP CCBs
HFrEF (except amlodipine and felodipine)
Why is it not recommended to use nitrates as monotherapy?
Can be challenging due to nitrate free period and tolerance
Cautions to consider when using nitrates
-Hypertrophic obstructive cardiomyopathy
-Severe aortic stenosis
-Phosphodiesterase use
Why would we use nitrates with beta blockers?
To block reflex tachycardia
