CCD Lecture1-6 Flashcards
Chronic Coronary Disease
-stable angina
-stable ischemic heart disease (SIHD)
-post-ACS
Clinical syndromes of CCD
-stable angina (macrovascular disease)
-stable outpatient post ACS
-variant/prinzmetal’s angina (vasospastic disease)
-INOCAD/Cardiac syndrome X
-silent myocardial ischemia
Types of angina
-prinzmetal/variant (vasospastic): artery closes bc spasm
-stable angina (fixed stenosis): plaque
-unstable: thrombus
Myocardial supply and demand
-imbalance = ischemia
-Contractility
-HR
-Preload
-Afterload
factors increasing demand
-inc HR
-inc afterload (from vasoconstriction)
-inc preload (from vasoconstriction)
-all = more O2 used
Factors decreasing supply
-inc HR
-inc preload
stable angina patho
-associated w ASCAD
-85% of pt have significant CAD (>70-75% reduction)
-most pt have at least one occlusion
-ischemia caused by fixed obstruction in epicardial artery
epicardial vessels
-Right Coronary Artery (RCA): big one on left side
-Left Main (LM): goes down back of heart
-Left circumplex (LCX): goes down right side towards back
-Left Anterior Descending (LAD): big one in middle also where widowmaker happens
Myocardial Ischemia
-imbalance between supply and demand
-effort induced when low supply
-disturbs heart function w/o necrosis
-presents as angina
Stable Angina
-resulting sx from ischemia
-chest discomfort
-relieves itself
Angina pain
-chest, left arm, jaw
-women and diabetics (nerve damage) often don’t present w pain
Angina ECG
-ST depression only during event
Diagnosis of angina
-hx and physical exam
-st depression during ischemia (elevation in variant angina tho)
-cardiac imaging (stress test, PET scan, heart scan that gives ca score but kinda sketchy)
-echocardiography (ultrasound)
-catheterization and angiography (dye in arteries)
Some true statements
-women and diabetes have atypical sx
-angina is discomfort associated w ischemia
-prinzmetal’s/variant angina is associated w vasospasm
-CCD is usually associated w ASCAD
Angina tx goals in dyslipidemia and HTN
-50% reduction of LDL
-BP < 130/80
angina risk factor mods
-respiratory virus vax
-minimize alc consumption (2 drinks/day for men 1 for women)
CCD treatment goals
-reduce ACS risk
-manage angina
Tx to reduce heart risk
- Antiplatelets
- Statin
- ACE/ARB
- Colchicine maybe
- Beta Blockers
Antiplatelet tx options
-Aspririn
-P2Y12 inhibitors (clopidogrel, prasugrel, ticagrelor, cangreor (IV only))
Aspirin
-COX-1 but COX-2 at high doses (bad)
-81mg maintenance dose
-bleeding side effects
-Ecotrin
COX-1 inhibition
-block TXA2 synthesis
-interferes w platelet aggregation and blocks thrombi
-COX-2 blocks PGI tho which is an anticoagulant = higher thrombotic risk if COX-2 blocked
P2Y12 inhibitors
-block P2Y12
-blocks ADP induced platelet activation/aggregation
-no effect on TXA2
-prodrugs are activated by CYP
-must stop 5-7days before surgery
-peak in 2-4 hours
-all increase bleeding risk when combo w aspirin
Clopidogrel (Plavix)
-P2Y12 prodrug (thienopyridine)
-75mg maintenance
-CYP dependent
-bleeding, diarrhea, RASH
-1% inc in bleeding risk w ASA
Prasugrel (Effient)
-P2Y12 prodrug (thienopyridine)
-10mg maintenance
-less CYP dependent than clopidogrel
-bleeding, diarrhea, RASH
-0.6% in bleeding risk w ASA
-DO NOT use in hx of TIA, ICH, stroke
Ticagrelor (Brillinta)
-direct acting P2Y12 (cyclopentyl-traizole-pyrimidine)
-90mg BID! maintenance
-bleeding
-bradycardia
-heart block
-dyspnea
Antiplatelet tx in different scenarios
- CCD no stent = SAPT, DAPT for high risk pt
- CCD PCI + drug stent (DES) = DAPT 6 months (1-3 months for high bleeding risk)
- CCD and CABG = DAPT 12 months
- Post-ACS (discussed ACS lectures)
Single Antiplatelet therapy (SAPT)
-all pt w CCD
-81mg ASA for life
-75mg clopidogrel if can’t take ASA (or maintenance of other P2Y12)
Dual-Antiplatelet therapy (DAPT)
-ASA + P2Y12 (clopidogrel 75mg preferred)
-prasugrel 10mg qd or ticagrelor 90mg BID
-some high risk CCD pt no stent
-6 months if PCI + stent (1-3 if high risk)
-12 months for CABG
CCD no stent tx for secondary prevention
-SAPT ASA (81mg) for life
-DAPT for certain high risk pt but not necessarily better
Intracoronary Artery stents
-bare metal (uncommon)
-drug eluting (reduce inflammation at site): names end in -olimus 1-3 generations
CCD PCI + DES tx for 2’ prevention
-BEFORE procedure: ASA and P2Y12 at LOADING dose (ACS lectures)
-DAPT 6 months for low risk
-DAPT 1-3 months for high bleed risk or SAPT w P2Y12 for 12 months???
-SAPT indefinitely
-guidelines prefer clopidogrel as P2Y12
CCD w CABG secondary prevention
-DAPT 12 months (some controversey)
-SAPT indefinitely
-clopidogrel may be reasonable for 12 months
Notes about antiplatelets
-for pt that don’t require antiCOAGULANTs for other probs
-ASA must be <100mg with ticagrelor
-use of PPI with DAPT might reduce GI bleeding risk
-must stop 5-7 days before a surgery
ACEs and ARBs
-stbailize plaque (prevent rupture)
-improve ET function
-inhibit vasc smooth muscle cell growth
-dec macrophage migration
-some antiox properties
-does NOT improve sx ischemia (angina)
-for all pt with CCD (esp LVEF<40%, DM, HTN, CKD)
-ARBs if cough
-dont combo ACE and ARB
Colchicine
-tx GOUT
-reduce inflammation (IL-1B and IL-18)
-large clinical trials evaluating benefit
-might reduce risk of MI, stroke, coronary revasc, and CV deaths in adults
-unclear role (hsCRP>2 high risk)
-CYP substrate
-do NOT use in renal and hepatic disease
Targets to relieve sx of ischemia/angina
-increase supply: dilation
-decrease demand: HR, contractility, preload (LVEV), afterload (systolic)
Nitrate effect on demand
-inc HR
-dec systloic pressure (afterload)
-dec LV volume (preload)
B-blocker effect on demand
-dec HR
-dec contractility
-dec systolic pressure (afterload)
-inc LV volume? (preload)
DHP CCB effect on demand
-inc HR
-no or dec contractility
-dec systolic pressure the most (afterload)
-no change or dec LV volume
non-DHP CCB effect on demand (verapamil and diltiazem)
-dec HR (more w verapamil)
-no or dec contractility
-dec systolic pressure (afterload)
-no or dec LV volume
Tx options to relieve angina
-Nitrates
-Beta Blockers
-CCBs
-Ranolazine
Nitrate MOA
-NO donors/releasers
-activate guanylate cyclase (GTP to cGMP = relaxation of vasc smooth muscle= dilation)
-venodilation =. dec preload
-less arteriole dilation, coronary and peripheral
-minor inhibition of platelet aggregation
-slide 74
Nitrate clinical effects
-dec demand by dec preload and dec LV volume via vasodilation
-inc supply by vasodilation of coronary vessels
Nitrate acute agents
-NTG tabs (Nitrostat) 0.4mg
-NTG spray (Nitromist) 0.4mg
-NTG packets (GOnitro) 0.4mg
-PRN repeat dose 1-3 time q5 min, call 911 if first dose doesn’t work
NTG tabs vs spray
-tabs lower shelf life, keep cool so NTG doesn;t evaporate
–spray can be stored anywhere
-either way keep on person at all times and sit down before taking in case pass out
NTG tabs education
-keep in og DARK GLASS container
-no safety cap
-place UNDER tongue NO SWALLOW
-don’t store in humid bathroom
-refill q6months
NTG spray education points
-spray UNDER tongue NO inhale
-do NOT shake
-refill q3 years
Nitrates adverse effects and monitoring
-headache
-hypotension
-dizziness
-lightheadedness
-flushing
-reflex tachycardia that could make angina worse
-use acetaminophen?
-caution w PDE5i
PDEi and nitrates
-inc ability of nitrates to dec BP
-if angina happens during intercourse do NOT take nitrate, call 911
-potentially fatal
-wait 12-48h from taking PDE to take nitrate (12h for avanafil, 24h for slidenafil and vardenafil and 48h for tadalafil)
Pharmacotherapy to PREVENT RECURRENT ischemia and angina sx
- B-blockers
- CCBs
- Nitrates
- Ranolazine maybe
Combos:
-nitrates and BBs
-nitrates and NON-dhp ccbs
-DHP-ccb and BB
-triple
B-blocker MOA
-block NE or EPI mediated activation of B1/B2 that inc HR, contracility, conduction velocity
-competitive, REVERSIBLE inhibitors of B-andreergic stimulation by catecholamines
B-blocker effects
-dec HR during sympathetic stimulation
-reduce contractility
-reduce arterial BP (afterload)
-undesired inc in preload bc reducing HR inc filling time which inc LVEDV = inc demand
-reduced ventricular arrhythmias and remodeling
-use B1 over nonselective in pt w airway disease
-high doses of B1 will block B2
B-Blocker drugs
-Atenolol (tenormin)
-Bisoprolol (Zebeta)
-Carvedilol
-Metoprolol succinate (toprol)
-metoprolol tartrate (Lopressor)
-Propranolol (Inderal)
Atenolol
-Tenormin
-B1
-100mg max until B2 effects
-low lipid solubility
-renal elimination
Bisoprolol
-Zebeta
-B1
-low lipid solubility
-renal elmination
Carvedilol
-Coreg
-B1, B2, a1 (more effect on BP)
-BID
-high lipid solubility
-hepatic elimination
Metoprolol succinate and tartrate
-Lopressor and Toprol
-B1
-max 200mg (succinate)until B2 effects
-Tartrate is BID
-mod lipid solubility
-hepatic elimination
Propranolol
-Inderal
-TID or LA qd
-high lipid solubility
-hepatic elimination
B-blockers to avoid
-Pindolol and acebutolol
-intrinsic sympathomimetic activity = inc HR at rest
B-blocker adverse effects
-sinus bradycardia
-sinus arrest
-AV block
-reduced LVEF
-bronchoconstriction
-mask hypOglycemia
-fatigue
-depression
-nightmare
-sexual dysfunction
-exercise intolerance
-withdrawal
B-blocker withdrawal syndrome
-up regulation of B receptors
-inc response to SNS = angina
-taper off
B-blocker monitoring
-start at lowest dose and titrate up
-goal HR: 50-60bpm, <100bpm during exercise or 75% of HR that causes angina
-use NTG for painful episodes
CCB MOA
-dec influx of Ca in myocytes
-dec chronotropy (rate) in nodal cells (less in non-DHPs)
-dec inotropy (contractility) in myocytes
-vasodilation
Myocardial vs vascular selectivity
-non-DHPs have myocardial selectivity = similar effect as B-blockers but also w vasodilation
-DHPs bind more in vasculature than heart = vasodilation
-nifedipine and amlodipine (DHPs) 10:1 vasc:myocardial selectivity
-100:1 in felodipine, isradipine, nicardipine
short-acting DHP CCBs
-DO NOT USE EVER
-TID versions of nifedipine and nicardipine
medium-acting DHP CCBs
-nicardipine BID
-isradipine BID
-prob not using as often as long acting
Long acting DHP CCBs
-amlodipine (Norvasc)
-felodipine (Plendil)
-nifedipine-CC or XL
-Nisoldipine
-all qd
non-DHP CCBs
-Verapamil
-Diltiazem
-lots of dif dosage forms
DHP adverse effects
-more vascular
-hypotension
-flushing
-HA
-dizziness
-peripheral edema from arteriolar vasodilation (not fixed by diuretics, lower the dose)
-reduced contractility
-reflex adrenergic activation
non-DHP adverse effects
-more heart related, similar to B-blockers
-Verapamil worse than diltiazem
-dec contractility
-bradycardia
-AV block
-CONSTIPATION
-hypotension
-flushing
-HA
-dizziness
CCB monitoring
-lowest dose then titrate up
-use NTG for painful episodes
-DHP: BP
-non-DHP: BP and HR
Nitrates
-NitroDur (patch)
-NitroBid (ointment)
-ISDN tabs (Isordil and )
-ISMN tabs (Ismo and monoket)
-other quizlet for dosing
Nitrate tolerance
-dec response in presence of continuous nitrates
-take a nitrate free period of 10-12 hours (concentration of zero)
Nitrate patch education
-apply between elbows and knees
-apply to clean, dry, hairless, unbroken skin
-dif area each day
-ok to shower
-do not cut patch
NTG ointment education
-like patched
-do not rub or masage ointment
-dont cover the area
Nitrate monitoring
-start at lowest dose and go up
-NTG for episodes
-reflex tachycardia
-dec BP
Ranolazine MOA
-inhibit lare Na current in ischemic myocytes
-dec intracellular Na = dec Ca influx
-does NOT affect HR, BP, inotropy, or perfusion
Ranolazine
-500mg BID go up to1000mg BID over 1-2 weeks
-add-on therapy when first-lines dont work
-add to CCBs, BBs, nitrates
-monotherapy only when BP/HR too low w first-line agents
Ranolazine stuff
-metabolized by CYP3A4 and CYP2D6
-prone to drug interations
-do NOT give w 3A inhibitors: KTZ, ITZ, PIs clarithromycin or inducers: CBZ, RIF, st.johns
-limit dose to 500mg BID w moderate inhibitors (DILT!!, VER!!, ERY, FLZ)
-inhibits CYP3A
Ranolazine adverse effects
-constipation
-nausea
-dizziness
-HA
-dose related inc in QT interval (dont use w other drugs w QTC prolongation): arrhythmia and severe tachycardia
Case for selecting B-blockers for angina prevention
-first choice if no Contraindications
-good for stable HF or hx of MI
-good in AFib, high HR, migraines
-AVOID in: vasospatiz/prinzmetal’s angina, conduction disturbances, cocaine induced MI
B-blocker contraindications
-bradycardia (HR<50)
-high degree of AV block or sick sinuse syndrome w no pacemaker
Place of CCBs in angina prevention
-non-DHPs preferred if containdiactions/AEs to B-blockers
-good for chronic lung diseases, HTN, DM, and PVD
nonDHP CCB contraindications
-HRrEF
-bradycardia
-high degree of AV block or sinus syndrome
DHP CCB contraindications
-HFrEF
-except amlodipine and felodipine u can use those
Nitrate place in therapy for angina prevention
-rarely as monotherapy
-combo w BB/non-DHPS to reduce nitrate induce HR inc
-short acting PRN nitrates are for discomfort
Nitrate cautions
-HOCM
-severe aortic stenosis
-PDI use
Clinical conditions that favor BB use
-prior ACS/MI!!!
-HF/LVD!!!!
-tachycardia
-Afib
-arrhythmias
-migraines
-Hyperthyroidism (block SNS response tot thyroid horomones)
Clinical conditions that favor CCBs
-HTN
-DM
-PVD/Raynaud’
-severe asthma/COPD
-prinzmetal’s angina
-bradycardia/AV block (DHP)
-tachycardia and Afib (non-DHP)
Clinical conditions that may limit BB use
-bradycardia
-AV block
-HF decompensation
-severe depression
-severe asthma/COPD
clinical conditions that may limit CCB use
-bradycardia/AV block, sick sinus syndrome (nonDHPs)
-HF
-severe hypertrophic obsturctive CM
-severe aortic stenosis
clinical conditions that may limit use of nitrates
-ED w PDE5
-severe hypertrophic obstructive CM
-severe aortic stenosis
combo therapies for angina prevention
-nitrates + BB: BB block tachycardia from nitrates
-nitrates + non-DHPs: non-DHPs block tachycardia from nitrates
-BB and DHP: BB blocks tachycardia from DHPs
-AVOID BB and non-DHP bc of reduce HR, inc BB first
-triple therapy
-add on ranolazine if its not working or HR and BP too low
NSAIDs and ASA
-weigh risk benefit
-potential GI, CV, and renal impacts
-use lowest dose for shortest time
-make patient keep a pain/effect diary
-try ibuprofen and naproxen w gastroprotection first (low dose)
-celecoxib up to 200mg lowkey not that effective,>200mg inc risk
-AVOID diclofenac
-take ASA at least 2 hours before NSAID
-adjunctive tylenol may minimize NSAID needs
-weight benefits within a week
Tx w no benefit or w potential harm
-postmenopausal HRT (inc thrombo risk)
-antioxidants and vitamins
-homocysteine/folic acid/B6 or B12
-herbals
-NSAIDs
-rosiglitazone
-chelation therapt
Prinzmetal’s/Variant?Vasospastic angina
-ischemia/angina occurs at rest
-ST elevation
-episodes happen in morning usually
-not necessarily associated w ASCAD
Management of vasospastic angina
-SL NTG for acute
-CCBs
-Nitrates
-combo
-AVOID beta blockers
