CARDIAC Part I & II- CAD, CHF, Arrythmias Flashcards
Left coronary artery
Supplies the anterior and lateral portions of
the left ventricle
• 2 branches
– Left anterior descending – supplies AV node, the septum,
anterior LV
– Circumflex – supplies the left atrium and posterior LV
Right coronary artery
Supplies SA node, right atrium, most of the
right ventricle
CAD Risk Factors
Family history: the younger the event in a 1st degree relative, the higher the risk • Male > Females • Smoking • Metabolic Syndrome: constellation of 3 or more – Abdominal obesity – Triglycerides > 150mg/dl – HDL 110mg/dl – hypertension • Physical inactivity • Stress
Classes I-IV Cardiac Disease: descibe
Class I: ordinary physical activity does not cause angina. Angina = with strenuous/ prolonged physical activity.
Class II: Comfortable at rest; slight limitations to physical activity, resulting in palpitations, fatigue, dypsnea, anginal pain.
Class III: Marked limitation of activity; walking 1-2 blocks or 1 flight stairs then issues… resulting in palpitations, fatigue, dypsnea, anginal pain.
Class IV: Inability to carry on any physical activity without discomfort; angina may be present at rest.
Pathophysiology of CAD
A pathologic continuum resulting in ineffective
pumping action of the heart resulting from:
– CAD
– Myocardial infarct
– Myocardial ischemia
– all deprive heart muscle of oxygen and
nutrients
– Coronary arteries supply O2 to the heart
– When there is an increase in demand, ischemia
occurs.
• Deposition of lipids and macrophages in
vascular wall – plaque formation
– Plaque can be stable and just cause stenosis
or unstable and ready to rupture
• HTN increases risk of plaque formation & rupture
• Stable plaques – fibrous cap, calcification, vascular
narrowing
• Unstable plaques – rupture, release of plaques
contents into blood vessel, clot formation
• Local inflammation: macrophages release
inflammatory mediators
Angina =
=pain/ discomfort in chest when some part of heart does not receive enough oxygen.
Symptoms can be atypical (location) or
even silent
• Typical angina: provoked with exertion,
relieved with rest
ST Elevation on EKG:
1 mm (perihperal lead) or 2mm (chest lead) elevation above baseline **look for in 2 + leads facing same area
Causes of Angina Pectoris
• Imbalance in myocardial oxygen supply/demand – Increased HR, contractility, ventricular wall tension (R/T HTN, LVH) – Decreased blood flow: occlusion of the coronary arteries •Atherosclerosis/plaque formation, thrombi, Prinzmetal’s angina – Decreased oxygenation: anemia, asphyxiation, hypoventilation, altitude
Types of Angina Pectoris
Variant angina (Prinzmetal’s)
– Vasospastic-coronary artery spasm
• Stable angina
– Predictable precipitants, location, duration,
alleviating factors
• Unstable angina - “pre-infarction angina”
– Unpredictable pattern; increasing symptoms
Treatment of Angina
Lifestyle modifications
• Surgical interventions: stents, CABG
• Pharmacologic approaches
– Aspirin
– Beta-adrenergic blockers
– Long-acting calcium channel blockers (CCB’s)
– Angiotensin-converting enzyme inhibitors (ACEi)
– 3-hyroxy-3methylglutaryl coenzymeA (HMG CoA)
– Reductase inhibitior (statins)
– Nitrates
– Ranolazine
Drug Treatment of Coronary Heart Disease (CHD/CAD)
Reduce ischemia by improving myocardial O2
supply &
demand, dilating coronary vessels and/or decreasing
demand by reducing cardiac work
– Nitrates
– Beta-adrenergic Blockers
• may help decrease risk MI
– Calcium channel blockers
– ACEI (recommended in chronic stable angina)
Other Meds in Angina
Plaque stabilization
– Antiplatelets
• Thioenopyridines:clopidogrel (Plavik), prasugrel
(Effient)
• Glycoprotein Iib/IIIa inhibitors: (abciximab
(Reopro), tirofiban (Aggrastat), and eptifibatide
(Intehrilin)–
NITRATES
Have maintained an important treatment
factor due to their ability to affect oxygen
supply rapidly
• Affect supply/demand on both sides;
– Low doses dilate veins > arterioloes, causing
a decrease in venous return; decreasing left
ventricular end-diastolic pressure, (preload)
– Higher doses, dilate arterioles; decreasing
systemic vascular resistance, (afterload).
Nitrates - Pharmacodynamic
Actions
Decreases myocardial O2
demand by
causing formation of nitric oxide, a
free radical, in smooth muscle
– Nitric oxide (NO): released by endothelium as
a local vasodilator
• Peripheral venodilation → decreased preload
• Peripheral arteriolar dilation → decreased afterload
Nitrates - Pharmacodynamic
Actions
• Increase myocardial oxygen supply by:
– Decreasing coronary spasm
– Dilation of epicardial and collateral vessels
– Seem to preferentially vasodilate areas of
ischemia
– Dilate coronary arteries to some degree, but
not very well in atheroscleroisis
• Therefore, nitrates increase O2 supply AND
decrease O2 demand
Absorption
– Lipid soluble
– Cross membranes easily
• Metabolism
– Rapid inactivation by organic nitrate
reductases (hepatic enzymes)
Nitrates - Indications
Short term relief of anginal episodes •Sublingual: short shelf life (6 months after opening) •Sprays: longer shelf life (3 yrs.) • Anginal prophylaxis (prevention) •Long-acting preps (i.e., Imdur)
Nitrates - Pharmacokinetics- Absorption
Absorption
– Sublingual – Tablets; onset 1-3 minutes
– Transmucosal – Sprays
– Transdermal: onset 30 minutes
– Oral – isosorbide dinitrate, isosorbide
mononitrate
Nitrates- Pharmcokinetics- Metabolism and Elimination
Metabolism
– Extensive first-pass effect on oral preps
• NTG (Preg Cat B) metabolized in liver by hepatic NTG
reductase into dinitrates (which have longer half life, but
only 10% of activity). Dinitrates are metabolized into
mononitrate (inactive), then to glycero & CO2
• Isosorbide dinitrate (Preg cat C) → isosorbide
mononitrate → isosorbide
Elimination
Urine
Nitrates -Short-Acting
Preparations
Sublingual Nitroglycerin (NTG)— Nitrostat : q 5 mins I tab SL – 0.3 mg, *0.4 mg, *0.6 mg •Onset 1-3 minutes; peak effect 4-8 mins •Short shelf-life • Nitrolingual spray - 0.4 mg metered spray1-2 sprays under tongue •Onset: 2 mins; peak effect: 4-10 mins
Nitrates - Long-Acting
Isosorbide dinitrate – Extensive 1st pass; rapidly metabolized to active metabolytes) – Isordil, Dilatrate-SR • 10-40 mg bid-tid or • SR 40-80 mg qd-bid • Isosorbide mononitrate – Minimal 1st pass, no active metabolytes – ISMO, Monoket, Imdur (SR) • 10-20 mg bid – 7 hours apart • SR 30-60 mg qAM; up to 240 mg/day Nitrates - Long-Acting Preps • Nitroglycerin ointment 2% (Nitro-Bid, Nitrol) – Dose: 1” = 20 mg; ½” – 2” q 6-8 hrs – total 12 hrs/day • Transdermal (Nitro-Dur) patch – Dose: 10-25 mg/24 hours (0.1 mg/hour) – total 12 hrs/day. • Apply to non-hairy areas, tape application paper (ointment) over area. Wash hands. Remove at hs.
Nitrogylcerin- Tolerance
Occurs with continued exposure, smooth muscle
develops tolerance, (tachyphlaxis)
• Should have peaks and troughs in the dose (8
hrs/day).Time doses to insure trough,usually
overnight
• Mechanism: May be R/T sulfhydryl depletion
resulting in decreased cGMP, leading to
decreased vasodilation
Nitroglycerin - Side-Effects
Headaches • Flushing • Reflex tachycardia • Orthostatic hypotension • Occasional syncope (fainting) • Caution: History of migraines, preexisting orthostasis
Nitroglycerin – Drug-Drug
Interactions
Alcohol – Added vasodilation/hypotensive effect (additive) • Sildenafil (Viagra) – Potentiation of vasodilation (synergistic) – CONTRAINDICATED w/ nitrates • Heparin – IV nitro may antagonize effects (probably metabolic). May need to decrease heparin dose when NTG Dc’d and monitor PTT Nitroglycerine Drug Interactions • Aspirin increases serum nitrate levels and may potentiate the effects • Drugs with anticholinergic effects may decrease absorption of SL or buccal NTG • Increase hypotensive effect seen when given in patients who are on; – Beta blockers – Calcium channel blockers – Haldol – phenothiazines
Sublingual Nitrates - Patient
Teaching
- Take sublingual while sitting down.
• 2. Pts with dry mouth should take a sip
of water first.
• 3. Store in cool dark place; discard and
replace unused tablets q 6 months.
• 4. Take up to 3 tablets over a 15 minute
period at 5 minute intervals. (if CP
continues, call 911)
• 5. Use prophylactically before
activities that might precipitate angina.
NTG: Patient Teaching
• Don’t carry in pants or shirt pocket – too warm
• Sprays last 3 years, tabs last 6 months – less if
stored improperly
Translingual Nitrates - Patient
Teaching
Take spray while sitting down. • 2. Spray onto/under tongue – 3 sprays over a 15 minute period at 5 minute intervals. • 3. Use prophylactically before activities that might precipitate angina. • 4. Do not shake container or inhale spray. • 5. Do not rinse mouth for 5-10 min after dose.
Newer Antianginal
Ranolazine (Ranexa)
– Approved in first line chronic angina
– Decreases late sodium current; decreases
intracellular calcium overload
– Has no effect on HR, BP, and helps prolong exercise
– Safe to use with erectile dysfunction drugs
– Dose is 500mg BID
– Caution in patients with QT Prolongation
(antiarhythmics)- however, there is a decrease in V.
arrhymias when used after acute coronary syndrome
– Decreased a fib
– Caution in significant liver and renal disease
ACEI IN CAD
Recommended by American College of Physicians ( Snow et. al. 2004). – For chronic stable angina – Prevent MI or death – Reduce symptoms – VAMC (2003) in diabetics and LVD
Angiotensin II Receptor Blockers (ARB)
Recommended for use in CAD – Diabetes with HTN – LV systolic dysfunction – When patients are intolerant of ACEI – Can be added to ACEI Rx in uncontrolled HTN, or insufficient vasodilation
Angiotensin-Converting Enzyme
Inhibitors and Angiotensin II Receptor
Blockers
Act by affecting the renin-angiotensinaldosterone
(RAA) system to lower blood
pressure
• Improve oxygenation to the heart muscle
• Decrease inappropriate remodeling of heart
muscle after an MI, or heart failure
• ARBS have similar effect in treating HTN and
Heart failure
ACEI & ARBS
• Work by inhibiting ACE activity
• Decrease angiotensin II and aldosterone
production
• AII- stimulates sm. muscle contractions;
– Increased blood pressure
– Increases intravascular volume ( stim. Of aldosterone)
– Alters glomerular function
• AII causes remodeling leading to hypertrophy
and fibrosis of cardiac tissue after ischemic
injury in response to persistent afterload
– primary mechanism in Heart Failure
Angina and Ischemic Heart Disease
ACEIs affect MOS (myocardial O2 supply) and MOD
(myocardial O2 Demand)
• Inhibition of A II decreases PVR (peripheral vascular
resistance), decreasing MOD.
• Decreases thickening of coronary arteries, therefore,
increasing MOS
• Decreases thickening of ventricular walls= MOD
• Because they decrease aldosterone, they decrease
sodium and water retention; decreasing ECF
(extracellular fluid volume), and preload
• ACEI are recommended by American College of
Physicians in chronic stable angina
ACEI examples:
start low and go slow
• Captropril: Heart failure; dose 6.25 - 25mg TID, increase
to 50mg TID
• Enalapril: Heart failure: start at 2.5mg daily and increase
to 40mg daily
• Lininopril: heart failure: 5mg daily, maximal dose 20mg
ACEI and ARBs in Heart Failure
These agents reduce remodeling
• An underlying cause of HF is chronic HTN: both are
effective treatments
• ACEIs are the cornerstone for treatment in Heart Failure,
in all the guidelines (Flather et. al, 2000; Hunt et al,
2005; ICSI, 2004; National Collaborating Center for
Chronic Conditions, 2003).
– Improve symptoms
– Decrease morbidity, increase life expectancy
– Only set of drugs that address all of the physiologic causes of
HF, they helpful in patients with ventricular dysfunction who have
no symptoms
– All patients with LVD should be on an ACEI
Drug Interactions
Additive hypotensive effect with diuretics
• Acute alcohol, nitrates, phenothiazides, other
antihypertensives
• Hyperkalemia can occur with concurrent use of
potassium supplements, cyclosporin and
potassium-sparing diuretics
• Antihypertensive response is diminished with
NSAIDS
Contraindications
Bilateral renal artery stenosis • Angioedema: occurs in .2% – Is life threatening and if occurs, can not switch to another agent in the same category – Seen with ACEI not ARBs • Pregnancy; category C in 1st trimester, and Category X in 2nd and 3rd . • Hyperkalemia • Hepatic impairment
Adverse Reactions
Reactions are usually mild and transient • Cough; can change to another drug from same class: ARBs do not cause cough • Hypotension: dizziness, headaches, fatigue, postural hypotension • Rash: most common with Captopril, not ARBs
Beta Blockers
• With no intrinsic sympathominimetic activity (ISA) recommended as initial Rx – With or without previous MI – Decrease MOD – Drug of choice for exertional angina (ACC/AHA, all classes) – Main goal is to prevent recurrence of MI in patients with CAD – In patients who have resting tachycardia (hyperthyroidism) Beta Blockers in CAD • Decreased sympathetic nervous system stimulation – Reduced cardiac workload by decreasing HR and contractility by blocking beta1 receptors; decrease afterload .Used for angina prevention. – Decreased activation of reninangiotensin-aldosterone •Used post-myocardial infarction Beta Blockers in CAD • Slowed Heart Rate – ➔ Increased diastolic filling time • → Increased coronary perfusion • → Increased O2 supply – ➔ Decreased myocardial workload • → Decreased myocardial O2 consumption • → Decreased O2 demand
Beta Blockers in CAD
Atenolol (Tenormin) • Metoprolol (Lopressor, Toprol XL) – Best BB for asthma patients • Nadolol (Corgard) • Propanolol (Inderal)
Beta Blockers - Dose Titration
Check resting HR and exercise HR.
HR 50-60 is usually good evidence of
beta blockade exertional HR should
be
