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Flashcards in CAD/HF Deck (68)
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1
Q

Significance of CAD?

A
  • Heart Disease is the leading cause of death in the US ~ 600,000 lives each year
  • ~7 million Americans experience angina
  • *Atherosclerosis is a leading cause of angina
  • Angina is an indication of myocardial ischemia which potentially can lead to
    • Ischemia/Infarction
    • Congestive heart failure
    • Life-threatening arrhythmias
2
Q

What is coronary blood flow in young, healthy heart at rest?

A
  • Coronary blood flow is 70ml/min/100g at rest
  • ~5% the cardiac output
  • % Oxygen extracted from myocardial tissue beds is VERY HIGH = 70%
3
Q

What is coronary blood flow in the young, healthy heart during intense exercise?

A
  • Intense Exercise
    • Coronary blood flow increases 2-4 fold
      • (Supply)
  • However cardiac demands increase proportionally higher
    • CO to the body increases 4-7 fold
      • Preload
      • Heart rate
      • Contractility
        • (Demand)
4
Q

What determines coronary blood flow throught the cardiac cycle?

A

Physical factors:

  • During systole, the pressure exerted by the myocardium on vessels that pass through it equals or exceeds the perfusion pressure, so coronary flow occurs only during diastole.
    • Systolic contraction impedes coronary artery filling because the increase in intramural pressure
      • Redistributes blood flow from the subendocardial to the subepicardial layers
      • Compresses the arterioles and capillaries
      • Perfusion pressure to the left ventricle = DBP – LVEDP
        • most interested in DBP in pt with CAD

Vascular control by metabolites

  • A change in the metabolites produced by myocardial cells in response to decreased PO2 causes coronary vasodilation (adenosine)
    • even slight dilation of coronary will hve profound impact on blood flow (remember pousilles law)

Neural and humoral control

  • Sympathetic innervation
  • Large vessels- Alpha (vasoconstriction effects);
  • smaller vessels (subendocardium)- Beta-2 (dilator effects)
5
Q

When are coronaries perfused?

A

Diastole

  • diastolic time is very important
    • treat by getting heart rate down is very improtant in order to allow filling time during diastole, and therefore better coronary perfusion
6
Q

Pathophysiology of angina? Normal healthy physio vs stable, usntable, variant angina?

A
  • Normal-
    • Patent lumen
    • Normal endothelial function
    • PLT aggregation inhibited
      • can release NO when stimulated by bradykinin which can cause dilation. smooth layer, discrouages plt from aggregating. allows coronaries to adapt to diff metabolic demand
  • Stable angina
    • lumen narrowed by plaque
    • inappropriate vasoconstriction
    • pt has atherosclerotic plaque (pouseille’s law)
    • internal diamater reduced, dramatic drop in flow
    • endothelial layer not as healthy and not as effective at releasing NO to influence smooth muscle/tone during exercise
    • usually have CP after exertion
  • Unstable angina
    • plaque ruptured
    • PLT aggregation
      • PLT can eventually occlude vessel and prevent downstream oxygenation causing infarction
    • thrombus formation
    • unopposed vasoconstriction
  • Varient angina (prinzmetal angina)
    • no overt plaque
    • intense vasospasm
    • very rare form, a/w reynaud’s dx
      • 2% case, don’t know what casuses it.
    • intense vasospasm, my be related to inappropriate thomboxane or excessive alpha adrenergic activitiy
      • ​avoid bb in variant angina because it’ll block beta 2. anytime you have excessive vasospasm, avoid blocking good guys (beta 2)
7
Q

What increases myocardial O2 demans?

A
  • Tachycardia
  • High afterload
  • High preload
  • Increased contractility
8
Q

What cna increase O2 supply?

A
  • Hemoglobin Concentration- also don’t want polycythemia, need normal
  • Oxygen Saturation
  • Bradycardia (within reason)- HR 30 not ok, but high 50/60s is optimizing diastolic filling time
  • Increased diastolic blood pressure- robust
  • Low Normal Preload
  • Decreased Contractility- increase supply, decrease demand
9
Q

What can be done to HR to achieve hemodynamic goal in CAD? Indicated drugs, Contraindicated/use with caution?

A

Goal: slow HR

Indicated drugs:

  • Beta blockers
  • Ca channel Blockers

Contraindicated

  • isoproterenol
  • dobutamine
  • ketamine
  • pancuronium
10
Q

Goal of preload in order to meet hemodynamic goals in CAD?

A

Goal- low normal

Indicated

  • NTG
  • Diuretics

Contraindicated/caution

  • Volume overload
11
Q

Goal for afterload to meet hemodynamic goal in CAD? Indicated meds? Contraindicated?

A

Afterload- high normal (referring to DBP)

Indicated

  • phenylephrine

Contraindicated/use with caution

  • Nitroprusside
  • High-dose volatile agent
12
Q

Contracitlity hemodynamic goals in CAD? Indicated drugs? ContrindicateD?

A

Goals- contracility normal- decreased

Indicated

  • Beta blocker
  • CCB
  • High dose VA

Contraindicated/use with caution

  • Epinephrine
  • Dopamine
13
Q

Stable angina treatment?

A
  • A: ASA, antianginals (nitrates, CCB, b-blockers)
  • B: Blood pressure (controlled)
  • C: cholesterol (statin), cigarettes (stop)
  • D: diet, diabetes
  • E: education, exercise
14
Q

What is microvascular angina?

A

aka coronary syndrome X

  • Women would have complaints of angina and evidence of ischemia on stress test, but angiography wouldn’t show any occlusions
  • Do have vasoreactive issues but in very small, microvascular arterioles
  • unsure what causes this, more common in women
    • recently dx condiiton and a lot of these drugs aren’t specifically tested for this
      • in next 10 years may have more discusison on what to use for these pt
    • right now we use smae meds…
15
Q

What are organic nitrates?

A
  • ↑ [] of nitric oxide in smooth muscle cells
    • for some reason, cells don’t produce enough NO on their own. this provides exogenous source
  • Used stable angina, MI, variant angina, microvascular angina
  • Chemical structure and metabolism
  • ​nitro most common rescue (SL)- short half life
    • avoids first pass effect with SL
  • Isosorbide dinitrate
    • ​developed for longer 1/2 life- taken once a day
    • has active metabolites and used for longer control
      • ​isosorbide 5-mononitrate
16
Q

NO Signal pathway?

A
  • Bradykinin stimulates G coupled receptors
  • goes on to increase Ca which increases Ca-calmodulin
  • Stimulates eNOS (endotheline nitric oxide synthase–> NO
  • NO diffuses across down to vascular smooth muscle cell and increase activity of soluble guanylyl cyclase
  • increase cGMP from GRP
  • Increase PKG activity
    • promotes intracellelar ca sequestration into SR
    • Decrease intracellular ca levels from VG Ca channels on plasma membrane
  • causes relaxation of smooth muscle

Figure 19-2. Regulation of vasorelaxation by endothelial-derived nitric oxide (NO). Endogenous vasodilators, eg, acetylcholine and bradykinin, activate NO synthesis in the luminal endothelial cells, leading to calcium (Ca2+) efflux from the endoplasmic reticulum into the cytoplasm. Calcium binds to calmodulin (CaM), which activates endothelial NO synthase (eNOS), resulting in NO synthesis from L-arginine. NO diffuses into smooth muscle cells, where it activates soluble guanylyl cyclase and cGMP synthesis from guanosine triphosphate (GTP). cGMP binds and activates protein kinase G (PKG), resulting in an overall reduction in calcium influx, and inhibition of calcium-dependent muscle contraction. PKG can also block other pathways that lead to muscle contraction. cGMP signaling is terminated by phosphodiesterases, which convert cGMP to guanosine monophosphate (GMP).

17
Q

How do nitrates produce NO?

A

Mitochondrial aldehyde dehydrogenase

(takes out endothelial cell requirement for NO)

18
Q

What is a potential interaction with phosphodiesterase inhibitors and nitrates?

A
  • Phosphodiesterase will inactivate cGMP normally
  • inhibitors will stop phosphodiesterase activity and increase signaling thorugh PKG pathway and prolong activity of cGMP
  • Nitrate with sidenafil (phosphodiesterase inhibitor) can get too much Ca inhibition and become profoundly hypotensive
19
Q

Nitrates MOA?

A
  • Nitrates release nitric oxide after they are metabolized
    • Probable enzymatic reaction with tissue –SH groups
  • NO activates soluble guanylate cyclase increasing cGMP, which increases protein kinase G
    • activating a cascade that ends with the dephosphorylation of myosin light chains and sequestration of intracellular calcium = relaxation of the vessel.
20
Q

What are the anti-anginal actions of nitrates?

A
  1. Venodilation= ↓ Ventricular preload
    • ↓ ventricular volume/ ↓ myocardial wall tension
    • ↓ O2 requirements
  2. ↓ Afterload (from arterial vessels)
  3. Dilation of epicardial stenosis
  4. Enhanced flow to ischemic regions (esp. subendocardium)
  5. Platelet inhibition
  6. Reduced oxygen consumption
    • ↓ cardiac preload (venodilation)
    • ↓afterload (dilation of large muscular arteries)
  7. Preferential dilation of collateral vessels serving ischemic areas
    • ​dilates areas that are ischemic!
  8. Attenuation of coronary spasm
  9. Also presumed to work like nitric oxide on cardiac muscle and increase the rate of relaxation (lusiotropic action= decrease in diastolic pressure. ability of the ventricle to relax)
21
Q

Routes for NTG?

A
  • Sublingual- ONSET 3 MIN
    • Tablets- shouldn’t swallow, keep under tongues
      • ​first pass is high, would need higher PO dose
    • Spray
  • Oral
  • Topical- long term control
    • Ointment
    • Patches
  • Intravenous
22
Q

NTG Metabolism and S/E?

A
  • 90% degraded by the liver to inactive metabolites
    • E1/2t IV = 1.5 minutes
  • Sublingual and transdermal bypasses liver and first pass metabolism
  • Adverse Effects:
    • headaches (cerebral vasodilation)
    • postural hypotension (fainting)
    • methemoglobinemia (usually only with high doses IV/liver disease)
23
Q

What is nitrate tolerance?

A
  • Pharmacologic tolerance
    • Limits efficacy irrespective of route of administration-
    • Tolerance to adverse effects
  • Nitrate-free intervals necessary (unsure why this happens maybe depeltes enzymes for ENOS-NO, or increases superoxide anion production which antagnoizes effect of NO)
    • Removal of patch at night
    • Oral isosorbide mononitrate
      • High bioavailability and long T1/2 provide adequately high levels followed by low levels
24
Q

Nitrat drug interactions?

A
  • Sildenafil(Viagra), tadalafil (Cialis), vardenafil (Levitra)
    • Inhibits phosphodiesterase which breaks down cGMP
    • Additive effect
    • Severe hypotension
    • Treat with phenylephrine
  • need 24 hours between drugs!!
25
Q

Use of beta adrenergic antagonists in CAD?

A
  • Essentially provide a more favorable O2 supply and demand balance
  • Used in the prevention of stable angina and in unstable angina
    • ↓O2 demand by decreasing CO
      • ↓catecholamine-mediated increases in automaticity (SA node- decrease stage 4 depolarization) and conduction (AV node) = (↓ heart rate)
      • Have some negative inotropic effect (↓contractility)
    • Improve diastolic filling time (increase supply)
    • ↓ CO is more dramatic during activity than at rest
  • Use primarily Beta-1 selective agents
    • Metoprolol
    • Atenolol
  • Improve survival in CAD
  • DO NOT discontinue suddenly!
  • Avoid in variant angina (theoretical) because we want B2 dilation of coronaries
26
Q

S/E Beta adrenergic antagonists?

A
  • depression
  • insomnia
  • mask hypoglycemic warning signs in DM
  • exercise intolerance
  • bronchospasm in asthmatics
27
Q

What is MOA of CCB?

A
  • Block entry of Ca2+(All classes)
    • Cardiac muscle: ↓ inotropic effect, ↓ contractility
    • Coronary vascular dilation (good choice in variant angina)
    • Systemic arterial dilation→decrease afterload→decrease wall tension
  • Slow Ca2+ channel recovery (Phenylalkylamines)
    • SA node: chronotropic effect, HR↓
    • AV node: dromotropic effect, decrease conductivity, HR↓
  • Non- -competitive antagonists
    • block voltage sensitive -L-type Ca channel
28
Q

What are the 3 classes of CCB?

A
  • Dihydropyridines- more selective vascular
    • Nifedipine (Procardia, Adalat)
    • Amlodipine (Norvasc)
    • Nicardipine (Cardene)
    • Felodipine
  • Phenylalkylamines- more selective cardiac
    • Verapamil
  • Modified Benzothiazepines- mix vascular/cardiac, intermediate
    • Diltiazem

sometimes phenylalkylamines and modified benzothiazepines are known as the non-dihydropyridines

29
Q

Nifedipine selectivity, a/e, contraindications, drug interactions

A

Selectivity- Vascular- can be good choice for pt with HTN and angina

Adverse effects

  • Reflexive tachycardia
  • Headache
  • Dizziness, Palpitations
  • Flushing, Hypotension
  • Leg edema

Contraindications/caution

  • Hypotension
  • Severe aortic valve stenosis

Drug interaction

  • Beta-blockers OK- because not getting cardiac effects of CCB and can have reflexive tachycardia
30
Q

Verapamil selectivity, a/e, contraindication/cuation, drug interactions?

A

Selective- Cardiac

A/E

  • Hypotension
  • Facial flushing
  • Constipation
  • Nausea
  • Headache
  • Dizziness
  • Gingival hyperplasia

Contraindications

  • Sick sinus syndrome
  • AV block
  • LV dysfunction
  • Digitalis/Quinidine toxicity

Drug interactions

  • Beta-blockers- NEVER OK TO COMBINE!!! Huge decrease at AV/SA node with cardiac-selective CCB and BB
  • Cimetidine
  • Carbamazepine
  • Cyclosporine
  • Digoxin
31
Q

Diltiazem selectivity, a/e, contraindication/caution, drug interactions?

A

Selectiviey –Vascular: Cardiac

A/E

  • “Relatively infrequent”

Contraindication/caution

  • Sick sinus syndrome
  • AV block
  • LV dysfunction

Drug interactions

  • Beta-blockers
  • Ecainide
  • Cimetidine
  • Cyclosporine
  • Carbamazepine
  • Lithium carbonate
  • Disopryramide
  • Digoxin
32
Q

What is ranolazine?

A
  • Inhibits the late sodium current (INA), reducing calcium overload in ischemic myocardial cells
    • Improves ischemic myocyte ATP levels
    • Enhances cardiac contractility
  • This med works on reducing metabolic demand (unlike previous CCB which affect supply/demand by some hemodynamic affect)
    • ​Late sodium current during plateau phase of myocardial cells can be significant in ischemia
    • this can place huge Na load on cell
    • can then end up with Ca overload
      • ​reversal of Na/Ca sarcolemma exchanger
    • end up with lots of Ca in cell
    • won’t get diastolic relaxation and can’t fill
  • Ranolazine improces microscopic o2 supply/demand balance
    • ​Good in microvascular angina
33
Q

Ranolazine metabolism? A/E? Drug interactions?

A
  • Cytochrome P-450 (CYP3A4) metabolism
  • Dose dependent adverse effects
    • Dizziness
    • Nausea
    • Constipation
    • Prolonged QT interval (average increase 2-5 ms.) (of note, not significant increase by med itself but when taken with other meds that increase qt interval)
      • Contraindicated in patients with hepatic disease
  • Drug Interactions
    • Digoxin, simvastatin, cyclosporine, macrolide antibiotics, ketoconazole (CYP3A4 inhibition)
    • Drugs that prolong the QT interval
34
Q

Unstable angina treatment summary?

A
  • Unstable angina, Non ST elevation MI (partial occlusion)
    • Antianginal drugs
    • Heparin, ASA
    • GPIIb/IIIa antagonists (eptifibatide (Integrilin)
    • Clopidogrel (Plavix)
  • ST elevation MI (total occlusion)
    • Surgery
    • Thrombolytics (Streptokinase, alteplase (tPA))
35
Q

Stable angina management when they have acute angina?

A
  • Nitrates
  • β-blockers
  • Ca2+ channel blockers
  • Ranolazine as well
36
Q

Unstable angina treatment during acute angina?

A
  • Nitrates
  • β-blockers
  • Ca2+ channel blockers (?)
  • Aspirin/clopidogrel
  • Heparin/thrombolytics
  • Glycoprotein IIb/IIIa receptor inhibitor
37
Q

Variant angina treatment during acute angina?

A
  • Nitrates
  • Ca2+ channel blockers
38
Q

What is impact of chronic SNS nad RAAS activation in SHORT TERM?

A
  • In failing heart, not getting adequate tissue perfusion
  • causes major activation of SNS nad RAAS
  • in short term- beneficial effect maintaining CO
    • allows pt to tolerate short term and meet O2 demands of tissue
  • ANG II stimualed by renin (rate limiting step)
  • release renin when decrease na/cl to juxtaglomerular apparatus
    • less flow through glomerulus, GFR reduced and increase renin release
    • Baroreceptos in kidney respond by releasing renin
  • beta 1 stimualted renin release as well
  • ang II causes additional downsteram effects
    • augments sns
    • enhance Na/Cl reabsorption and K excretion
    • enhance aldosterone secretion
    • arteriolar vasoconstriction
    • ADH secretion (increase H2O reabsorption in collecting ducts)
39
Q

What occurs with chronic SNS and RAAS activation?

A
  • Results in enhaned myocardial dysfunciton and ventricular and vascular remodeling (aldosteron major contributor)
  • pharmacologically we want to
    • 1) help pt feel better by reducing symptoms angina
    • 2) reduce pathological remodeling and overactivation of RAAS/SNS in order to slow progression HF
40
Q

What is the vicious cycle with RAAS system in HF?

A
  • Too much afterload (from vasoconstriction)
    • systemic vasuclar resistance/lv systolic wall stress
  • Too much preload (from na/h2o retention)
    • the stretch of LV myocytes at end diastole
41
Q

How is the frank starling curve different in physiologic states?

A
  • Preload
    • if normal person given lasix, will see dramatic drop in SV (CO)
    • if HF patient gets lasix, only partial decrease in CO but can get them out of pulmonary congestion
      • fairly preload independent
  • Afterload
    • if normal person has increase in afterload, can be pretty sig increase before we see drop off in CO
    • Someone with mod/severe HF can only tolerate a minimal increase in afterload before their CO drops significantly (afterload sensitive)
42
Q

Ventricular dysfunction in HF?

A

Systolic dysfunction (EF < 40%)

  • Coronary Artery Disease
  • Nonischemic Cardiomyopathy
    • Hypertension
    • Valvular disease
    • Alcohol
    • Thyroid disease
    • Cardiotoxic drugs

Diastolic dysfunction (impaired filling)

  • Cardiomyopathies
  • Incomplete relaxation of the LV during ischemia (myocytes need ATP for both contraction and relaxation).
    • Can also be due to late Na current causing increase Ca nd impairment in relaxation
43
Q

Physiologic goals of drug therapy for heart failure?

A
  • Reduce preload
    • Diuretics
    • Aldosterone antagonists
    • Venodilators
    • ACEIs
  • Reduce afterload
    • ACEIs
    • b-blockers
    • Vasodilators
  • Increase inotropy
    • Cardiac glycosides
    • Sympathomimetic amines
    • Phosphodiesterase inhibitors
44
Q

Hemodynamic goal of HR in CHF? Indicated drugs? C/I/caution?

A

Goal: Normal to Elevated

iNDICATED DRUGS:

  • Dopamine
  • Dobutamine

Contraindicated/caution:

  • Beta-Blockers (high doses)
45
Q

Preload hemodynamic goals in CHF? INdicated meds? contraindicated/caution?

A

Goal- Normal

Indicated drugs:

  • IV Fluids if decreased

Contraindicated/caution:

  • Nitroglycerin* – (use with caution if low preload)
  • Thiopental
46
Q

Afterload hemodynamic goals in CHF? Indicated drugs, c/i/caution?

A

Goal- Low

Indicated drugs

  • ACE inhibitors
  • Nitroprusside
  • Amrinone

Contraindicated/caution

  • Phenylephrine- too much afterload will cause CO to drop precipitously. avoid any drug with large amount of vasoconstriction like NE as well
47
Q

Contractility hemodynamic goal in CHF. Indicated drugs, contraindicated

A

Goal- Increased contractility

Indicated med:

  • Dopamine
  • Dobutamine
  • Epinephrine
  • Amrinone

Contrindicated/caution meds

  • High dose inhaled agents
  • High dose beta blockers
48
Q

Diuretic use in CHF?

A
  • Alleviate congestive symptoms – use with caution though consider preload status before giving
  • No evidence of mortality benefit with thiazide or loop diuretics
  • Loop diuretics most commonly used
    • Furosemide, bumetanide, torsemide
    • Inhibit Na+-K+-2Cl- cotransporter in loop of Henle
    • Increase excretion of Na+, K+, H2O
49
Q

How do distal tubule and loop diuretics use?

A
  • Distal tubule: 5-10% increase Na excretion (weak diuretic)
    • Thiazides
    • Metolazone (Zaroxolyn)
    • K+-sparing (spironolactone, eplerenone)
    • Lose effectiveness when Creat Cl < 30 ml/min
  • Loop diuretics: 20-25% increase Na excretion
50
Q

What are aldosterone antagonist

A
  • ex- Spironolactone
  • Potassium-sparing diuretic that acts as a competitive antagonist at aldosterone receptor
  • Decreases K+/Na+ exchange in distal tubule and collecting duct of nephron
    • mild diuretic effect as well
  • RALES showed 30% reduced mortality
    • antagnoizing aldosterone is best to prevent long term remodeling
    • good at prolongign life and decreasing progression CHF
  • If given with an ACE really have to monitor K levels as both decrease excretion
51
Q

What are sprionolactone and eplerenone?

A
  • Spironolactone (Aldactone)
    • Inhibits both androgen and mineralocorticoid receptors
    • AE: gynecomastia, impotence
  • Eplerenone (Inspra)
    • More selective
    • Less AE
52
Q

NTG as venodialtor in HF?

A
  • Increases venous capacitance which reduces venous return to heart
  • Decrease myocardial oxygen demand
  • Alleviate ischemia which improves diastolic relaxation
  • Improved LV compliance in addition to preload reduction
  • Use with caution though……don’t decrease preload too much these patients need adequate preload.
53
Q

MOA of ACE inhibitors?

A
  • MOA: Inhibits the enzyme (ACE) that coverts angiotensin I to angiotensin II. Angio II plasma concentration is reduced.
  • Cardiovascular Effects
    • Lowers afterload and preload:
      • arterial>venous dilation- great because preload is not as much of an issue, afterload more of an issue. getting afterload normalized is helpful
      • increase Na+ and H2O excretion and decrease K+ excretion (decrease aldosterone released)
    • Down-regulates sympathetic adrenergic activity reducing the effects of angiotensin II on release and reuptake of norepinephrine.
      • Improve oxygenation to heart muscle
  • *Reduces maladaptive compensatory responses and remodeling + prolongs life after heart failure diagnosis
54
Q

How have ACE inhibitors help in CHF?

A

Randomized clinical trials have demonstrated in heart failure ACE inhibitors IMPROVE:

  1. Reported quality of life
  2. Left ventricular function
  3. Myocardial and vascular remodeling
  4. Exercise tolerance
  5. # of hospitalizations
  6. Life expectancy
55
Q

A/E of ace inhibitors?

A
  • Orthostatic hypotension(especially with 1st dose)
  • Dry Cough- increase bradykinin because ACE inhibitors also block kinase II
  • Angioedema (rare but very serious)
    • also from increase bradykinin
  • Hyperkalemia (reduced aldosterone)
  • Dysgeusia and rash
  • Renal failure
    • Caution in patients with acute renal impairment or bilateral renal stenosis
    • renal artery stenosis depends on compensation from efferent vasoconstriction in order to keep GFR up. if you remove that vasoconstriciton, gfr drops and get renal failure
  • Neutropenia (rare but very serious)
  • Pregnancy (fetal injury)
  • Lung cancer??
56
Q

MOA of Angiotensin II Receptor BLockers (ARBS)?

A
  • MOA : Directly block angiotensin II receptors (AT1). Therefore, angiotensin II activity is antagonized.
    • NO impact on bradykinin levels.
  • Cardiovascular Effects (Similar to ACE-Inhibitors)
    • Lowers afterload and preload:
      • arterial>venous dilation
      • increase Na+ and H2O excretion and decrease K+ excretion (decrease aldosterone released)
  • Down-regulates SNS activity reducing the effects of angiotensin II on release and reuptake of NE.
    • Improve oxygenation to heart muscle
  • Reduce inappropriate remodeling of the myocardium & vasculature (not as well as ACE inhibitors though – no enhancement of bradykinin [] )

Randomized clinical trials have demonstrated decreased # of hospitalizations and mortality similar to ACEI

57
Q

A/E ARBS?

A
  • Adverse Effects- low incidence of side effects compared to other anti-hypertensive agents
  • Angioedema
  • Renal failure
    • Use caution in patient’s with acute renal impairment
  • “Might” promote cancer
  • Pregnancy (fetal injury)
58
Q

What are Angiotensin Neprilysin INhibitors (ARNIs)?

A
  • Neprilysin is enzyme that degrade natriuretic peptides
    • want to block nepilysin (SACUBITRIL) , so natriuretic peptides will remain in blood causing:
      • vasodilation
      • natriuresis
      • diuresis
      • inhibition of pathologic growth/fibrosis
  • neprilysin also degrade angiotensin II
    • If you give ARNIs, then more ANG II in blood causing effects
    • therefore, need to give ARB with ANRI to block AT1 receptor and negate effects of ang II
59
Q

Side effects ARNIs?

A
  • Hypotension
  • Hyperkalemia (from drop in aldosterone)
  • Increased bradykinin (sacubitril also increase bradykinin)
    • cough (5%)/angioedema (less than ACEI)
    • Contraindicated with ACEI (additive influence on bradykinin [] = additive angioedema risk)
  • Theoretical increased risk of Alzheimer’s Disease
    • Neprilysin also breaks down beta-amyloid peptide in the brain
60
Q

Beta blocker use in heart failure?

A
  • Improve LV ejection fraction, increase exercise tolerance, slow progression HF, increase survival (especially when given with an ACE inhibitor)
  • Why?
    • Many of the deleterious effects in the heart are β1-mediated
    • decrease SNS stimulation?
    • Protection from dysrhythmia?
      • decrease risk from beta blockade heart
    • Decreased angiotensin II and aldosterone concentrations
      • from blockade at Beta 1 receptors in kidney
  • Do not use in acute decompensated heart failure

slowly titrate BB on and overtime will see improvement in LV EF etc…

61
Q

What is Iso sorbide dinitrate/hydralazine combo?

A
  • AKA Bidil
  • Studies are with BiDil (fixed-dose combination of hydralazine and isosorbide dinitrate)
  • Gain the benefit of the arterial dilating effect of hydralazine and the venodilating effect of the nitrate
  • The combination of hydralazine and isosorbide dinitrate is recommended for black patients who remain symptomatic despite concomitant use of ACEIs, beta blockers, and aldosterone antagonist
    • Combination exerts a favorable effect on exercise capacity and has a significant life-prolonging effect
  • An alternative therapy to an ACE inhibitor/ARB when renal insufficiency, hyperkalemia, cough/angioedema preclude their use
  • A lupus-like syndrome in response to hydralazine has only rarely been reported
62
Q

What is digoxin?

A

Cardiac Glycoside- increases inotropy

  • MOA: Selective inhibitor of the sodium-potassium-adenosine triphosphate (ATPase) system: “sodium pump” in cardiac myocytes
    • block Na/K ATPase system–> influences Na/Ca exchanger to increase Ca–> improve contractility
    • Sensitizes the cardiac baroreceptors
      • decrease SNS tone and renin release (because we’re improving CO)
    • Increase parasympathetic (vagal) activity (according to rang and dale, the mechanism of this action is unknown)
      • decrease SA node activity
      • decrease conduction velocity; increase AV refractory period
    • increase intracellular calcium and sodium
  • Overall effects:
    • increase contractility ( inotrope used in heart failure)
      • TX of supraventricular dysrhythmias (atrial fib)
      • decrease HR, preload and afterload
      • Overall increased stroke volume and cardiac output
63
Q

Why is digoxin considered a 2nd/3rd line drug?

A
  • It has a narrow therapeutic index
    • 0.5 – 1.2 ng/ml
    • Multiple drug interactions, sensitive to serum potassium, calcium and magnesium levels, renal disease
  • It can increase automaticity and slow AV nodal conduction causing life threatening dysrhythmias
    • Onset of action 30 – 60 min
    • Half-life 36 hours
      • 7 days to reach steady state serum concentrations
  • 90% renally excreted
  • Antidote: digoxin immune Fab (Digibind, DigiFab)
  • * Improves symptoms NOT survival
    • women may hve higher mortality on digoxin
64
Q

Digoxin interactions?

A
  • Pharmacodynamic interactions
    • Increased risk of AV block with b-blockers
    • b-blockers and CCBs decrease contractility
  • Pharmacokinetic interactions
    • Antibiotics increase absorption
    • Verapamil, quinidine, amiodarone increase digoxin levels by affecting Vd and/or renal clearance
65
Q

Dobutamine?

A
  • Stimulation of b1 increases cardiac contractility
  • Stimulation of vascular b2 causes arterial vasodilation and reduced afterload
  • not useful for long term outcomes
  • can be used short term, icu OR
  • more potent B1 at myocytes, pronounced increase in contractility
    • ​not huge increase in HR
  • Stimulate B2 in arterial/venous beds reduced afterload as well
  • Normalization afterload and enhanced contractility
    • ​good if pt BP low d/t poor contractility
66
Q

Phophodiesterase inhbiitors MOA?

A
  • Selective PDE III
  • Inhibit degradation of cAMP in cardiac myocytes and vascular smooth muscle
  • “inodilators”
  • Combination effect
    • Increased contractility (increased intracellular Ca)
      • Minimal increase in myocardial oxygen demand
      • Good choice for B-blocker overdose
    • Arterial and venous dilation decreases afterload and preload
    • Mild bronchodilation
    • Improved diastolic relaxation by increasing Ca removal from mycoplasm after action potential
67
Q

What is Amrinone?

A

Phosphodiesterase inhibitor

  • Increased CO & Left ventricle EF
  • Decreased LVEDP, pulmonary wedge pressures
  • HR increase slightly and BP decreases slightly
  • E1/2t = 6hrs
  • 0.5-1.5 mg/kg IV; onset 5 minutes; DOA 2 hours
    • infusion 2-10mcg/kg/min; total max dose 24 hrs= 10 mg/kg.
  • Renal excretion (unchanged) predominate method of clearance
  • Hypotension and thrombocytopenia main adverse effects
  • May promote arrhythmias via increased intracellular calcium
  • Wide TI – toxicity unlikely
68
Q

What is Milrinone?

A

Phosphodiesterase inhibitor

  • Similar hemodynamic effects as Amrinone with less tachycardia & thrombocytopenia
    • popular post CPB & to manage acute heart failure
  • 50mcg/kg IV with gtt at 0.5mcg/kg/min.
  • E1/2 2.7 hours
  • 80% excreted unchanged kidneys
  • Wide TI – toxicity unlikely
  • Long term use has not been shown to improve M and M (may actually increase it – so more an acute mgt application)
    • Is helpful in treating pulmonary HTN