Cardiac Flashcards
Wolf-Parkinson White
Accessory pathway in heart bypassing AV node
- -> ventricular pre-excitation
- -> shortened PR, delta wave, widened QRS
- Re-entrant tachycardia= narrowed QRS
Mitral regurgitation
Blowing holosystolic murmur over 5th LICS, midclavicular line
Radiates to axilla
- Can lead to CHF, pulmonary edema
Prevent by decreasing LV afterload
–> decreased systolic pressure driving blood into LA, increased forward stroke volume
Treat with arterial vasodilators
Isoproterenol
Beta agonist
- Increases cardiac contractility (B1)
- Decreases peripheral resistance (B2)
Phentolamine
Alpha receptor blocker
- -> subcutaneous vasodilation
- Used in NE-induced tissue necrosis (reverse effects of alpha agonist)
Tetralogy of Fallot
Abnormal neural crest cell migration featuring:
- VSD
- Overriding aorta
- Pulmonary stenosis
- R ventricular hypertrophy
Features:
- Blue baby
- Squat–> increase systemic pressure–> decrease R-> L shunt–> more blood to lungs
**Seen in 22q11 syndromes
Truncus arteriosis
Abnormal migration of neural crest cells
- Doesn’t divide into pulmonary trunk and aorta (only partial septum formation)
** seen in 22q11 syndromes
Transposition of great vessels
abnormal migration of neural crest cells
- RV–> aorta
- LV–> pulmonary artery
Symptoms:
- Irritable
- Machine-like murmur between scapulae (PDA)
- Severe cyanosis
- only survives with shunt (PDA, Atrial shunt)
- seen in infant of diabetic mother
Endocardial cushion defect
Membranous septal defect= AV septum defect–> L to R shunt–> pulmonary HTN–> Eisenmenger syndrome
Eisenmengers= blood reverses to R–> L shunt
- Cyanosis, clubbing, polycythemia
Patent foramen ovale
Failure of septum primum and secundum to fuse after birth
- Fusion driven by increase in pulmonary blood flow (decreased resistance)–> increased L atrial presssure–> pushes flap of septum primum closed over foramen ovale
- Normally develops into fossa ovalis
Patent foramen ovale–> increased risk of venous clots causing stroke (bypass pulmonary system)
Umbilical vein
Carries oxygenated blood from placenta–> ductus venosus–> IVC–> heart
- After birth: ligamentum teres hepaticus (within falciform ligament)
** Vitelline veins–> portal venous system
Umbilical arteries
Two: Connect internal iliac arteries (carrying fetal venous blood)–> to placenta
- become medial umbilical ligaments after birth
Ductus arteriosus
Connects pulmonary artery (RV) and aorta (LV)
- Patency ensures oxygenated blood reaches aorta
- At birth–> baby breathes O2–> decrease in prostaglandins–> ductus arteriosus closes–> ligamentum arteriosum
PDA= patent ductus arteriosus
- Maintained by indomethacin (essential to have PDA in babies with transposition of great vessels until surgical correction)
- See in congenital rubella infection
Ductus venosus
Carries oxygenated blood from umbilical vein–> IVC
After birth: ligamentum venosum
Notochord
Becomes nucleus pulposus of IV disc
Bulbus cordis
Base of Truncus arteriosus
Becomes smooth parts (outflow tracts) of L and R ventricle
Left horn of sinus venosus
Between SVC and IVC in early heart
Becomes coronary sinus
Right horn of sinus venosus
Between SVC and IVC in early heart
Becomes smooth part of R atrium
Right common cardinal vein, R anterior cardinal vein
Drain into sinus venosus
Become SVC
Wide split S2
Conditions delaying RV emptying:
- Pulmonic stenosis
- RBBB
Exaggerrated normal splitting
Fixed S2 splitting
Seen in ASD (patent foramen ovale)
ASD–> L–>R shunt
–> RA, RV volume increased
–> increased flow thru pulmonic valve
–> Eisenmenger if untreated (increased pulmonary vascular resistance)–> permanent damage–> shunt reverses R–>L
Paradoxixcal S2 splitting
Conditions delaying LV emptying: - Aortic stenosis - LBBB P2 sound occurs before A2 - On inspiration, splitting "paradoxically" eliminates as P2 delayed--> closer to A2
Hand grip maneuver
Increases systemic vascular resistance
- Increases: MR, AR, VSD, MVP
- Decreases: AS, HOCM
Valsalva, standing from sitting
Decreases venous return (less blood in LV)
- Increases MVP, HOCM
- Decreases most other murmurs
Rapid squatting
Increases venous return, preload (afterload with prolonged squatting)
- Decreases MVP, HOCM
Ventricular AP
Occurs in bundle of his, Purkinje fibers as well
Phase 0= rapid upstroke
- Na+ channels open;
Phase 1= initial repolarization
- inactivate voltage-gated Na+ channels, K+ channels begin to open
Phase 2= plateau
- Ca+2 influx (depolarizing) through voltage-gated Ca+ channels balances K+ efflux
- Ca+2 influx–> Ca+2 release from SR–> myocyte contraction
- (different from skeletal muscle= electrical depolar–> dihydropyridine R–> RyR–> Ca+2 release)
Phase 3= repolarization
- K+ efflux through slow K+ channels
- Closure of voltage-gated Ca+2 channels
Phase 4= Resting potential
- High K+ permeability
** Cardiac myocytes electrically coupled via gap junctions
Pacemaker action porential
SA and AV nodes
Phase 0= upstroke
- Opening of voltage-gated Ca+2 channels–> slow conduction velocity (prolong transmission from A–> V (allow for ventricular filling))
- Permanent inactivation of fast Na+ channels d/t more positive resting voltage of nodal cells
Phase 3= Repolarization
- inactivation of Ca+2 channels
- Increased activation of K+ channels
Phase 4= Diastolic depolarization
- membrane depolarizes by action of “funny” Na+ channels (slow)
- Funny channels allow for automaticity in SA/AV nodes
- Slope of depolarization= HR
- Catecholamines increase slope–> inc HR
- ACh/adenosine decrease slope–> dec HR
P wave
Atrial depolarization
PR interval
Conduction through AV node
- Delayed by Ca+2 channels slow depolarization
- Normal < 200 ms
QRS complex
Ventricular depolarization
- Normal < 120 ms
T wave
Ventricular repolarization
- Inversion= recent MI; repolarization occurring away from dead tissue toward tissue
ST segment
Isoelectric period; ventricles completely depolarized
U wave
bradycardia, hypokalemia
Pacemakers in heart
- SAN (Crista terminalis)- (60-120 BPM)
- AVN (45-60 BPM)
- His-Purkinje-Ventricular (<40 BPM)
Speed of conduction
- Purkinje (fastest)
- Atria
- Ventricles
- AV node (slowest d/t Ca+2 channel depolarization–> ventricular filling)
QT interval
Mechanical contraction of ventricles
- Prolongation–> Torsades de Pointes
—> Vfib
Tx: Magnesium sulfate
Prolonged in congenital long QT:
- Defects in cardiac Na+ or K+ channels
- Romano-Ward syndrome (autosomal dominant)
- Jervell Lange-Nelson syndrome: autosomal recessive; May have congenital sensorineural deafness
Atrial fibrillation
Irregularly irregular
- Can cause atrial stasis–> stroke
Associated with:
- Valvular heart disease–> atrial enlargement
- Atherosclerosis
- Cardiomyopathy
- Sick sinus syndrome
Tx: Diltiazem, Verapamil, cardio-selective Beta-blockers, Warfarin, cardioversion, ablation
- Or digoxin–> vagus stim–> parasympathetic tone increases–> decreased AVN conduction
Atrial flutter
Circuit in R atrium (CCW) around tricuspid annulus (isthmus between tricuspid and IVC)
- Depolarization waves–> sawtooth appearance
Tx:
- Class IA, IC, III antiarrhythmics (Na and K channel blockers)
- Rate control: Diltiazem, verapamil, Beta-blocker
Ventricular fibrillation
Completely erratic rhythm (no identifiable waves)
- Fatal without immediate CPR, defibrillation
1st Degree AVN block
PR interval prolongation
- > 200 msec
- Asymptomatic
2nd degree Mobitz Type I (Wenckebach)
Lengthening of PR interval until beat “dropped” (P wave without QRS)
- Asymptomatic (usually)
Seen in athletes, sleep
AVN conduction slowed by:
- Beta blockers, diltiazem/verapamil
- Digitalis
- MI–> AVN ischemia
2nd degree Mobitz Type II
Dropped beat (QRS complex) with no preceding change in PR interval length
- Block below AVN
- Often 2:1 conduction block (2 p waves–> 1 QRS)
- May progress to 3rd degree block
Tx: pacemaker
3rd degree AVN block (complete)
Atria and ventricles beat independently of one another
- P and QRS present, but bear no relationship to one another
- P (atrial rate) faster than ventricular rate
Causes:
- Lyme disease
- Congenital/acquired defects
- Primary conduction system disease
- Cardiomyopathy, infiltrative heart disease
- myocarditis
- MI: inferior–> reflex vagal action (reversible); anterior–> his-purkinje necrosis (irreversible)
- Drugs
Tx: Pacemaker
ANP
Atrial natiuretic peptide:
Released from myocytes in response to increased blood volume, atrial P
- Vascular relaxation
- decreased collecting tubule Na reabsorption (counteracts aldosterone)
- constricts efferent arterioles, dilates afferents (via cGMP)–> diuresis
Aortic arch baroreceptor
Increased BP–> vagus–> solitary nucleus of medulla
Carotid sinus
Change in BP–> glossopharyngeal–> solitary nucleus of medulla
Baroreceptors
Hypotension–> decreased atrial pressure/stretch–> decreased afferent baroreceptor–> increased sympathetic efferent (decrease parasymp)–> vasoconstriction, increased HR, contractility, BP
* Seen in severe hemorrhage
Carotid massage–> increased pressure/stretch–> increased afferent firing–> decreased HR
Cushing’s triad
Increased intracranial P (ICP)–> constricted arterioles–> cerebral ischemia
- -> HTN to increase perfusion–> stretch
- -> reflex baroreceptor-induced bradycardia (decrease HR)
Autoregulation of perfusion (by tissue type)
Heart: local metabolites (CO2, adenosine, NO)–> vasodilate
Brain: local metabolites (CO2, pH)–> vasodilate (central chemoreceptors)
Kidneys: myogenic, tubuloglomerular feedback
Lungs: Hypoxia–> vasoCONSTRICTION
Skeletal muscle: local metabolites (adenosine, lactate, K+)–> vasodilation
Skin: Sympathetic stimulation–> vasoconstriction (keep in body heat)
- Buildup of metabolites–> forced vasodilation (hence white then red in cold)
** Peripheral chemoreceptors= carotid, aortic bodies stimulated by decreased PO2 (< 60 mmHg), increased PCO2, decreased pH
Tricuspid atresia
Absence of tricuspid valve
Hypoplastic R ventricle
- Requires ASD and VSD for viability
Total anomalous pulmonary venous return (TAPVR)
Pulmonary veins drain into R heart circulation (SVC, coronary sinus)
- Associated with ASD, PDA to maintain R–> L shunt, maintain CO
- Similar to transpostion of great vessels
Down syndrome cardiac defects
ASD, VSD, AV septal defect (endocardial cushion defects)
Congenital rubella cardiac defects
Septal defects, PDA, pulmonary artery stenosis
Monckeberg Arteriosclerosis
Calcification in media of arterias (radial or ulnar)
- Benign
- Pipestem arteries
- NO obstruction of blood flow
- No intimal involvement
Hyaline arteriosclerosis
Thickening of small arteries (intima and media) due to essential hypertension, DM–> narrrowed lumen
- DM–> non-enzymatic glycosylation of proteins–> hyalinization
Hyperplastic arteriosclerosis
“Onion skinning” of arterioles d/t malignant HTN (diastolic > 120)
- Most common in kidneys, intestine, retina)
Abdominal aortic aneurysm
Associated with atherosclerosis
- Male smokers with HTN, 50+ years
- Most common location of atherosclerosis followed by coronary arteries > popliteal artery > carotid artery
Thoracic aortic aneurysm
Associated with HTN, cystic medial necrosis (Marfans) and tertiary syphillis
Cystic medial degeneration= myxomatous change in media of large arteries
- Elastic tissue fragmented, separation of elastic and fibromusclular components–> fill with ECM
- Seen in Marfan (fibrillin-1 defect)
- Defect in lysyl oxidase (d/t copper deficiency or beta-aminopropionitrile= sweet peas)–> can’t cross link elastin and collagen–> angioathryrism)
Angina subtypes
Symptomatic with > 75% lumen narrowing, no myocyte necrosis
Stable= secondary to atherosclerosis
- ST depression
- Retrosternal chest pain on exertion
Prinzmetal’s variant=
- ST elevation
- Occurs at rest secondary to vasospasm
Unstable/crescendo= thrombosis with incomplete occlusion
- ST depression
- Worsening chest pain at rest or minimal exertion
** In MI, see ST depression–> ST elevation with increased ischemia and transmural necrosis
Treatment: Decrease myocardial O2 consumption:
- nitrates (lower preload)
- beta-blockers (decrease afterload)
- pindolol and acebutolol= beta blockers contraindicated in angina)
Evolution of MI
0-4 hours: no changes
- risk of arrhythmia, CHF exacerbation, cardiogenic shock
4-12 hours: early coagulation necrosis
- risk of arrhythmia
12-24 hours: contraction bands (reperfusion injury), necrotic cells release contents, neutrophils migrate
- risk of arrhythmia
1-3 days: Coagulation necrosis, tissue inflammation around infarct–>
- Fibrinous pericarditis (d/t inflammation)
3-14 days: Macrophages, granulation tissue
- yellow and soft tissue by 10 days, hyperemic border
- Risk of free wall rupture–> tamponade
- Papillary muscle rupture
- Ventricular aneurysm–> arrhythmia, thrombi
- IV septum rupture–> VSD
2 weeks +: scarring complete, contracted
- Risk of Dressler’s syndrome= autoimmune problems d/t fibrinous pericarditis
- Fever, pleuritic pain, pericardial effusion
Diagnosis of MI
- ECG in first 6 hours
- Cardiac troponin I (most specific enzyme)= 4 hours to 7 days
CK-MB: seen in cardiac and skeletal muscle
- Used to diagnose reinfarction (as levels normalize 48 hours after first infarct)
ECG changes:
- ST elevation= transmural (widespread= pericarditis from Dressler’s)
- ST depression= subendocardial
- Pathologic Q waves= transmural
- PR depression= pericarditis
Dilated (congestive) cardiomyopathy
Most common cardiomyopathy; due to ECCENTRIC HYPERTROPHY (sarcomeres added in series) Causes: - Idiopathic - Genetic: x-linked dilated cardiomyopathy= mutation in cardiac cytoskeleton or mitochondrial enzymes (ex: dystrophin) - Alcohol abuse - wet Beriberi - Coxsackie B - Chronic cocaine use - Chagas disease - Doxorubicin tox - Hemochromatosis - Peripartum cardiomyopathy
Findings:
- S3 (volume overload)
- Dilated appearance
- L Atrial enlargement can compress esopagus (dysphagia)
Tx:
- Na+ restriction
- ACE-I
- Diuretics
- Digoxin
- Heart transplant
Hypertrophic cardiomyopathy
CONCENTRIC HYPERTROPHY (sarcomeres added in parallel)
Hypertrophied IV septum: too close to mitral valve leaflet–> outflow tract obstruction
- Familial, AD
- cause: beta-myosin heavy chain mutation (35-50%), myosin binding protein C (15-25%), cardiac troponin C (15-20%), tropomyosin (< 5%)
- associated with Friederich’s ataxia
- Sudden death in young athletes
Findings:
- S4 (pressure overload)
- Normal heart
- Apical impulses (triple ripple)
- Bifid pulse
- Systolic murmur
Treatment:
- Beta-blocker
- non-dihydropyridine Ca+ channel blocker (Verapamil)
Restrictive/obliterative cardiomyopathy
Diastolic dysfunction due to:
- Sarcoidosis
- Amyloidosis (senile cardiac amyloidosis in atria due to deposition of beta-folded ANP)
- Post-radiation
- Endocardial fibroelastosis (young children)
- Loeffler’s syndrome (eosinophilic infiltrate)
- Hemochromatosis
Chronic constrictive pericarditis
Infiltration of pericardium
- Most common cause= TB
- Restricted ventricular filling, Low CO, R-sided heart failure resistant to meds
- Kussmaul’s sign= rise in JVP with inspiration (normally falls): increased venous return to restricted heart–> blood goes up!)
Treatment of CHF
Reduced mortality:
- ACE-I (inhibits remodeling/left ventricular hypertrophy)
- Beta-blockers (except in acute decompensated HF)
- Angiotensin receptor antagonists (ARB)
- Spironolactone (blocks aldosterone neurohormonal stimulation–> prevents cardiac fibrosis)
- Hydralazine with nitrate (symptoms and mortality)
Reduced symptoms:
- Thiazide/loop diuretics
Bacterial endocarditis
- Roth’s spots= white spots on retina with surrounding hemorrhage
- Osler’s nodes
- Janeway lesions
- Splinter hemorrhages on nail bed
Acute causes: S. aureus
- Large vegtations on previously normal valves
Subacute causes: S. viridans
- Small vegetations on congenitally abnL or diseased valves
- Seen in dental procedures
- S. epidermis on prosthetic valves
- S. bovis d/t colon cancer
IV drug use–> tricuspid valve endocarditis
- S. aureus, pseudomonas, candida
Nonbacterial:
- Malignancy, hypercoagulable state
- Lupus (marantic/thrombotic endocarditis)
Complications:
- Chordae rupture, glomerulonephritis, suppurative pericarditis, emboli
Rheumatic fever
** Antibodies to M protein (antiphagocytic)–> type II hypersensitivity reaction (NOT reaction to bacteria)
group A beta-hemolytic strep (strep pyogenes)
- Mitral > aortic»_space; tricuspid
Associated with:
- Aschoff bodies= granuloma in giant cells
- Anitschokow’s cells (activated histiocytes)
- Elevated ASO titers
Symptoms:
- Fevers
- Erythema marginatum
- Valvular damage
- ESR increase
- Red-hot joints (migratory polyarthritis)
- Subcutaenous nodules
- St. Vitus’ dance (Syndeham’s chorea)
Cardiac tamponade
Equilibration of diastolic P in all 4 chambers
- Hypotension, increased venous pressure (JVD), distant heart sounds, increased HR, pulsus paradoxus)
Pulsus paradoxus= decrease in systolic BP > 10 on inspiration
- d/t cardiac tamponade, asthma, obstructive sleep apnea, pericarditis, croup
Polyarteritis nodosa
Young adults
- Hep B seropositive in 30%
- Constitutional symptoms, melena, abdominal pain
- HTN, neurologic dysfunction, renal damage
Path:
- Renal, visceral vessels (not pulmonary)
- Immune-complex mediated (type III)
- Transmural inflammation of arterial wall, fibrinoid necrosis
Tx:
- Corticosteroids, cyclophosphamide
Buerger’s disease
Thromboengiitis obliterans
Heavy smokers, males < 40 years
Path:
- Intermittent claudication–> gangrene, autoamputation, superficial nodular phlebitis
- Reynaud’s
- Segmental thrombosing vasculitis
Tx: smoking cessation
Microscopic polyangiitis
Vasculitis in lung, kidneys, skin
- Pauci-immune glomerulonephritis
- Palpapable purpura
NO granulomas
- p-ANCA
Tx: cyclophosphamide, cortiocosteroids
Wegener’s granulomatosis
Upper respiratory tract problems: perforation of nasal septum, chronic sinusitis, otitis media, mastoiditis
Lower resp tract: hemoptysis, cough, dyspnea
Renal: hematuria, red cell casts
Triad:
- Focal necrotizing vasculitis
- Necrotizing granulomas in lung, upper airway (large nodular densities on x-ray)
- Necrotizing glomerulonephritis
Granulomas
- c-ANCA
Tx: cyclophosphamide, corticosteroids
Churg-Strauss
Asthma, sinusitis, palpable purpura, peripheral neuropathy (foot/wrist drop)
- Also heart, GI, kidneys (pauci-immune glomerulonephritis)
Granulomatous necrotizing vasculitis with eosinophilia
- pANCA, elevated IgE
Pyogenic granuloma
Polypoid capillary hemangioma
- Can ulcerate and bleed
- Associated with trauma, pregnancy
Cystic hygroma
Cavernous lymphangioma of neck
- Associated with Turner’s and Down syndrome
Glomus tumor
Benign, painful red-blue tumor under fingernails
- Arises from smooth muscle cells of glomus body
Bacillary angiomatosis
Benign capillary skin papules in AIDS patients
- Caused by Bartonella henselae infections
- Mistaken for Kaposi’s sarcoma
Angiosarcoma
Blood vessel malignancy in head, neck, breast
- Associated with radiation therapy (breast cancer, Hodgkin’s lymphoma)
- Aggessive, difficult to resect due to delay in diagnosis
Lymphangiosarcoma
Lymphatic malignancy associated with persistent lymphedema (post-radical mastectomy, filariasis)
Sturge-Weber disease
Congenital vascular disorder of capillary-sized blood vessels
- Port-wine stain
- Ipsilateral leptomeningeal angiomatosis (intracerebral AVM)–> seizures
- Early-onset glaucoma
Nifedipine, Amlodipine
Dihydropyridine Ca+2 channel blocker
- Blocks voltage-dependent L-type Ca+2 channels of cardiac, smooth muscle
- Highly effective on vascular smooth muscle
- Less effective on cardiac tissue
Use:
- HTN
- angina (similar effect to nitrates= n for nifedipine)
- Prinzmetal’s angina, Raynaud’s
- Post-SAH: lowers M+M d/t vasospasm
Tox:
- Cardiac depression
- AV block
- Peripheral edema
- Flushing
- Dizziness
- Constipation
Verapamil, Diltiazem
Non-dihydropyridine Ca+2 channel blocker
- Blocks voltage-dependent L-type Ca+2 channels of cardiac, smooth muscle
- Less effective on vascular smooth muscle
- Highly effective on cardiac tissue
Use:
- Arrhythmias
- angina (similar to beta-blockers)
- Prinzmetal’s angina, Raynaud’s
- Post-SAH: lowers M+M d/t vasospasm
Tox:
- Cardiac depression
- AV block
- Peripheral edema
- Flushing
- Dizziness
Hydralazine
MOA: increases cGMP–> smooth m. relaxation–> vasodilation (arterioles > veins)
- reduces afterload
Use: Severe HTN, CHF
- 1st line in pregnancy for HTN (with methyldopa)
- Coadministered with Beta-blocker (labetolol) to prevent reflex tachycardia
Tox:
- Reflex tachycardia (contraindicated in angina/CAD)
- Fluid retention
- Nausea
- H/A
- Angina
- Lupus-like syndrome (slow acetylators)
Treatment of malignant HTN
Nitroprusside Nicardipine Clevidipine Labetolol Denoldopam
Nitroprusside
Short acting
MOA: increases cGMP via release of NO
Tox: cyanide release
Fenoldopam
MOA: Dopamine D1 receptor agonist
- Coronary, peripheral, renal, splanchnic vasodilation
- Decreases BP, increases natriuresis
Nitroglycerin, isosorbide dinitrate
MOA: Vasodilate by releasing NO in smooth muscle–> increased cGMP, smooth m. relaxation
- Dilates veins»_space; arteries
- Main effect= decrease cardiac preload via venodilation (retain blood in venous system)
Use: Angina, pulmonary edema
Tox: Reflex tachycardia, hypotension
- Flushing, headache
- “Monday disease”= tolerance development–> tachycardia, dizziness, H/A on re-exposure
- Isosorbide DInitrate= tablet with extensive 1st pass metabolism compared to isosorbide MONOnitrate
- Nitroglyceride= sublingual
Statins
MOA: HMG-CoA reductase inhibitors
- Inhibit conversion of HMG-CoA to mevalonate (cholesterol precursor)
- Increased LDL-R in liver (increase LDL uptake from periphery)
Use:
- Most effective LDL-lowering therapy
- Increases HDL
- Lowers TGs
Side effects:
- Hepatotoxic (increased LFTs)
- Rhabdomyolysis
- Myopathy (greatly increased with Fibrate use–> increased [statin])
Niacin
Vitamin B3
MOA:
- Inhibits lipolysis in adipose tissue
- Reduces hepatic VLDL secretion
Use:
- Lowers LDL
- Most HDL increase
- lowers TG
Tox:
- Red, flushed face (pre-dose with aspirin, long term use decreases flusing)–> antihypertensives + niacin–> vasodilation!
- Hyperglycemia: decreases insulin sensitivity–> acanthosis nigricans)
- Hyperuricemia (exacerbates gout)
Cholestyramine
Colestipol
Colesevelam
Bile acid resins
MOA:
- Prevent intestinal reabsorption of bile acids
- Increases LDL-R on liver (so liver can make more cholesterol)
Use:
- Lowers LDL
- Slight HDL increase
- Slight TG increase
Tox:
- Patients hate taste, causes GI discomfort
- Decreases absorption of fat-soluble vitamins (Vit A, D, E, K)
- Decreases statin absorption
- Cholsterol gallstones (esp with fibrates)
Ezetimibe
Cholesterol absorption blocker
MOA: prevents cholsterol abs at small intestine brush border
Use:
- 20-30% decrease in LDL
- NO change on other profile
Tox:
- Rare increase in LFTs
- Diarrhea
- slight increased risk of myopathy with statins
Fibrates (gemfibrozil, clofibrate, bezafibrate, fenofibrate)
MOA:
Activate PPAR-alpha–> Upregulate LPL–> increased TG clearance
Use:
- Slight decrease in LDL
- Increase HDL
- Most decrease in TGs
Tox:
- Myositis, hepatotoxicity, cholseterol gallstones (with bile acid resins)
Digoxin
Cardiac glycoside
MOA:
- Inihibits Na/K ATPase–> accumulation of Na+ in cell–> inhibition of NCX (Na/Ca exchanger)–> slows Ca+2 efflux
- Positive inotrope (contractility)
- Stimulates vagus nerve–> negative chronotrope (decreases HR)
Use:
- CHF: increased contractility
- A fib: vagal nerve stimulation–> decreased AVN conduction, depression of SAN
PK:
- 75% bioavailable
- 20-40% protein bound
- t1/2= 40 hours
- Urinary excretion
Tox:
- Cholinergic: N/V/D, blurry yellow vision
- ECG: increased PR interval, decreased QT, ST scooping, T-wave inversion
- Arrhythmia (d/t increased intracell [Ca+2]–> delayed afterdepolarization)–> ventricular tachyarrhythmias
- AV block
- Hyperkalemia (poor prognostic indicator)
- Predisposed to toxicitiy with: renal failure (decreased excretion), hypokalemia, (binds at Na/K ATPase), quinidine (decreases clearance, displaces from tissues)
Antidote= slowly normalize K+, lidocaine, cardiac pacer, anti-digoxin Fab fragments, Mg+2 (KLAM)
Class IA antiarrhythmics
Na-channel blockers:
- Quinidine
- Procainamide
- Disopyramide
MOA:
- Increase AP duration, effective refractory period
- Increase QT interval
Use:
- Atrial, ventricular arrhythmias
- Especially reentrant, ectopic supraventicular, ventricular tachycardia
Tox:
- Quinidine= cinchonism (H/A, tinnitus)
- Procainamide= Reversible SLE
- Disopyramidine= heart failure
- ALL= Thrombocytopenia, TdP due to increased QT interval
Class IB antiarrhythmics
Na channel blockers:
- Lidocaine
- Mexiletine
- Tocainamide
MOA:
- Decreased AP duration
Use:
- Ischemic or depolarized Purkinje, ventricular tissue
- Acute ventricular arrhythmias (post-MI= Best!)
- Digitalis-induced arrhythmias
Tox:
- Local anesthetic
- CNS stim/depression
- CV depression
Class IC antiarrhythmics
Na channel blockers
- Flecainide
- Propafenone
MOA:
- No effect on AP duration
Use:
- Useful in Ventricular tachycardias–> Vfib, intractable supra-ventricular tachycardia
- Last resort in refractory tacharrhythmias
Tox:
- Proarrhythmic
- Contraindicated post-MI
- Prolongs refractory period in AVN
Class II antiarrhythmics
Beta-blockers:
- Metoprolol
- Propanolol
- Esmolol
- Atenolol
- Timolol
MOA:
- Decreases cAMP, Ca+2 currents–> decreased SA and AV node activity
- Decrease slope of phase 4 (suppressing abnormal pacemakers
- Works best on AVN–> increased PR interval
Use:
- Ventricular tacchycardia
- Supraventricular tacchycardia
- Slowing ventricular rate during Afib, Aflutter
Tox:
- Impotence, exacerbation of asthma, CV effects (bradycardia, AV block, CHF)
- CNS effects: sedation, sleep alterations
- May mask signs of hypoglycemia
- Metoprolol= dyslipidemia
- treat overdose with glucagon
*Propanolol= exacerbate vasospasm in Prinzmetal’s angina
Class III antiarrhythmics
K+ channel blockers
- Amiodarone
- Ibutilide
- Dofetilide
- Sotalol
MOA:
- Increases AP duration
- Increased effective refractory period (ERP)
- Increases QT interval
Tox:
- Sotalol= TdP, excessive beta-block
- Ibutilide= TdP
- Amiodarone= pulmonary fibrosis, hepatotoxicity, hypo/hyperthyroidism (40% iodine), corneal deposits, skin deposits (blue/gray)–> photodermatitis, neurologic effects, constipation, CV effects (bradycardia, heart block, CHF): check PFTs, LFTs, TFTs
- BUT, Amiodarone has class I, II, III, and IV effects due to alteration of lipid membrane
- Amiodarone decreases CytP450 activity–> increase in Warfarin (commonly given in atrial fibrillation)
Class IV antiarrhythmics
Non-dihydropyridine Ca+2 channel blockers:
- Verapamil
- Diltiazem
MOA:
- Slow AVN conduction by increasing phase 0, 4 of depolarization (increase PR interval)
- Increase ERP
Use:
- Nodal arrhythmias: supraventricular arrhythmias
Tox:
- Constipation
- Flushing
- Edema
- CV effects: CHF, AVN block, sinus node depression
Adenosine
MOA:
-Increases K+ flux out of cells–> hyperpolarizes the cell and decreases Ca+2 influx
Use:
Supraventricular tachycardia
- Short-acting
Tox:
- Flushing, hypotension, chest pain
- Sense of doom
- Administer with theophylline, caffeine to offset effects
Mg+2
Administered in TdP and digoxin toxicity
Mitral stenosis
Severity of murmur indicated by A2–> OS (opening snap) interval
- Shorter interval= more severe stenosis)
Arrhythmogenic right ventricular cardiomyopathy (ARVC)
Right ventricle wall replaced by fibrofatty tissue (idiopathic)
- May be due to mutation in Ca+2-binding protein of sarcoplasmic reticulum
