Carotid Sheath

3 structures include:

1. Internal jugular Vein (lateral)

2. Common carotid Artery (medial)

3. Vagus Nerve (posterior)

VAN

In the majority of cases, SA and AV nodes are supplied by RCA. 80% of the time, RCA supplies inferior portion fo the left ventricle via the PD artery (=right dominant)

Coronary artery occlusion occurs most commonly in the LAD which supplies teh anterior interventricular septum.

Coronary arteries fill during diastole

Most posterior part of the hear tis left atrium, enlargmeent can cause dysphagia.

CO=stroke volume x heart rate

CO= (rate of O2 consumption)/(arterial O2 content-venous O2 content)

Druing exercise, CO increases initially as a result of increase in SV. AFter prolonged exercise, CO increases as result of increase in HR. 

If HR too high, diastolic filling is incpomplete and CO decreases (ventricular tachycardia)

MAP=COx TPR

MAP=1/2 systolic +2/3 diastolic

Pulse pressure =systolic-diastolic

Pulse pressure = stroke volume

SV=CO/HR=EDV-ESV

Contractility, afterload and preload.

Increase SV when

1. Increase preload

2. Decrease afterload 

3. increase contractility

SV increases in anxiety, exercise and pregnancy. 

A failing heart has decreased SV

Contractility (and SV) increases with:

1. Catecholamines (Increase activity of CA2+ pump in sarcoplasmic reticulum)

2. Increase intracellular calcium

3. Decrease extracellular sodium

4. Digitalis (Increase intracellular Na+ resulting in increased Ca2+)

1. B1 blockade

2. Heart failure

3. Acidosis

4. Hypoxia/hypercapnea

5. Ca2+ channel blockers

Myocardial O2 demand is increased by:

Force of contraction:

1. Increased afterload (approximately diastolic BP)

2. Increased contractility

3. Increased heart rate

4. Increased heart size (increase wall tension)

proportional to initial length of cardiac muscle fiber (preload)

Ventricular EDV

Preload increases with:

1. Exercise (slightly)

2. Increased blood volume (overtransfusion)

3. Excitement (sympathetics)

Decreases with:

1. Venous dilators (nitroglycerin)

Systolic arterial pressure (proportional to peripheral resistance)

Vasodilators (hydralazine) decrease afterload

EF=SV/EDV

EF=(EDV-ESV)/EDV

EF is an index of ventricular contractility.

EF is normally> or =55%

Change in Pressure =QxR

Resistance =driving pressure (change in P)/flow (Q)

Resistanec =8n(viscosity) x length/pir^4

Viscosity depends mostly on hematocrit

Increases with:

1. Polycythemia

2. Hyperporteinemic states (multiple myeloma)

3. Hereditary spherocytosis

1. Isovolumetric contraction--period between mitral valve closure and aortic valve opening; period of highest O2 consumption.

2. Systolic ejection--period between aortic valve opening and closing.

3. Isovolumentric relaxation--period between aortic valve closing and mitral vavle opening.

4. Rapid filling--period just afer mitral valve opening

5. Slow filling--period just before mitral valve closure.

S1--mitral and triccupsid valve closure

S2--aortic and pulmonary valve closure

S3--at end of rapid ventricular filling

S4--high atrial pressure/stiff ventricle

S3 associated with dilated CHF

S4 (atrial kick) is associated with hypertrophic ventricle

S2 splitting: aortic voalve closes before pulmonic; inspiration increases this difference

a wave--atrial contraction

c wave--RV contraction (Tricupsid valve bulging into atrium)

v wave--Increased atrial pressure dueto filling against closed tricuspid valve.

Jugular venous distention seen in right heart failure

Normal splitting: S1, A2, P2

Paradoxical splitting (associated with arotic stenosis)

Expiration S1 P2, A2 (far or close)

Contraction of cardiac muscle dependent on extracellular calcium; enters celld during plateau of action potential and stimulates calcium release from SR. (calcium induced calcium release).

In contrast to skeletal muscle:

1. Cardiac muscle actoin potentail has plateau which is due to Ca2+ influx

2. Cardiac nodal cells spontaneously depolarize, reslulting in automaticity.

3. Cardiac myocytes are electrically coupled to one antoher by gap junctions. 

Occurs in atrial and ventricular myocytes and Purkinje finers

Phase 0=rapid upstroke--volage gated Na+ channels open

Phase 1=initial repolarization--inactivation of voltage-gated Na+ channels. Voltage gated K+ channels begin to open.

Phase 2=plateau--Ca2+ influx through votage gated Ca2+ channels balances K+ efflux. Ca2+ influx triggers antoher Ca2+ release from SR and myocyte contraction.

Phase 3=rapid repolarization--massive K+ efflux due to opening of voltage-gated slow K+ channels and closure of voltage-gated Ca2+ channels.

Phase 4=resting potential--high K+ permeability through K+ channels

Occurs in SA and AV nodes. Key differences from ventricular action potential include:

Phase 0=upstroke--opening of voltage-gated CA2+ channels. These cells lack fast voltage-gated Na+ channels. Results in a slow conduction velocity that is used byt he AV node to prolong transmission from atria to ventricles

Phase 2=plateau is absent

Phase 4=slow diastolic depolarizzation--membrane potential spontaneously depolarizes as Na+ coonductance increases (If different than INa above). Accounts for automaticity of SA and AV nodes. The slope of phase 4 in the SA node determines heart rate. ACh decreases and catecholamines increase the rate of diastolic depolarization, decreasing or increasing heart rate, respectively. 

P wave--atrial depolarization

PR segmetn--conduciton delay through AV node (normally <200 msec)

QRS complex--ventricular depolarization (normally <120 msec)

QT interval--mechanical contraction of the ventricles

T wave--ventricular repolarization

Atrial repolarization is masked by QRS complex.

ST segment--isoelectric, ventricles depolarized.

U wave--caused by hypokalemia.

Atrial fibrillation

Chaotic and erratic baseline (irregularly irregular) with no discrete P wave in between irregularly spaced QRS complex

Atrial Flutter

A rapid succession of identical, back to back atrial depolarizatoin waves. The  identical appearance accounts for "sawtooth" appearance of flutter waves

AV block

1st degree 

the PR interval is prolonged (>200 msec). Asymptomatic

AV block

2nd degree

Mobitz type I (Wenckebach)

Progressive lengthening of PR interval until a beat is "dropped (a P wave not followed by QRS complex). Usually asymptomatic.

Mobitz type II

Dropped beats that are not preceded by a change in the length of the PR interval (as in type I). These abrupt, nonconudcted P waves result in a pathologic condition. It is often found as 2:1 block, where there are 2 P waves to 1 QRS ressponse. May progress to 3rd-degree block.

3rd degree (complete)

The atria and the ventricles beat independently of each other. Both P waves and QRS complexes are present, although Pwaves bear no relation to QRS complexes. The atrial rate is faster than teh ventricular rate. Usually treat with pacemaker. 

Ventricular Fibrillation

Completely erratic rhythm with no identifiable waves. Fatal arrhythmia without immediate CPR and defibrillation

1. Medullary vasomotor center senses decrease and baroreceptors fire-->Increase Sympathetic activity

B1 (Inc HR, Inc contractility)-->Inc CO

A1 (venoconstriction: Inc venous return)--Inc CO

A1 (artereolar  vasoconstriction--< Inc TPR

2. JGA senses decrease ECV (effective circulatingi volume-->Renin Angiotensin System (kidneys)

Angiotensin II (Vasoconstriction)-->Inc TPR

Aldoserone (Inc blood volume)-->Inc CO

1. Aortic arch transmits via vagus nerve to medulla (responds only to increased blood pressure)

2. Carotid sinus trnasmits via glossopharyngeal nerve to medulla.

Baroreceptors:

1. Hypotension: Decrease arterial pressure-->decrease sretch-->decrease afferent baroreceptor firing-->increase efferent sympathetic firing and decrease efferent parasympatehtic stimulation-->vasoconstriciton, Increase HR, increase contractility, increase BP. Important in response to severe hemorrhage.

2. Carotid massage: Increase pressure on carotid artery-->increase stretch-->decrease HR

Chemoreceptors

1. Peripheral: Carotid and aortic bodies respond to PO2 (<60 mmHg), Increase PCO2 adn decrease pH of blood.

Central: REspond to change sin pH adn PCO2 of brain interstitial fluid, which in turn are influenced by arterial CO2. Do not directly respond to PO2. Responsible for Cushing reaction, response to cerbral ischemia, response to increased intracranial pressure-->hypertension (sympathetic response) and bradycardia (parasympatethtic response).

Liver has largest share of systemic caridac output.

Kidney has highest blood flow per gram of tissue

Heart has large arteriovenous O2 difference. Increased O2 demand is met by increased coronary blood flow, not by increased extraction of O2

PCWP-pulmonary capillary wedge pressure (in mmHg) is good approx of left atrial pressure.

Measured withSwwan Gantz catheter.

Autoregulation: Factors determining autoregulation

1. Heart

2. Brain

3. Kidneys

4. Lungs

5. Skeletal muscle

6. Skin

1. Local metabolites: O2, adenosine, NO

2. Local metabolites: CO2 (pH)

3. Myogenic and tubuloglomerular feedback

4. Hypoxia causes vasoconstriciton

5. Local metabolites: lactate, adenosine, K+

6. Sympathetic stimulation most important mechanism--temperature control

NEt filtration pressure =Pnet-[(Pc-Pi)-(pic-pii)]

Kf=filtration constant (capillary permeability)

Net fluid flow =Pnet (Kf)

1. Increased capillary pressur e(INcreased Pc; heart failure)

2. Decreased plasma proteins (Decreased pic; neephrotic syndrome, liver failure)

3. Increased capillary permeability (Increased Kf; toxins, infections, burns)

4. Increased interstitial fluid colloid osmotic pressure (increased pi i;lymphatic blockage)

1. Heart defects

2. Hypospaidas

 3. Cleft lip (wiht or without cleft palate)

4. Congenital hip dislocation

5. Spina bifida

6. Anencephally

7. Pyloric stenosis (associated with projectile vomiting)

Right to left shunts (Early cyanosis)--"blue babies"

1. Tetrology of Fallot (most common cause of early cyanosis)

2. Transporation of great vessels

3. Truncus arteriosus

Children may squat to increase venous return. 

Left-to-right shunts (late cyanosis) "blue kids"

1. VSD (most common congenital cardiac anomaly)

2. ASD (loud S1; wide, fixed split S2)

3. PDA (close with indomethacin)

Frequency--VSD>ASD>PDA

Incrased pulmonary resistance due to arteriolar thickening. 

LEads to progressive pulmonary hypertension; R-->L shunt (Eisenmenger's).

1. Pulmonary stenosis (most important determinant for prognosis)

2. RVH 

3. Overriding aorta (overrides VSD)

VSD

PROVe

Early cyanosis is caused by right to left shut across the VSD. On x-ray, a boot shaped aheard due to RVH. Patietns sufer "cynaotic spells." Tetralogy of FAllot is caused by anterosuperior displacement of the infundibular septum. 

Aorta leaves RV anterior and pulmonary trunk leaves LV posterior. LEads to separation of systemic and pulmonary circulations Not compatible with life unless a shunt is present to allow adquate mixing of blood (eg VSD, PDA or patent foramen ovale).

Due to failure of aorticopulmonary septum to spiral. Without surgicla correction, most infants die within the first few months of life. 

Infantile type--aortic stenosis proximal to insertion of ductus arteriosus (preductal)

Adulte type--stenosis distal to ductus arteriosus (postductal). ASsociated with notching of the ribs, hypertension in upper extremities, weak pulses in lower extremities. 

Male: female ratio 3:1. Check femoral pulses on phyiscal exam

INfantile: IN close to the heart

ADult: Distal to Ductus

In fetal period, shunt is right to left (normal). In neonatal period, lung resistance decreases and shunt becoems left to right with subsequent RVH and failure (abnormal). Associated with continuous "machine-like" murmur. Patency is maintained by PGE synthesis and low O2 tension.

Indomethacin is used to close a PDA. PGE is used to keep a PDA open, which may be necessary to sustain life in conditions such as trasnposition of great vessels.

1. 22q11 syndromes--Truncus arteriosus, tetralogy of Fallot

2. Down syndrome--ASD, VSD

3. Congenital rubella--Septal defects, PDA

4. Turner's syndrome--Coarctation of aorta

5. Marfan's syndrome--Aortic insufficiency

6. Offspring of diabetic mother--Transposition of great vessels

Defined as BP> or =140/90

Risk factors: Increase age, obesity, diabetes, smoking, genetics, black>white>Asian

Reatures: 90% of hypertension is first degree (essential) and related to increased CO -or increased TPR; remaining 10% mostly second degree to renal disease. Malignant hypertension is severe and rapidly progressing.

Predisposes to: Atherosclerosis, stroke, CHF, renal failure, retinopathy and aortic dissection.

1. Atheromata-plaques in blood vessel walls

2. Xanthooma--plaques or nodules composed of lipid-laden histiocytes in the skin, especially teh eyelids

3. Tendinous xanthoma-lipid deposit in tendon, espeically Achilles

4. Corenal arcus--lipid deposit in cornea, nonspecific (arcus senilis).

1. Monckeberg-calcification of arteries, especially radial or ulnar. Usually benign

2. Arteriolosclerosis-Hyaline thickening of small arteries in essential hypertension. Hyperplastic "onion skinning" in malignant hypertension.

3. Atherosclerosis-fibrous plaques and atheromas form in intima of arteries.

Disease of elastic arteries and large and medium-sized muscular arteries

Risk factors: Smoking, hypertension, diabetes mellitus, hyperlipidemia, family history

Progression: Fatty streaks-->proliferative plaque-->complex atheromas

Complications: Aneurysms, ischemia, infarcts, peripheral vascular disease, thrombus, emboli

Location: Abdominal aorta>coronary artery>popliteal artery>carotid artery

Symptoms: Angina, cluadication, but can be asymptomatic

1. Angina (CAD narrowing >75%)

a. stable-mostl second degree to atherosclerosis (retrosternal chest pain with exertion)

b. prinzmetal's variant--occurs at rest secondary to coronary artery spasm

c. unstable/crescendo--thrombosis but no necrosis (worsening chest pain)

2. Mycardial infarction--most often acute thrombosis due to coronary artery atherosclerosis. Results in myocyte necrosis. 

3. Sudden caridac death--death from cardiac causes within 1 hour of onset of symptoms, most commonly due to a lethal arrhythmia

4. Chronic ischemic heart disease--progressive onset of CHF over many years due to chronic ischemic mycoardial damage

Red (hemorrhagic) infarcs occur in loose tissuse with collaterals such as lungs, intesine or following repersuion.

Pale infarcts occur in solid tissue wiht single blood supply, such as brain, heart, kidney, and spleen.

REd=REperfusion

Coronary artery occluion: LAD>RCA>circumflex

Symptoms: Diaphoresis, nausea, vomiting, severe retrosternal pain, pain in left arm and/or jaw, shortness of breath, fatique, adrenergic symptoms

A. First day: No visible change by light microscopy in first 2-4 hours. Coagulative necrosis; contraciotn bands visible after 4 hours. Release of contents of necrotic cells into bloodstream and the begninning ofo neutrophil emigration

B. 2-4 days: tissue surrounding infarc shows acute inflammation. Dilated vessles (hyperemia). Neutrophil emigration. Muscle shows extensive coagulative necrosis.

C. 5-10 days: Hyperemic border, central yellow-brown softening--maximally yellow and soft by 10 days. Outer zone (ingrowth of granulation tissue). Macrophages, neutrophils.

D. 7 weeks Recanalizzed artery, gray white, contracted scarcomplete. 

In first 6 hours, ECG is gold standard.

Cardiac tropnonin I rises after 4 hours and is elevated for 7-10 days; more specific than other protein markers.

CK-MB is predominantly found in myocardium but can also be released from skeletal muscle. 

AST is nonspecific and can be found in cardiac, liver and skeletal muscle cells. 

ECG changes chan include ST elevation (trasnural infarct), ST depression (subendocardial infarct) and pathological Q waves (transmural infarct).

1. Cardiac arrhythmia--important cause of death before reaching hospital; common in first few days.

2. LV failure and pulmonary edema

3. Cardiogenic shock (large infarct--high risk of mortalitiy)

4. Rupture of ventricular free wall, interventricular septum, papillary muscle (4-10 dyas post-MI), cardiac tamponade

5. Aneurysm formation-Decrease CO, risk of arrhythmia, embolus from mural thrombus

6. Fibrinous pericardits-friction rub (3-5 days post MI)

7. Dressler's syndrome-autoimmune phenomenon resulting in fibrinous pericarditis (several weeks post-MI)

Dilated (congestive) cardiomyopathy-Most common cardiomyopathy (90% of cases) Etiologies include Alcohol abuse, Beriberi, Coxsackie B virus myocarditis, chronic Cocaine use, Chagas' disease, Doxorubicin toxicity, peripartum cardiomyopathy and hemochromatosis. Heart dilates and looks like a balloon on chest x-ray(Systolic dysfunction ensues)

Hypertrophic cardiomyopathy-often asymmetric and involving intraventricular septum. 50% of cases are familial, autosomal dominant. Cause of sudden death in young athletes. Findings: loud S4, apical impulses, systolic murmur. Treat with beta blocker (Diastolic dysfuncction ensues)

Restrictive/obliterative cardiomyopathy-majro cuases include sarcoidosis, amylooidosis, posttradiation fibrosis, endocardial fibroelastosis, and endomyocardial fibrosis (Loffler's)

1. Dyspnea on exertion-Failrue of LV output to increase during exercise

2. Cardiac dilation-Greater ventricular end-diastolic volume

3. Pulmonary edema, paroxysmal nocturanl dyspnea-LV failure-->Increased pulmonoary venous pressure leads to pulmonary venous distention and transudation of fluid. Prensence of hemosiderin-laden macrophages ("heart failure" cells).

4. Orthopnea (shortness of breath when supine)-Increased venous return in supine position exacerbates pulmonary vascular congestion

5. Hepatomegaly (nutmeg liver)-Increased central venous pressure leads to increased reesistance to portal flow. Rarely, leads to "cardiac cirrhosis"

6. Ankle, sacral edema-RV failure leads to increased venosu pressure leads to fluid transudation.

1. Fat-associated with long bone fracture and liposuction

2. Air

3. Thrombus

4. Bacteria

5. Amniotic fluid-can lead to DIC especially postpartum

6. Tumor

An embolus moves like a FAT  BAT. Approx 95% of pulm emboli arise from deep leg veins. 

Pulmonary embolus-chest pain, tachypnea, dyspnea

Predisposed by Virchow's triad

1. Stasis

2. Hypercoagulability

3. Endothelial damage

Compression of heart by fluid (ie blood) in pericardium, leading to decreased CO

Equilibration of pressures in all four chambers.

Findings: hypotension, increased venous pressure (JVD), distant heart sounds.

Pulsus paradoxus; ECG shows electrical alternans (beat to beat alterations of QRS complex height). 

NEw murmur, anemia, fever, Osler's nodes (tender raised lesions on finger or toe pads), Roth's spots (round white spots on retina surrounded by hemorrhage), Janeway lesions (small erythematous lesions on palm or sole), splinter hemorrhages on nail bed. Valvular damage may cuase new murmur. Multiple blood cultures necessary fro diagnosis.

1. Acute-S. aureus (high virulence). Large vegetations on previously normal valves, rapid onset.

2. Subacute-viridans streptococcus (low virulence). Smaller vegetations on congenitally abnormal or diseased valves. Sequela of dental procedures. More insidious onset. 

Endocarditis may also be nonbacterial ssecond degree to metastasis or renal failure (marantic/thrombotic endocarditis).

Mitral valve most frequently involved. Tricuspid valve endocarditis is associated with IV drug abuse.

Complications: 1. Chordaae rupture 2. Glomerulonephritis 3. Suppurative pericarditis 4. Emboli

Bacteria FROM JANE:

Fever

Roth's spots

Osler's nodes

Murmur

Janeway lesions

Anemia

Nail-bed hemorrhage

Emboli

Vegetations develop on btoh sides of valve (leads to mitral valve stenosis) but do not embolize. Seen in lupus.

SLE causes LSE

Consequence of pharyngeal infection with group A beta-hemolytic streptococci. Late sequelae include rheumatic heart disease, which affects heart valves-mitral>aortic>>tricuspid (high-pressure valves affected most). Associated with Aschoff bodies, migratory polyarthritis, erythema marginatum, elevated ASO titers.

Immune mediated, not direct effect of bacteria

FEVERSS

Fever

Erythema marginatum

Valvular damage

ESR increase

Red-hot joints (polyarthritis)

Subcutaneous nodules

St. Vitus' dance (chorea)

Aschoff bodies (granuloma wiht giant cells) and Anitschkow's cells (activated histiocytes) are found in rheumatic heart disease.

Think kof two RHussians with RHeumatic heart disease (Aschoff and Anitschkow)

Serous-Caused by SLE, rheumatoid arthritis, infection, uremia

Fibronous-Uremia, MI, rheumatic cfever

Hemorrhagic-TB, malignancy (melanoma).

Findings: pericardial pain, friction rub, ECG changes (diffuse ST elevations in all leads), pulsus paradoxus, distant heart sounds.

Can resolve withotu scarring or lead to chronic constrictive pericarditis.

Third degree syphilis disrupts the vasa vasora of the aorta with consequent dilation of the aorta and valve ring. Often affects the aortic root and calcification of ascending arch off the aorta.

May see calcification of aortic root and ascending aortic arch

Can result in aneurysm mof ascending aorta or arch and aortic valve incompetence. 

1. Hydrochlorothiazide-Hypokalemia, slight hyperlipidemia, hyper uricemia, lassitude, hypercalcemia, hyperglycemia

2. Loop diuretics-Potassium wasting, metabolic alkalosis, hypotension, ototoxicity

1. Clonidine-dry motuh, sedation, severe rebound hypertension

2. Methyldopa-sedation, positive Coombs' test

3. Hexamethonium-SEvere orthostatic hypotension, blurred vision, constipation, sexual dysfunction

4. Reserpine-Sedation, depression, nasal stiffness, ddiarrhea

5. Guanethidine-Orthostatic and exercise hypotension, sexual dysfucntion, diarrhea

6. Prazosin-1st dose orthostatic hypotension, dizziness, headache

7. Beta blockers-Impotence, asthma, cardiovascular effects (bradycardia, CHF, AV block), CNS effects (sedation, sleep alterations)

1. Hydralazine (use with betablockers to prevent reflex tachycardia, diuretic to block salt retention)-nausea, headache, lupus-like syndrome, reflex tachycardia, angina, salt retention

2. Minoxidil (same as above)-hypertrichosis, pericardial effusion, reflex tachycardia, angina, salt retention

3. Nifedipine, verapamil-dizziness, flushing, constipation (verapamil), nausea

4. Nitroprusside-cyanide toxicity (releases CN)

Captopril-hyperkalemia, Cough, Angioedema, Proteinuria, Taste changes, hypOtension, Pregnancy problems (fetal renal damage), Rash, Increased renin, Lower angiotensin II

CAPTOPRIL

Mechanism: increase cGMP-->smooth muscle relaxation. Vasodilates arterioles>veins; afterload reduction.

 Clinical use: Severe hypertension, CHF

Toxicity: Compensatory tachycardia, fluid retention. Lupus-liek syndrome

1. Nifedipine, 2. verapamil 3. diltiazem

Mechanism: Block voltage dependent L-type calcium channels of cardiac and smooth muscle and thereby reduce muscel contractility. Vascular smooth muscle--nifedipine>diltiazem>reapamil

Heart-verapamil>diltiazem>nifedipine

Clinical use: Hypertension, angina, arrhythmias (not nifedipine)

Toxicity: Cardiac depression, peripheral edeam, flushing, dizziness, and constipation

Mechanism: Vasodilate by releaseing NO in smooth muscle, causing increase in cGMP and smooth muscle relaxation. Dilates veins>>arteries. Decrease preload.

Clinical use: Angina, pulmonary edema. Also used as aphrodisiac and erection enhancer. 

Toxicity: Tachycardia, hypotension, headache, "Mondya disease" in industrial exposure, eveloping tolearance for vasodilating action during work week and loss of tolerance over weekend resulting in tachycardia, dizziness, headache

Goal-reduciton of myocardial O2 consumption (MVO2) by decreasing 1 or more determinants of MVO: EDV, bp, HR, contractility, ET

Nitrates: EDV deecrease, BP decrease, Contractility Increase, HR increase, ET decrease MVO2 decrease

Betablockers: EDV increase, BP decrease, Contractility decrease, HR decrease, ET increase, MVO2 decrease

Nitrates +betablockers: Decrease BP, Decrease HR, Decrease MVO2, little of no effect on everythign else.

Calcium channel blockers: Nifedipine similar to Nitrates, verapamil similar to B-blockers

Factors involved in excitation contraction coupling

1. Na/K ATPas-digitalis inhibits

2. NA/CA exchanger

3. Voltage gated Ca channel- ca channel blockers and beta blockers inhibit

4. Ca pump in SR

5. Cacilum release channel in SR-ryanodine stimulate

6. Site of calcium interaction wtih troponin-tropomysoin system-Ca sensitizers stimulate

Digitoxin-75% bioavailability, 20-40% protein bound, t1/2=40 hours, urinary excretion.

Mech: Inhibits Na/K ATPase of cell membrane, increasing intracellular Na. Na/Ca antiport odes not function as efficiently, causing increase in intracellular Ca; leads to positive inotropy. May cause increse PR, decrease QT, scooping of ST segment, Twave inversion on ECG

Clinical use: CHG (increase contractility): atrial fibrillation (decreased conduction at AV node)

Toxicity: Nausea, vomitting, diarrhea. Blurry yellow vision. Arrhythmia. Toxciities of digitoxin are increased by renal failure (decreased excretion), hypokalemia (potentiates durgs effects) and quinidine (decrease digoxin clearance and displaces from tissue binding sites

Antidote: Slowly normalize K+, lidocaine, cardiac pacer, anti-dig Fab fragments

Local anesthetics. Slow or block conduction especially in depolarized cells. Decreases slpe of phase 4 depolarization aind increases threshold for firing in abnormal pacemaker cells. Are state dependent (selectively depresses tissue thta is frequently depolarized (fast tachycardia)).

1. Quinidine

2. Aminodaronee

3. Procainamide

4. Dimsopyramide 

 Queen Amy Proclaims Diso's pyramide

Increase AP duration, increases effective refractory period (ERP), increases QT interaval, Affect both atrail and ventricular arrhythmias. 

Toxicity: quinidine (cinchonism--headache, tinnitus; thrombocytopenia, torsades de pointes due to increased QT interval); procainamide (reversible SLE like syndrome)

1. Lidocaine

2. Mexiletine

3. Tocainide

4. Decrease AP duration

Affect ischemic or depolarized Purkinje and ventricular tissue. Useful in acute ventricular arrhythmias (especially post-MI) and in digitalis-induced arrhythnias.

Toxicity: local anesthetic. CNS stimulation/depression, cardiovascular depression

1. Flecainide

2. Encainide

3. Propafenone

No effecton AP duration. Useful in Vtachs that progress to VF and in intractible SVT. Usually used only as last resort tin refractory tachyarrhythmias. 

Toxicity: proarrhythmic, especially post-MI (contraindicated)

1. Propranolol

2. Esmolol

3. Metoprolol

4. Atenolol

5. Timolol

Mechanism: decrease cAMP, decrease Ca2+ currents. Suppres abnormal pacemakers by decreasing slope of phase 4. AV node particularly sensitive--Increase PR interaval. Esmolol verhy short acting. 

Toxcitiy: Impotence, exacerbation of asthma, cardiovascular effects (bradycardia, AV block, CHF), CNS effects (sedation, sleep alterations). May mask signs of hypoglycemia

1. Sotalol

2. Ibutilide

3. Bretylium

4. Amiodarone

Mechanism: Increase AP duration, ERP. Used when other antiarrhythmics fial. Increase QT interval

Toxicity: Sotalol-torsades de pointes, excessive B block; ibutilide-torsades; bretylium-new arrhythmias, hypotension; amiodarone-pulmonary fibrosis, corneal deposits, hepatotoxicity, skin deposits resulting in photodermatitis, neurologic effects, constipation, cardiovascular effects (bradycardia, heart block CHF), hypothyroidism/hyperthyroidsim. 

Remmeber to check PFTs, LFTs and TFTs when using amiodarone

Verapramil, diltiazem

Mechanism: primarily affect AVA nodal cells. Decrease conduciton velocity, increase ERP, PR interval. Used in prevention of nodal arrhythmias (SVT)

Toxicity: Constipation, flushing, edema, CV effects (CHF, AV block, sinus node depression); torsades de points (bepridil).

1. Adenosine-drug of choice in diagnosing/abolishing AV nodal arrhythmias

2. K+-depresses ectopic pacemakers especially in digoxin toxicity

3. Mg+ Effective in torsades de pointes and digoxin toxicity