Cardiovascular Disease

Basic Heart Anatomy Chambers

Basic Heart Anatomy - Valves Heart Physiology Cardiac electrical conduction system Why is the heart strength, rate, & rhythm important?

Fast AP in cardiac cells

is the #1 cause of death in the U.S., Tx: Sx & mechanical devices, Majority of CV disorders still treated w/ medications atria & ventricles, must fxn in coordinated fashion on both sides of heart Problems cause inconsistency of flow & potential heart failure or clots thatmay result in embolism, heart attack, or stroke. May tx w/ anticoagulants (1) SA node (2) AV node (3) Bundle of His (4) Purkinje system The tissue requires a consistent level of O2 & nutrients atrial & ventricular cells, purkinje fibers, also in Bundle of His atrial & ventricular cells, purkinje fibers, SA node & AV node

Slow AP in cardiac cells

RAPID DEPOLARIZATION caused by rapid movement of Na+ ion into the cell thru AP in cardiac cells - selectively Phase 0 permeable channels QUICK REPOLARIZATION TO THE PLATEAU of the AP caused by the closing of the Na+ ion gate & the activation of an AP in cardiac cells - outward K+ ion Phase 1 current

The PLATEAU PHASE caused by the activation of the Ca++ ion channel (or slow channel) allowing Ca++ ion in & triggering the AP in cardiac cells - releaese of internal Phase 2 Ca++ ion.

The Ca++ ION CHANNELS CLOSE (deactivate) while the outward channels for K+ ion is increasing, AP in cardiac cells - COMPLETING Phase 3 REPOLARIZATION. A SLOW, GRADUAL DEPOLARIZATION due to a "background" of K+ AP in cardiac cells - ion movement out & Phase 4 Na+ & Ca++ ions in. (1) During phase 4 the nodes show background "pacemaker" current. (2) The nodal cells are of the "slow" variety which does not depolarize as rapidly as fast cells & has essentially no phase 2 plateau; repolarization occurs sooner readying the cells for the next impulse. (3) Resting membrane potential for the SA node is 60mV instead of the -80 to -90mV in other cardiac cells so it repolarizes sooner. capacity for spontaneous, repetitive selfexcitation

AP in cardiac cells In sinus nodal cells, the current caused by Na+ ion moving inward activates in a shorter time period than other cells, allowing sinus control of heart rhythm. This early activation occurs for 3 main reasons.


Chiefly in: SA & AV Automaticity - where node, Bundle of His, is it found? & Purkinje system

Due, in part, to a slow influx of Na+ & Ca++ ions. Ultimately triggered by a time-dependent "pacemaker" current Automaticity - how that opens the Na+ does it work? ion channels. may be modified by NERVES & Automaticity - rate HORMONES Both SA & AV nodes have ß₁ adrenergic & Automaticity - Type muscarinic of receptors cholinergic (1) Adrenergic stimulation: ↑ the background influx of Na+ & Ca++, ↑ the rate of the "pacemaker" current. (2) Vagal stimulation: ↑ K+ efflux which Automaticity - Type hyperpolarizes the of stimulants cells Time when heart may not be stimulated again. AV node limited to about 200bpm. Explains use of electroshock for: Ectopic foci, Circus Functional movements, Refractory Period Fibrillation out of place pacemakers, "escape" beats are Ectopic foci lifesavers same impulse travels around & around (damaged heart does not depolarize efficiently, abnormal movement caused by reentry)

Circus movements




cells fire individually w/ no unified beat the heart fails as a pump (many causes: heart attacks, faulty valves, rate & conduction issues) Heart pain due to a mismatch in O2 supply & demand Abnormalities related to the "impulse" (rate, impulse formation, patterns of electrical conduction) The SAME IMPULSE REACTIVATES TISSUE that it has already stimulated (Requires: 1 Normal conduction to be slowed, 2. Refractoriness to be shortened, 3. both) under 50-60 bpm 100-200 impulses/min 200-300 impulses/min (some beats are usually ectopic) over 300 /min (can't measure pulse b/c contraction noneffective, most ectopic sites are active, most dangerous arrhythmia)


Reentry Bradycardia Tachycardia



Arrhythmias Conduction issues

Heart Block (1st, 2nd, 3rd degree)

(1) A-V block from tissue damage (coronary infarction, vagal stimulation, ventricles contract on own - usually less than 50-60 bpm), (2) Circus movements (would not occur w/o damaged areas preventing proper depolarization of entire muscle mass in unison) 1st degree - slow conduction, rate ok, 2nd degree - Type I slower until skips, Type II just skips, 3rd degree complete

Actions seen: Drugs may change the Effects on Heart force, rate, & rhythm Medications of the heartbeat. influences CONTRACTILITY or FORCE OF Inotropic effect CONTRACTION Chronotropic effect influences RATE influences CONDUCTION thru specialized Dromotropic effect conducting tissues All have sugar structural group. Some can be Cardiac Glycosides extracted from (digitalis) - structure plants. Digoxin, of chemical group Digitoxin from white foxglove (can build toxic Cardiac Glycosides - levels if renal Digoxin failure) Cardiac Glycosides - from purple foxglove Digitoxin (Digitalis purpura) Positive INOTROPIC action. Negative Cardiac Glycosides - dromotropic & Actions chronotropic action

↑ Ca⁺⁺ release w/in cardiac muscle (stronger), ↑ Ca⁺⁺ movement into muscle (w/ slower conduction), ↑ vagal Cardiac Glycosides - tone (↓ HR, ↓ O2 Mechanism demand) heart fails to pump adequate amount of blood. Symptoms: enlarged heart, pulmonary edema, systemic edema, failing kidneys, increased HR, Causes: hypertension, rheumatic fever, Cardiac Glycosides - myocardial CHF infarction, etc. Supportive Tx: decreased wt, physical activity & Na+ intake, & tx hypertension if present. Result: heart size Cardiac Glycosides - decreased to Supportive Tx & normal, lower HR, Result diuresis Atrial Flutter, Fibrillation, Paroxysmal Tachycardia (irregular beats) Usually requires higher dose than treating CHF (MOA: PROTECT VENTRICLES, ↑ vagal tone & directly depresses electrical conduction in atria & Cardiac Glycosides - AV node, ↑ Therapeutic Uses refractory period

Digitalis is commonly prescribed yet poor margins of safety (Low therapeutic index), Order of appearance unpredictable, Very small dose required errors are significant, Poisoning usually due to "cumulative effect" - over long period of time, Dose must be carefully adjusted for each pt., Digitalizing Dose = priming dose or loading dose Cardiac Glycosides - (otherwise would Side Effects/Toxic take at least one Effects - Issues to week to reach Consider therapeutic levels) Loss of appetite (anorexia), nausea, VOMITING, diarrhea (in part, due to GI irritation; also may be due to toxicity), May take w/ food or Cardiac Glycosides - immediately after Side Effects/Toxic food but absorption Effects - GI may be altered Often SINGLE COLOR VISION (YELLOW/GREEN tinged vision), White Cardiac Glycosides - halos around Side Effects/Toxic objects, Blurred or Effects - Visual double vision Nervous irritability, Cardiac Glycosides - restlessness, Side Effects/Toxic weakness, HA Effects (usually not serious Symptoms? cut dosage)

many kinds - watch ventricles (If greatly ↓ BP may cause dizziness or fainting), VENTRICULAR TACHYCARDIA (↑ automaticity w/ more ectopic beats), "BIGEMINY" indicates toxicity (2 ventricles beats in a row), VENTRICULAR FIBRILLATIONS most common cause of death in Cardiac Glycosides - digitalis overdose, ASide Effects/Toxic V BLOCK - due to Effects negative Arrhythmias dromotropic effect (1) Recent MI (prone to developing arrhythmias, digitalis may have additive or synergistic effect), (2) Ventricular tachycardia (may throw into fibrillation, increased ectopic foci & automaticity), (3) Partial heart block (may produce complete block, pacemaker is better option), (4) Cardioversion (electroshock - may cause fibrillation that will not respond to further shocks), (5) Ca++ administration (Ca++ synergistic w/ digitalis - toxic effect), (6) K+ depletion (e.g. due to some diuretics, ↑ toxicity), (7) Renal or heptaic disorders of older pt. (lower Cardiac Glycosides - maintenance dose C/I or Cautions required)

(1) Phenobarbital (causes increased degradation, thus decreased effect), (2) Diuretics (Indirect only, which ↓ K+, ↑ digitalis toxicity), (3) Ca++ Cardiac Glycosides - ion (↑ in Ca++ will ↑ Drug Interactions toxicity) are now recommended FIRST for cases of ACE Inhibitors heart failure often used to control Diuretics edema slows progression in some pts., later in Beta Blockers (early disorder is only) contraindicated uncommon, approved 1993 for Flosequinan cases resistant to (fluoroquinolone) ACE inhibitors produced peripherally in heart & major vessels, directly induces myopathy, blocks reuptake epi/norepi Aldosterone so induces symp. blockers arrhythm. Positive inotropic dilates veins (less return), Dilates arteries (↓ afterload), Not supported by f/u Phosphodiesterase studies, Too many Inhibitors (amrinone cautions but try & milrionone) short term

any disorder of rate of conduction of electrical impulses (PVC - Premature ventricular contraction - 1 PVC/Hr increased mortality risk, 10/Hr see 20% mortality the first yr.) (Highly Lethal arrhthmias have 80% mortality in the 1st yr if not treated, 50% mortality w/ tx) (Meds are dangerous w/ multiple side effects) (Implantable Antiarrhythmics/Anti defibrillators an dysrhythmic drugs option) PROTOTYPE ANTIarrhythmic drug, originally for MALARIA, used less frequently than digitalis for Quinidine arrhythmias

Quinidine - MOA

(1) CARDIAC DEPRESSANT (Therapeutic effects - ↓ excitability, conduction velocity, & contractility, More effective on His & Purkinje than SA node, Prolongs effective refractory period), (2) ANTICHOLINERGI C (atropine-like action - AV node, Negative effects, Prevents cardiac slowing w/ muscarinic durg, May be hazard when used to tx flutter or fibrillation Atrial flutter may be transmitted to ventricles, Solution: Often used AFTER digitalis b/e digitalis does inhibit conduction thru A-V node)

Quinidine Therapeutic Uses

(1) ATRIAL FIBRILLATION (converts to normal sinus rhythm hospital setting, electrical conversion more commonly used than drug, sometimes used to prevent reoccurrence of fibrillation), (2) ATRIAL FLUTTER (used if digitalis fails to work), (3) VENTRICULAR TACHYCARDIA (common complication of MI, Electroshock implantable defibrillators, Lidocaine used in hospital if episodes repeatedly occur), (4) Premature systoles (PVC usually only tx if think will lead to more serious arrhythmias tachycardia, flutter, fibrillation)

CINCHONISM (from cinchona bark relate to malaria tx, aspirin), Mild to Moderate Symptoms: GI nausea, vomiting, diarrhea, abdominal pain, Ears: ringing, ↓ hearing, Eyes: blurred vision, night blindness, CNS: HA, Most toxic: alpha adrenergic blockage (Low BP, Respiratory Quinidine depression, Side/Toxic Effects - respiratory arrest, Antiarrhythmics low temp.)

Quinidine - C/I or Cautions

Complete A-V block, Cardiac failure, Allergy to drug or idiosyncrasy, due to anticholinergic properties - caution: Glaucoma, Urinary retention, Serum K+ must be normal hypokalemia ↓ drug effectiveness, hyperkalemia ↑ it Shortens repol. time & ↓ duration of AP, Tx ventricular arrhythmias, Doesn't seem to slow conduction, Undergoes rapid degradation - given as IV ↓ phase 4 depol, ↓ automaticity of the heart, prolong A-V conduction, ↓ HR, ↓ contractility, Tx Tachycardia, Atrial flutter, Fibrillation, Reentry tachycardia ↓ rate of depol, Slow down conduction, Alter contractility, Tx - atrial arrhythmias


Beta Blockers

Ca++ Channel Blockers

Therapy is ONLY A TEMPORARY measure until heart starts, electrical pacemaker fitted (overcome A-V block), Adrenergic Agents stimulates ß activity of the heart (Epinephrine - a & ß agonist, Isoproterenol - ß agonist - can be given orally or sublingually) (Anticholinergic Agents - atropine Cardiac Stimulants - blocks muscarinic MOA slowing) For most therapeutic uses try adrenergic agonist (1) Cardiac Arrest, (2) Hypotensive Crisis, (3) A-V block, (4) Bradycardia - chiefly Cardiac Stimulants - use anticholinergic Therapeutic Uses agent Cardiac Stimulants - Not crucial - drug Side Effects used acutely Heart: palpitations, tachycardia, ventricular arrhythmias, CNS: HA, fever, anxiety, Cardiac Stimulants - restlessness, BP: Toxic Effects may rise alarmingly NOT FOR CHRONIC USE make heart work too hard & ↑ its O2 use, CHF, Angina Pectoris, High BP, UNLESS CARDIAC Cardiac Stimulants - ARREST (life or C/I death situation)

Angina Pectoris cause

caused by mismatch of O₂ supply vs. O₂ demand, often think of CORONARY ARTERIES, Attacks precipitated by exercise or strong emotion.

Atherosclerosis in coronary arteries, Spasms of coronary Angina Pectoris arteries causes related to O (Prinzmetal's variant supply angina), Anemia Angina Pectoris HTN, Pulmonary causes related to O₂ HTN, Heart valves demand disease Angina Pectoris - If Condition Progresses... could lead to MI might Tx w/ Thrombolytics or w/ Angioplasty/bypass Sx

Angina Pectoris - If Early enough

(1) Nitrates & nitrites (vasodilator Nitroglycerine: a nitrate, is drug of choice), (2) ß blockers (Propranolo, nadolol - does not help during attack, used to PREVENT attack, ↓ workload of heart), (3) Ca⁺⁺ channel blocking agents (verapamil, nifedipine, diltiazem, nicardipine, Drugs to Tx Angina nimodipine), (4) Pectoris Dipyridamole Blocks extracellular Ca⁺⁺ into cells, Drugs to Tx Angina Dilation of coronary Pectoris - Ca⁺⁺ Ch. & peripheral Blocking Agents vessels, ↓ in cardiac Mechanism contractility

Useful chiefly in PRINZMETAL'S "VARIANT" ANGINA due to coronary artery spasm, however, not better than Drugs to Tx Angina nitrates. Not very Pectoris - Ca⁺⁺ Ch. useful if coronary Blocking Agents vessels are Therapeutic Uses occluded From relaxation of smooth & cardiac muscle, Hypotension, peripheral edema, dizziness, HA, Bradycardia & possible CHF if pt. Drugs to Tx Angina susceptible, Pectoris - Ca⁺⁺ Ch. Constipation, Blocking Agents nausea, diarrhea, Side Effects fatigue

Drugs to Tx Angina Pectoris Dipyridamole (Persantine) Drugs to Tx Angina Pectoris Nitroglycerine, Drug of Choice (Nitrates, Nitrites) - MOA

ANTIPLATELET AGENT, not for acute attacks, causes SELECTIVE VASODILATION of coronary arteries, seems to reduce nitrate requirements in some pts., Adverse effecs minimal & transient (HA, nausea, GI distres) - not very popular as an antianginal agent but being used as an anticoagulant due to its inhibition of platelet aggregation relaxes smooth muscle, ↓ workload of heart by ↓ BP, slight ↑ O₂ supply by dilating coronary arteries

Drugs to Tx Angina Pectoris Nitroglycerine, Drug of Choice (Nitrates, Nitrites) - Routes of Administration Drugs to Tx Angina Pectoris Nitroglycerine, Drug of Choice (Nitrates, Angina Pectoris, BP Nitrites) during Sx or Therapeutic Uses hypertensive crisis (1) Tachycardia (not serious), (2) HA (disappears w/ use tolerance) - Dilation cerebral bvs, (3) Postural hypotension Drugs to Tx Angina dizziness & Pectoris weakness upon Nitroglycerine, Drug standing (worse w/ of Choice (Nitrates, alcohol - also a Nitrites) - Side/Toxic vasodilator), (4) GI Effects nausea & vomiting

MUST BYPASS LIVER, (1) Sublingually - for acute attacks (onset: 1-2min., duration: 1560min.), (2) Ointment for longer lasting effect (onset: 15min - 1hr, duration: 2-12hrs), (3) Patch: should reduce sublingual use (onset: 1hr, duration: 24hrs), (4) IV controls BP during Sx

(1) Storage of med deteriorates in light, high temp, moisture, keep away from body heat, (2) Glaucoma - dilated Drugs to Tx Angina eye vessels may ↑ Pectoris intraocular pressure, Nitroglycerine, Drug (3) Head trauma of Choice (Nitrates, cerebrovascular Nitrites) - C/I, hemorrhage, Cautions intracranial pressure

Hypertension Hypotension

Pressor agent

Antipressor agent

sustained ELEVATED BP, CVD #1 killer in the US, Essential HTN: no identifiable cause that you can treat, Tx aimed a symptoms, Symptoms are unnoticeable, Risk factors: wt, sex, FHx, genetics sustained LOW BP Agent that will cause vasoconstriction, cause an ↑ in BP, will be given to hypotension Agent that will cause vasodilation, cause an ↓ in BP, will be given to hypertension Cardiac Output (1) HR, (2) Stroke Volume, (3) Blood Volume, (4) Venous return to the heart

What 4 factors affect BP?

Why is HTN damaging?

↑ workload on heart, Direct damage to arteries (roughens walls & leads to arteriosclerosis), Death du to damage in: kidney, brain, heart: heart failure, coronary occlusion

Kinds of HTN

(1) Specific or 2nd degree (less than 15% - only curable kinds), Pheochromocytom, Cushing's Disease (↑d adrenal cortex secretion, ↑d Na⁺ retention), Renal disease (↑s retention of fluid, also reninangiotensinaldosterone release), (3) Essential or primary HTN (more than 85% - use drugs to control symptoms)

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