Unit 04: Treatment of Angina Flashcards
what is angina
- angina pectoris
- refers to chest pain due to ischemia (restiriction of blood supply to tissues) of heart muscle
- typically due to obstruction of coronary arteries resulting in insufficient coronary blood flow
- oxygen deprivation decreases muscle strength, leading to chest pain (angina)
*caused by imbalance between the eharts oxygen supply and demand
what are the 3 types of angina, describe them
Atherosclerotic angina
- most common
- due to irreversible atherosclerotic obstruction of coronary arteries
- precipitated by exertion
Vasospastic angina
- occurs following spasm of part of the coronary vessel (often at site of atherosclerotic plaque)
- can occur at any time
Unstable angina
- product of an atherosclerotic plaque combines with platelet aggregation and vasospasm (precursor of myocardial infraction
what is coronary blood flow
- blood flow provides heart with oxygen and nutrients and local blood flow is regulated by the needs of the heart of oxygen demand
- during exercise the heart increases work load and oxygen consumption
- coronary blood flow increases to supply the heart via vasodilation of coronary arteries
what determines mayocardial O2 supply
- determine dby perfsion of the heart - thats determined by vascular tone of coronary arteries
- major coronary arteries are depicted on epicardial surface of the heart
what is myocardial demand determined by
- ventricular wall stress - function of both preload (venous tone) and afterload (arteriolar tone)
- venous tone determines myocardial O2 demand by regulating the amount of blood returning to the heart - determiens the end-diastolic ventricular wall stress
- artial tone determines myocardial O2 demand by regulating systemic vascular resistance (SVR) - the pressue against which the heart muscles contract *determines systolic ventircular wall stress
what is the goal for angina treatment? what is angina the result of?
- goal is to restore the balance between oxygen supply and demand
- angina is the result of decrease oxygen supply following an increase in demand - often result from an increase in heart rate/cardiac output and/or PVR
*oxygen supply needs to be increased - achieved by increasing coronary blood flow or demand needs to be reduced by decreasing HR and/or PVR
what is nitroglycerin
- vadodilator used to treat angina
- metabolized by the liver so oral bioavailablity is low - comes in multiple forms
what is the mechanism fo action of nitroglycerin
- mechanism of action of a vasodilator
- conversation of nitrate -> nitrite groups -> nitric oxide
- this increases cGMP and results in relaxation of smooth muscle cells in blood vessels (vasodilation)
- nitrates preferentially affect veins and coronary arteries - can also ahve activity on smooth muscle in other tissues (bronchioles)
- effect is a decrease in venous return and PVR and dilation of coronary arteries
*overall oxygen requirement decreases and delivery of oxygen increases
what are the toxicities associated with nitrates
- hypotension - tachycardia (reflex increases in SNS activity)
- tolerance - reduced effictiveness of same dose following exposure to long acting nitrates might also occur
- mechanism is not clear but it likely involves systemic compensation such as an increase in SNS activty or salt and water retention
what is sildenafil
- viagra
- inhibits phosphodiesterase and prevents breakdown of cGMP causing relaxation of smooth muscle
- initially developed as a treatment for angina pectoris - but better suited for erectile dysfunction
- can result in severe hypotension which can be dangerous and evn fatal if it results in myocardial infraction
*should wait 24 hrs between ingestion of sildenafil and nitrates
side effect: inhibition of phosphodiesterase increases sensitivity of rod cells in the eye - these are calls that are most effective at detecting blue light (causes altered vision
what is verapamil
- vasodilator - calcium channel blocker
- inhibits calcium influx into blood vessel smooth muscle cells and causes dilation
- also inhibits calcium influx into cardiac muscle cells and decreases cardiac contractility
- Overall: effects on smooth muscle and the heart decrease oxygen requirements
- toxicities associated include: cardiac depression leading to bradycardia, ehart failure and cardiac arrest
describe the mechansims of vascular smooth muscle cell contraction
- controlled by coordinated action of several intracellular signalling mediators
Contraction:
Ca2+ entry thoguh L type voltage gated Ca2+ channels = initial stimulus for contraction
Ca+ entry into the cell activates calmodulim CaM
Ca2+-CaM complex activates myosin light chain kinase (MLCK) to phosphrylate myosin light chain
phosphrylated myosin LC interacts with actin to forma ctin-myosin corss bridges - process that initiates vascular smooth muscle
describe the mechanism of vascular smooth muscle cell relaxation
- relaxation is a coordinated series of steps that act to dephosphrylate (hence inactivate) myosin LC
- NO diffuses into cell and activates duanylyl cyclase
- activated guanylyl cyclase catalyzes the conversation of guanosine triphosphate (GTP) to guanosine 3′,5′-cyclic monophosphate (cGMP)
- cGMP stimulates cGMP-dependent protein kinase to activate myosin LC phosphatase - dephosphorylates myosin light chain prevening actin-mysoin cross bridge formation
*results: vascular smooth muscle cells relax
*active form of enzyme is in light blue
what are symptholytics? how are they used to treat angina?
drugs that inhibit the post ganglionic functioning of the SNS
- examples used to treat angina = propranolol and metroprolol
- they are B blockers that decrease the rate and orce of contraction of the heart - this decreases myocardial oxygen requirement
- use is however contraindicted in patents with asthma and bradycardia
how is angina pectoris managed clinically?
- lifestyle changes - reduction of atherosclerotic risk factors (smoking, hypertension, high cholesterol)
- sublingual nitrates often prescribed for individuals suffering acute attacks (chest pain due to physical exertion)
- maintenace monotherapy for hypertensive pateints might include Ca2+ channel blocker
- maintenance therapy for normotensive patients involved long acting nitrates
*if monotherapy fails, Ca2+ channel blockers cna be combined with B blockers and some patients ma require nitrates added as well
what are arrhythmias
- electrical alterations that cause abnormalities in the rhythm of the heart
- can be the result of altered initiation of the sinoatrial node - which would affect the rate of contrction
what are bradyarrhythmias and tachyarrhythmias
- bradyarrhythmias = abnormal conduction that can occur via heart block (slow down)
- tachyarrhythmias = abnormal re-entry conduction (speed up)
how are arrhythmias classified?
- based on the chamber of th heart they affect and are therefore categorized as atrial or ventricular
-
what is normal heart rate? what what rate does atrial flutter occur?
- normal heart rate is 60-80 beats/min
- atrial flutters occur when regions of atria beat asynchroously between 200-350 beats/min
what is the most common type of arrhythmia?
artial fibrilation (a-fib)
-occurs when heart rate is increased (300-500 beats/min(, irregular and disorganized
relationship between atrial arrhythmias and ventricular arrhythmias
Atrial arrhythmias do not always result in ventricular arrhythmias - may not affect cardiac output
- can lead to more serious and lethal rhythm disturbances or even stroke
what are ventricular arrhythmias often the result of?
can be result of premature ventricular contrations - if they are occasional there is no need for treatment
- can also be result of ventricular tachycardia which deos require treatment
when is ventricular fibrilation?
- irregular and rapid contraction of ventricles which means tht the ehart cannot pump blood properly
- if not treated immediately result will be fatal
what do defibrillators do?
- used in emergencies stop fibrilation by temporarily stopping all electrical acitivty in heart to allow the SA and AV nodes to restore normal rhythm
describe normal cardiac rhythm
- cardiac rhythm refers to the rhythm of the beating heart - it is influenced by electrical activity in heart that arises at teh SA node, spreads through atria, discharges the atrioventricular node and propgates through purkinje cells
- cadiac muscle cells contract by process called excitation contraction coupling
how are resting membrane potential and action potential maintained
- maintained by dsitribution of ions on either side of the muscle cell membrane
- ions involve Na+, Ca+2 and K+
- at rest - Na conc insdie cell is low and maintained by Na+/K+ ATPase.
depolarization opens ion specific channels and activates an action potential
summarize the phases of action potential of a cardiac muscle fiber
- depolarization proceeds rapidly due to Na+ influx through rapidly opening Na+ channels
- plateau phase due to Ca+2 influx through more slowly opening Ca+2 channels
- repolarization due to closure of Ca+2 channels, K+ efflux through K+ channels
summarize how cardiac cells contract
* via excitation-contraction coupling
- action potential increases Ca+2 (ion channels + release from sarcoplasmic reticulum)
- increasing Ca+2 binds troponin C and uncovers myosin binding site on actin
- actin and myosin cross-linkages form which results in contraction
how does cardiac relaxation occur
Ca2+ is released frmo troponin and is pumped back into sarcoplasmic reticulum and out of the cell
- actin and myosin are no longer cross linked
what do anti-arrhythics do
- aims to normalize cardiac rhythm by altering ion flow across the plasma membrane though ion channel blockers
- anti-arrhythmics have a narrow therapeutic indec and can also cause arrhythmias
*phyician needs to evaluate risks and benefits of anti-arrhythmic therapy
what are the 4 classes of anti-arrhythmic agents
Class I: sodium ion channel blockers
Class II: includes B vlockers
Class III: rpolongs action potentials or blocks K+ channels
Class IV: are Ca2+ channel blockers
describe class I anti arrhythmic agents
- ion channel blockers
- capable of blocking ion channels like sodium
- Sodium channel blockers reduce the recovery of Na+ channels and decrease conduction and excitation in the heart
- ex: quinidine - oral anti-arrhymic that is efective at treating all types of arrhythmia but rarely used bc of side effects
- lidocaine also used as an IV antiarrhymic to treat ventricular tachycardia and fibrilation
what is quinidine
class I ion channel blocker
- oral anti arrhythmic effective for all types of arrhythmia - but rarely used due to side effects
what is lidocaine
class I ion channel blocker
- used as an IV anti-arrhythmic for treating ventricular tachycardia and fibrilation
describe class II anti-arrhythmics
- beta blockers
- ex: propranolol and metroprolol
- inhibit SNS effects and slow down HR
- drugs of choice for atrial arrhythmias
*good chocie for arrhythmias triggeredby inc sympathetic activity
describe class III anti-arrhythmics
K+ channel blockers
- inc duration of action potential and inc refractery period
ex: amiodarone (not selective for K+ channels - also affects B receptors and Na+ and Ca2+ channels) - prolong the action potential which also prolongs the refractory period
- Class III most commonly used anti-arrhythmics for atrial fibrillation and ventricular tachycardia
what is amiodarone
class III anti-arrhythmic - K+ channel blocker
- not selective for K+ channel also affects beta receptors and Na+ and Ca+2 channels
- used for artial fibrilation and ventricular tachycardia
describe class IV Anti-arrhythmics
Ca2+ channel blockers
- ex: verapamil - Ca+2 channel blocker that decreases cardiac contractility and induces vasodilation
- used for supraventircular tachycaria which can affect the AV node and purkinje fibers
what is verapamil?
Class IV anti-arrhythmic
- Ca+2 channel blocker
- decreases cardiac contractility and induces vasodilation
- used for supraventircular tachycaria which can affect the AV node and purkinje fibers
