7. ECG drugs Flashcards
ECG axis
The x-axis measure time (s)
• The y-axis measures voltage (mV)
5 steps of reporting an ECG
- Report the rhythm = the heartbeat
- Rate of the ecg
- Sinus rhythm
- Examine the waves separately
- Axis – net depolarisation captured by the lead
How to find ECG rhythm
○ Lead 2 rhythm strip look at the number of boxes between 2 r waves
○ Check for the same number of boxes between all r waves = regular rhythm
▪ Constant no of boxes btw r waves =regular rhythm
•10 times method - rate
– Rhythm strips are marked in 3 second increments
– Obtain 6 second strip
– Count P and/or R waves
– Multiply by 10
– Voila, you have the atrial and/or ventricular rate!
•1500 method (300 method) - rate
– Used for regular rate
– 1500 small squares (300 large squares) = 1 minute
– Count small squares between consecutive P and/or R waves
– Divide by 1500 (300)
– Voila, you have the atrial and/or ventricular rate!
Irregular rhythm
- If the rhythm is irregular
- Calculate heart rate by counting the number of QRS complexes in 6 seconds, then x by 10
•Can use same method for regular rhythms
– But quicker to calculate heart rate by dividing 300 by the number of squares of the R - R interval
- Sinus rhythm
• Rhythm originates from sa node
○ Check that p waves are upright in all leads – check each p wave originates from qrs complex
Left axis deviation
○ Left axis deviation - waves are leaving = left ventricular hypertrophy
Right axis deviation
○ Right axis deviation = right ventricular hypertrophy
Extreme axis deviation
○ Extreme axis deviation – going to the opposite direction
2 types of Arrhythmias
- Brady = decrease heart rate
* Tachy = increase heart rate
2 main reasons for brady arrythmia
- Reduced automaticity of sa node
* Conduction block
• Reduced automaticity of sa node
○ Seen in endurance athletes
○ Vagal tone
○ Low metabolic rate – caused by hypothyroidism, hypothermia
• Conduction block
○ Between atria and ventricles = heart blocks
Sinus brady arythmia
everything in the waves is normal, cardiac output is reduced
2 causes of heart blocks
- Acute myocardial infarction
* Degenerative changes
3 types of heart blocks
• First degree heart block • Second degree heart block ○ Mobitz type 1 ○ Mobitz type 2 • Third degree heart block (Complete Heart Block)
1st degree heart block
•PR interval prolonged >0.2 seconds (5 small boxes)
▪ some conduction btw sa and av node but it is slow= increase pr interval
▪ Increased pr interval throughout
2nd degree heart block
Mobitz type 1
- Also called Wenkebach type
- Successively longer PR intervals until one QRS dropped
- Then cycle starts again
2nd degree heart block
•Mobitz type II
- PR intervals do not lengthen, but suddenly dropped a QRS complex = abrupt and dangerous
- High risk of progression to complete third degree heart block
3rd degree heart block
- Complete failure of atrioventricular conduction – no conduction between atria nd ventricles
- Ventricular pacemaker takes over (Ventricular escape rhythm)
- Usually wide QRS complexes
- Ventricular Rate is very slow (~30 - 40 bpm), often too slow to maintain BP
- Urgent pacemaker insertion usually require
- P – P intervals constant and about about 93 pbm
- R – R intervals constant but much slower (about 37 bpm)
- No relationship between P waves and QRS complexes
- (the P-R interval completely variable from beat to beat)
Narrow QRs complex
Block above av node = it still generates impulse = narrow qrs
Broad QRs complex
Block below av node = ventricle is on its own, slow ventricular depolarisation = broad qrs
3 main reasons for tachy arrythmias
- Increased automaticity
- Triggered activity
- Re-entrant circuits
• Increased automaticity
Is due to
○ Increased sympathetic innervation
○ Increased metabolic rate – hyperthyroidism, hyperthermia
2 types of triggered activity
Early after depolarization EAD current
Delayed after depolarisations
Early after depolarization EAD current
triggered depolarization between phase 2 and 3, L type calcium channels open due to low potassium, magnesium, calcium, some drugs (antibiotics, antipsychotics, antidepressants)
Delayed after depolarisations
○ Delayed after depolarisations – myocardial ischaemia - due to sarcoplasmic calcium reserves being active
2 Classifications of tachy aryhtmias
- Supra ventricular (SVT) - arythmia is generated above ventricle
- Ventricular tachycardia
Example of ventricular tachycardia
○ Ventricular ectopic beats
Example of Supra ventricular (SVT)
○ Atrial fibrilation
Ventricular ectopic beats
- Aberrant beat which fires when not stimulated by the SA node
- QRS complex is wide
- Qrs is uniform = monomorphic vt
- Qrs is not regular there is an increase and decrease = polymorphic vt
- Both monomorphic and polymorphic vt can progress to a ventricular fibrillation – dangerous give immediate de fib
- Does not follow a P wave
- Can occur in healthy individuals randomly in the day
- Very common after MI
- Often due to DAD’s
Monomorphic ventricular tachycardia
Qrs is uniform
Polymorphic ventricular tachycardia
Qrs is not regular there is an increase and decrease
Atrial fibrillation
- Most common arrhythmia!
- Progressive development
- AF begets AF
—> multiple small ‘f’ waves replace P waves in ECG
•Irregularly irregular pulse and ventricular capture
Risk of clotting due to pooling of blood in atria
Ventricular fibrillation
- Numerous uncoordinated depolarisations within the ventricles
- No control of contraction
- No cardiac output
- Death will result unless successful defibrillation
- No distinct waveforms on ECG
Myocardial ischaemia - what is t
—> Inadequate blood supply = occlusion of the left anterior descending artery (could be due to plaque)
4 types of myocardial ischaemia
. Stable angina
Unstable angina
Subendocardial infarction
Transmural infarct
Stable angina
- Stable fibrous cap
- Chest pain only on exertion
- ischaema
Unstable angina
- Plaque can rupture – stable angina progresses
- Open plaque with no fibrous cap – contents spill out
- Chest pain at rest
- Increased occlusion of vessel
- Ischamia but no cell death – no troponin in blood
- st depression, t wave inversion
Subendocardial infarction
- Myocardial cells die after not receiving oxygen fro at least 30 mins
- NSTEMI – st depression, t wave inversion
- Unstable angina, with chest pain at rest but now there is infarction
- Infarct
- Impact endocardial layer
Transmural infarct
- Obstruction of the complete coronary artery
- Infarcted all of the coronary artery
- STEMI – st elevation, t wave inversion
- Chest pain at rest
- Infarct
- Ions move out of the infarct – that area of the myocardium are dead (low oxygen, low ATP, delayed after depolarisation currents)
Myocardial ischaemia causes
•Interstitial hyperkalaemia
•Myocyte depolarisation
•Reduced conduction velocity
– Rate and rhythm
Angina an infarcts on ECG
•Can reverse direction of ventricular repolarisation
– T wave inversion
•ST segment changes
• ST segment elevation most serious, positive charge move out of infarct so the pqrst waves are below normal baseline – transmural Infarct
• ST segment depression – subendocardial infarction, pqrst waves pushed above the baseline
Myocardial infarction on ECG
- The development of necrotic tissue after ischemia
- ST segment elevation resolves in days to weeks
- T wave inversion persists for a few months
- Q waves develop and persist
Necrotic tissue = can carry current
Dead infarctic fibrotic tissue = cannot carry current
Interstitial hyperkalaemia - and ECG
– Small or absent P waves – Atrial fibrillation – Wide QRS – Shortened or absent ST segment – Wide/tall T waves – Ventricular fibrillation
Arrhythmias
Arrhythmias are disturbances of:
– Impulse generation in the sa node
• Abnormal automaticity
• Triggered rhythms
– Conduction (ectopics)
• Reentry
Arrhythmias result in change or rate or timing of contraction
Abnormal automaticity
alterations in impulse initiation
can be due to
• Enhanced normal automaticity – due to enhanced catecholamines release, or increased sympathetic activation
• Ectopic foci – sites other than sa node that generate automatic rhthyms generate spontaneous action potentials
Normal automaticity
Driven by sa node
Abnormal automaticity can underlie
- Atrial tachycardia
- Accelerated idioventricular rhythms
- Ventricular tachycardia
•Triggered automaticity depends on after-depolarisations
2 types
- Occur as early after depolarisations (EAD’s) - before complete action potential
- Occur as delayed after depolarisations (DAD’s) - after complete action potential
Delayed after depolarisation _ details
- Abnormal depolarisation of phase 4 action potential
- Often due to elevated sarcoplasmic and intracellular [Ca2+]
- Influences duration of action potential, longer ap = more calcium influx
Delayed after depolarisation are accelerate by
– Digitalis toxicity
– β-adrenoreceptor stimulation
Anything which prolongs the AP duration can facilitate DAD development
– Greater transarcolemmal Ca2+
- Mutations in Ca2+ may underlie DAD’s – RyR2
- Can lead to catecholamine-stimulated polymorphic ventricular tachycardia (CVPT)
Early after depolarisations _ details
—> Interruptions of repolarisation - happen during the action potential
•Often due to re-activation of L-type calcium channel’s and increased intracellular Ca2+
•Longer action potential – longer QT
Early after depolarisations - causes
•Anything which prolongs the action potential duration can facilitate EAD development
– Hypokalaemia
– Hypomagnesemia
– Bradycardia
– LQTS – long qt syndrome
– Class Ia and III anti-arrhythmics (drug induced)
•Can lead to polymorphic ventricular tachycardia or Torsades de Pointes
•Re-entry
•Re-entry prevents synchronous propagation
– Due to areas of slow conduction
•Property of networks of myocytes
•Requires – Two electrophysiology dissimilar pathways
Multiple reentrant circuits
—> factor in developing atrial fibrillation
Rapid or asynchronous rhythm affecting atria
In atrial fibrillation
- Multiple reentrant circuits happening simultaneously
- Causes chaotic conduction patterns that propogate down to ventricles
- Problems with excitation and contraction of atria and ventricles
Drugs affecting the rate and rhthym of electrical excitation
•There are 4 main classes of anti-arrhythmic drugs (Von Williams classification system)
* Class I – Sodium channel blockers * Class II –β blockers * Class III – Potassium channel blockers * Class IV – Calcium channel blockers
Effect of Class 1 anti-arrhythmic - Na+ channel blockers
- Change phase 0, rapid depolarisation of ventricular ap
- Offset to the right
Marked slowing conduction in tissue (phase 0)
Minor effects on action potential duration (APD)
• Depolarisation is righteard shifted
Effect of class 2 anti-arrhythmics – Beta blockers
- Block beta adrenorecpetors, diminih the plateau phase 2 and influence automaticity at sa node level
- Slightly increase refractory period by prolonged ap duration
- Reduces spontaneous depolarisation
Diminish spontaneous depolarisation and automaticity
Effects of class 3 anti-arrhythmics – K+ channels blockers
- Definitive prolongation of plateau phase and ap duration
- Change in ap duration – so they are risky as they can run the risk of developing EADs
Increase action potential duration (APD)
Effects of class 4 anti-arrhythmics – Ca2+ channel blockers
Calcium channel blockers decrease inward Ca2+ currents – l type calcium channels
– resulting in a decrease in spontaneous depolarization at sa node
• Effect plateau phase of action potential
Effective drugs on SA node action potential
• Class 4- calcium channel blockers, reduce depolarisation of sa and av cardiomyocytes, slow conduction velocity = change refractory period
= Slope of phase 0 = Conduction velocity
Drugs affecting ANS and automaticity
• Class II, beta receptor agonists
○ Mimic activation of SNS, increase open probability of funny channels, increase pacemaker potential, decrease time taken to reach ap
• Muscarinic antagonists (adenosine) that affect PNS decrease open probability of funny current channels and increase time taken to reach ap threshold
These can help restore sinus rhythm from brady or tachy cardic rhthym
• Parasympathomemetic drug – restore tachy cardic rehtyhm
• Drugs that’s affect sna – restore tachy cardic rhthymy
Sodium channel blockers
- Typical example is the local anaesthetic lidocaine (class Ib)
- Use-dependent block. = Only blocks voltage gated Na+ channels in open or inactive state – therefore preferentially blocks damaged depolarised tissue
- Little effect in normal cardiac tissue because it dissociates rapidly
- Blocks during depolarisation but dissociates in time for next action potential
β blockers - function
•Block sympathetic action
− act at β1 -adrenoreceptors in the heart – can be selective to just impact heart
•Decrease slope of pacemaker potential in SA and slow conduction at AV node
β blockers - examples
•Some are selective for β1
-adrenoreceptors − Atenolol, Bisoprolol, Carvedilol
•Others are nonselective
− Propanolol, Soltalol
• Non selective aren’t good in patients with asthma as it can lead to bronchospasm
β blockers – mechanism
Beta blocker decreases slope of pacemaker potential and rising phase of AP
• Slow heart rate by reducing oxygen demand
• Decrease time to reach threshold mp
• Slow ventricular rate
• Useful in preventing supraventricular tachycardia
• Treatment of myocardial infarction
Potassium channel blockers
•Class III anti-arrhythmics
–> Prolong the action potential = mainly by blocking K+ channels
- This lengthens the absolute refractory period
- In theory would prevent another action potential occurring too soon
Potassium channel blockers - negative
- BUT must be used in caution
• In reality can be pro-arrhythmic – Prolong QT interval
• Risk of devloping EAD –> ventricular fibrilation
Potassium channel blockers - positives
Despite risks, this class supress tachyarrhythmias due to reentry – Use in AF atrial fibrilation • as they increase effective refractory period, so emerging ap can find tissue normal and reduce reentry type tachycardic rhythms
- Unlike other K+ channel blockers, amiodarone doesn’t demonstrate proarrhythmic effects
- Included as class III but has cross class action – Decreased phase 4 slope and conduction velocity
Calcium channel blockers - function
•Decrease Ca2+ entry into cardiac myocytes
– Decrease aberrant pacemakers
– Decrease CV conduction velocity and repolarisation
• Blocks re-entrant rhythms e.g. supraventricular tachycardia
Calcium channel blockers - examples
•Examples; verapamil, diltiazem
•Dihydropyridine Ca2+ channel blockers are NOT effective in treating arrhythmias – Act on vascular smooth muscle
– Examples; amlodipine, nicardipine
Adenosine
—> Produced endogenously at physiological levels BUT can also be administered intravenously
•Acts on A1 receptors at AV node (GPCR)
• When activated the receptors inhibit adenylyl cyclase, reduce cAMP production
– Depresses nodal AP
• Enhances K+ conductance – hyperpolarizes cells of conducting tissue
• Anti-arrhythmic – doesn’t belong in any of the classes mentioned
– Useful for terminating re-entrant SVT – supraventricular tacchycardias
Block av node conducting, convert arrythmias back to sinus rhythm
Other drugs acting on CVS
- ACE inhibitors and AngII receptor blockers
- Diuretics
- Calcium channel blockers
- Positive inotropes – cardiac glycosides, dobutamine
- α adrenoreceptor blocker and β blockers
- Antithrombotic drugs
ACE inhibitors (ACEi) - function
- Inhibits the action of angiotensin converting enzyme (ACE)
- Important in the cascade angiotensiongen –> angiotensin II, acts on adrenal medulla to release aldosterone and promote sodium and water reabsopriton
Important in the treatment of hypertension AND heart failure – inhibiting ACE
•Prevents conversion of angiotensin I to angiotensin II – Angiotensin II acts on the kidneys to increase Na+ and water reabsorption – Angiotensin II is also a vasoconstrictor
•ACEi can cause a dry cough (excess bradykinin)
ACE inhibitors (ACEi) - uses
- Very valuable in treatment of heart failure (Chronic failure of the heart to provide sufficient output to meet the body’s requirements – can lead to both peripheral and pulmonary oedema)
- ACEi → decrease vasomotor tone (decrease blood pressure)
- ALSO Decrease fluid retention (decrease blood volume)
- Reduce preload of the heart
- Reduce afterload of the heart
- BOTH effects reduce work load of the heart
ACE inhibitors (ACEi) - example
•Example: Perindopril
Angiotensin II recpetor blocker
- In patients who can’t tolerate ACEi can use ATII receptor blocker
- Example: Losartan
- Used in treatment of heart failure and hypertension
Diuretics
•Used in treatment of heart failure and hypertension
•Loop diuretics useful in congestive heart failure
– Example furosemide – Reduces pulmonary and peripheral oedema
Calcium channel blockers
Dihydropyridine
—> Dihydropyridine Ca2+ channel blockers are not effective in preventing arrhythmias, but act on vascular smooth muscle to reduce work of heart and afterload by:
•Decrease peripheral resistance
•Decrease arterial BP
•Reduce workload of the heart by reducing afterload
•Examples: Amlodipine, nicardipine
Calcium channel blockers
Verapamil and diltazem
- Other types of Ca2+ blockers e.g. verapamil and diltiazem act on heart
- Reduce workload of heart by reducing force of contraction
Positive inotropes
- Positive inotropes increase contractility and thus cardiac output
- Greater force of contraction = greater volume expelled by heart
•Cardiac glycosides
– Example: digoxin
•β-adrenergic agonists
– Example: dobutamine
Cardiac glycosides
– Have been used to treat heart failure for over 200 years
– improves symptoms but not long term outcome
Cardiac glycosides - digoxin
•Digoxin is the prototype used in herbal meds
– Extracted from leaves of the foxglove digitalis purpurea
•Primary mode of action is to block Na+ /K+ ATPase in cardiac myocyte cell membrane – Increases [Ca2+] i
Cardiac glycosides mechanism
- Ca2+ is extruded via the Na+ - Ca2+ exchanger – driven by Na+ moving down concentration gradient – move calcium at same time as sodium
- Cardiac glycosides block Na+ /K+ ATPase = Leads to rise in [Na+ ] in
- Rise in intracellular Na+ leads to decrease in activity of Na+ - Ca2+ exchanger
- Causes increase in [Ca2+] i – more Ca2+ stored in SR – sarcoplasmic reticulum
- On each cardiac cycle more calcium is stored in sarcoplasm ready for release = Increased force of contraction –
Cardiac glycosides – vagal centre of CNS
–> Cardiac glycosides also cause increased vagal activity
- action via central nervous system to increase vagal activity
- slows AV conduction
- slows the heart rate
•Cardiac glycosides may be used in heart failure when there is an arrhythmia such as atrial fibrillation
β-adrenoreceptor agonists
•Dobutamine
•Selective β1 – adrenoceptor agonist
– Stimulates β1 receptors present at SA node AV node and on ventricular cardiac myocytes
– uses
• treatment of cardiogenic shock
• acute but reversible heart failure (e.g. following cardiac surgery)
Treating heart failure
- Cardiac glycosides will relieve symptoms by making heart contract harder
- But there is no long-term benefit
- ACEinhibitors or ARBs (angiotension receptor blockers) and diuretics better for heart failure
- Beta blockers can also reduce workload of the heart
Angina
•Angina is generally transient ischaemia = partial blockage of coronary arteries
•Angina occurs when O2 supply to the heart does not meet its need
– But of limited duration and does not result in death of myocytes
Organic nitrates – treatment of angina
•Reaction of organic nitrates with thiols (-SH groups) in vascular smooth muscle causes NO2- to be released
•NO2- is reduced to NO (Nitric Oxide)
•Nitric oxide is released endogenously from endothelial cells
•Examples given into the body
– GTN spay (quick, short acting)
– Isosorbide dinitrate (longer acting)
Why do organic nitrates work on veins
•Maybe because there is less endogenous nitric oxide in veins
•At normal therapeutic doses it is most effective on veins
- less of an effect on arteries
•Very little effect on arterioles
How NO causes vasodilation
• NO in reduced form activates guanylate cyclase
• Increases cGMP
• Lowers intracellular [Ca2+]
• Causes relaxation of vascular smooth muscle
= faciliation of vasodialtion
Primary action of nitric oxide
- action on venous system -venodilation lowers preload
- reduces work load of the heart
- heart fills less therefore force of contraction reduced (Starling’s Law)
- this lowers O2 demand
Secondary action of nitric oxide
- action on coronary collateral arteries improves O2 delivery to the ischaemic myocardium
- acts on collateral arteries NOT arterioles
Vindication
- Venodilation reduces venous pressure and the return of blood to the heart
- Veins are capacitance vessels – transient pooling of the blood
- This reduces the work of the heart (Starling’s Law of the Heart) - reduce filling volume and pressure, venous return of the heart
- Reduces oxygen demand
Treating angina
Reduce the work load of the heart
– Organic nitrates (via venodilation)
– β-adrenoreceptor blockers
– Ca2+ channel antagonists
•Improve the blood supply to the heart
– Ca2+ channel antagonists
– Minor effect of organic nitrates
Condition that carry increase risk of thrombus formation
– Atrial fibrillation
– Acute myocardial infarction
– Mechanical prosthetic heart valves
Examples of anti thrombotic drugs
•Anticoagulants
•Prevention of venous thromboembolism – Heparin (given intravenously) • inhibits thrombin • used acutely for short term action – Fractionated heparin (subcutaneous injection) – Warfarin (given orally) • antagonises action of vitamin K – Direct acting oral thrombin inhibitors such as dabigatran
•Antiplatelet drugs
– Aspirin
– Clopidogrel
• following acute MI or high risk of MI
