Session 7 Flashcards
What is bradycardia?
Heart rate too slow (under 60bpm)
What is atrial flutter?
Atria beat too quickly
What is atrial fibrillation?
Irregular heartbeat due to rapid and irregular beating of the atria.
What is ventricular tachycardia?
- Regular, fast heartbeat
- Improper electrical activity in the ventricles
What is supraventricular tachycardia?
- Abnormally fast, regular heartbeat
- Activity abnormal in upper part of heart (AVN/SAN)
What is ventricular fibrillation?
- Ventricles are quivering and not contracting
- Cannot pump blood
- Rapid and erratic heartbeat
- CARDIAC OUTPUT NEAR 0
What can cause tachycardia?
- Ectopic pacemaker activity
- Afterdepolarisations
- Atrial flutter
- Atrial fibrillation
- Re-entry loop
What is ectopic pacemaker activity?
When damaged myocardium becomes depolarised and spontaneously active
- All no longer activated by SAN
- Dominates SAN
- Can lead to VFib
What are afterdepolarisations?
Abnormal depolarisations following an action potential
What are re-entry loops?
Electrical activity does not complete a normal circuit, but a circuit that is looping back on itself.
- Accessory pathways
- Conduction delays
What can cause bradycardia?
Sinus bradycardia:
- Sick sinus syndrome
- Fit and healthy people
- Extrinsic factors
Conduction block:
- AVN/BoH problems
- AVN slow conduction due to drugs
What is sick sinus syndrome?
Intrinsic SAN dysfunction, where the depolarisation is slow.
What extrinsic factors can cause bradycardia?
- Ca2+ channel blockers
- Beta-blockers
Heart beats in sinus rhythm but much slower
What are delayed afterdepolarisations?*
Abnormal action potential triggered by preceding action potential
- Occur when action potential nearly/fully repolarised
- Associated with high intracellular [Ca2+]
What are early afterdepolarisations?*
Abnormal action potential triggered by preceding action potential
- Can lead to oscillations
- More likely when action potential prolonged
- Prolonged QT interbal
- Common in hypokalaemia as that prolongs action potential
What re-entry mechanisms generate arrhythmias?*
- Incomplete conduction damage
- Excitation takes a longer route to avoid the damage, but conduction may be able to go UP the area of damage allowing conduction in the wrong way
Why does a complete block of conduction not generate an arrhythmia this way?*
- Nothing can get through, up or down
- Has to take the longer route as fibroblasts do not conduct
- Nothing goes the wrong way
What happens when there are too many re-entrant circuits in the atria?*
- AFib
- There are many impulses in the atria rather than one rhythm from the SAN
- Random depolarisation
How does this appear on an ECG?
- Irregular rhythm
- No P waves
What is AV nodal re-entry?*
- 2 pathways rather than one: 1 slow, 1 fast
- 2 pathways = more depolarisation and therefore a re-entry loop
= SUPRAVENTRICULAR TACHYCARDIA
What is ventricular pre-excitation?*
- There is an accessory/extra pathway that allows depolarisation from AVN to flow
- Creates re-entry loop
= WOLFF-PARKINSON-WHITE SYNDROME
What are the 4 basic classes of anti-arrhythmic drugs?
1) Voltage sensitive sodium channel blockers
2) B-adrenoceptor antagonists
3) Drugs blocking K+ channels
4) Drugs blocking Ca2+ channels
What is an example of a drug that blocks voltage sensitive sodium channels?
Lidocaine (IV)
How does lidocaine work?*
- Only blocks Na+v channels when they are in an open or inactive state, so they block damaged depolarised tissue
- Dissociates rapidly in normal tissue
- Blocks during depolarisation but is able to dissociate in time for another AP
When is lidocaine used?
- Following MI if patient shows signs of ventricular tachycardia (IV)
Why does lidocaine work?
- Damaged area of myocardium may depolarise automatically
- Open more Na+ channels
- Prevents automatic firing
What are examples of B-adrenoceptor antagonists?
Propranolol, atenolol (beta-blockers)
How do they work?*
Block sympathetic action by acting on B1 adrenoceptors
- Decrease slope of pacemaker potential
- Slow conduction at AVN
What are beta-blockers used for?
- Preventing supraventricular tachycardia (slow AVN conduction)
- Reducing cardiac output in tachycardia
- Reducing myocardial ischaemia due to low O2 demand
Why are beta-blockers often used in MIs?
- MIs often cause increased sympathetic activity (eg. people become pale/sweaty)
- This may cause arrhythmias
How do drugs that block K+ channels work?*
- Prolong action potential by blocking the channels
- Therefore lengthen absolute relative refractory period
= Prevent another AP too soon
What are the issues with K+ channel blockers?
- Prolong QT interval
- May predispose to EAD
- Can be pro-arrhythmic
What is an exception of K+ blockers that’s not pro-arrhythmic?
AMIODARONE
- Also Ca2+ blocker and beta-blocker
- Treat tachycardia associated with Wolff-Parkinson-White syndrome
- Suppress ventricular arrhythmias post MI
What are some drugs that block Ca2+ channels?
- Verapamil
- Diltiazem
(non-dihydropiridine)
How do they work?
- Block L-type Ca2+ channels
- Reduce slope of AP at the SAN
- Decrease AVN conduction
- Slow AP
- Negative inotropy (reduced force of contraction)
- Some coronary vasodilation
How are non-dihydropiridine blockers different from dihydropiridine blockers?
- Not effective in preventing arrhythmias
- Act on vascular smooth muscle instead
- Treat systemic vascular resistance and arterial pressure
What are some examples of dihydropiridine blockers?
- Amlodipine
- Nicardipine
What is adenosine?
- Drug that can be administered intravenously
- Acts on A1 adenosine receptors at AVN
- Enhances K+ conductance and hyperpolarises cells
= stops heart and lets it start again - Gi GPCR so low cAMP
What kind of drug is adenosine and what is it used to treat?
- Anti-arrhythmic
- Terminates re-entrant SVT
What are ACE-inhibitors?*
Drugs that inhibit the action of the angiotensin converting enzyme that converts angiotensin I to angiotensin II (physiologically active form)
What is an example of an ACE-i?
Perindopil
What are the actions of angiotensin II?
- Acting on kidneys to increase Na+ and water reabsorption
- Causes vasoconstriction
- Causes aldosterone release which stimulates Na+ reabsorption
When are ACEi used and why?
- Treatment of hypertension and heart failure
- Prevent fluid retention
- Reduce vasoconstriction so blood is easier to pump
Why can some people not tolerate ACEi?
Excess bradykinin can cause a dry cough.
How do ACEi treat heart failure?
- Decrease vasomotor tone (+ blood pressure)
- Reduce afterload and preload of heart
- Decrease fluid retention so reduce pulmonary oedema
= Reduce workload of heart
What are angiotensin II receptor blockers and when are they used?
- Prevent angiotensin from binding to its receptors
- Used in treatment of heart failure and hypertension in patients who cannot tolerate ACEi
- AT1 receptor blockers
What are loop diuretics?
Drugs that increase the amount of fluid lost in the kidneys (loop of Henle) by reducing the sodium content
What are loop diuretics used to treat?
- Heart failure
- Hypertension
- Congestive heart failure
- Reduces pulmonary and peripheral oedema
What are some diuretics?
- Furosemide (loop)
- Thiazide
How do dihydropyridine Ca2+ channel blockers act on vascular smooth muscles?
- Reduce peripheral resistance
- Prevents Ca2+ entry into smooth muscle cells
- Reduces contraction and therefore TPR
- Decrease workload by decreasing afterload
- Decrease arterial blood pressure
What are positive inotropes?
Drugs that increase contractility and cardiac output
What are examples of positive inotropes?
- Digoxin
- Dobutamine
How do cardiac glycoside positive inotropes work and what are they used to treat?
DIGOXIN
- Treat heart failure
- Act by blocking Na/K ATPase
Why are cardiac glycosides not great?
They make the heart work harder
- Improves symptoms
- Not good for long term outcomes
What is the mode of action of cardiac glycosides?*
- Block Na/K ATPase so that sodium builds up in the cell
- Ca2+ extruded by NCX which has diminished activity due to rise in intracellular Na+
- Rise of Na+ (main) and Ca2+ in cell SR stores
- More Ca2+ = POSITIVE INOTROPY
How do cardiac glycosides act on the heart rate?*
- Increase vagal activity via CNS
- Higher vagal activity slows HR and AVN conduction
When are cardiac glycosides used?
Heart failure treatment when there is an arrhythmia (eg. AF)
What is dobutamine and how does it act?
- Selective B1 adrenoceptor agonist
- Acts by stimulating B1 receptors at SAN and AVN on ventricular myocytes
When are B1 adrenoceptor agonists used?
- Cardiogenic shock (heart not pumping enough blood)
- Acute reversible heart failure
What are the best treatments for heart failure?
ACEi, Beta blockers and diuretics
- reduce workload of heart
Cardiac glycosides will make the heart give up quicker by making it work harder
What is angina?
- Reduced oxygen supply to the heart so needs are not met
- Limited duration so myocytes don’t die
- Ischaemia causes chest pain (exertion)
What is used in the treatment of angina?
Organic nitrates
How do organic nitrites work?
- React with thiols in vascular smooth muscles
- Cause NO2 release
- NO2 reduced to NO
- NO released endogenously from endothelial cells to keep vessels open anyway (powerful vasodilator)
What forms are used ?
Glycerol trinitrate spray under tongue (short acting)
What do organic nitrites act on?
Veins, NOT arterioles (very little effect on arteries)
How does nitric oxide cause vasodilation?*
- NO activates guanylate cyclase in vascular smooth muscle cells
- GTP converted to cGMP
- Activates PKG
- Lowers intracellular Ca2+ concentration
= Relaxation of vascular smooth muscle
What is the primary action of organic nitrates?*
- Acts on venous system to lower preload
- Reduces workload of heart
- Filling less so lower force of contraction and less O2 needed (Starling’s law)
What is the secondary action of organic nitrates?
- Act on coronary collateral ARTERIES
- Improves O2 delivery to myocardium
Why don’t organic nitrates dilate arterioles?***
- Local mediators already cause full dilation
- If bloodflow where there is no plaque is increased too, that may make situation worse
- Dilating COLLATERALS only increases flow to ischaemic area a little
Why do collateral arteries not make a massive contribution?
There are not many collaterals in end arteries
What is used to reduce workload of heart in angina?
- Organic nitrates (venodilation)
- B-adrenoceptor blockers
- Ca2+ channel antagonists
What drugs are used to improve blood supply to the heart in angina?
- Ca2+ channel antagonists
- Minor organic nitrates
When are antithrombotic drugs used?
When there is an increased risk of thrombus formation
- AF (stagnant blood)
- Acute MI
- Mechanical prosthetic heart valves
What are anticoagulants?
Antithrombotic drugs that prevent venous thromboemboli
What is heparin?
Anticoagulant that inhibits thrombin (IV or subcutaneous injection if fractionated)
What is warfarin?
Anticoagulant given orally that antagonises Vit K action (reduces formation of Vit K dependent clotting factors)
What are antiplatelet drugs?
- Drugs that prevent clots forming on the arterial side
- Aspirin and clopidogrel (following acute MI)
