Lecture 14 Flashcards
What are some examples of arrhythmias/dysrythmias?
- bradycardia
- atrial flutter
- atrial fibrillation
- tachycardia (ventricular/supraventricular)
- ventricular fibrillation (extreme- no contraction so CO is 0)
Causes of tachycardia:
- ectopic pacemaker activity (damaged area of myocardium/latent pacemaker region activated due to ischaemia becomes depolarised and is spontaneously active-fast rate dominating over SAN)
- afterdepolarisations (abnormal depolarisations following AP: triggering activity)
- atrial flutter/fibrillation
- re-entry loops
When could you develop sinus tachycardia?
Patient with overactive thyroid- enhances sympathetic nervous system
How do you develop sinus bradycardia?
-Fit and healthy person
-extrinsic factors (beta blockers)
-sick sinus syndrome (SAN not functioning normally, drives HR but at a slower rate)
(Sinus rhythm but going slowly)
What is a cause of bradycardia?
Conduction block
- problems at AVN/bundle of his
- slow conduction at AVN due to extrinsic factors (beta blockers/Calcium channel blockers)
When do delayed after depolarisation occur?
High intracellular calcium concentration (due to sodium/calcium exchanger)
What do delayed after depolarisations cause?
Trigger AP, before it should be triggered
-happening repeatedly= ventricular tachycardia (in ventricles)
What are early after depolarisations?
Occur in hypokalaemia-lengthens AP duration (QT interval) due to maybe the potassium channels reacting to low levels of potassium by reducing the permeability to potassium channels
- occur as repolarisation is starting
- lead to oscillations
- ventricular tachycardia
What makes you more prone to arrhythmias?
People with a longer QT intervals are more prone to arrhythmias
How does a re-entrant mechanism cause arrythmia?
Normally (triangle shape)
- spread of depolarisation meets a point where it diverges left and right
- when these meet they cancel each other out
-may be block on one side but this doesn’t create a problem as one branch still works and can spread in the other direction
Problem
Area that conducts at a slower rate setting up a circuit- causing tachycardia as it doesn’t require input form the SAN
What causes atrial fibrillation and what is it?
Cause:
-damage to atria, stretching
-multiple re-entry circuits created
=often supraventricular tachycardia as more impulses are getting through AVN
What is AV nodal re-entry?
Fast and slow pathway in AVN can set up a circuit
-many more depolarisations come down the bundle of his
=supraventricular tachycardia
What is an accessory conduction pathway?
Accessory pathway between ventricles and atria
Can create a re-entry loop
=ventricular pre-excitation
What are the 4 classes of anti-arrhythmic drugs?
- block voltage sensitive sodium channels
- beta adrenoceptor antagonists
- drugs that block potassium channels
- drugs that block calcium channels
How do drugs that block voltage gated sodium channels work and give example?
Lidocaine (local anaesthetic)
-given to affect cardiovascular system intravenously
-dissociates rapidly, so next AP is normal (not much effect)
Block voltage gated Na+ channels much more in the depolarised state (when they are inactive/open)
-allows AP to occur
Where does lidocaine have best effect?
Damaged myocardium-depolarised
Block channels preventing spread of depolarisation from damaged areas
Why is lidocaine sometimes given to a patient following an MI?
If patient shows signs of ventricular tachycardia (damaged areas of myocardium could be damaged, depolarised and fire automatically)
-intravenously
How is lidocaine administered?
IV
-not prophylactically (treatment to prevent reoccurrence) as does not work
How do beta adrenoceptor antagonists work to prevent arrhythmia? Give an example of one
Propranolol/atenolol
-block sympathetic action (slow down pacemaker potential slope at AVN/SAN)
- prevent supraventricular tachycardias (slow conduction at AVN, slowing ventricular rate in patients with AF)
- used following an MI: sympathetic activity increases (pale and sweaty)-arrythmias may be due to increased sympathetic activity
- reduces oxygen demand (beneficial following and MI)
Can tachycardia affect the CO?
Tachycardia can reduce CO as ventricles don’t have time to fill
How do drugs that block potassium channels work?
Prolong action potential
-lengthens the absolute refractory period so in theory would prevent another AP firing too soon
BUT BECAUSE THEY PROLONG THE AP THEY ARE NOW CLASSED AS PROARRYTHMIC
Which drug is an exception to K+ blocking drugs?
Amiodarone
- as well as blocking potassium channels, it blocks calcium channels/beta blocker
- works due to other actions
Prevents ventricular arrhythmias post MI
What drug is used to treat the Wolff-Parkinson-White syndrome (re-entry loop due to extra conduction pathway)?
Amiodarone
How do drugs that block calcium channels prevent arrythmias? Give examples
Verapamil/diltiazem (non-dihydropyridine-act more on heart)
(dihydropyridine-act on vasculature so not effective in preventing arrythmias)
Verapamil: block L-type calcium channels, decreasing slope (lengthening) of AP at SAN, decreasing AVN conduction and decreasing HR(Ca+ channels cause depolarisation)
-decreases force of contraction (negative inotropy)
Give some examples of dihydropyridine Ca+ blocking drugs:
Amlodipine
Nifedipine
Nicardipine
What is the function of adenosine?
Anti-arrhythmic drug (administered via IV/made in body)
-acts on A1 receptors at AV nodes
-very short half life: stops heart and lets things start
Enhances potassium conductance at AVN: hyperpolarises cells
Terminates supraventricular tachycardias
What are ACE inhibitors? Give example
Inhibit angiotensin converting enzyme
E.g. perindopril
TREATMENT OF HYPERTENSION AND HEART FAILURE
-in heart failure, body feels as if not enough blood being pumped around body
-responds by retaining more fluid
-ACEi prevents fluid retention and vasodilates the vessels
=reducing afterload and preload of heart
What is the function of angiotensin 2?
- vasoconstriction
- increase blood volume due to simulation of Na absorption
- secretion of aldosterone high stimulate Na reabsorption
What is the side effect of ACE inhibitors?
Dry cough
-causes excess bradykinin
What do patients who can’t tolerate ACE inhibitors use?
Act on an angiotensin 2 receptor: AT-1 receptor
E.g. Losartan
= same effect as ACE inhibitors as the angiotensin 2 made can’t act not eh AT-1 receptor
What class of drugs is used to treat patients with heart failure and hypertension?
Diuretics (act on kidneys to increase amount of fluid lost in kidneys- reduce amount of Na+ being taken up again)
-reduces pulmonary and peripheral oedema
Give an example of a diuretic:
Furosemide
Acts on loop of henle (loop diuretics)
How do dihydropyridine calcium blockers work?
Prevent calcium entering smooth muscle cells of the vasculature
- reduce contraction
- decreasing peripheral resistance
- decrease arterial BP
- reduce workload of the heart by reducing afterload
In what conditions are calcium channel blockers effective?
- hypertension
- angina
- coronary artery spasms
- SVT’s by reducing conduction at AVN
What are positive inotropes?
Things that increase contractility of the heart and therefore CO
Give some examples of positive inotropes:
Cardiac glycosides: digoxin
B-adrenergic agonists: dobutamine
What are cardiac glycosides used for?
Treat heart failure
-improves symptoms but not the long term outcome
Blocks Na+/K+ ATPase, causing a build up of Na in the cell
Na/Ca exchanger moves Na into cell, via sodium gradient, but if sodium concentration of cell increases, the activity of the Na/Ca exchanger doesn’t work as well
=increase in calcium concentration in the cell= more calcium in sarcoplasmic reticulum
=increased force of contraction
How do cardiac glycosides affect the heart rate?
Act on medullary centre in brain to increase vagal activity (parasympathetic) to heart
-slow down HR by slowing AV conduction
=may be used in atrial fibrillation as an anti-arrythmic agent
How does dobutamine increase force of contraction of the heart?
Selective B1 adrenoceptor agonist
-stimulate them at AVN/SAN/ventricular myocytes
=used in cardiogenic shock
What is the issue with cardiac glycosides?
They make the heart work faster which is not good in the long run
‘Don’t flog a dying horse’
-better to reduce workload of the heart by giving ACE inhibitors/diuretics/beta blockers
Why does angina occur?
Oxygen supply to the heart is compromised
-limited duration and doesn’t cause death to cardiac myocytes, only ischaemia
How do organic nitrates treat angina?
Release nitric oxide (NO), this is also release endogenously from endothelial cells, helping to keep vessels open
- given by GTN spray under tongue (quick and short acting)
- isosorbide dinitrate
=POWERFUL VASODILATOR ON VEINS
Which vessels does NO act on preferentially?
Veins
-as there is less endogenous NO released in veins
-lowering preload to heart, reducing workload of heart, lowering oxygen demand of the heart
-can act on coronary collateral arteries to improve oxygen delivery to ischaemic myocardium
(Very little effect on arterioles)
How does NO cause vasodilation?
Increases levels of protein kinase G, decreasing calcium concentration in vascular smooth muscle cells
=relaxation
What are the main aims for treating angina?
- reduce workload of the heart
- improve blood supply to heart
What conditions carry an increased risk of thrombus formation?
- atrial fibrillation: risk of stroke
- acute MI: risk of thrombus formation
- mechanical prosthetic heart valves (patient put on anticoagulation as it predisposes you to getting clots)
What are anti-thrombotic drugs?
Anticoagulants (prevent coagulation cascade to prevent thromboembolisms )
E.g. heparin (IV- inhibits thrombin)
E.g. warfarin (orally- antagonises action of vit K)
E.g. dabigatran (oral thrombin inhibitor)
Anti-platelets
- aspirin
- clopidogrel
- MI: in arteriole side: clots are platelet rich
