Lecture - Pharmacology (Anti-arrhythmics) Flashcards
1
Q
Depolarisation of ventricular muscle
- On the AP, what ions and their direction is the plateau marked by?
- The phase 0 is Na channel dependent (the same voltage gated Na that you see in neurons). If you slow it down, what will be seen on the upstroke? Do you cause a reduction in rate of ______.
- These channels can be stimulated by what? SO what will happen to the upstroke? - So phase 3 is the efflux of K+ and this causes r______
Depolarisation of nodal cells
- From the CCB lecture, where do CCB actually act? Like where in the heart and on what channel?
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2
Q
Pacemaker and excitation conduction cells
- Normal cardiac action is conducted in an orderly sequence but the pattern can become disrupted by what sort of things? What condition will this produce? So what’ll happen to the cardiac efficiency?
- explain why the conduction system won’t work as well (get arrhythmia) with eg if you abuse alcohol and drugs
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3
Q
Normal ECG
- What does the PR interval stand for? Where is it measured from?
- What does the QT interval stand for? Where is it measured from?
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4
Q
Arrhythmia
- What does this term describe?
- Mortality?
- May originate where?
- What kind of causes?
- What’re the clinical consequences like?
- What are the two major causes of arrhythmia (like, defects in….) and what may each result in?
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5
Q
So causes of arrhythmia #1: Defect in impulse generation SA node
- What happens to the automaticity?
- so automatic tissue besides the SA node begins to do what? What’re examples of automated tissue?
- what produces ectopic beats? - Examples of this defect?
- Mechanisms of triggered activity - what triggers the extra abnormal depolarisations?
- what’re early after-depolarisations associated with?
- what’re delayed after-depolisations associated with?
A
- In the vent AP: okay so earyl depolairsations are like when the Na+ channel will depolarise early (because they recover early so it’s a channelopathy) and you’ll see that the repolarisation doesn’t fully happen before the de-pol happens. And you might get repetitive after-depol so like waves. You’ll see this repetitive depolisation propagating itself as Torsades de Pointes and that will cause the twisting of the waves on the ECG and if it impacts the ventricles then you wont get output so it’s lethal. So this early depol is assicated with prolonged AP
Delayed after-depolisation is typically because of the result of Ca2+ overload. That can provoke the Na channels to recover and at that point, you have an after-depol (just after the repol) and this can sometimes reach the threshold voltage.
6
Q
So causes of arrhythmia #2: Defects in impulse conduction
- What’s a conduction block (loss of….), what causes it and what does it manifest as?
- Re-entry: what is it a major cause of? What does it require? What does it manifest as? Explain this to me
- Accessory tract pathways: mainfested as what? What is this?
A
- Okay so you can have a condunction block that basically leads to the loss of SA control of cardiac contraction since you have imapired condunction (since the conduction pathway may now have ischaemic or refractory tissue - refractory is where you cant depol so like, if abnormal refractory tissue in the middle of the conduction, you wont be able to propagate). Since you get a loss of this SA control, you’ll get bradycaria.
- Re-entry. Okay so this is where you have a unidirectional block of an impulse because of eg infarcted tissue. So the AP will keep going around in a loop depending on conduction veolocity and refractory period; whe it gets out of branch 2 (dependent on velocity), it needs to find excitable tissue (aka tissue that isnt in its refractory period so shorter = more likely to spread, I guess) and it’ll keep going around and can cause tacyarrthymia in ventricles. You can use anti-arrthymic drugs to slow down the velocity or to increase the refractory period and that will prevent the re-entry thing
7
Q
Atrial fibrillation:
- What can be the caues of this?
- What are the three types of AF? Which ones are responsive to treatment?
- Are most cases symptomatic or not?
- If you have increased sympathetic innervation then you increase SA nodal activity so what happens in relation to AF?
- What’s the risks assoaicted with AF? Think logically…..if you have uncooridnated pumping of heart, will the blood move as fast? What will hapeen then? (Virchow’s triad). Annnnd what’re the risks after that?
- What’re the two main aims of pharmacoogical treatment of AF? How do you do that like which drugs?
- is rate easy to treat or is rhytm? What’s the difference? - Okay so slide 20 has the drugs to use and for the rate control, sinus rhytm maintenance and stroke prevention - go have a look and make sure you can draw it after you revise
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8
Q
Okay so what are the important antiarrhythmic drugs that you need to know (4), and where do they act?
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9
Q
Vaughan Williams Classification
So this is where the drugs are classified on the drug’s ability to block specific ionic currents (i.e. Na+, K+, Ca++) and b-adrenergic receptor action
Digoxin doesnt fit in this classification though
- So, what are the classes
- What are examples of the drugs you should know in these classes
- What channel or receptor do they affect each?
- What phase of the AP do they work on (or what effect do they have?)
- What do they reduce or increase? (in terms of rate, conduction etc)
- What’re the side effects of each class? (focus on 2-4, I think)
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10
Q
Class 1 - Na+ channel antagonist
- What are the subclasses?
- What is an example of a drug?
- What is the mechanism?
- What’s this use-dependent thing?
- Effects:
- decreases the ______ of depolarisaiton during which phase? SO decreases ______ ______ in non-nodal tissue. What happens to the adjacent cells? - What are some unwanted effects (pretty obvious)
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11
Q
Class 2 - beta blockers
- What is their mechanism of action? Blocks effects of……
- Effects: So I know in the preveious lecture he said reduce the rate and force of contraction but here there are two other effects - what are they and how?
- What are its main uses - which one are we focussing on? (basically anything that’s the work of SNS)
- What’re some adverse effects of using beta blockers?
- is the drug lipophilic? So where is it lilely to travel?
- what effect did the guy in eCases 8 feel with taking the b-blockers
A
- So one is the reduce rate because you abolish the increased firing at the SA node which is produced by B-receptor activation. Since SNS innervation increases SA node automaticity and you’re reducing/blocking that.
It will also slow down the conduction velocity, particualrly at AV node since AV also has B1 receptors that are affected by SNS - this will lenghten the refractory period so slow the conduction and it might also prevent the re-entry thing that leads to tachycardia (remember, conudction velocity and refractory period time both affect if the impulse goes from branch 2 into some other branch because it needs to be excitable for it to transmit).
12
Q
Class 3 - affect the K+ channel and they prolong the AP
- So amiodrone: what is it used for and in what condition?
- effective against what? What’re we focussing on though? - SO there are a lot of adverse drug reactions with amiodarone but what are some you can think of? Why does it even have all these adverse drug reactions?
- most of these anti-arrhythmic drugs actually can provoke arrthymia. Can amiodarone? - There are some features of amiodarone that complicate its use like
- oral something?
- half life?
- what do you do if cardiac arrest?
- what does it do to veins?
A
- We’re just focussing on the rate control of amiodarone in AF
- Lots of ADRs because it’s highly toxic, and has a narrow therapeutic index.
13
Q
Class 4 - Ca++ channel antagonists
We’re talking about dltliizaem
- Spell the name of that drug correctly for starters
- What sort of channel does it affect - like, which type of Ca++ channel? Or does it affect both?
- Do you find these L-type in just pacemaker or you find them in ventricular too?
- Pacemaker cells:
- decreases rate of what at what?
- you slow what and lenghten what at what?
- what phases does it affect in the SA node?
- what does the triangle shape of AP look like if you increase the time between depol and repol - In ventricular cells
- depress what (which CCB mainly does this?) by inhbiitng the L-type Ca2+ channes
- have a negative ____ and ____ action - What’s the use of it in AF?
- Should you take it with beta blocker?
- What’re some ADRs?
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- It has some effect on T-type
14
Q
Summary of the class 1-4 drugs
What’s this table saying
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15
Q
Drugs that don’t fit the VW classification: Digoxin
- It’s a cardiac glycosie so what effect does it have?
- It has two mechaisms of action - what’s the first?
- What’s the deal with the pateint becoming hypokalemic with frusemide?
- What’s the beneficial effects of increased force of contraction?
- caution in what? - What’s the 2nd mechanism of action?
- What’re the indications for digoxin use?
- Why should you be careful of elevated digoxin levels?
- What are some adverse reactions?
- Why does digocin cause arrthymias? (amiodarone only one so far that didnt have this adverse reaction, I think?)
- And what do you do if the pateint does develop a dysrhythmia with digoxin overdose?
- what do you do immediately?
- keep track of what?
- adminster what?
- neutralise what?
A
- So in the cardiac myocyte membrane, there is a Na/K ATPase pump and a Na/Ca exhanger. Digoxin is a potent inhibitior of the Na/K ATPase pump. It competes with K on the ATPase pump. It will increase the inracellular Na since it isnt being able to leave through the Na/K ATPase pump and the increased intracellular conc of Na will prevent the Na/Ca exchnager from working since less gradient for the Na to come in for. This leads to increase Ca+ and that will increase the force of contraction
- Read the big sticky
- Secondly. it will also increase vagal activity (parasympathethic) and that will promote the release of ACh and reduce the SA firing rate (so you get heart drop and increase force of contraction from the first MAO). I think vagus nerve also affects the AV node (it doesnt affect the muscle like the cardiac accelerator sympathetic does) so you reduce the conducntion velocity which will decrease the ventricular rate. But apparently the mechansim of the vagal increase isnt fully understood.
