CVS Arrhythmias and Drugs Flashcards
What 4 things can drugs alter in CVS?
Blood vol
HR
Heart rhythm
Force of contraction
Name some causes of tachycardia
Ectopic activity, AF, Aflutter, afterdepolarisations, reentry loops (e.g WPW syndrome)
Name some causes of bradycardia
Heart block 1st 2nd 3rd degree - AVN dysfunction
Sick sinus syndrome - SAN dysfunction
Can beta blocker cause bradycardia by affecting both SAN and AVN? What other drug can from the lecture?
Yes
Ca channel blockers affect both too
What is triggered activity?
Afterdepolarisations (there are early and late ones)
Which type of after depolarisation is more common with high intracellular Ca2+ - which drug toxicity is associated with this?
Delayed
Digoxin
Which type of afterdepolarisation is more common in AP prolonged? Why? What drug can cause this?
Early
Because it lengthens the QT interval which predisposes to arrhythmias
K+ channel blockers can cause this due to increasing the length of the AP
Describe how a re-entrant mechanism can occur in the heart and give an example of an arrhythmia caused by this?
Damaged area of heart - fibrotic Unidirectional block Depolarisation spreads round and the wrong way through damaged area Forms a loop Reentry tachycardia
E.g. AF (many of these in atria)
Name two things can cause damage and fibrosis to the myocardium to predispose to arrhythmias?
Dilation (e.g. from mitral stenosis/regurg)
Necrosis (e.g. from MI)
Ischaemia (Atherosclerosis)
Briefly say how and AV Nodal Reentry tachycardia is formed
Fast and slow pathways in the AVN create reentry loop
Briefly say how ventricular pre excitation can occur? Which disease?
Accessory pathway between atria and ventricles creates a large reentry loop e.g. in wolf-parkinson-white syndrome
What are the 4 classes of drugs (4 areas they act)
I Block Na channels
II Block b adrenoceptors
III Block K+ channels
IV Block Ca2+ channels
Why is an ischaemic/damaged part of myocardium susceptible to tachyarrhythmias?
Because the NaKATPase fails and this causes the cell to spontaneously depolarise and may then act as the foci
What drug would you give to prevent the complication of tachyarrhythmia? Why?
Beta blocker
Negative chronotropic and inotropic effect - stabilises activity and prevents ventricular arrhythmias
How does Lidocaine work? Which tissue does it preferentially block and why? Why does it not have a big effect on normal tissue?
Use dependent block
Binds to open or inactivated Na channels so preferentially blocks damaged depolarised tissue - so prevents automatic firing from ventricular cells.
Little effect in normal cardiac tissue as it dissociates readily - within 1AP
Blocks during depolarisation - and dissociates in time for next AP
When would lidocaine be used post MI? How is it given?
If signs of VT
Given IV
Would you use it for VT in other patients not post MI?
No use other drugs
What effect do b blockers have on the SAN AP?
Decrease the slope of the pacemaker potential and the rising phase of the AP
What has sympathetic activity got to do with arrhythmias post MI? Which drug blocks this
post MI often have increased sympa activity
Increased sympa activity related to arrhythmias
B blocker
What type of arrhythmias can b blockers prevent with their action of slowing conduction at AVN? Give an example
Prevent supra ventricular tachys
can slow rate in AF
Can beta blockers help prevent both atrial and ventricular arrhythmias?
Yes
How do beta blockers reduce O2 demand of tissue?
As it reduces workload by reducing HR and contractility
How do K+ channel blockers (class III) work? What is the danger? What is the drug exception that is used in clinical practice?
Prolong AP by blocking K+ channels and prolonging the absolute refractory period
Should prevent another AP occurring too soon but in reality can be pro arrhythmic
Except amioderone - as it affects other channels not just K+ so ends up being quite helpful
When is amioderone useful?
Wolff-Parkinson-White syndrome tachys
Supresses ventricular arrhythmias post MI
What are three effects of Ca2+ channel blockers (class IV)? Give an example
Decreases slope of AP at SAN (reduces HR)
Decreases AVN conduction (Dromotropy)
Negative ionotropy
Verapamil
Which type of Ca channel blockers act primarily on vascular smooth muscle (e.g. for hypertension)? Give some examples
Dihydropyridine Ca2+ channel blockers
Amlodipine, felodipine, nicardipine
What role do Ca2+ channel blockers have? (Which diseases)
Angina/Post MI - reduce O2 demand/afterload
Anti arrhythmic
Anti hypertensive
Which class is adenosine? What does it do? How does it work? Long or short half-life?
Not in a class
Binds to A1 receptors on AVN coupled to Gi GPCR
Enhances K+ conductance - hyperpolarises
Short half life
Useful for terminating reentrant SVT (supra ventricular tachy)
Give 2 examples of ionotropes - why aren’t these generally used for HF? When would they be?
Glycosides = e.g. digoxin
b adrenergic agonists e.g. dobutamine
Improves symptoms but no long term outcome
AF with HF
How does digoxin/cardiac glycosides work?
Blocks Na K ATPase - Increases Na in cell - reduces NCX activity, so less Ca pumped out - more Ca intracellularly therefore more taken up in to SR stores for release next time –> increased force of contraction
Increased chronotropy and ionotropy e.g. dobutamine and digoxin
What do you target to treat HF (2)
Preload
Afterload
When else would you use an inotropic agent (b adrenergic agonist)? Give an example
Cardiogenic shock/acute reversible HF post surgery
E.g. dobutamine - acts on beta-1 receptors
Which drugs reduce preload and after load - useful in Hf?
ACE i - reduce preload by reducing blood vol by reduced Na reabsorption
reduce after load by reducing BP (by reducing vasomotor tone)
AngII antagonist can be used if ACEi not tolerated
B blockers – reduce workload of heart as said earlier
Diuretics - reduce blood vol - reduce preload
What would you target to treat angina? Give example of types drugs that would do this
Reduce workload
B blocker
Ca channel blocker
Organic Nitrates (GTN)
Improve blood supply to heart Organic Nitrates (GTN) Ca channel blocker
How do organic nitrites (NO) work (2)? Do they exert most of their action on the arterial or venous system? Which law of the heart do they relate to?
By converting to NO a powerful vasodilator Gia Guanyl Cycase (GC) producing GTP–>cGMP —> PKG —> decreases intracellular Ca in vascular smooth muscle cell = relaxation
Venous - lowers preload - reduces workload, heart fills less so less contraction (starlings law) - lowers O2 demand of myocardium
Also improve collateral flow in coronary ARTERIES (not arterioles) improves O2 delivery to ischaemia myocardium
Why do organic nitrates act preferentially on veins?
Probably because less endogenous NO in veins
Why don’t organic nitrates really work on arterioles? Why aren’t there many collateral arteries for NO to work on in the heart?
Because they are already fully dilated around ischaemic region
Because coronary arteries are end arteries
Give some examples of heart conditions that are more prone to thrombus formation
AF
MI (thrombus can form over necroses not moving bit)
Mechanical prosthetic heart valves
Give 4 examples of anticoagulants and how they are administers?
Heparin - IV
Fractionated heparin - sub cutaneous
Warfarin - Oral
Newer Oral Anticoagulant - Dabigatran - oral thrombin inhibitor
In what emergency would you give aspirin/antiplatelet?
Following acute MI or high risk of MI - reduce chance of thrombus that could occlude an artery
How would you treat hypertension (3)? How do the drugs work?
ACEi - reduce preload by reducing blood vol by reduced Na reabsorption, reduce after load by decreased peripheral resistant (decreased vasoconstriction)
Ca2+ channel blocker - Relaxation of smooth muscle - vasodilation reduces after load
Diuretic - reduce blood volume reduces preload
Which other drugs can technically help hypertension but not routinely used?
B1 blockers - reduce CO
alpha 1 antagonist - vasodilation
