Arrythmias And Actions Of Drugs On The CVS Flashcards
What is Bradycardia?
Slow heart rate
Less than 60bpm
What is atrial flutter?
When atria beat faster but regularly compared to the ventricles (like 4 atria contractions per 1 ventricular contraction)
What is atrial fibrillation?
When atrial electrical contraction/activity is chaotically irregular
Irregularly irregular
What is Tachycardia?
Fast heart rate
Over 100bpm
What are the 2 types of Tachycardia?
Ventricular tachycardia
Supraventricular tachycardia
What is ventricular fibrillation?
Irregularly irregular contractions/electrical activity of the ventricles
What is the definition of an arrhythmia?
Any deviation from the normal rhythm of the heart
What are the 2 types of arrhythmias?
Tachyarrythmias
Bradyarrythmias
What are some of the different causes of Tachyarrythmias?
Ectopic pacemaker activity
Early after depolarisations
Atrial flutter/atrial fibrillation
Re-entry loop
How does Ectopic pacemaker activity cause a Tachyarrythmia/tachycardia?
Damaged area of myocardium becomes depolarised and spontaneously active (rapidly depolarises)
Ischaemic damage can cause a region which depolarises faster than the SAN to form
How can early after depolarisations cause Tachycardia/tachyarrythmia?
Triggered activity (abnormal depolarisations following an action potential) cause more AP to be fired than should be
What type of tachycardia can Atrial flutter/atrial fibrillation cause?
Supraventricular tachycardia
How do re-entry loops cause tachycardia?
Either a conduction delay
or
Accessory pathway
What are the 2 causes of Bradyarrythmias?
Sinus bradycardia
Conduction block
What is sick sinus syndrome?
Cause of sinus bradycardia
Where the SAN doesn’t depolarise quickly enough
What type of drugs can cause sinus bradycardia?
Beta blockers
Somme Ca2+ channel blockers
How do Conduction blocks occur causing bradycardia?
Problems at AVN or bundle of his causing slow conduction
Slow conduction due to factors like Beta blockers and some Ca2+ channel blockers
The prolonged duration of what increases the chances of Early After Depolarisations (EAD)?
What interval on an ECG indicates a longer AP?
Action potentials
Longer QT interval = longer AP
What condition of the blood can increase chances of EADs and why?
Hyperkalaemia
Takes longer for ventricles to repolarise due to less steep gradient of K+
This prolongs the action potential making it more likely for EADs
What type of tachycardia is likely to develop when AP/QT interval is longer?
Ventricular tachycardia
What are Delayed after-depolarisations? (Triggered activity)
An action potential that occurs after repolarisation
What makes Delayed after-depolarisations more likely to happen?
High Intracellular [Ca2+]
Possibly involves Na+/Ca2+ exchanger
If threshold reached AP triggered
What is the re-entrant mechanism for generating arrhythmias?
A unidirectional conduction block (incomplete conduction damage)
Allows for conduction to only flow one way through or decreases speed of conduction, meaning there isn’t a point where impulses cancel out
Produces constant loop to be set up (excitation travels the wrong way)
What is AV Nodal Re-entry?
Fast and slow pathways in the AVN create a re-entry loop
Causes ventricles to contract early (Supraventricular tachycardia)
What causes Ventricular Pre-excitation?
Accessory pathway for electrical impulses between atria and ventricles creating a re-entry loop
What is a condition which has an accessory pathway between atria and ventricles?
Wolff-Parkinson-White syndrome
How can the re-entrant mechanism cause atrial fibrillation?
Several re-entry loops form in atria
What are the 4 basic classes of anti-arrhythmic drugs?
I. Block VOltage gated sodium channels
II. Antagonists of B-adrenoreceptors
III. Drugs that block K+ channels
IV. Drugs that block Ca2+ channels
What is an example of a drug which blocks Voltage gated Na+ channels? (Class I)
Local anaesthetic lidocaine
What type of arrhythmia is Lidocaine used to treat?
Ventricular Tachycardia
How is Lidocaine administered to treat Ventrcular Tachycardia?
Intravenously
What state are the VGSCs in when Lidocaine blocks it and why is this useful?
Only blocks Open or Inactivated channels so preferentially blocks damaged depolarised tissues
How does Lidocaine treat ventricular tachycardia?
Blocks the damaged areas of myocardium’s Voltage gated Na+ channels preventing these areas from firing automatically
What is another name for drugs that are B-adrenoreceptor antagonists?
Beta blockers
What are the names of some Class II B-adrenoreceptor antagonists (Beta blockers)?
Propranolol
Bisoprolol
Atenolol
How do Beta blockers act to prevent Supraventricular tachycardia?
Act on B1 receptors in heart
Slows down the funny current from reaching threshold in the SAN (HCN channels)
Slows conduction at AVN by reducing VG Ca2+ activity in the AP upstroke
Why are Beta blockers often used following MI?
MI leads to increased sympathetic activity of the heart
So Beta blockers often given to reduce this activity preventing ventricular arrhythmias
It makes the heart not work so hard decreasing its O2 demand minimising further ischaemic damage
Which stage of the action potential does Class III K+ channel blockers affect?
Repolarisation
What affect do Class III antiarrhythmics have on the heart?
(Amiodarone)
Lengthens the Absolute refractory period
HOWEVER
Prolongs the action potential (prolong QT interval) so can be PRO-arrhythmic
What is a Class III anti-arrhythmic that blocks K+ that is the exception which is used and why?
Amiodarone
Has other affect like Beta blocking as well as blocking K+ channels
Treats Wolff-Parkinson-White syndrome
What are the 2 types of Ca2+ channel blockers?
Non Dihydropyridine Ca2+ channel blockers
Dihydropyridine Ca2+ channel blockers
What is the type of Ca2+ channel blocker which acts as an anti-arrhythmic drug affecting heart rate and rhythm?
Non Dihydropyridine Ca2+ channel blockers
Like a Phenylaklyamine like Verapamil
What are some examples of Ca2+ channel blockers that act as Class IV anti-arrhythmics?
Phenylalkylamine = Verapamil
Benzothiazapine = Diltiazem
How do Ca2+ channel blockers affect the heart?
Decreased influx of Ca2+ into cells
Decreases speed of upstroke of AP at SAN
Decreases AVN Conduction (both above have -Ve chronotropic effect)
Decreases force of contraction (-Ve inotropic effect)
What do Dihydropyridine Ca2+ channels work on if they don’t prevent arrhythmias?
Vascular smooth muscle
What type of receptor is the Alpha 1 adrenoreceptor?
G protein coupled receptor
How does adenosine act to treat arrhythmia?
Acts on A1 receptors at AVN
Enhances K+ conductance causing hyperpolarisation
Temporarily stops the heart allowing the APs to re align
What is an example of an ACE-inhibitor?
Perindopril
Enalapril
Lisonopril
Ramipril
How does the ACE inhibitor Perindopril act to treat hypertension and Heart failure?
Prevents conversion of Angiotensin I to Angiotensin II
Prevents Angiotensin II s effects of increasing Na+ and water reabsorber and its acton as a Vasoconstrictor
What is the goal of ACE inhibitors in treating heart failure and how do they acheive this?
Reduce how hard the heart has to work
Decrease vasomotor done (dec BP) reducing afterload
Decrease fluid retention (dec blodo vol) reducing preload
What is afterload?
Pressure the heart must work against to eject blood during systole
Why might someone not be able to tolerate ACE-inhibitors?
Can cause a dry cough
What can be given to patients who cant tolerate ACE inhibitors?
(Have a dry cough, why do they have this?)
Angiotensin II receptor blockers
Losartan
Due to Bradykinin accumulating as a result of inhibiting ACE being inhibited
How do Diuretics treat heart failure and hypertension ?
Reduce Na+ and water retention
Helps reduce pulmonary and peripheral oedema
What is the name of a drug that can treat congestive heart failure which is a loop diuretic?
Furosemide
How do the Dihydropyridine Ca2+ channel blockers help reduce workload of the heart?
Act on vascular smooth muscle
Decreases peripheral resistance
Decreases arterial BP
Which reduces the afterload
What are some Dihydropyridine Ca2+ channel blockers (act on vascular sm)?
Amlopidine
Nicardipine
What 2 types of drugs are positive inotropes?
(Increase contractility of the heart)
Cardiac glycosides
B-adrenergic agonists
What do both Cardiac glycosides and the B-adrenergic agonist Dobutamine do?
Block Na+/K+ ATPase leading to stronger contractions
What is an example of a cardiac glycoside?
Digoxin
How does the cardiac glycoside digoxin act to increase strength of heart contraction?
[Na+] in cell inc due to Na+/K+ ATPase being blocked by Digoxin
Means activity of Na+/Ca2+ exchanger decreases since gradient of Na+ decreases so [Ca2+] in cell INCREASES
More Ca2+ in cell = STRONGER contraction
Why are cardiac glycosides not normally used to treat heart failure?
Only normally improve symptoms but not long term outcome because the heart is being made to work harder
What affect do cardiac glycosides have on the heart?
Increased vagal activity on heart
Slows AV conduction
Slows heart rate
When are cardiac glycosides like Digoxin used as a form of treatment for heart failure?
Only when the heart failure is accompanied by arrhythmia since into an anti-arrhythmetic
How does the B-adrenoreceptor agonist Dobutamine act on the heart?
Stimulates B1 receptors at SAN and AVN and on myocytes in ventricles
Can be used to help restart heart
What receptors does the Beta blocker Propranolol act on?
Non selective so on B1 and B2
What affect does Propranolol have on the body?
-Ve chronotropic affect on heart (B1)
-Ve Isotropic affect on heart (B1)
Bronchoconstriction can happen (B2)
Bisoprolol is often used when a patient is asthmatic when the heart is too fast, why is this the case?
Its cardio selective so only affects B1 receptors
Means that bronchoconstriciton is less likely
What is an example of an alpha adrenoreceptor antagonist and what receptor does it work on?
Prazosin (doxazosin too)
On A1 receptor
What is Prazosins mechanism of action as an A1 adrenoreceptor antagonist?
Inhibits Noradrenalines action on the A1 receptors of vascular smooth muscle causing VASODILATION
What is Angina?
When O2 supply to the heart does meet its requirements so some ischaemia of the heart occurs causing pain
When do you normally feel the pain with stable angina?
Upon exercise/exertion due to increase O2 demand of heart
How do organic nitrates cause venous dilation?
Organic nitrate forms NO2-
This is reduced to NO (nitric oxide)
What blood vessels do organic nitrates/NO (nitric oxide act on?
Powerful vasodilator of veins
Likely due to less endogenous nitric oxide in veins
On a basic level how does Nitric oxide cause vasodilation of veins?
Reduces Intracellular [Ca2+] causing the vascular sm to relax
How does the action of nitric oxide causing vasodilation of veins help treat angina?
Lowers central venous pressure
Reduces the PRELOAD since less blood returns to the heart (heart fills less so doesn’t contract as hard)
This lowers the hearts demand for Oxygen
Has minimal action on coronary collateral arteries improving O2 supply to heart
What are the 2 general principles to treating angina?
Reduce workload of heart
Improve blood supply to the heart
How can the workload of the heart be decreased to treat angina?
Organic nitrates (venodilation)
B-adrenoreceptor blockers (propranolol or bisoprolol)
Ca2+ Channel antagonists (Amlopidine, nicardipine, verapamil and Diltiazem)
How can the blood supply to the heart be increased to treat angina?
Ca2+ channel antagonists
(Minor affects of organic nitrates)
What heart conditions increase risk of thrombus formation?
Atrial fibrillation
Acute myocardial infarction
Mechanical prosthetic heart valves
What are the anticoagulants that prevent venous thromboembolism?
Heparin (inhibits thrombin)
Warfarin (inhibits action of vitamin K)
What are 2 anti platelet drugs and when are they typically given?
Aspirin
Clopidogrel
Following acute MI or people with high risk of MI
What is the definition of a supra-ventricular tachycardia?
Tachycardia which arises as a result of problems in the atria or AV node
What is the definition of ventricular tachycardia?
Tachycardia which arises as a result of problems in the bundle of His, Purkinje fibres or the ventricular myocytes
What is the key difference between early after depolarisations and delayed after depolarisations?
EAD when an action potential is fired during repolarisation (Hyperkalaemia cause)
DAD when an action potential is fired after repolarisation (High Intracellular Ca2+ cause)
