S10) Arrythmias & CVS Drugs Flashcards
Outline, briefly, the possible action of drugs on the cardiovascular system
CVS drugs can alter:
- The rate and rhythm of the heart
- The force of myocardial contraction
- Peripheral resistance and blood flow
- Blood volume
What are arrhythmias/dysrhythmias?
Arrhythmias are abnormalities of heart rate or rhythm
Provide 5 examples of arrhythmias
- Bradycardia <60 bpm
- Tachycardia (ventricular/supraventricular) >100bpm
- Atrial flutter
- Atrial fibrillation
- Ventricular fibrillation (most dangerous as there is no coordination and no output of blood to body so they can die quickly)
Describe four causes of arrhythmia which manifest as tachycardia
- Ectopic pacemaker activity – latent pacemaker region activated due to ischaemia and dominates over SAN // damaged area of myocardium is depolarised and becomes spontaneously active
- After depolarisations – abnormal depolarisations following the action potential
- Atrial flutter / atrial fibrillation
- Re-entry loop – conduction delay due to accessory pathway
Describe two causes of arrhythmia which manifest as bradycardia
- Sinus bradycardia
I. Intrinsic SAN dysfunction
II. Extrinsic factors e.g. drugs (beta blockers, CCBs)
- Conduction block
I. Problems at AVN / bundle of His
II. Slow conduction at AVN due to extrinsic factors e.g. drugs
When are delayed after-depolarisations likely to happen?
Delayed after-polarisations are more likely to happen if intracellular Ca2+ high = stimulate an A.P and cause ventricular tachycardia
When are early after-depolarisations likely to happen?
- Early after-polarisations are more likely to happen if AP prolonged
- Longer AP = longer depolarisation = longer QT (time myocardium is depolarised to polarised)
Describe the re-entrant mechanism for generating arrhythmias
- Incomplete conduction damage (unidirectional block)
- Excitation can take a long route to spread the wrong way through the damaged area, setting up a circus of excitation
How does atrial fibrillation occur?
Atrial fibrillation arises due to several small re-entry loops in the atria
(mitral stenosis)
Briefly, explain how AV nodal re-entry occurs
Fast and slow pathways in the AV node create a re-entry loop = will go down though bundle of his and cause excitation = ventricular tachycardia
Briefly, explain how ventricular pre-excitation occurs
An accessory pathway between atria and ventricles creates a re-entry loop such as in Wolff-Parkinson-White syndrome = supraventricular fibrillation
There are 4 basic classes of anti-arrhythmic drugs affecting the rate and rhythm of the heart.
What are they?
- Drugs that block voltage-sensitive Na+ channels
- β-adrenoreceptors antagonists
- Drugs that block K+ channels
- Drugs that block Ca2+ channels
Describe the action of drugs which block voltage-dependant Na+ channels (Class I)
- Only blocks voltage-gated Na+ channels in open/inactive state, thus preferentially blocks damaged depolarised tissue and prevents ventricular fibrillation
- Blocks during depolarisation but dissociates in time for next action potential
- eg. lidocane (class Ib) -> mild Na channel block
- > slows upstoke
- > shortens AP
- > slows conductivity
In four steps, describe the action of β-adrenoreceptor antagonists (class II)
helps treat tachycardia/ atrial fibrillation = slow down heart rate
⇒ Act at β1-adrenoreceptors in the heart
⇒ Block sympathetic action
⇒ Decrease deploarisation/ slope of pacemaker potential in SAN
⇒ Slows conduction at AVN
eg. propranolol, atenolol
reduce effects of funny current channels, reduces CAMP being activated
Describe the effects of beta blockers
Beta blockers slow conduction in AV node:
- Prevent supraventricular tachycardias (decrease in SNS activity)
- Slows ventricular rate in patients with AF
Explain why beta blockers are beneficial following myocardial infarction
- MI causes increased sympathetic activity
- β-blockers reduce O2 demand at heart, hence reducing myocardial ischaemia
Describe the action of drugs that block K+ channels (class III)
- Block K+ channels
- Prolong the action potential = prolong QT intervals = pro-arrythmic
- Lengthens the absolute refractory period
- Preventing another action potential occurring too soon (can be pro-arrhythmic)
Describe the actions of drugs that block Ca2+ channels (class IV)
= antiarrythmic drugs
- non-dihydropyridine = verapamil, diltiazem
- Decreases slope of action potential at SAN
- Decreases AV nodal conduction
- Decreases force of contraction (negative inotropy)
- Some coronary and peripheral vasodilation
treat hypertension, angina = decrease resistance and BP
What is heart failure?
Heart failure is the chronic failure of the heart to provide sufficient output to meet the body’s requirements
Identify 4 features of heart failure
- Reduced force of contraction or reduced filling
- Reduced cardiac output
- Reduced tissue perfusion
- Oedema
Which types of drugs are used in the treatment of heart failure?
- Positive inotropes to increase cardiac output (not routinely used)
- Drugs which reduce work load of the heart (afterload and preload)
Which drugs increase myocardial contractility in the treatment of heart failure?
- Cardiac glycosides
- β adrenoreceptor agonists
In 5 steps, explain how cardiac glycosides increase myocardial contractility
⇒ Ca2+ is extruded via the Na+-Ca2+ exchanger
⇒ Cardiac glycosides block Na+/K+ ATPase
⇒ Rise in [Na+]i decreases activity of Na+-Ca2+ exchanger
⇒ Causes increase in [Ca2+]i
⇒ Increased force of contraction
Cardiac glycosides may be used in heart failure when there are arrythmias.
Describe the action of cardiac glycosides on heart rate
- Action via CNS to increase vagal activity
- Slows AV conduction
- Slows the heart rate
Describe two uses of β – adrenoreceptor agonists
eg dobutamine
stimulates B1 receptors present at SA node
- Cardiogenic shock
- Acute but reversible heart failure e.g. following cardiac surgery
Which drugs reduce the work load of the heart?
- ACE inhibitors
- Diuretics
- β – adrenoreceptor antagonists
Describe the action of ACE-inhibitors
Prevent the conversion of angiotensin I to angiotensin II (vasoconsitriction, Na reabsoption in blood, aldosterone):
- Reduce Na+ and H2O reabsorption
- Vasodilation of systemic vasculature
- can increase bradykinin = dry cough => symptom
Explain why ACE inhibitors are so useful in the treatment of hypertension
- Decrease vasomotor tone (blood pressure) / inhibit vascocinstriction
- Reduce afterload of the heart (easier for heart to pump around)
- Decrease fluid retention (blood volume reduces odema)
- Reduce preload of the heart = workload of heart
What is angina?
- Angina is a condition arising due to insufficient O2 supply to the heart for a limited duration caused by artheromatous plaque formation in the coronary arteries
- It results in heart tissue Ischaemia which presents as chest pain
- pain gets bad at exercise but relieved at rest
How does one treat angina?
- Reduce the work load of the heart:
I. β blockers
II. CCBs
III. Organic nitrates
- Improve the blood supply to the heart:
I. Organic nitrates
II. CCBs
Describe the action of organic nitrates
- Reaction of organic nitrates with thiols in vascular smooth muscle causes NO2- to be released
- NO2- is reduced to nitrous oxide
- NO is a powerful vasodilator
- venodilator = reduce return of blood to heart = reduce 02 demand
How does nitrous oxide cause vasodilation?
⇒ NO activates guanylate cyclase
⇒ Increases cGMP
⇒ Lowers [Ca2+]i
⇒ Causes relaxation of vascular smooth muscle
In four steps, describe the primary action of nitrous oxide
Acts on venous system (venodilation):
⇒ Reduced venous pressure
⇒ Reduced filling → reduced contractility (Starling’s Law)
⇒ Lowers O2 demand
⇒ Reduces work load of the heart
they have very little effect on arteries
What is the secondary action of nitrous oxide?
Acts on coronary collateral arteries to improve O2 delivery to the ischaemic myocardium
Why do organic nitrates preferentially act on veins?
Less endogenous nitric oxide in veins:
- Most effective on veins > arteries
- Little effect on arterioles
Illustrate how venodilation by organic nitrates is a major contribution to their overall action
Illustrate how the dilation of collateral coronary arteries by organic nitrates is only a minor contribution to their overall action
Provide an example of an organic nitrate
Glyceryl trinitrate (GTN spray – sublingual)
Why do we need antithrombotic drugs?
To treat certain heart conditions which carry an increased risk of thrombus formation e.g. atrial fibrillation (cause stroke), AMI (thromus in coronary artery), mechanical prosthetic heart valves
What are the two types of antithrombotic drugs?
- Anticoagulants
- Antiplatelet drugs
Identify some anticoagulants and describe their actions
- IV Heparin – inhibits thrombin / clots forming(short term)
- Oral Warfarin – antagonises action of vitamin K / inhibits thrombus forming (long term)
- Other: fractionated subcutaneous heparin, oral thrombin inhibitors
DVT (deep vein thrombosis) / atrial fibrillation - clot breaks off and travels to the brain / clot goes into left ventricle and can cause a stroke
What is the most common antiplatelet drug and when is it given?
Aspirin – following AMI / in high risk of MI
What is hypertension?
Hypertension is the persistent elevation of blood pressure
What are the possible targets of hypertensive drugs?
- Lower blood volume
- Lower cardiac output directly
- Lower peripheral resistance
Identify 5 hypertensive drugs and describe their respective actions
- ACE-inhibitors – decrease Na+ and H2O retention and TPR
- CCBs – vasodilation in vascular smooth muscle
- Diuretics – decrease Na+ and H2O retention
- β-blockers – decrease cardiac output (not routinely used)
- α1 adrenoceptor antagonist – vasodilation (not routinely used)
role of amiodarone
blocks K channels
blocks Ca channels
blocks b blockers
anti-arrythmic drug => reduce supraventicuar arrythmia
adenoisne (antiarrhythmic)
- produced endogenously
- administered via IV
- acts on a1 receptors at AV node + short half life
- enhances K conductance
- alpha unit inhibits CAMP while beta/gamma unit acts on K channels at AV node = hyperpolarise cells = terminates heart = heart can settle and start again
- powerful but stops working quickly
What medication can people use if they cant use ACEi
AT1 receptor blocker
treats heart failure and hypertension
diuretics
- treats heart failure and hypertension
- reduce blood volume
- blocks Na/K/Cl exchanger
- lose more Na and so lose water in urine
cardiac glycoside
- treat heart failure (short term)
- blocks Na/K ATP ase
- increase intracellular Na conc so the Na/Ca exhanger doesnt work = Ca store up in cell = more ca can be released during AP = increase force of contraction
cardiac glycoside on heart
eg digoxin
- increases vagus activity
- slows down conduction at AVN
- slows heart rate
- used in arrhythmia and heart failure
