cardiac drugs Flashcards
what is an arrhythmia?
Describes a condition where there are disturbances in the electrophysiology of the heart as a result of either:
- Abnormal impulse formation
- Abnormal impulse conduction
- Or a combination of the two
= this results in altered rate and/or timing of excitation & contraction and will alter cardiac output (vol by ven per min)
what is inotropy?
description of force of contraction (+ = greater force of contraction = increase CO and SV)
what is luisitropy?
relaxation ( we want to be able to relax during diastole so it can adequately fill with blood that we can expel)
what is chronotropy?
heart rate or speed at which it beats - time (+ = increase heart rate)
what happens when calcium flows through L-type calcium channel?
- during diastole - calcium sequestered into sarcoplasmic reticulum (SR) and interacts with protein, Ryanodine receptor which is a channel in membrane of SR that allows calcium to exit SR and enter cytoplasm of cell→ greater rise of Ca2+ inside cell = causes force generation & contraction (allows actin & myosin to overlap) - ultimately drives ventricular systole
what are 2 different rhythm types due to abnormal impulse formation?
- trigger rhythm
- automatic rhythm
what are causes of triggered rhythms?
ectopic foci = action potentials rise from sites other than the SA node
enhanced normal automaticity = increased action potentials from SA node (mostly driven by sympathetic)
what is cause of automatic rhythms? (what does that mean?)
early afterdepolarizations
= triggers new action potential before fully returned to resting state - this can start loop
delayed afterdepolarizations
= excessive intracellular calcium can lead to delayed afterdepolarization →increased calcium activates sodium-calcium exchanger which causes small delayed depolarisation - automatic arrhythmias
what are 2 types of abnormal conduction?
- conduction block = has 3 types and is defined by ECG
- re-entry = circus movement & reflection (means continuous re-excitation and we need break to let atria properly fill)
what is each of the 3 degrees of conduction block (degrees of abnormal conduction)?
- PR interval which exceeds 0.2seconds (200ms) →excitation from atria not making to ventricle quickly
- 2 sub types but simple: AV node, PR progressively lengthens until point that there is missing QRS complex (usually happens cyclically)
- complete block of conduction through AV node - atria & ventricles work in isolation from each other
what is the aim of drugs for management of arrhythmias?
abnormal impulse formation = decrease in slope of pacemaker potential in SA nodal cells and raise threshold
abnormal conduction = decrease conduction velocity (phase 0) and increase in effective refractory period
what is Vaughan-Williams anti-arrhythmic drugs classification system?
class I = Na+ channel blockers
a = moderate, b = weak, c = strong
class II = beta adrenoreceptor blockers
class III = potassium channel blockers
class IV = calcium channel blockers
what is the effect of class 1 antiarrhythmic drugs?
= Na+ channel blockers (in ventricular myocytes AP)
- largely affect rapid depolarisation of ventricular AP (phase 0 - the dramatic upstroke) prevent Na+ entering cell
- depending on which specific drug, might see prolongation of action potential (APD) - may or may not see depending
→slow heart rate and increase AP duration
what is the effect of class 2 antiarrhythmic drugs?
= beta adrenoceptors blockers
- decrease funny current channels
- funny current channels activated by something (polarisation by PKA due to cAMP) that occurs as result of beta 1 receptor so increase funny current channels mean increase time to reach threshold
- if block beta 1 then decrease funny current channels = less depolarisation, decrease speed we reach threshold
how are beta adrenoceptors affect the funny current and what effect does that have?
activation of beta 1 by adrenaline - activation of beta 1 which is Gs →stimulates adenylyl cyclase →increases ATP to cAMP →cAMP →increased PKA →phosphorylates stuff (like funny current channels) to increase positive lusitropy, inotropy, chronotropy (increase SV & CO as heart beats stronger & faster)
what is the effect of class 3 antiarrhythmic drugs?
= K+ channel blockers
- largely affect repolarization in SA node and cardiac myocytes
- prolong time it takes to re-polarize cells →increase in AP duration
- risky as can increase QT elongation which can lead to lethal arrhythmias if not managed effectively
what is the effect of class 4 antiarrhythmic drugs?
- block Ca2+ channels which means slow conduction of atrium
- affects plateau by decreasing amount of calcium entering cell
what are the 3 cycles of voltage gated Na+ channels?
- open, closed, inactive = cycles these 3 states in action potential
- they can’t go from inactive →open they need to go inactive→closed and that’s only triggered by repolarisation
what can Class I antiarrhythmics be used to manage? (when prescribed?)
used to manage atrial fibrillation, fast beating (life threatening ventricular arrhythmias), ischaemic tissue, inherited long QT syndrome etc
- Use-dependent block – these drugs bind preferentially to open and inactive sodium channels
what are examples of Class I antiarrhythmics?
Flecainide, Lidocaine and Mexilitine
what is atrial fibrillation?
the most common cardiac arrhythmia – characterised by chaotic electrical excitation of the atria which can cause irregular and rapid heart rate and ineffective atrial contraction
- typically first experience low frequency and severity then progress
what drugs are often used in atrial fibrillation?
Flecainide & propafenone
- used as pill in pocket strategy, given early in progression and usually very effective
what are some examples of non selective beta blockers?
propranolol, sotalol
what are some examples of selective beta blockers?
atenolol, bisoprolol, carvedilol
when would you prescribe beta blockers?
for hypertension - also non sustained ventricular arrhythmias, atrial tachycardia, angina etc
beta blockers = decrease open of funny current = slow rate we achieve threshold in SA = reduce action potentials in same unit of time
what is an example of a potassium channel blocker?
amiodarone
when would you prescribe potassium channel blockers?
they’re effective for managing arrhythmias where other classes of drugs have failed (they do have increased risk of adverse drug effects like hyperthyroidism and pulmonary toxicity)
what is big problem of K+ channel blockers?
absolute refractory period = time where we can’t trigger another excitation
K+ = increase time of refractory period →can be big problem
what are examples of calcium channel blockers?
verapamil & diltiazem
what is angina?
a mismatch between myocardial perfusion and oxygen demand. Can be stable or unstable and is characterised by retrosternal chest pain which may radiate to jaw and left arm
what drug type (classification) is used in management of hypertension, angina and supraventricular arrhythmias?
calcium channel blockers
what is atropine?
= a muscarinic antagonist that binds to & blocks muscarinic acetylcholine receptors therefore, antagonizing the effects of acetylcholine
- used in management of beta blocker induced-bradycardia & bradycardia after MI
what is ivabrodine?
= inhibits funny current in SA node cells and can reduce heart rate and useful in patients who poorly tolerate beta blockers
- used in management of angina & heart failure
what is digoxine?
= acts as positive inotrope to increase contractility and thus cardiac output
- used in management of atrial fibrillation or flutter & heart failure
what is adenosine?
= natural nucleoside which binds to adenosine A1 receptors in AV primarily
- useful for terminating re-entrant supraventricular tachycardia
