cardio renal L10

Question 1

3 types of dysrhythmias

Answer 1

Escape beats and rhythms

Premature beats and extrasystoles

Ectopic tachycardia:

Question 2

describe Escape beats and rhythms

Answer 2

Extra beats that interrupt the dominant sinus rhythm. If the SAN fails for a long period, then one of the other subsidiary pacemakers produces a relatively slow escape rhythm

Question 3

describe Premature beats and extrasystoles

Answer 3

Premature beats can arise from ectopic foci in the atria, nodal tissue or ventricles. If it occurs in the atria it discharges the SAN which then starts a cycle of normal pacemaker activity

Question 4

Ectopic tachycardia:

descibe

Answer 4

A run of three or more extrasystoles. They can be either atrial or ventricular

Question 5

what is • Atrial paroxysmal tachycardia:

Answer 5

Ectopic pacemaker gives rise to bouts of regular beating at rates of 100 to 180 beats per minute.

Question 6

descrieb atrial flutteR>

Answer 6

An ectopic pacemaker discharges at 250-350 beats per minute. This only results in about half of the impulses being converted into ventricular beats

Question 7

descrieb atrial fibrilation

Answer 7

Continuous uncoordinated atrial activity. Impulses reach the AV node at 500 to 600 per minute. Ventricular activity is limited by the ability of the AV conducting system to respond

Question 8

describe • Ventricular paroxysmal tachycardia

Answer 8

Ectopic pacemaker in the ventricles. Can be rather serious because the ventricular rate exceeds the atrial rate

Question 9

describe ventricular fibrilation

Answer 9

Uncoordinated contraction of the ventricles
The ventricles look like ‘a bag of wriggling worms’

Question 10

describe class 1 antidysrhythmic drugs

Answer 10

These drugs block voltage-gated Na+ channels.They are subdivided (originally on the basis of their effects on action potential duration,

but more recently on the kinetics of the association and dissociation with the channel) into:

• IA Quinidine and procainamide
• IB Lidocaine
• IC Flecainaide

Question 11

describe class2 antidysrhythmic drugs

Answer 11

Sympathetic antagonists (i.e.ß-blockers)

Propranolol (non-specific), atenolol (ß1-selective)

Question 12

describe class 3 antidysrhythmic drugs

Answer 12

These drugs prolong the action potential and thus also the refractory period

Amiodarone

Question 13

describe class 4 antidysrhythmic drugs

Answer 13

calcium channel blockers: reduce Ca2+ entry

Verapamil

Question 14

Class I antidysrhythmic drugs affect …..

Answer 14

drugs affect voltage-gated Na+ channels

Question 15

Class 1 antidysrhythmic drugs are useful to supress what?

Answer 15

useful for suppression of inappropriate action potentials in the types of cells that depend on the voltage-gated Na+ channels to generate the action potential.

Question 16

The affinity of Class IA drugs (e.g. quinidine) for the open (activated) state is _______ than for the inactivated.

Answer 16

The affinity of Class IA drugs (e.g. quinidine) for the open (activated) state is greater than for the inactivated.

Question 17

These drugs work against atrial and ventricular dysrhythmias and they show use-dependence at normal resting potentials. They are not commonly used now.

Answer 17

class 1A antidysrhythmics

Question 18

T or F

for class 1 antidysrhythmics:

Drugs with high affinity for the resting state would be toxic

Answer 18

t

Question 19

do class 1 drugs have differnet behaviour in differnt parts of the heart?

why is this strange>

Answer 19

For some odd reason (which is not understood at all) the Class I drugs show different behaviour in different parts of the heart. This is despite the Na+ channels being the same throughout the heart

Question 20

describe Classes IA Antidysrhythmics

Answer 20

• The affinity of Class IA drugs for the open (activated) state is greater than for the inactivated
• Action potential duration has no effect on the drug action, but the drugs lengthen the action potential and the refractory period
• Used for atrial and ventricular dysrhythmias, including atrial tachycardias (SVTs)

Question 21

describe Class IB antidysrhythmics

Answer 21

• The most common drug of this class is lidocaine
• The dose of drug given is much lower than that which acts on nerves and produces local anaesthesia
• These drugs associate and dissociate rapidly within the time of a normal heartbeat
• They bind readily during Phase 0, but because they do not bind until the channels are open they do not affect the rate of rise of the action potential
• Many channels are however not available for further activation once the action potential reaches its peak
• The drugs dissociate in time for the next action potential (if it arrives at the right time)

Question 22

why do class 1B prevent premature beats?

Answer 22

If the action potential arrives early, the IB drugs are still associated (bound) with the channel and they prevent an action potential from being propagated

They thus prevent premature beats

Question 23

T or F

Class IB drugs are thus useful in preventing ventricular dysrhythmias which often occur subsequent to myocardial infarctions (or during cardiac surgery)

Answer 23

T

Question 24

describe Class IC antidysrhythmics

Answer 24

Flecainide is the only drug now used in the UK

They associate and dissociate very slowly

This means they cause a steady state Na+ channel block which does not vary throughout the cardiac cycle

Question 25

Class IC antidysrhythmics such as flecainide are very slow both to associate and dissociate. This means that they are very good at suppressing ....

Answer 25

Class IC antidysrhythmics such as flecainide are very slow both to associate and dissociate. This means that they are very good at suppressing **ectopic beats**

Question 26

are class 1C antidysrhythmics actually bad for the heart?

Answer 26

yes! ## Footnote However, because of their extraordinarily slow kinetics they suppress almost everything else as well. They are **pro- dysrhythmic** **CASST trial results below (image)**

Question 27

is 1C antidysrhythmics arent used to treat ischaemic heart disease, what are they used to treat\>

Answer 27

These drugs are now only used for treatment of patients with **anomalous conducting pathways** (like **Wolff-Parkinson-White syndrome**). They are not used for people with ischaemic heart disease

Question 28

Answer 28

A highly schematic explanation of the effects of class IA, IB, IC and III on the ventricular action potential. The black line shows the ‘normal’ action potential, the grey line in the presence of the drug.

Question 29

describe Class II antidysrhythmic agents

Answer 29

* ß1 antagonists **decrease** the effects of **catecholamines** on the heart * They have **negative** **chronotropic** and **inotropic** effects * Used in dysrhythmias where the tissue abnormality leads to increased excitability * Example: Myocardial infarction where catecholamines can produce enough enhanced inward current to produce action potentials and resultant ectopic foci * Some drugs also sensitize the myocardium to the effects of catecholamines (e.g. cardiac glycosides and volatile anaesthetics) * Curiously, some ß-blockers have other antidysrhythmic effects 1. D and L-propranolol have Class I actions (although only L-propranolol is a ß-blocker) 2. Sotalol has Class III actions

Question 30

describe Class III antidysrhythmic agents

Answer 30

Amiodarone is the best known example in this class. They prolong the action potential and thus also the refractory period and they probably do this by inhibiting the K+ currents that result in repolarisation may however also affect the inactivation of Na+ channels, prolonging inactivation and thus lengthening the action potential. This helps to prevent re-entry and circus dysrhythmias.

Question 31

what currents does amiodarone inhibit TLDR: explanation for amiodarones action are conflicting and confusing.

Answer 31

Recent work has shown that amiodarone inhibits both inward and outward currents. The inhibition of inward Na+ and Ca2+ currents is enhanced in both a use-dependent manner and in a manner depending upon the voltage at which channels become de-inactivated. The result is suppression of excitability and conductivity in both INa- and ICa- dependent cardiac tissues. The inhibition is greater in the tissues stimulated at higher frequencies and in those with less negative resting membrane potentials. Various outward K+ currents are also inhibited, but exactly which depends on the concentration of amiodarone present. This all means that explanations of the mode of action of amiodarone on action potential duration can be conflicting, because different ionic currents are responsible for the repolarisation of action potential in different cardiac tissues and under experimental conditions. Action potential duration would be shortened if the inhibitory action of amiodarone on the inward current is greater than on the outward current, and vice versa.

Question 32

describe Class IV antidysrhythmic agents

Answer 32

* Ca2+-channel antagonists that are selective for the myocardium (eg **verapamil**) * Related to the kinetics of the drug * Ca2+ channels are ubiquitous in the heart, so they are useful for many types of dysrhythmia * Since Ca2+ entry is important for producing the excitation-contraction coupling in cardiac muscle, it is important that excessive Class IV drugs are not given because this can inhibit contraction * This means that these drugs are not normally used when cardiac function is severely compromised

Question 33

Other Ca2+ channel blockers, like nifedipine, are not effective as antidysrhythmic agents but may find use in myocardial salvage explain how?

Answer 33

decreasing Ca2+ loading of damaged tissue (which leads to cell death). Their vasodilator effects will also decrease myocardial oxygen demand. In the case of verapamil, the slowing of the heart it also produces will also decrease oxygen demand. Ca2+ influx will be decreased by ß-blockers which have also been used to improve survival after a myocardial infarction ß-blockers also slow the heart and decrease its contractility, both important for reducing oxygen demand.

Question 34

describe adenosine as an antisythrhythmic?

Answer 34

* Adenosine: This acts on A1 receptors in the AV node * Coupled via the Gi G-protein and activation thus reduces cAMP levels * The net result is activation of I_K-ACh and adenosine thus hyperpolarises cardiac pacemaker and conductive tissue * It is can be used for certain supraventricular tachycardias and its short half-life can have some advantages under these circumstances

Question 35

describe cardiac glycosides as antidysrhythmic drugs?

Answer 35

Cardiac glycosides: Act by increasing vagal activity through an action in the CNS This leads to inhibition at the AV node (so slowing AV conduction) It also affects atrial refractory period

Question 36

note:L

Answer 36

the mechanisms by which cardiac glycosides affect the vagus seemingly remain elusive.

Question 37

fat

Answer 37

mamba