Lectures 16-19 Flashcards
how is the heart electrically controlled?
Electrical activity starts in the SA node, which is the primary pacemaker, and then spreads through the atria to the AV node. From the AV node it travels down the bundles of His into the Purkinje fibres and thence to the ventricles.
This pattern ensures that the contraction of the atria and ventricles is coordinated.
How can you look at cardiac activity?
ECG - electrocardiogram
map events to wave
P - atrial depolarisation
QRS - ventricular depolarisation and atrial repolarisation.
T - ventricles repolarise.
what is turbulence?
risk factor for blood clots increases, can lead to strokes or a heart attack.
what is a cardiac arrhythmia/dysrhythmia?
any disorder of heart rate or rhythm.
arthymia (no rhythm technically)
what is tachycardia?
heartbeat is too fast
what is bradycardia?
heartbeat is too slow
what is a ectopic pracemaker?
cardiac tissue other than SA node initiates heart beats.
what is a delayed after depolarisation dysrhythm?
build up of calcium in cells leads to a train of action potentials.
what is a re entry circuit dysrhythm?
tissue damage or abnormality causes action potentials to travel in circles.
functional - above
structural - due to congenital abnormality.
?
what are congenital abnormalities?
additional conducting pathways between atria and ventricles.
what is a heart block?
damage to conducting pathways disrupts atrial-ventricular signaling.
describe a functional reentry circuit
check lecture 16 for diagram.
an area of damaged tissue causes the AP to have to go around.
usually mutual annihilation of AP where they meet at the bottom.
when damaged AP not annihilated, can travel back and forth in a loop.
describe wolff parkinson white syndrome.
structural re entry circuit.
extra conducting pathway between atria and ventricles known as Kent bundles.
AV node limits the upper rate for ventricular contractions, this doesn’t exist for Kent bundles. They have no pace limit.
This can cause two problems. First, signals from the atria to the ventricles go by the Kent bundle as well as the AV node. The Kent bundle does not have the rate limiting properties of the AV node, however, so this is very dangerous in atrial flutter – the ventricles will try to keep pace with the atria and sudden death often occurs. Secondly, the Kent bundle can set up a giant re-entry type circuit between the atria and ventricles.
who has an increased risk of cardiac dysrhythmias?
anyone with previous cardiac problems.
any drug that speeds up the heart causes tachycardia.
what is a side effect of antidysrhymic drugs?
if taken without underlying problem or take too much can causes dysrhymia themselves.
describe the ECG of an ectopic pacemaker.
increased heart rate.
can have several P waves close together.
describe the ECG of a bradycardia
irregular heart rate.
two p waves and no QRS waves.
describe the ECG of ventricular fibrillation
no pattern in ECG - true arhythmia.
Caused by the development of ventricular ectopic foci/re-entry circuits
Ventricles cease beating in a co-ordinated way
The ECG shows no QRS waves
Rapidly fatal
DC electrical shock may be the only way of restoring co-ordinated ventricular contraction.
how can you treat dysrhythmias?
drugs
electrical - ie defibrilator
surgical - destroy tissue causing dysrhythmia.
what is the vaughan williams system?
4 categories dependent on the site of action.
I - sodium channels (a, b, c) II - beta 1 adrenoceptors III - potassium channels IV - calcium channels unclassified due to various targets.
look at slides for visual of where they act on the AP.
what is the most important drug for each class?
I - lidocaine
II - atenolol
III - amiodarone
IV - verapamil
what are problems with the vaughan williams classification?
many drugs have multiple mechanisms or targets.
in diseased tissues the drugs act differently, targets are according to healthy tissue.
excludes some potential sites of drug actions.
how do medics categorise the drugs?
by utility.
describe amiodarone.
Class III, blocks K channels.
stopping repolarisation prolongs the AP.
Longer, fewer AP slows the heart down.
doesn’t depress the force of contraction.
Also Class I and IV, blocks Na and Ca channels.
useful for both supraventricular and ventricular arrhythmias.
treats Wolff-Parkinson-White syndrome.
When use amiodarone?
atrial fibrillation.
wolff parkinson white
ventricular tachycardia/fibrillation.
what are the side effects of amiodarone?
very lipophilic, can dissolve into fats easily. Forms micro crystals which can cause problems with night vision in cornea.
Can take months to stabilise plasma levels, tricky to use.
microcrystals in skin react with light, get photoxic reactions.
toxic to liver and lungs.
can cause bradycardia.
describe sotalol
class III, blocks K channels, prolongs AP.
2 isomers: L isomers also class II - beta blocker. D isomer class III
L class II and III D class III
describe adenosine
unclassified. NT.
used for supraventricular arrhythmias.
treats tachdardias.
Activation of adenosine receptors (purinoceptors) leads to activation of potassium channels and a slowing of the pacemaker potential and thus the heart rate.
LOOK ON SLIDE FOR DETAILS
effects only last 20-30 seconds.
given big dosage.
emergency usage.
what can adenosine be used for?
paraoxysmal (occurs in attacks) superventricular (AV node) tachycardia (speed up HR).
ventricular tachycardias associated with wolf parkinson white.
emergency treatment if tachcardia occurs in local anaesthesia.
describe propranolol and atenolol
class II Vaughan williams, beta 1 adrenoceptor antagonists.
Activation of the sympathetic nervous system (SNS) is one of the factors that can lead to the development of arrhythmias and beta blockers can be useful in controlling arrhythmias that have a sympathetic component.
how does the sympathetic nervous system affect the heart?
how is this related to beta blockers.
Pro-arrhythmic
increased discharge rate of the SA node (Speeds up).
increased automaticity in the atrial/ventricular myocardium (makes more sensitive).
improved conduction through the AV node.
Beta blockers try to stop all this shit.
what is automaticity?
pacemaker like properties, generate AP.
what are the general effects of beta blockers?
reduced chance of arrhythmia.
interfere with pacemaker.
reduces phase 4/depolarisation.
reduce heart rate.
reduce discharge rate of SA node, reduce automaticity, reduce conduction through AV node.
reduces force of contraction (more important for heart failure)
When else are beta blockers useful?
when there are excessive catecholamines (adrenaline/noradrenaline).
increased tissue sensitivty to catecholamines (thyrotoxicosis).
following myocardial infarction.
what are unwanted side effects of beta blockers?
bronchoconstriction (beta 2 receptors in bronchial tract, not all selective to only beta. bad for asthma).
precipitation of cardiac failure/heart block.
hypoglycaemia (can mask effects of hypoglycaemic attack for people with diabetes).
cold extremities.
vivid dreams - only propranolol.
structure of Na and Ca channels?
6 TMD, 4 pseudo subunits.
between 5/6th TMs is a membrane dipping domain that form the lining of the channel.
4th TM is charged and is voltage sensitive.
inner and outer facing side?
what are the states of Na/Ca receptors?
closed/resting state
open state
inactivated state
describe how Ca/Na receptors are open and closed.
depolarise the membrane, the positive charge in the channel to repel, and causes the gate to open.
ions flood in and depolarise the membrane even further.
this causes the ball to repel towards the channel and blocks it.
describe lidocaine.
local anaesthetic and anti dysrhythmic drug. class I of VW.
what are nociceptor neurones?
pain nerve endings, they hurt.
bare nerve ending.
A delta fibres fast sharp pain. myelinated.
C fibres slow burning. unmyelinated.
describe the dorsal root ganglia.
nociceptors here -
These neurons have their cell bodies in the dorsal root ganglia and their axons split with one branch going to the periphery and the other into the spinal cord.
just outside spinal cord.
how do local anaesthetics work GENREALLY?
block na channels.
thus block AP.
also block nociception.
what is the structure of local anaesthetics?
aromatic - confers lipid solubility.
linker - breakdown route. either ester or amide.
amine - when positively charged can block na channel.
can’t be quaternary since needs to accept H+.
how can you tell what the linkage group in an anaesthetic is?
—caine
prefix can have an i in it.
if so its an amide linkage, if not ester.
ie lidocaine has amide.
mostly works.
describe the action of local anaesthetics.
The amine is in an equilibrium between un-protonated and protonated states both inside and outside the cell.
action dependent on pH.
increasing pH make LA work better. ie don’t work as well in acidic enflamed tissue.
uncharged form can cross membrane easily, charged cannot. Once inside it picks up H+ and acts on Na channel.
Only binds to open or inactivated states.
describe QX314.
QX314 (pharmaceutical that didn’t make it to a clinic).
can’t cross the membrane cos protonated, inactive outside of the cell.
if injected inside the cell it blocks the Na channel. It acts on the inner face of the Na channel.
what is use dependence block?
?
what is the hydrophilic and hydrophobic pathway?
across the membrane, become protonated and access via cytoplasm inside the cell - hydrophilic.
go into membrane, side step through TMDs and block the channel, works when channel is closed or inactivated - hydrophobic. only 10% of action.
