Lectures 16-19 Flashcards
1
Q
how is the heart electrically controlled?
A
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.
2
Q
How can you look at cardiac activity?
A
ECG - electrocardiogram
map events to wave
P - atrial depolarisation
QRS - ventricular depolarisation and atrial repolarisation.
T - ventricles repolarise.
3
Q
what is turbulence?
A
risk factor for blood clots increases, can lead to strokes or a heart attack.
4
Q
what is a cardiac arrhythmia/dysrhythmia?
A
any disorder of heart rate or rhythm.
arthymia (no rhythm technically)
5
Q
what is tachycardia?
A
heartbeat is too fast
6
Q
what is bradycardia?
A
heartbeat is too slow
7
Q
what is a ectopic pracemaker?
A
cardiac tissue other than SA node initiates heart beats.
8
Q
what is a delayed after depolarisation dysrhythm?
A
build up of calcium in cells leads to a train of action potentials.
9
Q
what is a re entry circuit dysrhythm?
A
tissue damage or abnormality causes action potentials to travel in circles.
functional - above
structural - due to congenital abnormality.
?
10
Q
what are congenital abnormalities?
A
additional conducting pathways between atria and ventricles.
11
Q
what is a heart block?
A
damage to conducting pathways disrupts atrial-ventricular signaling.
12
Q
describe a functional reentry circuit
A
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.
13
Q
describe wolff parkinson white syndrome.
A
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.
14
Q
who has an increased risk of cardiac dysrhythmias?
A
anyone with previous cardiac problems.
any drug that speeds up the heart causes tachycardia.
15
Q
what is a side effect of antidysrhymic drugs?
A
if taken without underlying problem or take too much can causes dysrhymia themselves.
16
Q
describe the ECG of an ectopic pacemaker.
A
increased heart rate.
can have several P waves close together.
17
Q
describe the ECG of a bradycardia
A
irregular heart rate.
two p waves and no QRS waves.
18
Q
describe the ECG of ventricular fibrillation
A
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.
19
Q
how can you treat dysrhythmias?
A
drugs
electrical - ie defibrilator
surgical - destroy tissue causing dysrhythmia.
20
Q
what is the vaughan williams system?
A
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.
21
Q
what is the most important drug for each class?
A
I - lidocaine
II - atenolol
III - amiodarone
IV - verapamil
22
Q
what are problems with the vaughan williams classification?
A
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.
23
Q
how do medics categorise the drugs?
A
by utility.
24
Q
describe amiodarone.
A
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.
25
When use amiodarone?
atrial fibrillation.
wolff parkinson white
ventricular tachycardia/fibrillation.
26
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.
27
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
```
28
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.
29
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.
30
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.
31
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.
32
what is automaticity?
pacemaker like properties, generate AP.
33
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)
34
When else are beta blockers useful?
when there are excessive catecholamines (adrenaline/noradrenaline).
increased tissue sensitivty to catecholamines (thyrotoxicosis).
following myocardial infarction.
35
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.
36
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?
37
what are the states of Na/Ca receptors?
closed/resting state
open state
inactivated state
38
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.
39
describe lidocaine.
```
local anaesthetic and anti dysrhythmic drug.
class I of VW.
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40
what are nociceptor neurones?
pain nerve endings, they hurt.
bare nerve ending.
A delta fibres fast sharp pain. myelinated.
C fibres slow burning. unmyelinated.
41
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.
42
how do local anaesthetics work GENREALLY?
block na channels.
thus block AP.
also block nociception.
43
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+.
44
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.
45
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.
46
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.
47
what is use dependence block?
?
48
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.
49
What are class I drugs?
Na channel blockers.
a,b,c
use dependent.
channel must be active for drugs to bind and block.
50
what class is lidocaine?
Ib.
51
what are side effects of class I.
if it enters the CNS it can cause convulsions or coma.
52
Ib drugs?
dissociate easily.
| use dependent.
53
when is lidocaine best used?
it is use dependent and has rapid dissociation, so in a slow heart beat doesn't affect it much. It has dissociated before the next heartbeat.
In a high heart rate, the block extends into the period when the heart tries to beat again.
It stops the rapid 2nd AP from happening.
given intravenously, similar to defib in terms of emergency use.
54
what are the uses of class Ia drugs?
ventricular and atrial arrhythmias (paroxysmal atrial fibrillation).
55
what are the uses of class Ic drugs?
ventricular and atrial arrhythmias (paroxysmal atrial fibrillation), Wolff-Parkinson- White
56
name class Ia drugs.
disopyramide, procainamide.
57
what is a myocardial infarction?
heart attack.
58
name a class Ic drug.
flecainide.
| risk of sudden death following cyocardial infarction
59
what are class IV drugs?
block L type voltage gated Ca channels. L type generate cardiac AP.
reduced after-depolarisation.
suppress ectopic pacemakers.
uses: paroxysmal supraventricular tachycardia, decrease ventricular rate in atrial fibrillation.
60
examples of class IV drugs?
verapamil and diltiazem.
61
what are side effects of class IV drugs?
dangerous in ventricular dysrhythmias, Wolff-Parkinson-White. cardiodepression (less cardiac output), hypotension, AV node block oedema (swollen ankles),headache, constipation..
62
describe nifedipine
a dihydropyridines.
L type Ca channel blockers.
bind to different site to verapamil. can't be used to treat dysrhythmias. can treat angina maybe.
they are not use dependent, they block all sites.
63
what can't be used to treat dysrhythmias?
not all L type Ca blockers, not dihydropyridines, only verapamil.
64
what is angina?
deprivation of oxygen temporarily.
65
what is a heart attack?
heart deprived of oxygen for a long period of time by a blockage.
"time is muscle".
ischaemia leads to muscle death.
66
what is a heart failure?
heart is not pumping properly, can't meet the bodies needs.
67
what is a dysrhythmia?
heart rhythm disturbed.
68
describe the hearts blood supply.
has it's own blood supply, doesn't get it from the blood it pumps.
this is what fails in agina or heart attack.
69
how can you counter coronary artery disease?
improve lifestyle
reduce bp
statins to reduce cholesterol.
70
what is coronary artery disease?
atherosclerosis in a cornoary artery.
71
what is a angiogram?
inject radioopaque dye and let it travel to the heart then take an xray. allows you to see the path it takes and look for a narrowing.
72
what is ischaemia?
loss of oxygen, can lead to muscle death if prolonged.
73
what are glyceryl trinitrate and propranolol used for?
reduce workload and oxygen demand.
improve blood flow through coronary arteries.
reduce pain.
74
what is a tissue plasminogen activator?
"clot buster"
| only work if given within a few hours.
75
what is angioplasty?
vessel is re opened using a tiny balloon and stent, releases symptoms of angina.
76
what is bypass surgery?
grafted blood vessel from another part of body bypasses area of stenosis.
risk of embolism and decline in mental function.
77
what is stenosis?
narrowing of vessel.
78
what is angina pectoris?
pain in left chest and possibly arm, neck or jaw.
results from cardiac ischaemia.
when cardiac muscle is deprived of o2, it releases pain signalling molecules, ie K+, H+, bradykinin and adenosine.
79
what is stable angina?
angina of effort.
most common form.
caused by atherosclerosis of coronary arteries.
triggered by excercise, excitemtn or cold weather.
relieved by rest.
80
what is unstable/brittle angina?
pre existing atherosclerotic plaque disrupted.
can occur when sleeping or resting.
very likely to lead to a heart attack.
81
what is variant or prinzmetal's angina?
rare.
caused by vasospasm (coronary blood vessel clamps down).
happens at rest.
no real obstruction present.
likely to lead to a heart attack.
82
what is the main goal of treating angina?
reduce oxygen demand and increase oxygen supply.
83
how can you treat stable angina?
aspirin - prevents platelet aggregation.
statins - lower lipid/cholesteral levels. prevents plaque formation.
organic nitrates.
beta blockers.
ca channel blockers.
K+ channel activators.
84
what is extensive first pass metabolism?
will be almost completely broken down in the liver.
a drug with a high first pass metabolism needs another route of administration.
85
how are drugs absorbed?
GI tract to the hepatic portal vein, this is taken to the liver.
enzymes there break down foreign substances.
some turned to metabolites, and some drug passed through to the body.
86
what is bioavailibilty?
the amount of drug that reaches the rest of body.
87
describe nitrovasodilators.
(activate soluble guanylate cyclase.)
ie nitroglycerine.
88
describe nitroglycerine.
vasodilator, treatment for angina.
glyceryl trinitrate.
first pass metabolism.
given sublingually or buccally. (mouth or under tongue).
20-30 mins action.
has to be broken down close to the target tissue, due to active principle being nitric oxide - NO.
89
How do nitrates relieve angina?
body already naturally dilates coronary arteries as a reflex to angina.
nitrates dilate peripheral blood vessels, less blood returns to heart so lower force of contraction needed - frank/stalin law.
reduce preload and afterload.
also reveals collateral vessels by dilation, an alternate route for blood to travel. Can bypass the blockage.
90
what is preload and afterload?
Preload is the filling pressure of the heart at the end of diastole. The greater the preload, the greater will be the volume of blood in the heart at the end of diastole.
Afterload is the tension or stress developed in the wall of the left ventricle during ejection. In other words, it is the end load against which the heart contracts to eject blood.
91
what is the frank stalin law of the heart?
more blood that goes back to the heart, the harder the heart will contract.
92
what is isosorbide dinitrate?
2 nitrate groups, one group makes it through the liver.
can be swallowed.
up to 12 hours active.
develop tolerance
93
what are side effects of nitrates?
flushing of skin and sweating.
throbbing headache - dilation of cranial vessels.
orthostatic hypotension - fainting due to standing up.
reflex tachycardia - reduce in bp can cause increased heart rate.
94
what is nicorandil?
activator of K+ channels and a NO donor.
dilates arteries and veins.
similar to nitrates.
also has vomiting and headaches.
not use dependent, can be used to treat hypertension but not for dysrhythmias.
95
why are beta blockers useful for treating angina?
beta 1 receptors activate sympathetic nervous system, reduce cardiac workload if blocked.
Blood can only flow through coronary vessels during diastole. Beta blockers prolong diastole so the window for coronary blood flow is increased. This means that more O2 will get to the muscle.
96
when does blood flow into the myocardium?
during diastole.
97
what receptors do verapamil and nifedipine block?
alpha subunit of the L type calcium channels
98
where are L type calcium channels present?
the heart.
99
describe verapamil in regards to angina.
use dependent blockage of Ca channels.
acts on the heart.
reduces heart rate and cardiac output.
dilation of arterioles reduces afterload.
workload and oxygen demand are reduced.
100
describe nifedipine in regards to angina.
more potent on vascular smooth muscle since not use dependent.
block ca channels.
dilation of arterioles to reduce afterload.
dilation of capacitance veins to reduce preload.
cardiac work and oxygen demand are reduced.
101
how do you treat angina and myocardial infarction? brief overview.
first statins to treat the athersclerotic plaque.
aspirin and heparin are anti platelet agents to prevent thrombosis.
organic nitrates, calcium antagonists or beta blockers for angina.
(bypass) surgery to remove the plaque would be ideal.
ace inhibitors for ventricular dysfunction, and beta blockers to treat the increased sympathetic activity and arrhythmias.
opioids to treat pain.
102
what is cardiomyopathy?
a failure in the contractile mechanism of the heart muscle.
103
what is congestive heart failure?
thickened myocardium (muscle). less room for blood to fill, less elastic.
so named for the build up of fluid in the body that occurs.
104
what are them fat ankles bro?
oedema, accumulation of fluid in the extremities.
can't return blood to the heart properly.
sign of heart failure.
105
describe a dilated heart.
next stage of heart failure after hypertrophy.
enlarged ventricles fill more than normal, become "baggy".
can't pump as much blood.
106
what are common causes of heart failure?
hypertension.
myocardial ischaemia - ie atherosclerosis and thrombus.
valvular disease.
107
what is heart failure?
inability to pump properly
108
describe how the body responds to cardiac failure.
cardiac output decreases due to loss of contractility.
renal blood flow goes down.
causes salt and water retention, increases the volume of fluid in the body.
activates the renin angiotensin system.
causes vasoconstriction, increasing peripheral resistance and increasing afterload.
SHORT TERM compensatory, increases blood pressure.
salt and water retention leads to an increase in plasma volume - oedema.
also increases central venous pressure, increases preload.
SHORT TERM compensatrory, increased blood pressure.
body tries to counter by increasing bp, in the long term this exacerbates the heart problems.
109
how can you classify heart failure?
left vs right.
forward (pushed out of heart) vs backward (returning blood).
systolic vs diastolic.
110
describe symptoms of forward heart failure.
low output.
easily tired.
peripheral cyanosis (underperfusion of skin - blue of fingers)
salt and water retention (underperfusion of kidneys).
111
describe symptoms of backward heart failure.
congestive.
pulmonary hypertension, blood pressure in lungs increases.
breathlessness.
oedema of legs/ankles.
engorgement of liver, no blood returned.
112
how do you reduce cardiac workload to treat heart failure?
reduce cardiac workload:
rest
ace inhibitors - captopril to reduce preload and afterload.
organic nitrates - reduce preload and afterload, and reduce oedema
reduce pulmonary congestion and peripheral oedema:
diet - reduce salt intake.
thiazide diuretic and loop diuretics remove lots of fluid.
113
how do you increase cardiac output to treat heart failure?
positive iontropic agent - digoxin. increases force of contraction of the heart.
digoxin is sweet at reducing symptoms but doesn't reduce mortality rate.
114
where is digoxin derived from? describe it
foxglove plant.
lipid and water soluble.
?
115
what does digoxin act on?
inhibits the Na/K ATPase pump.
increases internal Na and Ca levels.
AP now release more Ca from sarcoplasmic reticulum, increased force of contraction (+ inotropic) with no increase in o2 demand.
increases vagus nerve activity, slowing SA node firing rate, AV node conduction velocity.
at toxic doses fucks u up.
small window between toxic dose and therapeutic dose.
116
what are signs of digoxin toxicity?
2:1 theraputic index.
nausea and vomiting.
disturbances of vision.
ventricular tachyarrhythmias (increases).
117
what is a theraputic index?
ratio between toxic dose and theraputic dose.
118
when should digoxin be used?
to treat chronic rapid atrial fibrillation. it slows and stabilises ventricular rate and improves refilling.
in combination iwth diuretics or ace inhibitors. it increases the force of contraction.
119
why does low K levels make digoxin more toxic?
hypokalaemia (low K levels) makes digoxin toxicity worse. Both compete for same site on Na/K ATPase.
120
how can you treat digoxin toxicity?
stop taking it lol.
correct hypokalaemia - increase K levels.
propranolol or phenytoin to control arrhythmias.
digoxin specific antibodies.
121
how else can you treat heart failure?
phosphodiesterase (PDE) inhibitors. ie milrinone.
used when other treatments fail.
increases cAMP, increases cardiac output and vasodilation.
beta1 adrenoceptor AGONSIT - dobutamine.
increases cardiac output.
decreases arterial and ventricular filling pressure.
rapid tolerance building.
certain beta blockers - carvedilol, metaoprolol.
decreases sympathetic tones.
have to start at very low dose and increase gradually.
122
One criticism of the Vaughan-Williams system for antidysrhythmic drugs is that some drugs have multiple sites of action. One such drug is sotalol. This drug acts at:
potassium channels and β1 adrenoceptors
