Nigel's Lectures

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  • Created by: Sarah
  • Created on: 13-05-19 16:21
what is pharmacology about?
inteferring with normal physiology or pathophysiology
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what can you see on an electrocardiogram?
ultrasound of the heart- see RV, septum and mitral valve
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what is the black areas on the ultrasound?
blood
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how do you get an electrocardiogram from a patient?
place transducers on the chest wall
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what happens to the heart muscle (myocardium) when the heart contracts?
it thickens (normally muscles shorten)
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why does the myocardium thicken when the heart contracts?
the ventricles thicken so the cavity's reduced and this ejects the blood
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what is the direction of blood flow based upon?
the heart valves
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how many times does the heart contract a day?
100,000
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what's a normal heart rate (approx)?
70bpm
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what controls the heart rhythm?
the heart controls its own rhythm and rate it spontaenously contracts if you do nothing- will ocntract in a sdish
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what keeps the heart beating?
waves of depolarisation across the heart- cardiac APs, changes in MP, ions important
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how is the cardiac AP similar to other APs?
neurons and muscles AP and cardiac APs they have a MP and their activation is controlled by changes in the cell membrane
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what happens in one cardiac cycle (briefly)?
heart fires off -> sequence of events -> heart muscle contracts -> CO
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what is phase 0 in the AP when the MP is increasing (becoming more +ve)?
rapid depolarisation
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what causes rapid depolarisation?
reaches threshold (Critical) MP, all or nothing depolarisation, rapid sodium influx
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what is phase 1 of the cardiac AP (when the starts to drop rapidly from the peak)?
partial repolarisation
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why do you get partial repolarisation?
rapid sodium influx depolarisation
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what is phase 2 when the curve is plateau?
plateau
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what causes the plateau?
slow inward calcium current, initial fall in outward K
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what causes repolarisation back down to the resting MP (phase 3)?
inactivate calcium current, increase outward K current
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what is phase 4 when theres a slow rise from the lowest MP?
pacemaker potential
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when does the gradual depolarisation of the pacemaker potential occur?
diastole
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what happens in the pacemaker potential?
gradual depolarisation in diastole, increase inward Na, calcium, decrease in outward K = everything to keep +ve ions in
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what tissue is the pacemaker potential in?
nodal and conducting tissue
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where does bachmanns bundle spread the depolarisation to?
spreads AP form right to left atria- is across left atria
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why do you need a resting MP?
it keeps the CM -ve on the inside, has the capacity to change very quickly- it's a potential energy that can suddenly change
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where about is the threshold?
about -60mV
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what happens when you reach threshold?
voltage dependent, Na, K and Ca channels snap open
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in the rapid depolarisation phase 0 where does Na move from-to?
Na moves from outside to inside the cell
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why do you get partial repolarisation after a few msecs?
Na channels inactivate with the MP, voltage dependent inactivation
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in the resting state the cell has more permeability to what?
K
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what happens to K permeability in partial repolarisation?
K conductance decreases
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2 things that happen in the plateau phase?
1) increase in Ca conductance into cell 2) fall in outward K
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what is the difference between APs in neurons and cardiac APs?
in cardiac tissue we extend the depolarisation. In neurons APs can fire off at a high rate but the heart can't fire off loads as there'd be no time to fill/eject blood
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what prevents the heart muscle from firing off loads of APs?
the refractory period
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what would you get if the heart fired off APs like neurons did?
tetany- muscle spasms, nom ehcnaical output of th eheart and you'd die
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what is the refractory period?
the time that you cannot contract the heart again
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what does the MP move from in repolarisation?
from positive to negative
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what happens in repolarisation?
make cell more negative so stop influx of ca and increase outward K
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how does the heart gradually reach threshold potential over time?
pacemaker potnetial- Na and ca slowly increase and outwards K decreases
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what is the main pacemaker in the heart?
the SAN (Sinoatrial node)
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what happens once the SAN fires off an AP?
depolarisation spreads across the atrial myocardium conducting tissue (bachmanns bundle to the LA), then activates the muscle. Atria contract in response but much more slowly
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what happens after the impulse reaches the AVN?
reaches the bundle of his and spreads down the purkoinje fibres acros sthe ventricles
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why is the AV node important?
because it's the only electrical connection between the atria and ventricles. It introduces a delay as when you activate the heart want the atria to contract 1st to fill ventricles then after filled want ventricles to contract. seq atria->ventricles
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where is the SAN?
lies on the right atria
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what does AVN produce?
a sequential delay activate atria -> delay -> activate ventricles
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why is conduction extremely rapid after AVN conduction?
you want all the ventricles ejecting together to get a single CO
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where does pacemaker activity occur
conducting+nodal tissue = SAN, AVN + purkinje fibres
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is there pacemaker activity int he myocardial cells?
no
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why is it important that we have more than one pacemaker?
it's important as if SAN fails we have backups
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what is different about other pacemakers further down the heat?
they tend to be slower- SAN is the fastest depolariser and overrides everything else
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what can take over if the SAN fails?
AVN or purkinje fibres
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why is the AVN or purkinje fibres not always ideal to take over from the SAN?
can produce an ectopic rhythm but it's enough to keep you alive
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how is the AP in the SAN/AVN different from myocardial cells?
you don't have the rapid upstroke phase - in the SAN/AVN so no rapid inward Na current
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what causes the depolarisation in the nodal tissue then?
calcium channels
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why is it important that in nodal tissue its ca causing depolarisation?
important pharmacologically
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what is long in the nodal tissue?
long AP- long plateau phase giving the long refractory period
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what maintains the plateau phase?
calcium
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why are drugs affected by ca so important in the heart?
the SAN + AVN have an absence of Na current has a slow long Ca AP (plateau)
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what is an arrythmia?
abnormal heart rhythms
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what are the 2 ways the heart can get into an abnormal rhtym (arrhythmias)?
1) abnormality in impulse generation 2) abnormality in they way you propagate impulses
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what is the 2 examples of abnormla impulse genetation?
1) triggered activity 2) increased automaticity
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what is triggered activity?
triggering of abnormal impulses
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how is a common way to get triggered activity?
2 stimuli- get increase in voltage, closer you bring the 2, the greater the after depolarisation. if you stimulate the heart quickly enough fire train APs- too much IC in disease causes arrhymia tendency
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where do you get the plateau?
purkinje fibres and ventricle
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what is increased automaticity?
AP firing increases spontaneously so automatic pacemaker can takeover and create ectopic beats
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why can increased automaticity occur?
because of biochemical upset (like triggered activity eg too much IC Ca)- patients start to fire off extopic beats
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where are the ectopic beats coming from?
a different part of the heart
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what are the 2 ways there's abnormal impulse propagation?
1) heart block 2) re-entry
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what is heart block?
AVN blocked can't carry impulses to ventricles- HB is about propagation between atria and ventricles through the AVN, in various degrees
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where is the delay at the AVN shown on the ECG?
P wave = atria depolarisation, gap between P wave and the QRS ocmplex is delay at AVN
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what is the AVN delay usually?
0.2 seconds/200msecs- between atria and ventricles
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what is first degree HB?
delay is longer than it should be (over 200msecs) , all the beats get through they're just delayed so atria depol followed by ventricular depol
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what is 2nd degree heart block?
3 impulses all get through then 1 P wave with nothing following so its been completely blocked- you're dropping beats
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what is 3rd degree HB?
complete HB- atria are doing one thing and ventricles are doing something else- complete dissociation no connection between atria and ventricles
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how do you see 3rd degree heart block on the ECG?
P waves firing off atria contracting away in the background but ventricles aren't responding, lower pacemaker takes over and ventricular beats are coming from the ventricles themselves not normal activation- complexes wider as activation longer
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what is probably the commonest cause of arrhythmias?
re-entry
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why does re-entry normally not occur?
send an impulse down myocardial tissue the impulse gets propagaeted but doesn't go back on itself because the tissue behind is refractory so can only go forward, heart contracts and impulse disappears
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why can you get re-entry in a damaged heart?
part of the heart transmits impulses normally but par doesn't then you can get a forward or block or a complete block of the impulse, can be uni or bidirectiona
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what can you get if its unidirectional?
the impulse can find its way back to the area in a circus movement and then finds tissue thats repolarised because of the time delay to activate again and goes round and round
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because circuit re-entry movement can occur every time the heart contracts what happens as a result?
get a tachycardia- increased HR
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what is re-entry commonly caused by?
disease of the heart muscle eg heart attacks, myocardial infarction and scarring
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how can arrhytmias be classified?
by origin or heart rate
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what is the origins of arrhytmias?
sinus, nodal, atrial and ventricular
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what happens in a normal sinus rhythm?
P wave (Atrial depol), delay at AVN (200msecs), ventricles contract rapidly, T wave (ven repol cells summated together)
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what is a slower heart rate called?
bradycardia
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how is a bradycardia seen on the ECG?
longer between complexes
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is the origin of the rhytm still form the sinus node in a bradycardia?
yes still from SAN so have a sinus bradycardia
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when do you get a sinus bradycardia?
when we go to sleep
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when do you get a sinus tachycardia?
when you exercise- HR speeds up
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what is atrial tachycardia?
ventricles firing off quickly so it's a tachycaria. Atria are contracting very rapidly but AVN delay means not all impulses get to ventricles so offers some protection- heart contracts at finite rate
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how is the very serious condition of ventricular tachycardia shown?
complex is wider
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where does the impulse come from in a ventricular tachycardia?
from the ventricles
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what's more serious generally ventricular or atrial arrhytmias?
ventricular
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what is atrial fibrillation?
atria aren't contracting normally they are fibrillating. No output from atria- depols hit AVN some get thro some don't very erratic gives irregular heart rhythm atria don't contract
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what usually happens to the rhythm in atrial fibrillation?
rhytms ireegular and often fast
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who is atrial fibrillation common in?
elderly population (1/20 in over 65's)
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what is a big problem with atrial fibrillation?
atria are not contracting properly, atrial stands still and blood clots can collect in the atia = atrial thrombosis can occur. If it breaks off can get a stroke
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what therapy is usually based on atrial fibrillation?
anticoagulants like warfarin because of arterial thromobosis with AF
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what kind of fibrillation makes people drop dead in the street?
ventricular fibrillation
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why is ventricular fibrillation such a problem?
there's no CO
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what is ventricular fibrillation usually based on?
coronary artery disease
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when can defibrillation save lives?
in ventricular fibrillation- can get back into a normal rhythm
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why does the HR increase when you take it out of the body?
usually HR supressed by vagal tone/nerve
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is the intrinsic HR faster or slower in a dish?
faster no vagal tone
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what hormones in the sympathetic system stimulate the heart and where do they come from?
adrenaline- adrenal glands, noradrenaline- sympathetic nerves
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what does the sympathetic NS do to the heart?
increases HR and BP and force of contraction
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what is a chronotropic response?
increase in HR
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what is the chronotropic response by the sympathetic NS mediated by?
beta 1 adrenoceptors (Adrenaline receptors)
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what happens to the APs SAN pacemaker potential when you give sympa stimulation?
you increase the slope of the pacemaker potential so it reaches threshold quicker -> increases HR. Faster responses as reach depol faster
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what is the downside of sympa stimulation?
it increases automaticity- more likely to get a rhytm disturbance if you thrash with sympa stimulation
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how does the parasympa NS wokr on nodal tissue?
vagus nerve acts on nodal tissue by acetylcholine slows the HR down
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how does acetylcholine slow the HR down with the vagus nerve?
ach acts on muscarinic recs and slope of pacemaker potential decreases so resting HR decreases
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what dominates your HR when you're asleep
vagal tone
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what good effect does vagal tone on the heart have?
it stops automaticity from occuring- prevents arrhytmias
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how else (other than muscarinic recs deceeases pakemaker potential slope) does the parasympa system slow HR?
slows down AVN conduction - PR prolongation that 200msecs delay is made longer- it causes a degree of heart block
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what happens to your PR interval when you sleep because of vagal tone?
PR interval increases
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what classification system is used for antiarrhythmic drugs?
Vaughan Williams Classification
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how many main classes does the Vaughan WIlliams classification divide antiarrhythmic drugs into?
4
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what are the 4 main classes of antiarrhytmic drugs
class I- Na channel blockers class II- B adrenoceptor antagonists (beta blockers) Class 3- prolong AP Class 4- Ca channel blockers
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why are sodium channel blockers split into a, b, c?
to do with the way they interact with ion channels but don't need to know
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main 3 examples of Na channel blockers?
1a) disopyramide 1b) lidocaine 1c) flecainide
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all 1a Na channel blockers?
disopyramide, quinidine, procainamide
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all 1B Na channel blockers?
Lidocaine, mexiletine
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1c Na channel blockers?
flecainide, propafenone
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what is used as a local anaesthetic that has the same effect on the heart?
lidocaine- can work on neurons and excitable tissues
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what does it mean that Na channel blockers are use dependent?
Na channels inactive/resting -> open -> refractory. Blockers just work on resting state for drug to bind you will only affect the channels in a deactivated state and resting channels remain unblocked
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what is class 2 antiarrhytmics?
beta adrenoceptor antagonists = beta blockers
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what do beta blockers do?
block beta adrenoceptors- so block effects of adrenaline on adrenoceptors
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examples of beta blockers?
propanolol, nadolol, carvedilol (non-selective), BS- Bisoprolol, metoprolol (B1-selective)
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what are class 3 antiarrhytmics?
prolong the AP- Amidoranone and sotalol
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what do amidoranone and sotalol do?
prolong the AP- prolong the refractory period so heart is not susceptible to new impulses coming along
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what are class 4 antiarrhytmics?
ca channel blockers
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what are the ca channel blockers used?
verapamil, dilitazem
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drug that doesn't fit into the Vaughan Williams classification?
digoxin
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where does digoxin come from?
foxglove plant
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what kind of drug is digoxin?
cardiac glycoside (because they have a sugar element_
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what does digoxin works on?
Inhibits the Na/K pump, prevent RMP
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how does digoxin work?
has effects on other systems main effect is on heart. Encourages vagal tone to work on nodal tissue so get a bradycardia
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what is the problem with digoxin?
slowing of conduction between the atria and ventricles due to vagal tone but it can cause ectopic activity as it increases Ca inside the heart- so proarrhytmic effect fine line when treating arrhytmias of causing them
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what is good about digoxin compared to other antiarrhytmics?
most supress heart function but digoxin increases heart contraction- has a positive intropic effect thro ca effects
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why does digoxin work by inhibiting the Na/K pump and increasign Ca conc inside cells?
Na/K pump interacts indirectly with Na/Ca so normally high Na outside cell pump it out with Na/K but inhinit that decrease grad for Na/Ca pump so ca doesn't get pumped out of cells = IC Ca high
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what does increased IC ca do?
increases the force of contraction but also increases ectopic beats
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why is the dose of digoxin so important?
has a very narrow therapeutic range, need a certain level in the bloodstream to get beneficial effects but slightly higher get adverse effects- hard to control range
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what side effects do you get if digoxin is too high?
nausea, vommiting, diarrhoea and confusion. might think gastroenteritis but its digoxin toxicity
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where is digoxins main use?
atrial fibrillation (+HF) because digoxin slows heart rate but increases force of cotnraction, in AF have fast bentricular response so block some waves going to ventricles
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what is the QT interval?
the interval between the QRS and the T wave- it represents a comination of depolarisation and repolarisation
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what are drugs that increase the time it takes to repolarise the cell doing?
prolonging re-polarisation so prolonging the QT interval
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what does every drug get looked at for in manufacture?
does it affect the QT interval? does it affect repolarisation
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what serious problem does QT prolongation have?
polymorphic ventricular tachycardia- torsades du pointes widening and narrowing on ECG. PV can kill people
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what is an example where drugs prolong the QT interval to reduce HR to treat arrhytmias but can be lethal and trigger an arrhytmia?
polymoprhic ventricular tachycardia
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2 drugs that prolong the QT interval
sotalol and amiodraone
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what is amiodarone used to treat?
arrhytmias
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what does amiodarone do to the QT interal?
prolongs it
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why is it a problem that amiodarone prolongs the QT interval?
if it prolongs it too much you can trigger an arrhytmia, opposite of what you wanted to do, try to treat arrhytmia and trigger a different one
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why does amiodarone affect numerous tissues?
it has a large volume of dsitribution- distibutes in muscle, fat goes everywhere
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a patient getting breathless on amiodraone may have developed what as a result of its large volume of distribution?
interstitial pneumonitis- a lung inflammatory condition
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what organs does amiodraone particularly affect?
gives abnormality in liver function (have to monitor) and thyroid gland metabolism
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why does amiodarone affect thyroid gland metabolism?
thyroid gland metabolism based on iodine, iodine = really important for thyroid hormones, amiodarone = iod in middle as it containes iodine so influences iodine metabolism. Gives abnormal thyroid function
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why do people on amiodarone have to avoid direct contact with the sun, wear hats and high factor suncreen?
amiodarone makes you sensitive to the sun- will get sunburn all over very rapidly
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what can happen if you're on amiodarone for a very long time (15yrs+)?
slate grey- discolouration of the skin
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how does amiodarone affect the eyes?
get corneal microdeposits, doesn't affect visual acuity but get scintillating lights at night flash in their eyes etc, optic neuropathy- very serious
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why is amiodraone not good with other drugs?
it affects many drugs and their metabolism (british national fromularly lots of drug interactions). it displaces drugs from protein binding in the serum
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example of amiodarone affecting drug interactions?
warfarin- on warfarin and give amiodarone will displace warfarin from serum proteins and suddenly become over anticoagulated
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why can it take up to 3 months to get amiodarone out of the system completely?
it has a very large volume of distribution- goes everywhere, takes a long time to build up in the system
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Other cards in this set

Card 2

Front

what can you see on an electrocardiogram?

Back

ultrasound of the heart- see RV, septum and mitral valve

Card 3

Front

what is the black areas on the ultrasound?

Back

Preview of the front of card 3

Card 4

Front

how do you get an electrocardiogram from a patient?

Back

Preview of the front of card 4

Card 5

Front

what happens to the heart muscle (myocardium) when the heart contracts?

Back

Preview of the front of card 5
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