PED2007 L12-L15

Question 1

what are sinoatrial node pacemakers

Answer 1

the rate of firing of the SA node sets the heart rate
it initiates the cardiac cycle

Question 2

what is phase 0 of the cardiac cycle

Answer 2

calcium ion influx
upstroke of the slow pacemaker action potential
triggered at the threshold potential of -55mV
increase in movement of Ca2+ into cell

Question 3

what is phase 3 of the cardiac cycle

Answer 3

calcium ion channels inactive
delayed potassium ion efflux
increase in potassium efflux
membrane hyperpolarises

Question 4

what is phase 4 of the cardiac cycle

Answer 4

pacemaker sodium ion influx
calcium ion channels recover from inactivation
pumps restore ion gradients

Question 5

what is the HCN channel

Answer 5

found in pacemaker cells
pacemaker cell membranes contain HCN-gated channels (hperpolarisation-activated, cyclic nucleotide-dependent nonspecific channels)

Question 6

how is the HCN channels involved in phase 4 of the cardiac cycle

Answer 6

activated by hyperpolarusation
HCN mediated a funny current - simultaneous potassium ion efflux and sodium ion influx
sodium ion influx dominates causing slow depolarisation of membrane
reaches threshold
upstroke inactivated HCN

Question 7

what is phase 0 of the ventricular myocyte action potential

Answer 7

sodium ion channels open
permeability to sodium ion increases
membrane potential approx -90mV

Question 8

what is phase 1 of the ventricular myocyte action potential

Answer 8

sodium ion channels close; fast potassium ion channels open
permeability to sodium ions decreases
membrane potential approx 20mV

Question 9

what is phase 2 of the ventricular myocyte action potential

Answer 9

calcium ion channels open; fast potassium ion channels close
permeability to potassium ions decreases and permeability to calcium ions increases
membrane potential approx 10mV

Question 10

what is phase 3 of the ventricular myocyte action potential

Answer 10

calcium ion channels close; slow potassium ion channels open
permeability to potassium ions increases and permeability to calcium ions decreases
membrane potential approx -55mV

Question 11

what is phase 4 of the ventricular myocyte action potential

Answer 11

resting potential

Question 12

how do the sympathetic nerves effect heart rate

Answer 12

activation causes release of noradrenaline - binds to beta1-adrenoceptors on the cardiac pacemaker and myocyte cell membranes
increases opening of HCN channels in pacemaker cells - increases sodium ion influx
opens calcium ion channels
increases in slope of pre potential (phase 3)
heart rate increases 75 –>113

Question 13

what would we give to slow heart rate

Answer 13

noradrenaline

Question 14

what effects does the parasympathetic nerves have on heart rate

Answer 14

activation causes release of acetylcholine - binds to muscarinic cholinergic receptors
decreases opening of HCN channels - decreased sodium ion influx
slows opening of calcium ion channels - decreases calcium ion influx
opens additional potassium ion channels - increases potassium efflux
hyperpolarises membrane and reduces slopes of prepotential
heart rate decreased 75 –> 50

Question 15

what is the vagal tone to the heart

Answer 15

intrinsic rate of firing of SAN cells ~100-110 Aps per min
constant tonic activation of some parasympathetic nerves on SA node

Question 16

when does early after depolarisation occur

Answer 16

occur when normal heart rate low - suppressed by high heart rate
occurs when AP prolonged - some calcium channels inactivates during shoulder, reactivate to give EAD, calcium L channels, calcium T channels, need different drugs to Rx

Question 17

what is delayed afterdepolarisations

Answer 17

seen at increased heart rates
associated with elevated [Ca2+]
ca2+ activation of Na/K channels (depolarising)
NaCa exchange 3:1 - electrogenic
toxic doses of cardiac glycosides

Question 18

what are beta agonists

Answer 18

slows heart rate rhythms or bradycardias - need to increase heart rate

Question 19

what are 2 examples of beta agonists

Answer 19

atropine - switch of vagus nerve - muscarinic antagonist drug
isoproterenol - activate beta receptors

Question 20

what is class 1 of the Vaughan Williams classifications

Answer 20

sodium channel blockers
drugs to treat abnormal fast heart rhythms - tachycardia
lidocaine/lignocaine

Question 21

what is class 2 of the Vaughan Williams classifications

Answer 21

beta blockers
atenolol, metoprolol, sotalol

Question 22

what is class 3 of the Vaughan Williams classifications

Answer 22

potassium channel blockers - effect the last bit of the action potential - takes longer to reset so action potential lasts longer
amiodarone

Question 23

what is class 4 of the Vaughan Williams classifications

Answer 23

calcium channel blockers
effect upstroke of SA node
effect plateau of ventricular
verapamil

Question 24

what is adenosine used for

Answer 24

drugs to treat adnormally fast heart rhythms - tachycardia

Question 25

which drugs are used in the treatment of cardiac arrest

Answer 25

systole - adrenaline/epinephrine ventricular fibrillation - amiodarone, lignocaine

Question 26

what is atropine

Answer 26

naturally occurring antimuscarinic alkaloid blocks vagal inhibition of sinus and AV node intravenous bolus administration predominately hepatic metabolism short half lifer

Question 27

what are the anticholinergic adverse effects

Answer 27

dry mouth mydriasis postural hypotension

Question 28

what are the 3 drug groups of class 1 drugs

Answer 28

class 1a - lengthen action potential duration and refractory period e.g. quinidine, propafenone, disopyramide class 1b - shorten action potential duration and refractory period e.g. lignocaine/lidocaine class 1c - no effect on action potential duration and refractory period, delay conduction velocity in purkinje fibres e.g. flecainide

Question 29

what is the action of class 1b drugs

Answer 29

e.g. lidocaine blocks fast sodium channels and slows phase 0 depolarisation shortens action potential duration specific effect on rapidly depolarising tissue

Question 30

what are the indication of class 1b drugs

Answer 30

ventricular arrhythmias

Question 31

what is the pharmacology of class 1b drugs

Answer 31

short half life - must be given a bolus plus IV infusion not absorbed via oral route (hepatic first pass metabolism) hepatic clearance decreased in elderly, heart failure, liver disease

Question 32

what are the adverse effects of class 1b drugs

Answer 32

hypotension, heart block neurotoxicity

Question 33

what are the types of class 2 beta blockers

Answer 33

non-cardioselective - also blocks beta2 receptors e.g. propranolol cardioselective - less potent blockers of beta2 receptors e.g. atenolol others - e.g. beryllium

Question 34

what is the pharmacology of beta blockers

Answer 34

can be beta 1 selective (atenolol, metoprolol) or beta1, beta 2 non-selective (propranolol) oral and IV (metoprolol, propranolol) use first pass hepatic metabolism, e.g. propranolol renal excretion e.g. atenolol

Question 35

what is the action of beta blockers

Answer 35

beta adrenoceptor antagonists reduce intrinsic rate in sinus and AV nodes reduces heart rate, blood pressure and cardiac work reduces renin secretions

Question 36

what are the adverse beta 1 effect of beta blockers

Answer 36

bradycardia heart failure

Question 37

what are the adverse beta 2 effects of beta blockers

Answer 37

exacerbation of asthma cool peripheries muscular aches worsening intermittent claudication

Question 38

what are the other adverse effects of beta blockers

Answer 38

fatigue nightmares, sleep disturbances withdrawal effects (angina, MI) unawareness of hypoglyceamia

Question 39

what is the action of class 3 drugs - amiodarone

Answer 39

prolongs action potential duration and refractory period lengthened QT interval on ECG

Question 40

what are the indications of class 3 drugs - amiodarone

Answer 40

effective for ventricular and supra ventricular tachycardia first line for treatment of ventricular fibrillation improves survival in patients with recurrent ventricular tachycardia

Question 41

what is the pharmacology of class 3 drugs - amiodarone

Answer 41

long half life hepatic metabolism

Question 42

what are the adverse effects of class 3 drugs

Answer 42

serious adverse effects limit use to high risk patients

Question 43

what are the serious adverse effects of amiodarone

Answer 43

thyroid disturbance pulmonary fibrosis pro-arrhythmia and torsade de pointes peripheral neuropathy hepatitis blue-grey skin discolouration

Question 44

what are the 3 classes of calcium channel blockers

Answer 44

dihydropyridines benzothiazepines phenylalkylamine

Question 45

what are dihydropyridines

Answer 45

nifedipine, amlodipine predominately vascular effects (arterial vasodilation)

Question 46

what are benzothiazepines

Answer 46

diltiazem mixed vascular and cardiac effects

Question 47

what are phenylalkylamine

Answer 47

verapamil predominately cardiac effects (negative ionotrope and chronotrope, anti arrhythmic)

Question 48

what is an example of a class 4 drug

Answer 48

verapamil

Question 49

what is the action of class 4 drugs

Answer 49

calcium channel blockers slows phase 1 and 2; slow calcium entry reduces rate and conduction velocity in sinus and AV nodes

Question 50

what are the indication of class 4 drugs

Answer 50

supraventricular arrhythmias

Question 51

what is the pharmacology of phase 4 drugs

Answer 51

actions on heart >> actions on blood vessels oral and IV use first pass hepatic metabolism

Question 52

what are the adverse effects of class 4 drugs

Answer 52

heart failure, hypotension constipation vasodilation, oedema, flushing