PED2007 L12-L15 Flashcards
what are sinoatrial node pacemakers
the rate of firing of the SA node sets the heart rate
it initiates the cardiac cycle
what is phase 0 of the cardiac cycle
calcium ion influx
upstroke of the slow pacemaker action potential
triggered at the threshold potential of -55mV
increase in movement of Ca2+ into cell
what is phase 3 of the cardiac cycle
calcium ion channels inactive
delayed potassium ion efflux
increase in potassium efflux
membrane hyperpolarises
what is phase 4 of the cardiac cycle
pacemaker sodium ion influx
calcium ion channels recover from inactivation
pumps restore ion gradients
what is the HCN channel
found in pacemaker cells
pacemaker cell membranes contain HCN-gated channels (hperpolarisation-activated, cyclic nucleotide-dependent nonspecific channels)
how is the HCN channels involved in phase 4 of the cardiac cycle
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
what is phase 0 of the ventricular myocyte action potential
sodium ion channels open
permeability to sodium ion increases
membrane potential approx -90mV
what is phase 1 of the ventricular myocyte action potential
sodium ion channels close; fast potassium ion channels open
permeability to sodium ions decreases
membrane potential approx 20mV
what is phase 2 of the ventricular myocyte action potential
calcium ion channels open; fast potassium ion channels close
permeability to potassium ions decreases and permeability to calcium ions increases
membrane potential approx 10mV
what is phase 3 of the ventricular myocyte action potential
calcium ion channels close; slow potassium ion channels open
permeability to potassium ions increases and permeability to calcium ions decreases
membrane potential approx -55mV
what is phase 4 of the ventricular myocyte action potential
resting potential
how do the sympathetic nerves effect heart rate
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
what would we give to slow heart rate
noradrenaline
what effects does the parasympathetic nerves have on heart rate
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
what is the vagal tone to the heart
intrinsic rate of firing of SAN cells ~100-110 Aps per min
constant tonic activation of some parasympathetic nerves on SA node
when does early after depolarisation occur
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
what is delayed afterdepolarisations
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
what are beta agonists
slows heart rate rhythms or bradycardias - need to increase heart rate
what are 2 examples of beta agonists
atropine - switch of vagus nerve - muscarinic antagonist drug
isoproterenol - activate beta receptors
what is class 1 of the Vaughan Williams classifications
sodium channel blockers
drugs to treat abnormal fast heart rhythms - tachycardia
lidocaine/lignocaine
what is class 2 of the Vaughan Williams classifications
beta blockers
atenolol, metoprolol, sotalol
what is class 3 of the Vaughan Williams classifications
potassium channel blockers - effect the last bit of the action potential - takes longer to reset so action potential lasts longer
amiodarone
what is class 4 of the Vaughan Williams classifications
calcium channel blockers
effect upstroke of SA node
effect plateau of ventricular
verapamil
what is adenosine used for
drugs to treat adnormally fast heart rhythms - tachycardia
which drugs are used in the treatment of cardiac arrest
systole - adrenaline/epinephrine
ventricular fibrillation - amiodarone, lignocaine
what is atropine
naturally occurring antimuscarinic alkaloid
blocks vagal inhibition of sinus and AV node
intravenous bolus administration
predominately hepatic metabolism
short half lifer
what are the anticholinergic adverse effects
dry mouth
mydriasis
postural hypotension
what are the 3 drug groups of class 1 drugs
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
what is the action of class 1b drugs
e.g. lidocaine
blocks fast sodium channels and slows phase 0 depolarisation
shortens action potential duration
specific effect on rapidly depolarising tissue
what are the indication of class 1b drugs
ventricular arrhythmias
what is the pharmacology of class 1b drugs
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
what are the adverse effects of class 1b drugs
hypotension, heart block
neurotoxicity
what are the types of class 2 beta blockers
non-cardioselective - also blocks beta2 receptors e.g. propranolol
cardioselective - less potent blockers of beta2 receptors e.g. atenolol
others - e.g. beryllium
what is the pharmacology of beta blockers
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
what is the action of beta blockers
beta adrenoceptor antagonists
reduce intrinsic rate in sinus and AV nodes
reduces heart rate, blood pressure and cardiac work
reduces renin secretions
what are the adverse beta 1 effect of beta blockers
bradycardia
heart failure
what are the adverse beta 2 effects of beta blockers
exacerbation of asthma
cool peripheries
muscular aches
worsening intermittent claudication
what are the other adverse effects of beta blockers
fatigue nightmares, sleep disturbances
withdrawal effects (angina, MI)
unawareness of hypoglyceamia
what is the action of class 3 drugs - amiodarone
prolongs action potential duration and refractory period
lengthened QT interval on ECG
what are the indications of class 3 drugs - amiodarone
effective for ventricular and supra ventricular tachycardia
first line for treatment of ventricular fibrillation
improves survival in patients with recurrent ventricular tachycardia
what is the pharmacology of class 3 drugs - amiodarone
long half life
hepatic metabolism
what are the adverse effects of class 3 drugs
serious adverse effects limit use to high risk patients
what are the serious adverse effects of amiodarone
thyroid disturbance
pulmonary fibrosis
pro-arrhythmia and torsade de pointes
peripheral neuropathy
hepatitis
blue-grey skin discolouration
what are the 3 classes of calcium channel blockers
dihydropyridines
benzothiazepines
phenylalkylamine
what are dihydropyridines
nifedipine, amlodipine
predominately vascular effects (arterial vasodilation)
what are benzothiazepines
diltiazem
mixed vascular and cardiac effects
what are phenylalkylamine
verapamil
predominately cardiac effects (negative ionotrope and chronotrope, anti arrhythmic)
what is an example of a class 4 drug
verapamil
what is the action of class 4 drugs
calcium channel blockers
slows phase 1 and 2; slow calcium entry
reduces rate and conduction velocity in sinus and AV nodes
what are the indication of class 4 drugs
supraventricular arrhythmias
what is the pharmacology of phase 4 drugs
actions on heart»_space; actions on blood vessels
oral and IV use
first pass hepatic metabolism
what are the adverse effects of class 4 drugs
heart failure, hypotension
constipation
vasodilation, oedema, flushing
