cardiovascular current treatments 2 Flashcards
cardiac action potential
change in membrane potential/ voltage across cell membrane of myocardial cells
not initiated by nervous activity unlike skeletal muscle fibres, instead heart has pacemaker cells that automatically generate action potentials
where are pacemaker cells found
in sinoatrial SA node in the right atrium
dysregulation can cause arrhythmia
cardiac action potential differs from neuronal action potential due to
differences in ion flux
neuronal action potential stages - 5
stimulus
depolarisation (sodium ion influx)
repolarisation (potassium ion efflux)
hyperpolarisation
resting potential
cardiac action potential stages phase 0 -4
phase 0 - depolarisation due to sodium ion influx
phase 1 - initial repolarisation due to sodium ion channels closing, potassium ion channels opening and closing rapidly
phase 2 - plateu due to calcium ion influx balanced by potassium ion efflux
phase 3 - rapid repolarisation due to calcium ion channels closing and rapid potassium ion efflux
phase 4 - resting potential due to sodium potassium ion pump stabilising membrane potential
cardiac cells have ___ refractory periods where they reset the membrane potential before a second stimulus
2
cardiac cells have 2 refractory periods where they reset the membrane potential before a second stimulus. when are these
phase 0 - part way through phase 3
impossible to produce another action potential during this - absolute refractory period
immediately after is the relative refractory period until end of phase 3
how is cardiac action potential activity recorded
electrocardiogram ecg
arrhythmias can be seen here if looks irregular
what are antiarrythmic drugs used to treat
abnormallyfast heart rhythms aka tachycardia
tachycardia examples
atrial fibrillation
supraventricular tachycardia
ventricular tachycardia
atrial fibrillation
rapid irregular beating on the atria
supraventricular tachycardia
fast heart rhythms from the top of the heart
ventricular tachycardia
rapid beating of ventricles
amiodarone used when
antiarrythmic drug - cardiac dysrhythmias
target SA node
amiodarone has ___ mechanisms of action
several
amiodarone mechanisms of action
inhibit potassium ion channels reducing efflux in phase 3
inhibits sodium ion channels in phase 0, thus depolarisation and repolarisation slowed down
blocks calcium channels so longer plateu
overall reduces cardiac action potential, slows heart rate down, prevent rapid heart beating
digoxin used when
treatment of atrial fibrillation, atrial flutter, heart failure
reduces heart rate, increases myocardial contractility - strength at which heart can push blood out of chambers
digoxin mechanism of action
inhibits alpha subunits of sodium-potassium ATPase ion channels
mainly but not exclusively inhibits these pumps in myocardium
also reverses sodium calcium exchange pump, increasing intracellular cacium
inc binding of calcium to troponin C
promotes stronger contraction between two filaments thus muscular force during heart contraction but without increasing energy expenditure
sodium potassium ion pump
exports 3 sodium ions
imports 2 potassium ions
needs ATP
net export of 1 charge per pump cycle, so membrane potential of cells is negative - net loss of positive charge
sodium calcium ion pump
imports 3 sodium ions
exports 1 calcium ion
is reversible, so can export 3 sodium ions for every calcium ion imported after digoxin treatment
increases intracellular calcium
troponin C
protein that forms part of thin filaments alongside actin
calcium binding causes conformational change of troponin C allowing better interaction of actin and myosin
promotes stronger contraction between two filaments thus muscular force during heart contraction but without increasing energy expenditure
hypertension
high blood pressure in arteries
long term or acute
long term hypertension is a risk factor for
stroke, heart attack, coronary artery disease
high blood pressure is considered
above 140/90mmHg
normal blood pressure is considered
less than 120/80 mmHg, dec if more active
what is used to treat hypertension
verapamil
used for angina and supraventricular tachycardia also
verapamil mechanism of action
L-type calcium channel blocker
inhibits calcium ions into cell
dec impulse conduction in SA and AV node
for hypertension specifically, relax smooth muscle lining blood vessels so dec blood pressure by inhibiting calcium ions in smooth muscle cells, reduction in actin myosin interaction
where are L-type calcium channels found
SA node and AV atrioventricular nodes
also in smooth muscle lining blood vessels
what is blood pressure the result of
balance of vasoconstriction and vasodilation
also hormones
what is vasoconstriction endogenously controlled by
epinephrine and norepinephrine
epinephrine and norepinephrine signalling
via alpha 1 adrenergic receptor
(Gq coupled receptor)
raises intracellular caclium
activates myosin light chain kinase
what hormones control blood pressure
angiotensin
what is angiotensin
peptide hormone
where is angiotensin produced
liver
what precursor is angiotensin produced in the liver as
angiotensinogen
angiotensinogen pathway
activated by renin
to angiotensin 1
converted by angiotensin-converting enzyme ACE
to angiotensin II
angiotensin II can interact with angiotensin II receptor 1 or 2 ATR1 or ATR2
Gq signalling
inc intracellular calcium
inc smooth muscle contractility, raises blood pressure
what is renin
enzyme secreted by kidneys
how many angiotensin II receptors are there
two
angiotensin II receptor 1 or 2 ATR1 or ATR2
what are angiotensin II receptors
GPCRs
Gq-coupled
inc intracellular calcium ions
IP3 can interact with the IP3 receptor on the _____ to release calcium ions
sarcoplasmic reticulum, inc caclium ions intracellularly
what do hypertension drugs target - 2
block angiotensin II receptors directly, thus intracellular calcium ions
stop production of angiotensin II/ binding of agonist via angiotensin II receptor antagonists
(can also use ACE inhibitors to prevent conversion of angiotensin 1 to 2)
examples of angiotensin II receptor antagonists - 4
competitive:
losartan
valsartan
irbesartan
non competitive:
candesartan
drugs ending in sartan
ART antagonists
candesartan mechanism of action
candesartan cilexitil undergoes rapid conversion to candesartan
metabolism in liver and GI tract prior to liver - hydrolytic reaction in intestinal wall
candesartan can interact with ATR receptors
candesartan is a prodrug administered as
candesartan cilexitil
angiotensin converting enzyme inhibitor examples - 4
enalapril
lisinopril
ramipril
captopril
drugs ending in PRIL
ace inhibitor drugs
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