L15 - drug effects on the heart Flashcards
define myocardial infarction
heart attack
define heart failure
insufficient CO to match body’s needs
in what ways can drugs act to improve heart function
- act on heart muscle (pacemaker)
2 act on coronary arteries - act on other arteries and veins (reduce cardiac work)
how does PNS decrease HR
- releases ACh which acts on M2 receptors in SA node
- causes opening of K+ channels and hyperpolarisation
- also inhibits funny current
give example of drug that can increase HR
- muscarinic (M2) antagonists (atropine)
give example of drug that can decrease HR
anticholinesterases (ACEs) - increase [ACh] in synapse
what does ivabradine do
inhibits funny current slowing HR
independent of ANS
why is ivabradine a good treatment of angina & heart failure
decreases cardiac O2 demand
how does the SNS increase HR
- NA acts on B1 adrenoreceptors causing cAMP release, which activates PKA causing :
- increased HR (funny current)
- increased contractility (and SV, and therefore CO)
what is the effect of the SNS on funny current
- NA binding to B1 causes release of cAMP 2nd messenger
2. cAMP activates HCN channels (funny current is HCN channel)
does PNS or SNS dominate heart rate at rest?
PNS
describe the process of B1 activation increasing HR
processes lead to PKA release
- PKA phosphorylates Ca2+ channels opening them
- PKA phosphorylates phospholamban which causes increase Ca2+ uptake into SR
give examples of B1 agonists at the heart
dopamine/dobutamine (B1)
ispoprenaline (B1 & B2)
name the cardiac glycosides
digoxin
digitoxin
what do digoxin and digitoxin do
treat severe heart failure and atrial fibrillation by increasing contractility
describe digoxin mechanism of action on heart cells
- partially blocks Na/K ATPase pump which increases intracellular Na+
- means less Ca2+ is pumped out via antiport mechanism (of Na in, no gradient)
- increased Ca2+ uptake into SR
- during AP more Ca2+ can be released
- increased contractility
what is the late Na current? (late/Na)
the late / incomplete inactivation of Na channels after depolarisation
(more channels left open)
what causes late Na current
ischaemia / hypoxia causes increased [reactive oxygen species]
these act on /Na so it doesn’t fully inactivate
describe the effect of the late Na current
- increases [Na] due to more channels being open
- less Ca2+ out via Na antiport (no gradient for Na in)
- increases intracellular Ca2+
- leads to :
- myocardial stunning
- diastolic stiffness
what is diastolic stiffness
ventricles dont fully relax
less ventricular filling
-decreases CO
-increases cardiac work
what is myocardial stunning
when cardiac cells dont contract correctly
what does ranolazine do?
blocks late Na current
examples of Ca2+ blockers for heart
verapamil & diltiazem
effects of Ca2+ blockers on heart
decrease contractility, HR, cardiac work
vasodilation
what 2 ways can cardiac arrhythmias arise?
heart block
abnormal pacemaker
explain heart block
impulse blocked between SAN and ventricles
ventricles beat slowly
how can heart block be treated
pacemaker
explain arrhythmias caused by abnormal pacemaker
abnormal pacemaker arises outside SAN firing impulses and overriding SAN
causes discoordination and decrease in CO
define supraventricular arrhythmia
abnormal pacemaker has origin in atrial tissue/AV node
define ventricular arrhythmia
abnormal pacemaker has origin in ventricle
what can cause development of abnormal pacemaker?
ischaemia
structural abnormalities
what are the 2 basic strategies for arrhythmic drugs
- increase refractory period so less signals can be fired
2. suppress conduction in the zone of abnormal conduction
when is supressing conduction of abnormal pacemaker especially effective?
supraventricular tachycardia
