Session 7- Cardiac Arrhythmias and CVS drugs Flashcards
ectopic pacemaker activity
damaged area of myocardium becomes depolarised and spontaneously active
latent pacemaker region activated due to ischaemia
-dominates over SA node
TACHYCARDIA
early afterdepolarisations
can lead to oscillations
more likely to happen if AP prolonged
Longer AP- Longer QT interval
TACHYCARDIA
a longer AP means there is more time for recovery of Ca2+ channels from inactivation. They need to be recovered to cause depolarisations
sinus bradycardia
sick sinus syndrome (intrinsic SA node dysfunction)
extrinsic factors such as drugs (beta blocker, some Ca2+ channel blockers)
conduction block
- problems at AV node or bundle of His
- slow conduction at AV node due to extrinsic factors (beta blockers, some Ca2+ channel blockers)
delayed after-depolarisations
delayed after depolarisation
can trigger activity
be self-perpetuating causing oscillations
more likely to happen if intracellular Ca2+ high
May involve Na+-Ca2+ exchanger
rentrant mechanism for generating arrythmias
block of conduction through damaged area region
incomplete conduction damage (unidirectional block)
-excitation can take a long route to spread the wrong way through the damaged area setting up a circus of excitation
atrial fibrillation
multiple re-entrant circuits in the area
it is possible to get several small re-entry loops in the atria
woff-parkinson-white syndrome
an accessory pathway between atria and ventricles creates a re-entry loop
drugs that block voltage-dependent Na+ channels
use dependent block. Only block voltage gated Na+
channels in open or inactive state- therefore preferentially blocks depolarized tissue
little effect in normal cardiac tissue because it dissociates rapidly
blocks during depolarization but dissociates in time for next AP
lidocaine
give intravenously mild Na+ channel block slows upstroke shortens AP slows conduction velocity
beta-adrenoceptor antagonists
propanolol atenonol
block sympathetic action
-b1 adrenoceptor in heart
decrease slope of pacemaker potential in SA and slows conduction at AV node.
when are beta-adrenoceptor antagonists used
used in supraventricular tachycardia to slow impulses getting to AV
-slows ventricular rate in patients with AF
used following MI
- MI causes increased sympathetic activity
- arrythmias may be partly due to increased sympathetic activity
- b-blockers prevent ventricular arrythmias
Reduce oxygen demand
- reduces MI
- beneficial following MI
drugs that block K+ channels
anti-arrhythmics
prolong the AP
- mainly by blocking K+ channels
- lenghthens ARP
CAN BE PRO-ARRHYTHMIC- prolong QT interval
amiodarone
block K+ channels
used to treat tachycardia associated with Wolff-Parkinson-White syndrome
Effective for suppressing ventricular arrhythmia post MI
drugs that block Ca2+ channels
non-dihydropyridine type - verapamil and diltazem
decreased slope of AP at SA node
slow conduction
also decreased force of contraction (negative intropy)
-plus some coronary and peripheral vasodilation
act on vascular smooth muscle- reduce calcium entry to smooth muscle which brings about relaxation therefore you get reducd TPR and reduced constriction therefore reduced BP and reduced afterload and reduced workload
adenosine
produced endogenously at physiological levels
can be administered intravenously
Acts on A1 receptors at AV node but has a short half life
Enhances K+ conductance
-hyperpolarises cells of conducting tissue
anti-arrhythmic
ACE-inhibitors
Inhibits the action of angiotensin converting enzyme
important in the treatment of hypertension AND heart failure
prevents conversion of angiotensin 1 to angiotensin 2
-angiotensin II acts on kidneys to increase Na+ and water reabsorption
-Angiotensin II is also a vasoconstrictor
ACEi can cause a dry cough- excess bradykinin
reduce afterload of heart, decreased fluid retention, decreased blood volume, reduced preload f heart, reduced workload of heart
angiotensin II receptor blockers
in patients who cant tolerate ACEi can use AT1 receptor blocker
used in heart failure and hypertension
diuretics
used in heart failure and hypertension
loop diuretics useful in congestive heart failure
-reduced pulmonary and peripheral oedema
block sodium potassium ATP exchanger
reduce NA+ RETENTION
lose more sodium in urine and water follows
positives inotropes
increase contractility and thus cardiac output
cardiac glycosides
beta adrenergic agonists
cardiac glycosides
have been used to treat heart failure but not useful in the long term
primary mode of action is to block Na+/K+ ATPase
Ca2+ is extruded via the Na+-Ca2+ exchanger
-driven by Na+ moving down concentration gradient. Leads to increase in [Na+] intracellularly
this leads to decrease in activity of Na/Ca exchanger causing an incease in Ca intracellularly, increased force of contraction
action of glycosides on the heart
cardiac glycosides also cause increased valgal activity
- action via central nervous system to increase valgal activity
- slows AV conduction
- slows HR
may be used in heart failure when theres arrhythmia
beta adrenoceptor agonists
selective b1-adrenoceptor agonist
stimulates b1 receptors present at SA node AV node and on ventricular myocytes
used in cardiogenic shock and acute but reversible heart failure
treating heart failure
cardiac glycosides dont have a long term benefit- making the heart work harder is not goof in the long run
better to reduce workload
ACE inhibitors or ARBs and diuretics better for heart failure
beta blockers can also reduce workload of the heart
nitrates in the treatment of angina
angina occurs when 02 supply of the heart does not meet its need
they react with thiols in vascular smooth muscle which causes No2- to be reduced to NO
NO is a vasodilator
how does NO cause vasodilation
it activates guanylyl cyclase
increases cGMP
lowers intracellular calcium
causes relaxation of vascular smooth muscle
why do organic nitrates preferentially act on veins
mayve because there is ;ess endogenous nitric oxide in veins
at normal therapeutic doses it is most effective on veins
how does NO help alleviate symptoms
primary action
action on venous system- venodilatation lowers preload
-reduces workload of heart
-heart fills less and therefore force of contraction reduced
-lowers o2 demand
also acts on coronary collateral arteries which improves o2 delivery to the ischaemic myocardium- NOT ARTERIOLES
Anti-thrombotic drugs
certain heart conditions carry an increased risk of thrombus formation
- atrial fibrillation
- acute MI
- mechanical prosthetic heart valves
anticoagulants
prevention of venous thromboembolism -heparin- intravenously inhibits thrombin -fractionated heparin -warfarin direct acting oral thrombin inhibitors such as dabigatran
anti-platelet drugs
prevention of platelet-rich arterial thrombus formation
following acute MI or high risk of MI
- asprin
- clopidogrel
Explain the effect of the pharmacological dose of
adrenaline on vessels
At high concentrations as used clinically, adrenaline will also activate α1 receptors, which causes vasoconstriction. At normal physiological concentration circulating adrenaline will preferentially bind to β2 adrenoceptors, which causes vasodilation, as circulating adrenaline has a higher affinity for β2 adrenoceptors than for α1 receptors.
