Session 7- Cardiac Arrhythmias and CVS drugs

Question 1

ectopic pacemaker activity

Answer 1

damaged area of myocardium becomes depolarised and spontaneously active

latent pacemaker region activated due to ischaemia
-dominates over SA node

TACHYCARDIA

Question 2

early afterdepolarisations

Answer 2

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

Question 3

sinus bradycardia

Answer 3

sick sinus syndrome (intrinsic SA node dysfunction)

extrinsic factors such as drugs (beta blocker, some Ca2+ channel blockers)

Question 4

conduction block

Answer 4

• problems at AV node or bundle of His

- slow conduction at AV node due to extrinsic factors (beta blockers, some Ca2+ channel blockers)

Question 5

delayed after-depolarisations

Answer 5

delayed after depolarisation
can trigger activity
be self-perpetuating causing oscillations
more likely to happen if intracellular Ca2+ high
May involve Na+-Ca2+ exchanger

Question 6

rentrant mechanism for generating arrythmias

Answer 6

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

Question 7

atrial fibrillation

Answer 7

multiple re-entrant circuits in the area

it is possible to get several small re-entry loops in the atria

Question 8

woff-parkinson-white syndrome

Answer 8

an accessory pathway between atria and ventricles creates a re-entry loop

Question 9

drugs that block voltage-dependent Na+ channels

Answer 9

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

Question 10

lidocaine

Answer 10

give  intravenously
mild Na+ channel block
slows upstroke 
shortens AP 
slows conduction velocity

Question 11

beta-adrenoceptor antagonists

Answer 11

propanolol atenonol

block sympathetic action
-b1 adrenoceptor in heart

decrease slope of pacemaker potential in SA and slows conduction at AV node.

Question 12

when are beta-adrenoceptor antagonists used

Answer 12

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

Question 13

drugs that block K+ channels

Answer 13

anti-arrhythmics

prolong the AP

• mainly by blocking K+ channels
• lenghthens ARP

CAN BE PRO-ARRHYTHMIC- prolong QT interval

Question 14

amiodarone

Answer 14

block K+ channels
used to treat tachycardia associated with Wolff-Parkinson-White syndrome
Effective for suppressing ventricular arrhythmia post MI

Question 15

drugs that block Ca2+ channels

Answer 15

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

Question 16

adenosine

Answer 16

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

Question 17

ACE-inhibitors

Answer 17

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

Question 18

angiotensin II receptor blockers

Answer 18

in patients who cant tolerate ACEi can use AT1 receptor blocker

used in heart failure and hypertension

Question 19

diuretics

Answer 19

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

Question 20

positives inotropes

Answer 20

increase contractility and thus cardiac output

cardiac glycosides

beta adrenergic agonists

Question 21

cardiac glycosides

Answer 21

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

Question 22

action of glycosides on the heart

Answer 22

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

Question 23

beta adrenoceptor agonists

Answer 23

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

Question 24

treating heart failure

Answer 24

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

Question 25

nitrates in the treatment of angina

Answer 25

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

Question 26

how does NO cause vasodilation

Answer 26

it activates guanylyl cyclase
increases cGMP
lowers intracellular calcium
causes relaxation of vascular smooth muscle

Question 27

why do organic nitrates preferentially act on veins

Answer 27

mayve because there is ;ess endogenous nitric oxide in veins

at normal therapeutic doses it is most effective on veins

Question 28

how does NO help alleviate symptoms

Answer 28

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

Question 29

Anti-thrombotic drugs

Answer 29

certain heart conditions carry an increased risk of thrombus formation

• atrial fibrillation
• acute MI
• mechanical prosthetic heart valves

Question 30

anticoagulants

Answer 30

prevention of venous thromboembolism 
-heparin- intravenously 
  inhibits thrombin
-fractionated heparin
-warfarin
direct acting oral thrombin inhibitors such as dabigatran

Question 31

anti-platelet drugs

Answer 31

prevention of platelet-rich arterial thrombus formation

following acute MI or high risk of MI

• asprin
• clopidogrel

Question 32

Explain the effect of the pharmacological dose of

adrenaline on vessels

Answer 32

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.