Pharmacology of Cardiac Contractility

Question 1

two ways drugs can effect cardiac contractility

Answer 1

directly- drugs that directly affect myocardial cells, usually by controlling intracellular calcium ions via voltage gated calcium channels o intracellular Na+, affecting sodium calcium exchange

indirect drugs drugs which effect heart contractility through changing vascular tone, determining cardiac contractility through changing preload and EDV

Question 2

examples of direct acting drugs

Answer 2

catecholamines, cardiac glycosides

Question 3

Examples of indirectly acting drugs

Answer 3

diuretics, ACE inhibitors

Question 4

2 main cardiac glycosides + difference between them

Answer 4

digoxin and ouabain

ouabain is shorter acting

Question 5

basic structure of cardiac glycosides

Answer 5

sugar moiety, a steroid and a lactone ring

Question 6

key cardiac affects of cardiac glycosides

Answer 6

cardiac slowing, reducing rate of conduction through AVN

increased force of contraction

disturbances in rhythm, especially block of AV conduction and increased ectopic pacemaker activity

Question 7

briefly, main mechanisms of action of cardiac glycosides

Answer 7

increased vagal activity and inhibition of sodium/potassium pump

Question 8

explain stages of the positive inotropic effect

Answer 8

1. glycosides binds to the extracellular alpha unit of the Na+/K+ ATPase
2. binding inhibits the pump
3. increased intracellular sodium concentration slows extrusion of calcium by reducing the inward directed sodium gradient for the sodium calcium exchanger
4. increased intracellular calcium stored in the SR and thus an increased amount of calcium released with each action potential

Question 9

explain use in treatment of atrial fibrillation

Answer 9

slows the AV conduction by increasing vagal activity

increases refractory period of the AVN, increasing the interval between impulses and the ventricular rate decreases, allowing time for diastolic filling

Question 10

main conditions treated

Answer 10

congestive heart failure, by increasing inotropic activity, meaning enough blood can be pumped round the body

Question 11

what are used alongside cardiac glycosides + why?

Answer 11

diuretics, which decrease extracellular potassium, which means there’s reduced competition at the binding site

Question 12

example of a catecholamine drug

Answer 12

dobutamine

Question 13

what is dobutamine used to treat?

Answer 13

acute but potentially reversible heart failure, such as after cardiac surgery

Question 14

dobutamine results

Answer 14

increase chronotropy and ionotropy, increasing cardiac output and cardiac oxygen consumption

Question 15

dobutamine mechanism

Answer 15

1. activates Gs proteins of B1
2. eventual activation of PKA, which phosphorylates the RAD subunit of the L type calcium channel increasing open state probability. This leads to an enhanced sarcoplasmic release of calcium, increasing contractility
3. PKA may phosphorylate troponin C, increasing calcium sensitivity
4. phosphorylates phospholamban, activates SERCA, more calcium taken up

increases heart rate by opening ion channels responsible for pacemaker currents in the SAN

Question 16

what are the limitations of dobutamine and adrenaline?

Answer 16

leads to an increase need for oxygen for the heart to contract

can’t be used in haemorrhage

can’t be used in myocardial infarction, where coronary arteries are blocked

can only be used for shock

Question 17

examples of adrenoreptor antagonists

Answer 17

propranolol and atenolol

Question 18

actions of adrenoreceptor antagonists

Answer 18

have the opposite effect to agonists, mainly reducing contractility by blocking sympathetic stimulation of beta receptors

Question 19

another name of adrenoreceptor antagonists

Answer 19

beta blockers

Question 20

beta blocker uses

Answer 20

used to manage abnormal heart rhythms and to protect the heart from a secondary myocardial infarction

treat hypertension

Question 21

explain propranolol and atenolol briefly

Answer 21

propanolol- blocks beta 1 and beta 2 equally, it has little effect on the heart rate at rest but reduces the effects of exercise and excitement

atenolol- beta 1 selective antagonists, used more commonly as it has fewer side effects, only targets the heart

Question 22

heart effects explained

Answer 22

blocks Gs coupled receptor, less cAMP

reduced Ca2+ entry into myocytes

decreased contractility and heart rate

decreased SERCA and Ca2+ stores

overall decreases chrontropy, inotropy, lusitropy and conduction velocity

Question 23

blood vessel effects explained

Answer 23

propranolol

inhibits Gs coupled receptor, less cAMP and PKA

PKA does not phosphorylate MLK so cannot cause smooth muscle relaxation, causing vasodilation

Question 24

arrhythmia definition

Answer 24

a group of conditions in which the heart beat is irregular, too slow or too fast

Question 25

examples of arrhythmias

Answer 25

tachycardia- heart rate is above 100 bpm bradycardia- heart rate is below 60bpm palpitations

Question 26

four main groups of arrythmias + examples

Answer 26

extra beats- premature atrial contractions, premature ventricular contractions supra ventricular tachycardias- atrial fibrillation, atrial flutter ventricular arrhythmias- ventricular fibrillation and ventricular tachycardia bradyarrthymias- bradycardia

Question 27

what causes arrhythmias?

Answer 27

problems with the electrical conducting system of the heart

Question 28

explain atrial fibrillation

Answer 28

an abnormal heart rhythm characterised by rapid and irregular beating which becomes longer or continuous over time thought to be due to fibrosis of the atria due to atrial dilation

Question 29

explain ventricular fibrillation

Answer 29

ventricles quiver rather then pumping normally due to disorganised electrical activity hypoxic myocardium forms hyper irritable myocardial cells that then may act as pacemakers, stimulating the ventricles

Question 30

explain ventricular tachycardia

Answer 30

monomorphic- increased automaticity of a single point polymorphic- abnormalities of ventricular muscle depolarisation

Question 31

what is heart block?

Answer 31

a disorder in the heart's rhythm due to a fault in the pacemaker which causes an obstruction in the electrical conduction system of the heart blockage normally occurs between the SAN and AVN or at or below the Bundle of His

Question 32

three types of heart block

Answer 32

first degree AV block- where electrical impulses from the cardiac atria to the ventricles pass through the AVN more slowly than normal- slowed conduction second degree- conduction block between the atria and ventricles, block of the AVN, where one or more atrial impulses fail to conduct third degree- complete block, where nerve impulse generated in SAN cannot propagate to the ventricles

Question 33

how does atrial fibrillation appear on an electrocardiogram?

Answer 33

absence of P wave irregular R-R interval due to irregular conduction of impulses from the ventricles

Question 34

ventricular fibrillation on ECG

Answer 34

irregular electrical activity with no discernible pattern no visible P waves, QRS complexes or T waves

Question 35

ventricular tachycardia on ECG

Answer 35

rate greater than 120 bpm at least three wide QRS complexes in a row

Question 36

different heart blocks on ECG

Answer 36

1st degree- regular rhythm, elongated PR 2nd degree- irregular rhythm/increasingly prolonged, more P waves than QRS 3rd degree- regular rhythm, lack of any apparent connection between P waves and QRS complexes

Question 37

sinus rhythm definition

Answer 37

any cardiac rhythm in which depolarisation of the cardiac muscle begins at the sinus node

Question 38

5 examples of anti dysrhythmics

Answer 38

lidocaine, propranolol, amiodarone, verapamil, adenosine

Question 39

explain lidocaine use and mechanism of action

Answer 39

used for ventricular arrhythmias binds to voltage gated sodium channels, acting as a competitive antagonist, preventing action potential generation stabilise the excitability of over excitable cells, thus act as membrane stabilising agents

Question 40

explain propranolol and mechanism of action

Answer 40

used to treat tachycardia binds to beta 1 adrenoreceptors and act as an antagonist, inhibiting sympathetic stimulation of the heart also thought to act similarly to lidocaine

Question 41

explain amiodarone and mechanisms of action

Answer 41

used to treat ventricular tachycardia, ventricular fibrillation and atrial fibrillation blocker of voltage gated potassium and calcium channels, this slows the conduction rate and prolongs the refectory period of SA and AV nodes also acts by blocking voltage gated sodium channels and as a beta blocker

Question 42

explain verapamil and mechanisms of action

Answer 42

treats supraventricular tachycardia calcium channel blocker, decreasing impulse conduction through the AV node, thus protecting the ventricles from atrial tachyarrhythmias- only respond to the main impulses also block calcium channels in smooth muscle found in blood vessels, causing them to dilate and thus can be used to treat high blood pressure and angina

Question 43

explain adenosine and mechanisms of action

Answer 43

treats supraventricular tachycardia causes transient heart block in the AVN, mediated by the A1 receptor, which inhibits adenyl cyclase, reducing cAMP and thus causing cell hyperpolarisation by increasing potassium efflux, subsequently inhibiting calcium current

Question 44

angina definition

Answer 44

chest pain or pressure usually due to not enough blood flow to heart muscle, usually due to obstruction or spasm of coronary arteries

Question 45

Vaughan Williams classification of drugs explained + examples

Answer 45

classification of cardiac drugs dependent on how they treat arrhythmias Class I- interfere with sodium channels, lidocaine class II- interfere with beta receptors, propranolol class III- interfere with potassium channels, amiodarone class IV- interfere with calcium channels, and affect AVN, verapamil, sotalol Class V- agents work by other or unknown mechanisms, adenosine, digoxin

Question 46

use of ouabain

Answer 46

blocks sodium potassium pump, which in turn prevents the movement of calcium due to the increase in intracellular sodium reducing the activity of sodium-calcium exchanger used to treat reversible heart failure as it increases contractility and vagal tone

Question 47

what anti muscarinic drug can also be used + explained?

Answer 47

atropine used for bradycardia and 2nd and 3rd heart blocks a competitive antagonist of nonselective muscarinic acetylcholine receptors, increasing firing of the SA and conduction through the AVN oppose actions of the vagus nerve

Question 48

secondary pacemaker explained

Answer 48

if the SAN is non functional, the AVN will take over pacemaker responsibility becoming the ectopic pacemaker of the heart

Question 49

vagal tone definition

Answer 49

the continuous nature of baseline parasympathetic action that the vagus nerve exerts