Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

*Y2 LCRS Pharmacology* > Cardiovascular System - Heart > Flashcards

Cardiovascular System - Heart Flashcards

1
Q

What are the secondary messengers for the two signalling pathways in the heart?

A

cAMP and Ca2+

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Briefly summerise how the heart contracts on a molecular level:

A
  • After depolarisation Ca2+ enters through dihydropyridine receptors
  • It then binds to the Ryanodine receptors to stimulate Ca2+ release from the sarcoplasmic reticulum
  • It then stimulates contraction by binding to troponin in the thin filament
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What happens to the calcium after it has stimulated contraction in the cardiomyocyte?

A
  • either:*
  • Removed from cell by Na+/Ca2+ exchangers or Plasma Membrane Calcium ATPase (PMCA)
  • or*
  • Taken back into the sarcoplasmic reticulum by Sarco-endoplasmic reticulum calcium ATPase (SERCA2a)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Which enzyme is responsible for the removal of >70% of myoplasmic Ca2+?

A

SERCA2a

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

How is the activity of SERCA2a regulated?

A

Phospholamban (PLN) - the target of phosphorylation by Protein Kinase A via the adrenergic receptor pathway

Dephosphorylated form: PLN inhibits SERCA2a

Phosphorylated form: PLN dissociates from SERCA2a activating it

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What happens to the activity of the Myocardium when beta-adrenergic activity increases, and by which pathway?

(explain each step)

A
  • More cAMP
  • More Protein Kinase A
  • More Phospholamban is phosphorylated and therefore dissociates from SERCA2a
  • More Ca2+ is pumped back into the sarcoplasmic reticulum

Therefore the rate of cardiac relaxation is increased

Contractility of subsequent beats is increased - due to increased size of SR Ca2+ store

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are the four main ion channels involved in regulating the sinoatrial action potential?

A

If - Funny Channel

ICa (T) - Transient T-type Ca2+ channel

ICa (L) - Long-lasting L-type Ca2+ channel

IK - K+ channel

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the If Channel?

What is its role in regulating the Sinoatrial action potential?

What ion does it transfer?

A

Funny channel:

Hyperpolarisation-activated cyclic nucleotide-gated channel

(HCN Channels)

Na+

Responsible for allowing the action potential to propagate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

When does the If channel open?

What does it do?

A

Opens at the most negative potential

Propagates the action potential by causing a certain amount of depolarisation before the calcium channels open

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Recall what a graph of the action potential of the Sinoatrial node looks like:

(Including which ion channels are open at specific periods)

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is the function of the Calcium channels in regulating the SAN AP?

A

They do the majority of the depolarisation

Transient first (T-type)

then

Long-lasting (L-type)

for the longest time obvs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the role of Potassium Channels in regulating the AP of the SAN?

A

They are responsible for repolarisation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

How does sympathetic stimulation effect the Action potentials of the Sinoatrial node?

A

Beta adrenoceptors are coupled with adenylate cyclase which increases cAMP

This is important in opening the If channel so with more cAMP the HR is increased

(cAMP is also responsible for increasing Calcium entry so also increases contractility)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How does Parasympathetic stimulation effect the Action Potential of the Sinoatrial node?

A

It is negatively coupled with Adenylate cyclase so reduces cAMP

It therefore promotes Potassium channel opening and prolongs repolarisation slowing the HR

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What four factors affect Myocardial Oxygen demand?

A

Heart rate

Preload

Afterload

Contractility

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Why does an increased preload increase myocardial oxygen demand?

A

Preload is linked to venous return

Higher venous return increases cardiac contractility

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

How does an increase in Afterload increase myocardial oxygen demand?

A

An increase in Afterload is associated with an increase in TPR so the heart has to work harder against the increased TPR

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are three classes of drugs that reduce HR to lower the Myocardial Oxygen demand?

What are their targets?

A

Beta blockers: If + ICa

Calcium channel antagonists: ICa

Ivabradine: If

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

How can myocardial Oxygen demand be reduced?

A

By lowering the Heart rate and reducing contractility

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

How do calcium antagonists reduce cardiac contractility?

A

They block Plasma membrane Calcium channels so the influx of external calcium is reduced

This also lowers the amount of Calcium-induced calcium-release

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are the two types of Calcium channel antagonists?

Where do they have their effects?

A

Rate-slowing - Cardiac and smooth muscle

e.g. Verapamil and Diltiazem

Non-rate slowing - Smooth muscle (more potent)

e.g. Amlodipine

22
Q

Why is a non-rate slowing Calcium channel antagonist not a good drug to give to reduce myocardial oxygen demand?

A

(Amlodipine) has no effect on the heart, but causes vasodilation

The leads to a reflex tachycardia so the O2 demand would actually increase

23
Q

How do Organic nitrates work as drugs?

A

Substrates for nitric oxide production - enter endothelial cells and promote NO production

NO diffuses into the vascular smooth muscle and relaxes it by activating guanylate cyclase

24
Q

What can organic nitrates be used to treat?

A

Angina when there is profound atherosclerosis reducing blood supply to the heart.

Given before exercise to dilate coronary vessels so blood flow is improved

25
Q

How do potassium channel openers work?

A

They promote potassium efflux, hyperpolarising the smooth muscle, reducing its ability to contract.

26
Q

How does Ivabradine affect Myocardial Oxygen demand?

A

Reduces HR - Reduced O2 demand

27
Q

How do Beta-Blockers affect Myocardial oxygen demand?

A

Decrease HR and Contractility - Reduced Demand

28
Q

How do Calcium Channel blockers affect Myocardial Oxygen Demand?

A

Decrease HR and Contractility - Reduced Demand

29
Q

How do Organic nitrates and K+ Channel Openers affect Myocardial Oxygen Supply and Demand?

A

Supply - Increase Coronary Blood Flow and Arterial O2 Content

  • Increased Supply

Demand - Venodilation decreases Preload and Vasodilation decreases Afterload

  • Reduced Demand
30
Q

What group of Patients should you be careful prescribing beta-blockers to?

A

Those with Heart Failure as they reduce HR and Contractility and can lead to death

31
Q

Why do you get side-effects with beta blockers?

A

Because they are not completely cardioselective; B1 receptors are present at multiple sites and they also have B2 effects

32
Q

Name five unwanted effects of Beta Blockers:

A

Worsening of Cardiac Failure

Bradycardia (Heart block - decreased conduction through AV node)

Bronchoconstriction (Blockafe of B2 in airways)

Hypoglycemia

Cold Extremities (B2 blockade in skeletal muscle vessels)

33
Q

What are the side effects of Calcium Channel Blocker Verapamil?

A

Bradycardia and AV block

Constipation (Gut Ca2+ channels)

34
Q

What are the side effects of Dihydropyridine Calcium Channel Blockers like Amlodipine?

A

Ankle Oedema - Vasodilation means more pressure on capillary vessels

Headache/Flushing - Vasodilation

Palpitations

35
Q

What are three simple classifications of Arrhythmias and what drugs may be used to treat them?

A

Supraventricular Arrhythmias (Amiodarone and Verapamil)

Ventricular Arrhythmias (Flecainide and Lidocaine)

Complex (Disopyramide)

36
Q

What is the Vaughan-Williams Classification?

A

Classification of Anti-Arrhythmic drugs based on their mechanism of action

37
Q

Where does each Class of Anti-Arrhythmic drugs effect on a Ventricular membrane potential?

A
38
Q

What is the mechanism of action of each class of antiarrhythmics?

A

1: Sodium Channel Blockers
2: Beta Adrenergic BLockade
3. Prolongation of repolarisation (Membrane stabilisation mainly due to potassium channel blockade)
4. Calcium Channel blockade

39
Q

What is Adenosine used to treat?

A

Used to terminate Supraventricular Tachyarrhythmias

40
Q

How does Adenosine work as an antiarrhythmic?

A

Adenosine binds to adenosine receptors on cardiac muscle and vascular smooth muscle

They are negatively coupled with adenylate cyclase so less cAMP is produced in the nodal tissue reducing chronotropy in the SAN

41
Q

Why is Adenosine considered safer than Verpamil?

A

Its actions are very short lived - 20-30s

42
Q

What is the main use of Verapamil as an antiarrhythmic?

A

Reduction of ventricular responsiveness to atrial arrhythmias

43
Q

What is the mechanism of action of Verapamil as an antiarrhythmic?

A

Targets L-Type Calcium Channels

Reduces ability of nodes to depolarise so can restore normal contraction in tachyarrhythmias

44
Q

What is a reentry arrhythmia?

A

When cardiac muscle is damaged an action potential may have difficulty passing through the damaged section

The damage usually only blocks propagation in one direction

A potential from another branch can then reenter from the other direction and cause cyclic depolarisation

45
Q

How may a reentry arrhythmia be treated?

A

Using Amiodarone - Prolonging repolarisation can prevent a reentry potential from propagating

(Using potassium channel blockade)

46
Q

How does Amiodarone work?

A

Complex multi-channel blockade - mainly through potassium channel blockade

Prolongs repolarisation and hence restores a normal rhythm

47
Q

What are the adverse effects of Amiodarone?

A

Photosensitive skin rashes

Hypo or Hyperthyroidism

Pulmonary Fibrosis

(Accumulates in body; t1/2 10-100 days)

48
Q

What does blocking the Na+/K+ ATPase in a cardiac myocyte with a Cardiac Glycoside like Digoxin lead to in terms of ion concentrations

What does this mean in terms of Contraction?

A

Na+ cannot leave cell and K+ cannot enter

  • Na+ builds up

Na+ is also removed via Na+/Ca2+

  • Ca2+ also builds up

So HR slows and Contractility is more effective

49
Q

What are the uses of Digoxin?

A

In treatment of Atrial Fibrillation and Atrial Flutter

  • Both lead to rapid ventricular rate and impair ventricular filling reducing cardiac output (can lead to clot formation)

Digoxin reduces conduction of impulses within AVN via Vagal stimulation so Ventricular rate falls

50
Q

When must you find out before giving Digoxin?

A

Plasma Potasssium levels

Hypokalemia leads to less competition on the Na+/K+ pump between Potassium and Digoxin and can lead to digoxin toxicity at lower doses

51
Q

Give an example of a Cardiac Ionotrope

A

Dobutamine

52
Q

When are Cardiac Ionotropes given?

A

When you need to increase the force of contraction in an acute setting

e.g. after Cardiac surgery or in cardiogenic and septic shock

*Y2 LCRS Pharmacology* (20 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions