Brainscape's Knowledge GenomeTM

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


See full index

LCRS Pharmacology and Therapeutics > Drugs and the cardiovascular system: The heart > Flashcards

Drugs and the cardiovascular system: The heart Flashcards

1
Q

What is the major store of calcium within the myocyte?

A

Sarcoplasmic reticulum

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

What are the two intracellular second messengers that the heart has two signalling pathways to elevate the levels of?

A

cAMP and Ca2+

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

What happens in terms of calcium in response to depolarisation?

A

It enters the cell through calcium channels in the plasma- dihydropyridine receptors

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

What happens once the calcium has entered the cell?

A

The calcium then goes on to bind to calcium release channels (ryanodine receptors) to stimulate calcium release from the sarcoplasmic reticulum

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

What does the calcium released from the sarcoplasmic reticulum do?

A

It 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
6
Q

How is the calcium removed from the myoplasm?

A

By plasma membrane calcium ATPase (PMCA) or Na+-Ca2+ exchangers both found on the plasma membrane

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

How is the calcium taken back up into sarcoplasmic reticulum?

A

Sarco-endoplasmic reticulum calcium ATPase (SERCA2a)

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

What percentage of removal of myoplasmic Ca2+ is SERCA2a responsible for?

A

> 70%

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

What does SERCA2a controlling the rate of Ca2+ removal consequently control?

A

Rate of cardiac muscle relaxation

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

What else does SERCA2a control?

A

Size of Ca2+ store which will affect cardiac contractility in subsequent beat

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

What regulates SERCA2a?

A

Its interaction with phospholamban (PLN)

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

What is phospholamban a target for?

A

Phosphorylation by protein kinase A via second signalling pathway

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

What are the two different forms of phospholambans and what effect do they have on SERCA2a?

A

Dephosphorylated- Inhibitory

Phosphorylated (by PKA)- PLN dissociates from SERCA2a activating Ca2+ pump

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

What dephosphorylates phospholamban?

A

Protein phosphatase (PP1) -This terminates the stimulation phase

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

What is the full name of If?

A

Hyperpolarisation-activated cyclic nucleotide-gated channel (HCN channels)

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

What is If commonly known as?

A

Funny channel

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

What is If?

A

It is a sodium channel that is responsible for allowing the action potential to propagate

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

When does If open?

A

At the most negative potential

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

What is the normal progression of depolarisation in terms of ions?

A

You initially have sodium influx then a certain amount of depolarisation and then the calcium channels open

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

What are the two forms of calcium channel?

A

T type= transient

L type= long lasting

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

What is responsible for repolarisation?

A

Potassium channels opening

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What effect do beta adrenoceptors have on If channel?

A

They are coupled with adenylate cyclase which causes an increase in cAMP which is important for opening the If channel

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

How does the sympathetic nervous system increase heart rate?

A

Via positive effect on If channel by causing increasing cAMP and also calcium entry

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

How does the parasympathetic nervous system have an effect on the heart?

A

It is negatively coupled with adenylate cyclase and promotes the opening of potassium channels and prolongs repolarisation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Why is relatively easy for myocardial oxygen demand to exceed supply?

A

The heart isn’t very well perfused

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What do coronary vessels deliver oxygen and nutrient based on?

A

How hard the heart is working

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What does how hard the heart is working depend on?

A

Heart rate
Preload
Afterload
Contractility

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What does increased venous return lead to and why?

A

Increased cardiac contractility because preload is linked to venous return

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What is an increase in afterload associated with?

A

Increase in TPR so heart has to work harder against it

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What effect do beta blockers have on the heart?

A

They block the amount of cAMP being produced which leads to reduced activation of If and calcium channels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What does the reduced activation of If and calcium channels lead to?

A

Reduced ability of SA node to depolarise

32
Q

What do beta blockers target?

A

If and Ica

33
Q

What do calcium channel antagonists target?

A

Ica

34
Q

What does ivabradine target?

A

If

35
Q

What do beta blockers and calcium antagonists reduce?

A

Cardiac contractility by their effect on calcium channels

36
Q

How do beta blockers reduce cardiac contractility?

A

Block beta receptors hence meaning that less cAMP is produced so there is less downstream signalling that promotes cardiac contractility

37
Q

How do calcium antagonists reduce cardiac contractility?

A

They block calcium channels in plasma membrane so the reduced influx of external calcium means there is also reduced release of calcium from the SR

38
Q

What are the two classes of calcium channel antagonists?

A 
Rate slowing (Cardiac and smooth muscle actions)
Non-rate slowing (smooth muscle actions- more potent)
39
Q

Give some examples of rate slowing CCAs

A

Phenylalkylamines e.g. verapamil

Benzothiazepines e.g. diltiazem

40
Q

Give an example of non-rate slowing CCAs

A

Dihydropyridines e.g. amlodipine

41
Q

What do non-rate slowing calcium channel blockers cause?

A

Reflex tachycardia

42
Q

What effect do rate slowing calcium channel blockers have?

A

They reduce heart rate and cause vasodilation

43
Q

Why do non-rate slowing ones like amlodipine cause reflex tachycardia?

A

Because they have no effect on heart but vasodilation occurs

44
Q

What are organic nitrates?

A

Substrates for nitric oxide production

45
Q

How does nitric oxide cause smooth muscle relaxation?

A

It diffuses from the endothelial cells to the vascular smooth muscle where it activates guanylate cyclase which causes relaxation

46
Q

What are organic nitrates often used to treat?

A

Angina (profound atherosclerosis reducing blood flow to the heart)

47
Q

When would you give organic nitrates to angina patients?

A

Before exercise because it dilates coronary vessels so blood flow is improved

48
Q

What effect do potassium channel openers have?

A

They promote potassium efflux so it’ll hyperpolarise the smooth muscle and reduce its ability to contract

49
Q

How does vasodilation decrease the amount of work that the heart has to do?

A

Vasodilation causes a fall in TPR which leads to a decrease in the afterload so the heart has to work against decreased resistance

50
Q

How does venodilation decrease the amount of work that the heart has to do?

A

Reduced venous return to the heart which causes reduced preload and contractility

51
Q

What are the unwanted effects of beta blockers?

A

Worsening of cardiac failure
Bradycardia- due to less conduction through AV node
Bronchoconstriction- blockade of b2 in airways
Hypoglycaemia (diabetics on insulin) (decreased glycogenolysis and gluconeogenesis)
Cold extremities and worsening of peripheral arterial disease
Fatigue
Impotence
Depression
CNS effects

52
Q

What are the side effects of verapamil (CCB)?

A

Bradycardia and AV block (Ca2+ channel block)

Constipation (Gut Ca2+ channels)- 25% patients

53
Q

What are the side effects of dihydropyridines? (CCB)

A

Ankle oedema- vasodilation means more pressure on capillary vessels
Headache/flushing- vasodilation
Palpitations

54
Q

How many people are affected by cardiac rhythm disorders in the UK?

A

700,000

55
Q

What are the three aims of arrhythmia treatment?

A

Reduce sudden death
Prevent stroke
Alleviate symptoms

56
Q

What is used to treat arrhythmia?

A 
Droogs
Cardioversion
Pacemakers
Catheter ablation therapy
Implantable defibrilators
57
Q

What is arrhythmia classification based on?

A

Site of origin

58
Q

What are the three types of arrhythmia?

A

Supraventricular (amiodarone and verapamil)
Ventricular (flecainide and lidocaine)
Complex (both)

59
Q

What is the Vaughan-Williams classification?

A 
Classification of anti-arrhythmic drugs based on where in the membrane potential they effect
Class 1- Sodium channel blockade
Class 2- Beta adrenergic blockade
Class 3- Prolongation of repolarisation
Class 4- Calcium channel blockade
60
Q

What is the relationship between adenosine and adenylate cyclase?

A

They are negatively coupled so less cAMP within nodal tissue and so it acts on the depolarisation within AV node

61
Q

What does verapamil target?

A

L-type calcium channels

62
Q

What effect does verapamil do?

A

Slows down ability of nodal tissue to depolarise

63
Q

How do CCBs restore normal contraction?

A

They block membrane calcium channels so there is less calcium entry so the speed at which a membrane can depolarise is reduced which restores normal contraction

64
Q

What does amiodarone do?

A

Prolongs repolarisation- by potassium channel blockade

65
Q

How does prolonging repolarisation restore normal rhythm?

A

It prolongs the time during which the heart can’t depolarise as you’re preventing re-entry

66
Q

What is the basis of arrhythmias?

A

If you have damaged cardiac tissue, action potentials can struggle to pass through but this struggle is only unidirectional so the action potential goes another way where there isn’t any resistance and so the action potential can pass back up the tissue and you get cyclical depolarisation

67
Q

What does digoxin and cardiac glycosides do?

A

Inhibit Na+/K+ pump

68
Q

Explain the mechanism of digoxin

A

It blocks the Na/K channel which leads to buikd up of Na+ in cell and K+ outside cell but another mechanism to remove Na+ is by a Na+/Ca2+ exchanger which causes increased calcium in the cell which binds to troponin more and causes inotropy, slowing down the heart and making it contract more effectively

69
Q

How does the Na/K channel normally work?

A

Na+ binds to intracellular component of channel and K+ binds to extracellular component and then the protein flip flops

70
Q

How does Digoxin act on the pump?

A

It accesses the pump from outside the cell (blood) and it interferes with the potassium binding site

71
Q

How does the potency of digoxin change in someone with hypokalaemia?

A

There is less competition between the potassium and digoxin so it has a far more powerful effect which leads to toxicity

72
Q

What else does digoxin have an effect on?

A

Vagal stimulation- stimulates parasympathetic innervation of heart so slows heart rate

73
Q

What is a common problem with atrial fibrillation?

A

Turbulent blood flow can lead to some being turbulent which can lead to static blood with a high risk of clots forming which can embolise and go to the brain and cause a stroke

74
Q

What are cardiac inotropes?

A

Agents that increase the force of cardiac contraction which are commonly used to treat acute heart failure

75
Q

What does dobutamine do?

A

It is a b1 agonist that stimulates cardiac contraction without a major effect on heart rate

76
Q

When would you use dobutamine?

A

If you were worried that the heart was going to fail in an acute setting

77
Q

What effect do phosphodiesterase inhibitors like milrinone have?

A

Inotropic effects by inhibiting the breakdown of cAMP in cardiac myocytes

LCRS Pharmacology and Therapeutics (33 decks)

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