Drugs and the Cardiovascular System – The Heart Flashcards

1
Q

What is the major store of calcium within the cardiomyocyte?

A

Sarcoplasmic reticulum

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2
Q

The heart has two signalling pathways that are involved in elevating the level of two intracellular second messengers. What are these second messengers?

A

Ca2+ and cAMP

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3
Q

Which plasma membrane proteins allow calcium to enter the cell in response to depolarisation?

A

Dihydropyridine receptors

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4
Q

What happens to the calcium once it has passes into the cell viathis channel?

A

It binds to ryanodine receptors on the sarcoplasmic reticulum and cause calcium release from the SR

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5
Q

How does the calcium stimulate contraction?

A

It binds to troponin on the thin filament

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6
Q

What are the different ways in which calcium is removed from the myoplasm after it has stimulated contraction? Which method is responsible for the majority of calcium removal?

A

Plasma membrane calcium ATPase Na+/Ca2+ exchanger SERCA2a (sarcoendoplasmic reticulum calcium ATPase) –responsible for >70% of calcium removal

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7
Q

What features of contraction is SERCA2a responsible for andwhy?

A

Rate of calcium removal and so it’s responsible for the rate of cardiac muscle relaxation Size of calcium store, which affects the contractility of the subsequent beat

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8
Q

What regulates the action of SERCA2a and how does it do this?

A

Phospholamban (PLN) Phospholamban phosphorylation is stimulated by beta-adrenergic activity It is a target for phosphorylation by protein kinase A When dephosphorylated it is an inhibitor of SERCA2a When phosphorylated it dissociates from SERCA2a and activates the Ca2+ pump As a result, the rate of cardiac relaxation is increased and, on subsequent beats, contractility is in proportion to the elevation in the size of the SR calcium store

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9
Q

What is phospholamban dephosphorylated by?

A

Protein phosphatase 1

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10
Q

What are the three main channels that are responsible for the action potential in the sinoatrial node?

A

If channel – hyperpolarisation-activated cyclic nucleotide-gated (HCN) channel Calcium channel (T and L type) Potassium channel

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11
Q

Describe how these channels are responsible for the action potential of the sinoatrial node.

A

If channel is a sodium channel that opens at the most negative membrane potential Opening of the sodium channel causes sodium influx, which begins to depolarise the membrane and stimulates the opening of calcium channels, which further depolarises the membrane Potassium channels are responsible for repolarisation

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12
Q

What are beta adrenoceptors coupled with?

A

Adenylate cyclase – it increases cAMP, which is important in the opening of the If channel to begin depolarisation

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13
Q

How does the parasympathetic nervous system affect heart rate and contractility?

A

It is negatively coupled with adenylate cyclase

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14
Q

What are the determinants of myocardial oxygen supply?

A

Arterial oxygen content Coronary blood flow

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15
Q

What are the determinents of myocardial oxygen demand?

A

Heart rate Contractility Preload Afterload

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16
Q

What effect do beta-blockers and calcium channel blockers haveon the channels responsible for the SA node action potential?

A

Beta-blockers decrease If and calcium channel activity Calcium channel blockers only decrease calcium channel activity

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17
Q

Name a drug that decreases If activity.

A

Ivabradine (blocks the If channel)

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18
Q

What effect does this drug have on contractility?

A

It has no effect on contractility because it doesn’t affect the calcium channels

19
Q

What are the two types of calcium channel blocker? Name the drugs in each category including their drug class.

A

Rate slowing Phenylalkylamines – verapamil Benzothiazepines – diltiazem Non-rate slowing Dihydropyridines – amlodipine

20
Q

What is a consequence of non-rate slowing calcium channel blockers?

A

Reflex tachycardia (baroreceptor reflex)

21
Q

How do organic nitrates cause vasodilation?

A

Organic nitrates are substrates for nitric oxide production The NO then diffuses into the smooth muscle and causes smooth muscle relaxation by activating guanylate cyclase They are often in angina patients before they exercise

22
Q

How do potassium channel openers work?

A

They open the potassium channels and hyperpolarise the vascular smooth muscle so that it is less likely to contract

23
Q

How do vasodilation and venodilation reduce myocardial oxygen demand?

A

They reduce the pressure against which the heart is pumping (reduce afterload) and it also causes reduce venous return to the heart (reduced preload) meaning that contractility is decreased

24
Q

As these drugs reduce the myocardial oxygen demand, what condition can they all be used to treat?

A

Angina pectoris

25
Q

State some unwanted effects of beta-blockers.

A

Bradycardia Hypotension Hypoglycaemia in diabetics on insulin Cold extremities (because of beta-2 blockade) Bronchoconstriction Fatigue Impotence Depression CNS effects

26
Q

Under what circumstance must caution be taken when giving beta-blockers?

A

Cardiac failure – because they reduce heart rate and contractility it can have catastrophic consequences in cardiac failure patients

27
Q

What are the side effects of verapamil?

A

Bradycardia and AV block Constipation

28
Q

What are the side effects of dihydropyridines?

A

Ankle oedema Headaches/flushing Palpitations

29
Q

What is a simple classification of arrhythmias?

A

Based on its point of origin Supraventricular, Ventricular and Complex

30
Q

What is the main classification of anti-arrhythmic drugs and how are the drugs ordered?

A

Vaughan-Williams classification I – sodium channel blockers II – beta-blockers III – prolongation of repolarisation (mainly due to potassium channelblockade) IV – calcium channel blockers

31
Q

What is adenosine used to treat?

A

It is used to terminate supraventricular tachycardia

32
Q

How does adenosine work?

A

Adenosine binds to adenosine receptors in the cardiac muscle and vascular smooth muscle Adenosine receptors are negatively coupled with adenylate cyclase Reducing the cAMP in nodal tissue will impact on depolarisation within the AV node

33
Q

What is verapamil used to treat?

A

Supraventricular tachycardia Atrial fibrillation

34
Q

What is the target of verapamil and how does it work?

A

L-type calcium channel Reducing calcium entry means that the speed with which the tissue is depolarise is reduced

35
Q

What is amiodarone used to treat?

A

Supraventricular tachyarrhythmia Ventricular tachyarrhythmia

36
Q

How does amiodarone work?

A

It works by blocking many ion channels Its main effect seems to be through potassium channel blockade This prolongs repolarisation, so you’re prolonging the time during which the tissue can’t depolarise

37
Q

Describe re-entry.

A

Some damaged cardiac tissue will make it difficult for depolarisation to pass through it in one direction, but it will allow the action potential to propagate in the opposite direction This could mean that you get a miniature circuit set up within the tissueand you get re-entry of action potentials

38
Q

What is the target of cardiac glycosides like digoxin?

A

Na+/K+ ATPase

39
Q

How does digoxin work and what are its effects on the heart?

A

By blocking Na+/K+ ATPase it causes an accumulation of Na+ in the cell The excess Na+ is then removed by Na+/Ca2+ exchanger, thus increasing the intracellular calcium concentration This has an inotropic effect It also causes vagal stimulation, which has a chronotropic effect

40
Q

What is an important factor to consider before starting treatment with digoxin?

A

Hypokalaemia Digoxin binds to the potassium binding site on the extracellular component of Na+/K+ ATPase so it competes with potassium for the binding site If hypokalaemic, there is less competition for digoxin and so the effects of digoxin are exaggerated

41
Q

What is digoxin used to treat?

A

Atrial fibrillation Atrial flutter

42
Q

What is an adverse effect of digoxin?

A

Dysrrhythmia

43
Q

What are cardiac inotropes? Name two.

A

They increase the contractility of the heart (it is used in acute heart failure in some cases) Dobutamine (beta-1 agonist) Milrinone (phosphodiesterase inhibitor)