Brainscape's Knowledge GenomeTM

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


See full index

Cardiovascular > Pharmacology 1 > Flashcards

Pharmacology 1 Flashcards

1
Q

What is phase 0, 3 and 4 of the action potential in nodal tissue of the heart? (3)

A
  • Phase 0 - Depolarisation, calcium influx via L-type Ca+ channels (ICAL)
  • Phase 3 - repolarisation, inactivation of L-type Ca+ channels and activation of K+ channels causing K+ efflux (delayed rectifier K+ current)
  • Phase 4 - pacemaker potential, decrease in K+ efflux, funny current and transient T-type Ca+ channel influx
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What membrane potential value does upstroke head towards? Downstroke?

A

Positive

Negative

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

Why is downstroke not maintained in pacemaker cells?

A

Pacemaker potential - depolarisation towards threshold

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

What is determined by pacemaker potential slope? (2)

A

HR and AP frequency

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

Why is the AP not very tall in nodal tissue?

A

Background currents act against Ca+ channels (outward movement of positive charge)

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

How are funny current channels activated?

A

Negative membrane potentials (hyperpolarisation)

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

Why is action potential generated far more quickly in atrial and ventricular myocytes than in nodal tissue?

A
  • It is the opening of Na+ channels that causes depolarisation in cardiac myocytes
  • Na+ channels open much more quickly than Ca++ channels
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is another name for phase 4 - resting membrane potential?

A

Diastolic potential

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

What is phase 2 (plateau) a balance between?

A
  • Inward Ca+ current that slowly inactivates

* Outward K+ current that slowly activates

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

Can another AP be fired during plateau?

A

No, as NA+ channels are inactivated

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

What is the purpose of plateau?

A

Provides calcium which drives cardiac contraction

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

Why is long duration of plateau beneficial?

A

Stops heart beating too rapidly

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

What does phase 3 involve in cardiac myocyte action potentials?

A

Repolarisation via activation of 2 K+ channels:

  • Inward rectifier K+ current
  • Delayed rectifier potassium current
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What do noradrenaline (post-ganglionic transmitter) and adrenaline (adrenomedullary hormone) activate?

A

B1 adrenoceptors in (i) nodal cells and (ii) myocardial cells
(sympathetic)

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

What does activation of B1 adrenoceptor by adrenaline/noradrenaline result in?

A

Coupling through Gs protein activates adenylyl cyclase to increase [cAMP]

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

What is the role of adenylyl cyclase?

A

Conversion of ATP to cAMP

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

What does increased [cAMP] result in? (7)

A
  • Positive chronotropic effect
  • Positive inotropic effect
  • Decrease in AV nodal delay (positive dromotropic effect)
  • Increase in automaticity
  • Decrease in duration of systole (positive lusitropic effect)
  • Increase in activity of Na/K ATPase pump
  • Increase in mass of cardiac muscle (cardiac hypertrophy)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

How does noradrenaline/adrenaline increase pacemaker potential slope?

A

Via enhanced funny current and Ca+ current

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

How does sympathetic system increase heart rate (positive chronotropic effect)? (2)

A
  • Increase in pacemaker potential slope

* Reduction in threshold for AP generation

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

How does noradrenaline/adrenaline reduce threshold for AP generation?

A

Enhanced Ca+ current

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

How does sympathetic system increase contractility (positive inotropic effect)? (2)

A
  • Increase in phase 2 of AP in atrial and ventricular myocytes (enhanced Ca+ influx)
  • Sensitisation of contractile proteins to Ca+
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

How does sympathetic system decrease AV nodal delay (positive dromotropic effect)?

A

Enhancement of funny current and calcium influx

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

What is automaticity?

A

Tendency for non-nodal regions to exhibit spontaneous activity

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

How does sympathetic system decrease duration of systole (positive lusitropic action)?

A

Due to increased uptake of Ca++ into SR

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

What is the importance of sympathetic system increasing the activity of Na/K?ATPase pump?

A

Important for repolarisation

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

Why is positive lusitropic action advantageous in sympathetic stimulation?

A

To allow for complete relaxation (refilling) of ventricle before next contraction occurs

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

What does acetylcholine (post-ganglionic transmitter) activate?

A

M2 muscarinic cholinoceptors in nodal cells (parasympathetic)

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

What does activation of M2 muscarinic receptor by acetylcholine result in?

A

Coupling through Gi protein:

(i) decreases activity of adenylyl cyclase and reduces [cAMP]
(ii) opens potassium channels (GIRK) to cause hyperpolarization of SA node

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

What does reduced [cAMP] and opening of GIRK channels result in? (3)

A
  • Negative chronotropic effect
  • Negative inotropic effect (atria only)
  • Negative dromotropic effect (increase in AV nodal delay)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

How does parasympathetic system decrease heart rate (negative chronotropic effect)? (3)

A
  • Decreased slope of pacemaker potential
  • Hyperpolarisation caused by opening of GIRK channels
  • Increase in threshold for AP generation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

How does parasympathetic system decrease pacemaker potential slope? (2)

A

Reduced funny current and calcium influx

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

How does parasympathetic system increase threshold for AP generation?

A

Reduced calcium influx

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

How does parasympathetic system cause a negative inotropic effect in the atria?

A

Decrease in phase 2 of cardiac AP (decreased Ca++ entry)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Why does negative inotropic effect (decrease in force of contraction) affect atria only?

A

Ventricles are only very sparsely innervated by parasympathetic NS - contraction largely unaffected

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

How does parasympathetic system cause a negative dromotropic effect? (2)

A
  • Decreased activity of voltage-gated Ca++ channels

* Hyperpolarisation via operino of K+ channels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

What can cause arrhythmias to occur in the atria?

A

Parasympathetic stimulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

What do vagal manoeuvres do? What are they used for?

A

(i) Increase parasympathetic output

(ii) Used in atrial tachycardia, atrial flutter and atrial fibrillation to suppress impulse conduction through AV node

38
Q

What are examples of vagal manoeuvres? (2)

A
  • Valsalva manoevre - activates aortic baroreceptors
  • Massage of bifurcation of carotid artery - stimulates baroreceptors in carotid sinus (not recommended as can cause stroke)
39
Q

What is pacemaker potential modulated by?

A

Funny current channels (depolarising)

40
Q

What are funny current channels activated by? (2)

A
  • Hyperpolarisation

* Cyclic AMP

41
Q

What are funny current channels called?

A

Hyperpolarisation-activated Cyclic Nucleotide-gated (HCN) channels

42
Q

How does hyperpolarisation lead to phase 4 (depolarisation) phase?

A

Activates HCN channels in SA node causing depolarisation

43
Q

What does blockage of HCN channels result in? (2)

A
  • Decreases pacemaker potential slope

* reduces HR

44
Q

What is an example of a drug used to block HCN channels? What is it used for?

A
  • Ivabradine

* Used to slow heart rate in angina to reduce O2 consumption and lower need for cardiac blood supply

45
Q

Is Ca++ influx into cytoplasm from L-type channels enough to trigger cardiac muscle contraction?

A

No, calcium must be amplified

46
Q

How is intra-cellular calcium amplified? How does this facilitate cardiac muscle contraction?

A
  • Ca++ influx into cytoplasm activates ryanodine receptor causing release of Ca++ from SR
  • Ca++ binds to troponin C, allowing cross bridge formation between actin and myosin
  • Contraction via sliding filaments
47
Q

How is relaxation of cardiac muscle caused? (6)

A
  • Repolarisation (phase 3)
  • Inactivation of L-type Ca++ channels
  • Ca++ efflux via Na/Ca exchanger 1 (NCX1)
  • Active sequestration of Ca++ into SR via Ca++ ATPase
  • Ca++ dissociates from troponin C
  • Cross bridges break resulting in relaxation
48
Q

What is NCX1?

A

Antiporter that moves Na+ into cell and Ca+ out

49
Q

What is Ca+ ATPase present in SR called?

A

SERCA

50
Q

How does B1 adrenoceptor activation modulate cardiac contractility? (6)

A
  • B1 adrenoceptor coupled to Gs protein which activates adenylyl cyclase
  • Adenylyl cyclase converts ATP into cAMP
  • cAMP activates protein kinase A which phosphorylates L-type Ca+ channel
  • Greater calcium influx, increased calcium-induced calcium release meaning greater force of contraction
  • PKA also phosphorylates contractile proteins making them more sensitive to calcium and enhancing contractility
  • Also phosphorylates phospholamban which increases pumping of Ca+ and thus rate of relaxation
51
Q

What is milrinone?

A

Phosphodiesterase inhibitor that is seldom used, except IV in acute heart failure

52
Q

What are examples of B-adrenoceptor agonists? (3)

A
  • Dobutamine
  • Adrenaline
  • Noradrenaline
53
Q

What are dobutamine, adrenaline and noradrenaline classed as?

A

Catecholamines

54
Q

What are the pharmacodynamic effects of dobutamine, adrenaline and noradrenaline? (2)

A
  • Increase in force of contraction, rate and cardiac output

* Decrease in cardiac efficiency (increased O2 consumption)

55
Q

What can increase in O2 consumption result in?

A

Can cause disturbances in cardiac rhythm e.g. arrhythmias

56
Q

What is adrenaline? How is it administered? What is it’s half life?

A
  • Mixed agonist acting on both a and B receptors
  • IM, SC or IV
  • plasma T 1/2 ~2min due to uptake/metabolism
57
Q

What is adrenaline used to treat?

A
  • Cardiac arrest (IV) as part of the advanced life support (ALS) treatment algorithm
  • Anaphylactic shock (IM)
58
Q

What are the effects of adrenaline?

A
  • positive inotropic and chronotropic actions (β1)
  • redistribution of blood flow to the heart - constricts blood vessels in the skin, mucosa and abdomen (α1)
  • dilation of coronary arteries (β2)
59
Q

What is Dobutamine? How is it administered? What is its half life? What is special about Dobutamine?

A
  • Selective B-adrenoceptor agonist
  • IV
  • plasma T 1/2 ~2 min due to uptake/metabolism
  • Causes less tachycardia than other B1 agonists
60
Q

What is Dobutamine used to treat?

A

Acute but potentially reversible heart failure e.g. following cardiac surgery, cariogenic shock, septic shock

61
Q

What do the physiological effects of B-adrenoceptor blockage depend on?

A

The degree to which sympathetic nervous system is activated

62
Q

What are examples of non-selective B-adrenoceptor antagonists? (2)

A
  • Propranolol

* Alprenolol (partial agonist)

63
Q

What are examples of selective B1-antagonists?

A
  • Atenolol
  • Bisoprolol
  • Metoprolol
64
Q

What are pharmacodynamic effects of non-selective B-adrenoceptor antagonists? (3)

A
  • At rest little effect on rate, force, CO, or MAP (agents with partial agonist activity increase rate at rest, but reduce it during exercise)
  • During exercise or stress rate, force and CO are depressed – reduction in maximal exercise tolerance
  • Coronary vessel diameter reduced, but myocardial O2 requirement falls, thus better oxygenation of the myocardium
65
Q

What are the pharmacodynamic effects of non-selective B-adrenoceptor partial antagonists?

A

B blockers with partial agonist will increase rate at rest but decrease rate during exercise

66
Q

What are clinical uses of B-adrenoceptor antagonists? (4)

A
  • Treatment of arrhythmias
  • Angina
  • Compensated heart failure
  • Hypertension
67
Q

What are examples of cardiac arrhythmias? (3)

A
  • Excessive sympathetic activity associated with stress, emotion, heart failure or MI can lead to tachycardia or activation of pacemakers outside of nodal tissue
  • Atrial fibrillation
  • Supraventricular tachycardia
68
Q

How are beta-blocker used to treat the different kinds of arrhythmia? (3)

A
  • Tachycardia or activation of non-nodal pacemakers - B-blockers decrease excessive sympathetic drive and restore normal sinus rhythm
  • Atrial fibrillation and supra ventricular tachycardia - b-blockers day conduction through AV node and restore sinus rhythm
69
Q

Why are beta-blockers used to treat compensated heart failure? Seems paradoxical?

A

LOW dose beta-blockers (e.g. Carvedilol) improve morbidity and mortality by reducing excessive sympathetic drive

70
Q

What are adverse effects of B-blockers? (6)

A
  • Bronchospasm
  • Aggravation of cardiac failure (but low dose b-blockers used in compensated heart failure)
  • Bradycardia
  • Hypoglycaemia
  • Fatigue
  • Cold extremities
71
Q

Why are agents like atenolol, bisoprolol and metoprolol preferred?

A

Less risk associated with B1 selective agents

72
Q

What is an example of a non-selective muscarinic ACh receptor antagonist?

A

Atropine (competitive antagonist)

73
Q

What are pharmacodynamic effects of non-selective muscarinic ACh receptor antagonists on the heart? (3)

A
  • Increase in HR in normal subjects – more pronounced effect in highly trained athletes (who have increased vagal tone)
  • No effect on arterial BP (resistance vessels lack parasympathetic innervation)
  • No effect on the response to exercise
74
Q

What are clinical uses for muscarinic ACh receptor antagonists in relation to the heart? (2)

A
  • Treatment of bradycardia (e.g. following MI)

* Treatment of anti cholinesterase poisoning

75
Q

Why do some practitioners recommend no less than 600 micrograms of atropine?

A

Low-dose atropine may paradoxically slow heart rate

76
Q

What is Digoxin?

A

Cardiac glycoside that increases contractility of the heart (inotrope)

77
Q

What is heart failure?

A

A cardiac output insufficient to provide adequate tissue perfusion

78
Q

What are causes of heart failure?

A

Any structural, or functional disorder, that impairs the ability of the heart to function as a pump

79
Q

What drugs enhance contractility of the heart?

A

Inotropic drugs (e.g. digoxin, dobutamine)

80
Q

What is the effect of inotropes on ventricular function curve?

A

Upward and leftward shift of ventricular function curve so SV increases at any given EDP

81
Q

How does digoxin increase contractility?

A

By blocking sarcolemma ATPase

82
Q

Explain how digoxin blocks the sarcolemma ATPase (Ca-ATPase) (4)

A
  • Blocks Na/K/ATPase pump meaning intracellular Na+ conc increases
  • Less drive for sodium to enter cell meaning sodium calcium pump is lost, resulting in increased intracellular Ca++
  • Increased storage of Ca++ in SR meaning increased calcium-induced calcium release
  • Increased contractility
83
Q

How does Digoxin block Na/K/ATPase pump?

A

Binds to a-subunit of Na/K/ATPase in competition with K+

effects can be dangerously enhanced by low plasma [K+] i.e. hypokalaemia

84
Q

What are the direct effects of digoxin on electrical activity of the heart? (2)

A
  • Shortens action potential and refractory period in atrial and ventricular myocytes (pro-arrhythmic)
  • Toxic concentrations cause membrane depolarization and oscillatory afterpotentials (due to Ca2+ overload)
85
Q

What are the indirect effects of digoxin on electrical activity of the heart? (2)

A

Increases vagal activity which:-

  • slows down SA node discharge
  • increases AV nodal delay (refractory period)
86
Q

What are clinical uses of digoxin? (3)

A
  • IV in acute heart failure
  • Orally in chronic heart failure
  • Heart failure with atrial fibrillation

Only used when other drugs do not help in reducing symptoms of heart failure

87
Q

What are adverse effects of digoxin? (6)

A
  • Excessive depression of AV node conduction (heart block)
  • Arrhythmias
  • Nausea
  • Vomiting
  • Diarrhoea
  • Disturbances of colour vision

Only used when other drugs do not help in reducing symptoms of heart failure

88
Q

What are other classes of inotropic drugs (other than digoxin)? (2)

A
  • Calcium-sensitisers e.g. Levosimendan

* Inodilators e.g. amrinone and milrinone

89
Q

What is the pharmacodynamics of levosimendan? (2)

A
  • Binds to troponin C in cardiac muscle sensitising it to Ca++ so increases cross bridge formation between actin and myosin and cardiac force
  • Opens K+ channels in vascular smooth muscle causing vasodilation (reduces after load and cardiac work)
90
Q

When is levosimendan used clinically?

A

Treatment of acute decompensated heart failure (IV)

91
Q

What are the effects of amrinone and milrinone (inodilators)? (4)

A
  • Inhibit phosphodiesterase in cardiac and smooth muscle cells so increase cAMP
  • Increase myocardial contractility
  • Decrease peripheral resistance
  • But WORSEN survival :O perhaps due to increased incidence of arrhythmias
92
Q

What are clinical uses of inodilators?

A

IV in acute heart failure (only used when no other treatment works cause can fucking worsen survival)

Cardiovascular (28 decks)

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