Brainscape's Knowledge GenomeTM

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


See full index

Pharmacology and therapeutics > Drugs and the heart > Flashcards

Drugs and the heart Flashcards

1
Q

What do the cardiovascular drugs tend to target

A

Drugs affecting heart rate, contractility and myocardial oxygen supply

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

What is important to remember about depolarisation of the SA node

A

Depolarisation of SAN is largely Ca2+ mediated, as opposed to Na+ mediated
There are, in fact, no fast Na+ channels and currents operating in SA nodal cells.

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

Ultimately, how is coordination of contraction achieved

A

Coordination of contraction is achieved by a specialised conducting system. Normal sinus rhythm is generated by pacemaker impulses that arise in the sinoatrial (SA) node and are conducted in sequence through the atria, the atrioventricular (AV) node, bundle of His, Purkinje fibres and ventricles.

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

What are the ion channels found in the SA node

A

 If = hyperpolarisation-activated cyclic nucleotide-gated (HCN) channels – “funny” channels.- open when cell is most hyperpolarisaed and use cAMP to drive Na+ entry
o Predominantly a sodium channel.
 ICa (T or L) = Transient T-type Ca2+ channel or Long-lasting L-type.
o Mediates fast calcium influx.
 IK = Potassium channels.

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

Describe the generation of an action potential in the SAN

A

If- uses cAMP to drive sodium ion entry to initiate depolarisation (this starts the process, but full depolarisation is not achieved)
The current rises leading to transient and long-lasting Ca2+ channels opening- action potential reached (mostly by long-acting calcium channels)
-60- 0mV
Ik channel open, K+ efflux, repolarisation (inward directing K+ channels).

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

What is phase four in the SAN

A

Phase 4 is the spontaneous depolarization (pacemaker potential) that triggers the action potential
Mediated primarily by Ca2+ influx

Phase 0= Pacemaker potential — AP
Phase 3 – AP – hyperpolarisation

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

What is a key property of the SAN

A

Cells within the sinoatrial (SA) node are the primary pacemaker site within the heart. These cells are characterized as having no true resting potential, but instead generate regular, spontaneous action potentials.

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

What are the effects of the SNS on the SAN

A

Increased cAMP which increases If opening and direct effect on Ica channels- more likely to see depolarisation.

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

What are the effects of the PSNS on the SAN

A

Decreased cAMP, increased Ik
Less likely to see depolarisation.
Extend the length of time between depolarisaitons.

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

Describe the depolaristion of cardiomyocytes

A

Electrical excitation of the cell from action potentials arising from the sino-atrial node induce membrane depolarization that promotes gating of Ca2+ channels, which open and cause a small release of Ca2+ into the cytoplasm. The small Ca2+ current induces a release of Ca2+ from the SR by a process called Ca-induced Ca-release. The release occurs through Ca2+ release channels commonly referred to as ryanodine receptors (RyR2). Depolarization-induced influx of Ca2+ current (ICa) through the L-type channels contributes approximately 20–25% of the free Ca2+ in a cardiac twitch. The release of Ca2+ through the RyRs contributes the remaining 75–80% of Ca2+ necessary for cardiac contraction.

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

What plasma membrane protein allows calcium to enter the cell following depolarisation

A

Dihydropyridine receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
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 (mediated by adenylate cyclase)

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

How does the Ca2+ then initiate contraction

A

It binds to troponin on the thin filament - allowing the actin and myosin to bind together

(relaxation occurs when Ca2+ unbinds from troponin).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
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 (Na+/K+ ATPase maintains Na+ gradient)

SERCA2a (sarcoendoplasmic reticulum calcium ATPase) – responsible for >70% of calcium removal

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

What features of contraction is SERCA2a responsible for and why?

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

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

Essentially, what should there be a balance between in healthy heart function

A

Myocardial Oxygen supply and myocardial work (myocardial oyxgen demand)
Imbalance between supply and demand in angina

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

What are the determinants of myocaridal oxygen supply

A

Arterial oxygen content

Coronary blood flow (main determinant)

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

What are the determinants of myocardial oxygen demand

A

Heart rate

Contractility

Preload

Afterload

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

What is the primary determinant of myocardial oxygen demand

A

Myocyte contraction = primary determinant of myocardial oxygen demand
↑ H.R. = more contractions; ↑ afterload or contractility = greater force of
contraction; ↑ preload = small ↑ in force of contraction ( 100% ↑ ventricular
volume would only ↑ F.O.C. by 25%)

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

Why would an increase in preload and afterload increase myocarial contraction and thus myocardial work

A

Afterload- more resistance in vessels- heart needs to contract more forecefully to pump the blood into the vasculature.
Preload- Starling’s Law- more blood returned- heart needs to work harder to eject this volume (preload is linked to SV).

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

What are the main effects of the SNS on the heart

A

The main effects of the sympathetic nervous system on the heart are:

increased force of contraction (positive inotropic effect)
increased heart rate (positive chronotropic effect)
increased automaticity
repolarization and restoration of function following generalized cardiac depolarization
reduced cardiac efficiency (i.e. cardiac oxygen consumption is increased more than cardiac work)

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

How are the sympathetic effects on the heart achieved

A

These effects are largely due to activation of β1 adrenoceptors. Activation of β1 adrenoceptors stimulates adenyl cyclase resulting in production of cyclic AMP from ATP. This acts as an important intracellular messenger to increase intracellular Ca2+ (probably largely as a result of effects on L-type calcium channels and the sarcoplasmic reticulum) and stimulate Na-K ATPase in cardiac myocytes.

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

Describe the parasympathetic effects on the heart

A

Activation of the parasympathetic system results in:

Cardiac slowing and reduced automaticity
Inhibition of AV conduction

Cardiac work also depends on the load the heart experiences i.e. venous return (preload) or the impedance of the arterial circulation (after-load).

PSNS will reduce TPR, thus reducing afterload and thus cardiac work

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

What effect do beta blockers and calcium antagonists have on the channels responsible for SAN activation.

A

Beta-blockers decrease If and calcium channel activity

Calcium channel blockers only decrease calcium channel activity

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

Describe the effect of Ivabradine on heart rate

A

Blocks the If current
Less pronounced effect as only blocks Na+ entry, however it will still decrease the rate of depolarisation, thus increasing the ‘spacing’ between depolarisations, thus decreasing heart rate.

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

Which channels will calcium antagonists bind to

A

These agents act by binding to and inhibiting opening of L-type calcium channels.

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

What drugs affect contractility

A

β-blockers – Decrease contractility (reduced stimuli for calcium entry)- remember the effects of beta-1 adrenoreceptor stimulaiton

Calcium antagonists – Decrease Ica -less entry of Ca2+

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

What are the two classes of calcium antagonists

A

o Rate-slowing – cardiac + VSM:

§ Phenylalkylamines – Verapamil.

§ Benzothiazepines – Diltiazem.

o Non-rate slowing – VSM (more potent):

§ Dihydropyridines – Amlodipine

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

What is important to remember about non-rate slowing calcium antagonists

A

No effect on the heart. Profound vasodilation can lead to reflex tachycardia

This is due to the stimulation of arterial baroreceptors, which will decrease in firing rate- thus leading to increased HR to try and increase the BP

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

How do organic nitrates cause vasodiation

A

Organic nitrates are substrates for nitric oxide production

The NO then diffuses into the smooth muscle and causes smooth muscle relaxation by activating soluble guanylate cyclase (which converts GTP — cGMP)

This cGMP will lead to relaxation of the VSMC (dilation) and will also open K+ channels, leading to K+ efflux, hyperpolarising the cell, making it less favourable for Ca2+ to enter the VSMC and cause contraction.
Hence NO has direct and indirect effects to induce VSMC relaxation.
They are often in angina patients before they exercise

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

What other class of drugs can be used to cause vasodilation

A

Potassium Channel Openers

Hyperpolarise the cell to make it harder for Ca2+ to enter and cause contraction.

32
Q

What are the effects of organic nitrates and potassium channel openers on myocardial oxygen supply and demand

A

§ These drugs decrease preload/afterload (demand) and increase oxygen supply (increase blood flow):
o Vasodilation = decreased afterload (less TPR).
o Venodilation = decreased preload.v

33
Q

What is meant by stable angina

A

Cardiac stitch
Usually pain upon exercise- due to atherosclerosis which is usually fine for normal activities
However the coronary vessels cannot deliver enough oxygen to the cardiac myocytes upon exercise- leading to the pain (cardiac stitch).

34
Q

Summarise the treatment for stable angina

A

Nitrates and K+ channel openers (improve coronary flow, decrease afterload and preload)
Beta Blockers (decrease HR and contractility)
CCBs (same effects as Beta blockers if rate-slowing)
Ivabradine (reduce HR).

35
Q

Outline the NICE guidelines for the treatment of stable angina.

A

Offer a beta-blocker or CCB as first line treatment
if symptoms don’t improve- switch to the other or combine both
If these drugs cannot be tolerated (or are contra-indicated) consider:
ivabradine
a long-acting nitrate
nicorandil (K+ channel opener)

36
Q

What is important to remember about beta blockers and heart failure

A

Beta Blockers can worsen HF:
Reducing Q further (due to decreased HR and contractility)- HF is essentially the inability to match cardiac output to tissue need.
Beta 2 receptor blockade will reduce B2 mediated vasodiation, thus increasing TRP and hence afterload, making it harder for the heart to eject blood into the vasculature.

37
Q

Describe a key potential consequence of beta blockers causing bradycardia

A

Heart block – decreased conduction through AV node

38
Q

How can we overcome some of these side effects for beta blockers

A

Give non-selective Beta blockers (act on B1 and B2) with ISA (e.g pindolol). Under normal physiological conditions (when sympathetic activity is low)- Pindolol will agonise B-adrenoreceptors and thus will stimulate B2 receptors to cause vasodilation. Pindolol is also beneficial for patients with stabile angina as when the exercise. they will decrease cardiac work.

Give mixed beta and alpha blockers (carvedilol) which will give alpha 1 blockade thus giving an additional vasodilator property, reducing TPR.

39
Q

State the side effects of beta blockers

A

§ b-Blockers – mainly due to actions on b1 (sometimes on b2):
o Cardiac failure worsening (CO reduction) - b1.
o Bradycardia - b1.
o Bronchoconstriction - b2.
o Hypoglycaemia (watch in diabetics on insulin) - b2 glycogenolysis/gluconeogenesis.
o Cold extremities and peripheral artery disease worsening.
o (fatigue, impotence, depression and CNS effects (e.g. nightmares) – studies question validity).

40
Q

Which two conditions should you be look out for when giving beta blockers and why

A

Diabetes- B2 blockade can mask detection of hypoglycaemia ( thus inhibiting gluconeogenesis and glycogenolysis to increase blood glucose again)

Asthma- loss of B2 mediated bronchodilation will lead to bronchoconstriction.

41
Q

What are the different sympathetic effects on blood vessels

A

Depends on their location
If in skeletal muscle (B2 mediated vasodilation)

If in skin, mucous membranes and splanchnic area- alpha 1 mediated constriction.

42
Q

Explain why patients taking beta blockers suffer from cold extremities and worsening peripheral artery vascular disease

A

Loss of β2 receptor mediated cutaneous vasodilation in

extremities

43
Q

Which side effects of Beta Blockers are debated in the literature

A

Fatigue
Impotence (sexual dysfunction)
Depression
CNS effects (lipophilic agents) e.g. nightmares

RCTs question the validity of these side effects.

44
Q

What is important to remember about the side effect profile of CCBs

A

Not as dangerous as that of beta blockers.

45
Q

What are the side effects of rate-limiting calcium channel blockers

A

Verapamil
Bradycardia and AV block (Ca2+ channel block)
Constipation (Gut Ca2+ channels) – 25 % patients

46
Q

What are the side effects of non-rate limiting calcium blockers

A

Dihydropyridines – 10-20% patients
Ankle Oedema – vasodilation means more pressure on capillary vessels (gravity brings blood to extremities- vasodilation and force of gravity increase the pressure for blood in the capillaries to leak into the interstitium).
Headache / Flushing – vasodilation
Palpitations ( due to vasodilation triggering baroreceptor reflex and adrenergic activation- increasing HR +TPR).

K+ channel openers and organic nitrates will also have these side effects.

47
Q

Describe the scale of abnormalities in cardiac rhythym

A

Abnormalities of cardiac rhythm (arrhythmias/dysrhythmias) affect around 700,000 people in UK.

Arrythmias- beating too fast
Dysrhythmias- any rythym issue

48
Q

Appreciate the complex management of patients with abnormalities in cardiac rythym

A

Management is complex; usually undertaken by specialists ; and may involve cardioversion, pacemakers, catheter ablation therapy and implantable defibrillators as well as drug therapy

49
Q

Ultimately, what are the aims of management in patients with abnormalities in cardiac rhythm

A

Reduce sudden death
Prevent stroke ( as when the heart isn’t beating properly- it can increase the risk of clot formation, which can shoot off to the brain and cause a stroke).
Alleviate symptoms

50
Q

Describe the Vaughan- Williams classification

A

Vaughan-Williams classification
I – sodium channel blockers
II – beta-blockers (will prolong repolarisation and prevent depolarisation)
III – prolongation of repolarisation (mainly due to potassium channel blockade)
IV – calcium channel blockers (prolong plateau phase)

This is within the ventricular muscle

51
Q

What can arrhythmias be associated with

A

May be associated with decreased heart rate (bradyarrhythmias) or increased heart rate (tachyarrhythmias).

52
Q

What is a simple classification of arrhythmias

A 
Supraventricular arrhythmias (e.g. amiodarone, verapamil)- originating in the atria or AVN)
Ventricular arrhythmias (e.g. flecainide, lidocaine).
Complex (supraventricular + ventricular arrhythmias) (e.g. disopyramide).
53
Q

Why is the Vaughan-Williams classification not that useful clinically

A

The drugs described have a mixture of mechanisms and don’t fall into a particular class.

54
Q

What is the use of adenosine

A

Used intravenously to terminate supraventricular tachyarrhythmias (SVT). Its actions are short-lived (20-30s) and it is consequently safer than verapamil.

55
Q

Describe the effects of adenosine on cardiac nodal tissue

A

In cardiac tissue, adenosine binds to type 1 (A1) receptors, which are coupled to Gi-proteins. Activation of this pathway opens potassium channels, which hyperpolarizes the cell. Activation of the Gi-protein also decreases cAMP, which inhibits L-type calcium channels and therefore calcium entry into the cell. In cardiac pacemaker cells located in the sinoatrial node, adenosine acting through A1 receptors inhibits the pacemaker current (If), which decreases the slope of phase 4 of the pacemaker action potential thereby decreasing its spontaneous firing rate (negative chronotropy and dromotropy).

56
Q

Why are the effects of adenosine on cardiac nodal tissue useful to the treatment of arrhythmias

A

Reduces the ‘jerky’ set of depolarisations- if you slow the tissue down- you give it more chance to repolarise- increasing the likelihood of restoring normal rythym.

57
Q

Describe the effects of adenosine on VSMC

A

In coronary vascular smooth muscle, adenosine binds to adenosine type 2A (A2A) receptors, which are coupled to the Gs-protein. Activation of this G-protein stimulates adenylyl cyclase (AC in figure), increases cAMP and causes protein kinase activation. This stimulates KATP channels, which hyperpolarizes the smooth muscle, causing relaxation. Increased cAMP also causes smooth muscle relaxation by inhibiting myosin light chain kinase, which leads to decreased myosin phosphorylation and a decrease in contractile force. There is also evidence that adenosine inhibits calcium entry into the cell through L-type calcium channels.

58
Q

Describe the uses and mechanisms of action of Veramipril in arrhythmias

A

Uses:
Reduction of ventricular responsiveness to atrial arrythmias

Mechanism of action:
Depresses SA automaticity and subsequent AV node conduction
o Class IV anti-arrhythmic drug.
Block L-type Ca2+ channels, thereby decreasing the gradient of the pacemaker potential, slowing the rate of depolarisaion in the SAN and prolonging the conduction delay in the AVN. They also have negative inotropic effects by limiting the influx of Ca2+ during the plateau phase.

59
Q

What are the uses of amiodarone

A

superventricular and ventricular tachyarrhythmias – often due to re-entry

60
Q

Describe what happens in normal purkynje fibres in terms of normal AP propagation

A

In normal tissue (top panel of figure), if a single Purkinje fiber forms two branches (1 & 2), the action potential will travel down each branch. An electrode (*) in a side branch off of branch 1 would record single, normal action potentials as they are conducted down branch 1 and into the side branch. If branches 1 & 2 are connected together by a common, connecting pathway (branch 3), the action potentials that travel into branch 3 will cancel each other out.

61
Q

Describe re-entry

A

Reentry (bottom panel) can occur if branch 2, for example, has a unidirectional block. In such a block, impulses can travel retrograde (from branch 3 into branch 2) but not orthograde. When this condition exists, an action potential will travel down the branch 1, into the common distal path (branch 3), and then travel retrograde through the unidirectional block in branch 2 (blue line). Within the block (gray area), the conduction velocity is reduced because of depolarization. When the action potential exits the block, if it finds the tissue excitable, then the action potential will continue by traveling down (i.e., reenter) the branch 1. If the action potential exits the block in branch 2 and finds the tissue unexcitable (i.e., within its effective refractory period), then the action potential will die.

62
Q

Describe the importance of timing in cardiac re-entry

A

Therefore, timing is critical in that the action potential exiting the block must find excitable tissue in order for that action potential to continue to propagate. If it can re-excite the tissue, a circular (counterclockwise in this case) pathway of high frequency impulses (i.e., a tachyarrhythmia) will become the source of action potentials that spread throughout a region of the heart (e.g., ventricle) or the entire heart. Local sites of reentry may involve only a small region within the ventricle or atrium and can precipitate ventricular or atrial tachyarrhythmias, respectively.

63
Q

Which key factors can affect the likelihood of re-entry

A

Because both timing and refractory state of the tissue are important for reentry to occur, alterations in timing (related to conduction velocity) and refractoriness (related to effective refractory period) can either precipitate reentry or abolish reentry. For this reason, changes in autonomic nerve function can significantly affect reentry mechanisms, either precipitating or terminating reentry. Many antiarrhythmic drugs alter effective refractory period or conduction velocity, and thereby affect reentry mechanisms (hopefully abolish).

64
Q

What actually causes cardiac 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

65
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
o Class 1, 2, 3 and 4 – hence limited clinical importance.
Essentially, prolongs the AP and refractory period

66
Q

What are the adverse effects of amiodarone

A

Amiodarone accumulates in the body (t½ 10 - 100days)
Has a number of important adverse effects including:
photosensitive skin rashes
hypo- or hyper-thyroidism
pulmonary fibrosis

67
Q

What are the uses of cardiac glycosides (digoxin)

A

Atrial fibrillation and flutter lead to a rapid ventricular rate that can impair ventricular filling (due to decreased filling time) and reduce cardiac output.

Digoxin via vagal stimulation reduces the conduction of electrical impulses within the AV node. Fewer impulses reach the ventricles and ventricular rate falls.

68
Q

Describe the mechanism of action of digoxin

A

central vagal stimulation causes increased refractory period and reduced rate of conduction through the AV node
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 (positive)

69
Q

What are the adverse effects of digoxin and what can increase their toxicity

A

dysrhythmias (e.g. AV conduction block, ectopic pacemaker activity)

Note – if co-administered with diuretics (maybe to reduce BP), hypokalaemia may be present and can LOWER the threshold for digoxin toxicity – digoxin is a K+-receptor competitive antagonist and so low blood potassium means less competition and so the effects of digoxin are enhanced.

70
Q

What are the cardiac inotropes

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)
Glucagon

71
Q

Describe the administration of digoxin

A

oral

I.V rarely effective for rapid control of ventricular rate

72
Q

How is amiodarone administered

A

oral or I.V (I.V acts more rapidly)
has the advantage if causing little or no myocardial depression
requires hospital supervision
can also be used to treat paroxysamla supraventricular, nodal and ventricular tachycardias and ventricular fibrillation. It can also be used to treat tachyarrythmias associated with Wolff-Parkinson-White syndrome- whereas cardiac glycosides and veramipril cannot.

73
Q

What is a key difference between verampiril and adenosine

A

Veramipril preferable in asthmatics

Adenosine can be used after beta-blockers.

74
Q

What is adenosine

A

An endogenous mediator produced by the metabolism of ATP

75
Q

Describe the interactions of digoxin

A

Clinically important interactions occur with drugs that reduce digoxin excretion and tissue binding (e.g. amiodarone, verapamil) or agents that reduce plasma [K+] (e.g. diuretics).

76
Q

What are inhibitors of phosphodiesterase

A

Inhibitors of phosphodiesterase, the enzyme that metabolizes cAMP, such as milrinone, have inotropic effects but despite increasing cardiac function in heart failure actually impair survival and at present inotropes are not used in chronic heart failure.

Pharmacology and therapeutics (30 decks)

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