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► Med Misc 01 > CVS S9 - Drugs and the CVS > Flashcards

CVS S9 - Drugs and the CVS Flashcards

1
Q

What are some of the cardiovascular disorders that drugs can be used to treat?

A 
Arrhythmias
Heart failure
Angina
Hypertension
Risk of thrombus formation
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2
Q

What about the cardiovascular system can drugs alter?

A

Rate and rhythm
Force of myocardial contraction
Peripheral resistance and blood flow
Blood volume

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3
Q

List the ways arrhythmias can arise?

A

Ectopic pacemaker activity
After-depolarisations
Re-entry loops

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4
Q

Explain how ectopic pacemaker activity can lead to arrhythmia

A

Damaged area of the myocardium can become spontaneously active

Latent pacemaker region due to ischaemia

This dominates over the SA node, causing arrhythmia

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5
Q

What are after-depolarisations?

Explain how after-depolarisations can lead to arrhythmia

A

Abnormal depolarisations following the action potenial thought to be caused by high intracellular Ca2+

This lengthened action potential causes an elongated QT interval (arrhythmia)

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6
Q

What is a re-entry loop?

A

Re-entry loops occur when excitation through a section of damaged myocardium is blocked from travelling in the normal direction (uni-directional block)

The excitation can spread through the surrounding myocardium and travel through the damaged myocardium in the wrong direction

This sets up a small circuit of excitation (re-entry loop) that can lead to arrhythmia

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7
Q

Give a typical example of how a condition caused by a re-entry loop occurs

A

Atrial fibrillation

Several small re-entry loops are set up in the atrial myocardium as a result of damage (E.g. being stretched over time)

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8
Q

What are the classes of anti-arrhythmic drug?

A

Voltage gated Na+ channel blockers
B-adrenoceptor antagonists
K+ channel blockers
Ca2+ channel blockers

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9
Q

Explain the action of voltage gated Na+ channel blocking drugs and give an example of a drug in this class

A

Normal AP firing is not stopped, but it prevents another AP being fired to soon after the previous AP

Channels in open or inactive states are blocked

The drug dissociates from the channels rapidly in time for the next AP

E.g. Lidocaine

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10
Q

Explain the action of B-adrenoceptor antagonist drugs and give an example of a drug in this class

Give an example(s) of drug(s) in this class

A

Block sympathetic action by blocking B1 adrenoceptors in the heart

This inhibits adenylyl cyclase/cAMP levels

This in turn decreases the slope of the SAN pacemaker potential, decreasing heart rate

E.g. Propanolol, atenolol (beta-blockers)

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11
Q

Give a common use of B-adrenoceptor antagonists

A

Used after an MI

Reduces sympathetic activity and slow the heart, decreasing O2 demand of the myocardium, reducing ischaemia

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12
Q

Explain the action of drugs that block K+ channels?

A

Blocking K+ channels slows repolarisation and lengthens the absolute refractory period preventing another AP from occuring to soon after the last AP

Hence heart rate is decreased

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13
Q

Why are K+ channel blockers not commonly used?

Give an exception and its use

A

Not generally used as they can be pro-arrhythmic

Amiodarone

Used to treat tachycardia related to Wolff-Parkinson-White syndrome (re-entry loop due to an extra conduction pathway)

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14
Q

Explain the action of Ca2+ channel blocking drugs and give an example of a drug in this class

A

They decrease the slope of the SAN pacemaker potential as well as decreasing AV nodal conduction and decreasing the force of contraction

They also cause some coronary and peripheral vasodilation

E.g. Verapamil

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15
Q

Give an example of an anti-arrhythmic drug that doesn’t fall into the 4 categories and explain its action

A

Adenosine

Acts on A1 receptors (Not Alpha 1, A the letter) at the AV node

This is a GPCR, adenosine inhibits adenylyl cyclase/cAMP levels leading to increased K+ conductance

This hyperpolarises cells in the conduction tissues

This causes the heart to ‘reset’

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16
Q

What is heart failure?

Give some of the main features

A

Chonic failure of the heart to provide sufficient output to meet the body’s needs

Reduced force of contraction
Reduced cardiac output
Reduced tissue perfusion
Oedema

17
Q

What are ionotropic drugs?

A

Drugs that affect the force of contraction of the heart

Can reduce or increase force of contraction

18
Q

What are the two types of positive ionotropic drugs?

A

Ionotropic drugs include:

  • Cardiac glycosides
  • B-adrenergic agonists
19
Q

Explain the action of cardiac glycosides and give an example of one such drug

A

E.g. Digoxin

Blocks Na+/K+ ATPase causing a rise in intracellular Na+

This leads to decreased NCX activity and rise in intracellular Ca2+ (more is stored in SR) leading to stronger contractions

Also increase vagal activity via the CNS:

  • Slows AV conduction
  • Slows HR
20
Q

Explain the action of B1-adrenergic agonists on the heart, give an example of one such drug

What are some of the uses of these drugs?

A

Acts on B1 receptors to increase SAN pacemaker potential slope and increase heart rate

Used to treat:

  • Cardiogenic shock
  • Acute but reversible heart failure (E.g. in a post-op scenario)
21
Q

What are the advantages and disadvantages to using positive ionotropic drugs to treat heart failure?

A

Increase the cardiac output, which alleviates symptoms

However making the heart work harder is not good long term

22
Q

When are negative ionotropic drugs used?

Give examples a class of drugs that is negatively ionotropic

A

To reduce the workload of the heart, often following MI to limit damage

B-adrenergic antagonists are negatively ionotropic

23
Q

What types of drugs can be used to reduce the workload of the heart?

A

ACE inhibitors
B-adrenergic antagonists
Diuretics

24
Q

What are ACE inhibitors?

A

Drugs that inhibit Angiotensin converting enzyme (ACE)

Prevent the conversion of angiotensin I to angiotensin II

25
Q

Explain the action of angiotensin II

A

Angiotensin II works by promoting aldosterone release from the zona glomerulosa of the adrenal cortex

This increases Na+ and water reabsorption

Also a vasoconstrictor

26
Q

Why are ACE inhibitors useful in the treatment of heart failure?

A

Decrease vasomotor tone (decrease blood pressure):
- Reduces afterload on the heart

Decreases fluid retention (decreases blod volume)
- Reduces pre-load on the heart

This reduces the workload of the heart

27
Q

What is angina?

A

Myocardial ischaemia (O2 supply to myocardium is insufficient)

Ischaemia of the myocardium leads to pain, usually on exertion

Can be due to narrowing of the coronary arteries (atheromatous disease)

28
Q

How is angina treated?

Give the drug classes that may be used

A

Reduce workload of the heart:

  • B-adrenoceptor antagonists
  • Ca2+ channel antagonists
  • Organic nitrates

Improve blood supply to the heart:

  • Organic nitrates
  • Ca2+ channel antagonists
29
Q

Explain the action of organic nitrates on the vasculature

A

Reaction of organic nitrates with thiols (-SH groups) in vascular smooth muscle causes NO2- to be released

NO2- is reduced to NO (nitric oxide)

NO is a powerful vasodilator

NO activates guanylate cyclase increasing cGMP

Lowers intracellular Ca2+

Causes relaxation of the vascular smooth muscle

30
Q

How does the action of organic nitrates alleviate symptoms of angina?

A

Primary action:

  • Reduces preload via venodilation
  • Heart fills less and force of contraction reduced (starling’s law)
  • Lowers O2 demand

Secondary action:

  • Action of coronary arteries improves O2 delivery to the ischaemic myocardium
  • Acts on collateral arteries not arterioles
  • Collateral arteries dilate causing blood to be diverted into ischaemic areas (perhaps bypassing the atheromatous plaque causing ischaemia)
31
Q

Why are anti-thrombotic drugs used?

Give examples of some cases when they might be used

A

Certain heart conditions can increase the risk of thrombogenesis

Eg.

  • Atrial fibrillation
  • Acute myocardial infarction
  • Mechanical prosthetic heart valves
32
Q

Give some examples of anti-thrombotic drugs

A

Anti-coagulants

Heparin:

  • Inhibits thrombin
  • Used acutely for short term action
  • Normally IV
  • Subcutaneous Fractionated Heparin can be given

Warfarin:

  • Antagonises action of Vit K
  • Can be used long term
  • Given orally
33
Q

What are the two major factors that can cause hypertension?

Express blood pressure as the product of a mathematical equation

A

Increased blood volume
Increased TPR

BP = Cardiac output x TPR

Analogous to

Pressure = Flow x Resistance

34
Q

What are the major drug targets for treating hypertension?

A

Lower blood volume (also lowers cardiac output)
Lower cardiac output directly
Lower peripheral resistance

35
Q

List the classes of drugs that can be used to treat hypertension and give the drug target(s) that they work on

A

Diuretics:
- Decrease blood volume (reduce Na+/water retention)

ACE inhibitors:

  • Decrease blood volume (reduce Na+/water retantion)
  • Decrease TPR (vasodilation)

B-adrenoceptor antagonists:
- Decrease cardiac output directly

Ca2+ channel blockers selective for smooth muscle:
- Decrease TPR (vasodilation)

A1 adrenoceptor antagonists:
- Decrease TPR (vasodilation)

► Med Misc 01 (35 decks)

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