CVS 9.1 - Drugs and the Cardiovascular System Flashcards
1
Q
What is arrhythmia? What can cause arrhythmia?
A
- Abnormal heart rate or rhythm
- Atrial flutter
- Atrial fibrillation
- Ventricular fibrillation
- Tachycardia ([supra]ventricular)
- Bradycardia
2
Q
What can cause arrhythmias?
A
- Ectopic pacemaker activity
- After depolarisations
- Re-entry loops
3
Q
How can ectopic pacemaker activity cause arrhythmias?
A
- Damaged myocardium becomes depolarised
- Causes hidden pacemaker areas due to ischaemia that over power SAN
- Activates spontaneously
- Slower depolarisation so prolonged QRS complex
4
Q
What does an early ectopic pacemaker activity cause?
A
Increased myocyte excitability
5
Q
What does a late ectopic pacemaker activity cause?
A
Conduction failure
6
Q
What is an after depolarisation?
A
- Premature depolarisations after an action potential due to triggered activity
7
Q
What is triggered activity?
A
- Impulse initiation in cardiac fibres dependent on after depolarisation
- Another action potential is caused if threshold is reached leading to arrhythmia
8
Q
What can after depolarisations cause?
A
- Really long action potentials/ increased QT interval
- Increases intracellular calcium concentration
- Increases force of contraction
9
Q
How are re-entry loops caused?
A
- Conduction is blocked at a damaged area
- Unidirectional block = incomplete conduction damage
10
Q
How can re-entry loops cause arrhythmias?
A
- Excitation spreads in wrong direction through damaged area
- Causes a circuit looping back on itself
- Re-excites tissue in a circle
- Causes a circle of contractions = tachycardia
11
Q
What can multiple re-entry loops result in?
A
- Lots of small entry loops in atria
- Multiple foci
- Mitral stenosis = increased difficulty to fill
12
Q
What are the four groups of anti-arrhythmic drugs?
A
- Block vgNa+ channels
- Beta-adrenoceptor antagonists
- K+ channel blockers
- Ca2+ channel blockers
13
Q
What are some risk factors for arrhythmia?
A
- Age (more common in older age)
- Heart disease/attack
- Leaky/narrow valves
- High blood pressure
- Diabetes
- Sleep apnoea (heart doesn’t get enough O2 = stress)
- Over-under active thyroid
14
Q
How does bradycardia affect systemic circulation?
A
- Decreases cardiac output
- Decreases arterial pressure
15
Q
How does tachycardia affect systemic circulation?
A
- Decreased stroke volume
- Decreased cardiac output
- Decrease preload when contraction rate is high
16
Q
How does atrial fibrillation affect systemic circulation?
A
- Decreases stroke volume and cardiac output during exercise
- Increased risk of thrombus formation
17
Q
How does ventricular fibrillation affect systemic circulation?
A
Cardiac output is 0
18
Q
How are drugs blocking Na+ channels e.g. local anaesthetics, used to treat arrhythmias?
A
- Block vg Na+ channels when open/inactivated (use-dependent)
- Depolarisation needs to happen first
- Rapid dissociation means that the next normal action potential can happen
19
Q
Why do Na+ channel blockers only affect damaged areas rather than normal tissue?
A
- Damaged areas are depolarised
- Na+ channels are open during depolarisation
- Blocked by drugs as they are use dependent
- Ensures there is no automatic firing
20
Q
When would be an appropriate time for local anaesthetics to be used to treat arrhythmias?
A
- Ventricular tachycardia before/after myocardial infarction
- Administered intravenously
21
Q
How are beta adrenoreceptor antagonists used to treat arrhythmias?
A
- Block sympathetic action
- Block beta1 adrenoreceptor in the SAN
- Decreases pacemaker potential
- Negative chronotropy and inotropy
22
Q
What are the overall effects of beta adrenoreceptor antagonists?
A
- Decrease work load
- Decrease blood volume
- Decrease O2 demand therefore decreasing myocardial ischaemia
- Negative chronotropy and inotropy
23
Q
What are the effects on the heart in a beta adrenoreceptor antagonist acts on the AVN? When would this be an appropriate treatment?
A
- Slows AVN conduction
- During atrial fibrillation to prevent supraventricular tachycardia
24
Q
Why can’t propanolol be given to asthmatics?
A
- Non-selective for beta1 and beta2 adrenoreceptors
- Causes bronchoconstriction as well as decreasing HR and FOC
25
Why is atenolol a more appropriate treatment for asthmatics?
- Cardioselective for beta1
| - Doesn't cause bronchoconstriction
26
What is meant by a therapeutic use?
The use of a drug where the effects are beneficial
27
What is the action of K+ channel blockers in treating arrhythmias?
- Theoretically prolongs action potential therefore prolonging absolute refractory period
- Prevents another action potential from being generated too soon
28
What is the problem with using K+ channel blockers?
- Actually promotes arrhythmias
- More likely to happen during long action potentials
- Due to after depolarisations
- Causes another action potential if threshold is reached
29
Which K+ channel blocker can actually be used to treat arrhythmias and why?
- Amiodarone
| - Blocks other channels too which balances out effects
30
When would amiodarone be used?
Treatment of Wolff-Parkinson-White syndrome
31
What is Wolff-Parkinson-White syndrome?
- There is an extra electrical pathway between atria and ventricles
- Causes heart to beat really fast for periods of time (supraventricular tachycardia)
32
What is the action of Ca2+ channel blockers in treating arrhythmias when given intravenously?
- Block Ca2+ entry into the cell
- Decreases pacemaker potential at SAN
- Decreases AVN conduction
- Negative inotropy
- Vasodilation of some coronary and peripheral vessels
33
What is the significance of using dihydropyridines?
Only act on smooth muscle
34
Why are Ca2+ channel blockers given intravenously?
- Due to vasoconstrictive nature
| - Could cause tissue necrosis
35
When would Ca2+ channel blockers be used as treatment?
- Anti-hypertensive
- Arrhythmias
- Heart failure
- Angina
36
What is the general action of negative inotropic drugs?
- Decrease heart rate
| - Decrease force of contraction
37
What is the action of adenosine when given intravenously?
- Enhances K+ conductance at A1 receptors on AVN
- Hyperpolarisation of cell = further from threshold
- Restores sinus rhythm
38
What is heart failure?
Chronic failure of the heart to provide sufficient output to meet the requirements of the body
39
What are the effects of heart failure on the heart and circulation?
- Decreased force of contraction
- Decreased cardiac output
- Decreased perfusion
- Oedema (peripherally if RV fails)
40
Why does heart failure cause oedema?
- Causes venous congestion
| - Increases hydrostatic pressure
41
What can be used to treat heart failure?
- Positive inotropes to increase cardiac output
- Beta adrenoreceptor AGONISTS (cardiogenic shock)
- Cardiac glycosides (only if there's a lot of oedema and want to increase CO)
42
What is the action of cardiac glycosides?
- Block Na+K+ATPase
- Increases [Na+]in
- Increases [Ca2+]in
- NCX is more inefficient
- Increases force of contraction/ positive inotropy
43
Why can cardiac glycosides be used during heart failure and atrial fibrillation?
- Increase in vagal activity
- Slows AVN conduction
- Decreases heart rate
44
What are the overall effects of drugs used to treat heart failure?
- Decrease work load of the heart
- Decrease afterload and therefore TPR
- Decrease preload (venous return)
45
What is the general action of ACE inhibitors?
Inhibit the angiotensin converting enzyme
46
What is the renin-angiotensin-aldosterone system?
Hormonal regulation of blood pressure and fluid balance. It is up-regulated during heart failure
47
What is the first step of the renin-angiotensin-aldosterone system?
- Liver releases angiotensin (hormone)
- Kidney releases renin (enzyme)
- Renin cleaves angiotensin to form angiotensin 1
48
What stimulates the release of renin?
- Decrease in Na+ delivery to distal tubules
- Renal artery hypotension
- Beta1 agonism by the SNS
49
What is the second step of the renin-angiotensin-aldosterone system?
- Vascular endothelium in the lungs releases ACE (converting enzyme)
- ACE + Angiotensin 1 = angiotensin 2 forms
- Causes heart to work harder
50
What is the effect of angiotensin 2 in the zona glomerulosa of the adrenal glands?
- Stimulates aldosterone secretion
- Increases Na+ absorption
- Increases fluid which increases blood pressure
- Decreases K+ absorption
51
What is the effect of angiotensin 2 in the kidneys?
- Vasoconstriction in arterioles
- AT1 receptors are coupled to G-alphaQ proteins
- Follows IP3 pathway
- Increases blood pressure due to increased resistance
52
What is the action of ACE inhibitors?
- Prevent angiotensin 2 from forming
- Vasodilates arterioles in kidneys
- Venous dilation = decreased afterload (↓ vasomotor tone and ↓ blood pressure) and ↓preload (↓ fluid retention = ↓blood volume)
- ↓blood volume by ↓Na+ absorption in zona glomerulosa = ↓ preload (antihypertensive treatment)
53
Which three groups of drugs decrease the work load of the heart?
- ACE inhibitors
- Beta adrenoreceptor antagonists
- Diuretics
54
What is angina?
- Severe chest pain that spreads due to an inadequate coronary blood supply that is caused by atheromatous arteries
- Is transient and has no cell death (just ischaemia)
55
How can angina be treated?
- ↓ work load
- Beta adrenoreceptor blockers
- Ca2+ channel antagonists (improves blood supply)
- Organic nitrates (improves blood supply a little)
56
What is the action of organic nitrates?
- React with smooth muscle
- Releases NO2-
- NO2- is reduced to NO (produced by endothelium anyway)
- Causes vasodilation
57
How does NO cause relaxation of cardiac smooth muscle?
- Activates guanylate cyclase = ↑cGMP = ↓[Ca2+]in = activates protein kinase G = ↑[Ca2+] in SR
- Activates K+ channels = hyperpolarises the cell
- Stimulates a protein kinase for activation of MLCP = myosin light chain is dephosphorylated
58
What is the result of vasodilation of veins when organic nitrates are pharmalogically administered?
- ↓ preload = ↓ filling = ↓ work load
| - ↓ O2 demand
59
What can happen in the heart to increase the risk of thrombus formation?
- Atrial fibrillation
- Acute myocardial infarction
- Prosthetic heart valves
60
What is the action of anticoagulants and antiplatelets?
- Anticoagulations = thrombin/vitamin K inhibition
| - Antiplatelets = ↓ platelets
61
What are the effects of hypertension on circulation?
- ↑ arterial blood pressure
- ↑ total peripheral resistance
- ↑ Na+ and water uptake
62
What is the equation for pressure?
Pressure = Flow x Resistance
63
What is the equation for blood pressure?
Blood pressure = Cardiac output x Total Peripheral Resistance
