Session 9 - Drugs and CVS Flashcards
1
Q
What are ACE inhibitors?
A
-Drugs which inhibit angiotensin converting enzyme
2
Q
What is the function of angiotensin converting enzyme?
A
-Converts inactive angiotensin I to the active angiotensin II
3
Q
What is the function of angiotensin II?
A
- Act on the adrenal cortex to cause aldosterone secretion
- Vasoconstrictor
4
Q
What are ACE inhibitors used for?
A
- Heart failure to reduce work load
- Hypertension
5
Q
How do ACE inhibitors reduce the workload of the heart?
A
- Prevent the conversion of angiotensin I to angiotensin II
- Decreases Na reabsorption and thus water reabsorption decreasing blood volume-> reduces preload
- prevention of angiotensin II-> decreased vasomotor tone -> reduced afterload
6
Q
What types of cvs disorders are treated with drugs?
A
- Heart failure
- Angina
- Hypertension
- Arrythmias
- Risk of thrombus formation
7
Q
What types of actions can drugs have on the CVS?
A
- The rate and rhythm of the heart
- The force of myocardial contraction
- Peripheral resistance and bloodflow
- Blood volume
8
Q
Name the general types of arrythmias/dysrhytmias
A
- Bradycardia
- Atrial flutter
- Atrial fibrillation
- Tachycardia (ventricular or supraventricular)
- Ventricular fibrillation
9
Q
What are the three general causes of arrhythmias?
A
- Ectopic pacemaker activity
- Afterdepolarisations
- Re-entry loop
10
Q
What are the common causes of ectopic pacemaker activity?
A
- Damaged area of myocardium becomes depolarised and spontaneously active causing atrial and/or ventricular AP
- Latent pacemaker region activated due to ischaemia (dominates over SAN)
11
Q
What is an afterdepolarisation?
A
-Spontaneous, yet triggered, abnormal depolarisation following an action potential
12
Q
What are the causes of re-entry loops?
A
- Conduction delay (unidirectional block)
- Accessory pathway (Wolfe-Parkinson-White syndrome)
13
Q
What is a re-entry loop?
A
-Conduction block or accessory pathway causes electrical signal to take an alternative route to normal which becomes a self-sustaining circulating pathway as the electrical signal circles back upon itself
14
Q
What is the establishment of a re-entry loop dependant upon?
A
-The refractoryness of the cells and the timing as the electrical signal needs to find excitable tissue when it circles back on itself. If it can’t find excitable tissue the loop will not be entered
15
Q
What are the two types of re-entry loop?
A
- Global re-entry between atria and ventricles
- Re-entry within a local region
16
Q
What are the two kinds of afterdepolarisation?
A
- Delayed after depolarisation
- Early after depolarisation
17
Q
What type of Arrythmias do afterpolarisations cause?
A
-Atrial or ventricular tachycardia
18
Q
What is an early afterdepolarisation? What is there most likely cause?
A
- Occur during late phase 2 or phase 3 of an AP and usually leads to several rapid AP
- Caused by a prolonged duration of AP
19
Q
What is a delayed afterdepolarisation? what is the most associated cause?
A
- Occur when the AP is nearly or fully repolarised
- Associated with high intracellular Ca
20
Q
What syndrome characteristically has a prolonged action potential?
A
-Long QT syndrome
21
Q
How can re-entry loops lead to atrial fibrillation?
A
-If multiple small re-entry loops appear in the atria
22
Q
What are the 4 basic classes of antiarrhythmic drugs?
A
I) Voltage-sensitive Na channel blockers
II) B-blockers
III) Potassium channel blockers
IV) Calcium channel blockers
23
Q
Name a typical antiarrhythmic class I drug
A
-Lidocaine
24
Q
What is lidocaine and how does it work?
A
- Local anaesthetic
- Blocks voltage gated Na channels in the open or active state, ie it has use dependance
- Then dissociates rapidly in time to block the next AP
25
When is lidocaine used in the CVS and why?
- Used intravenously following MI if signs of ventricular tachycardia
- Tachycardia caused by areas of damaged myocardium which are depolarised firing AP spontaneously
- Lidocaine blocks the Na as they open upon firing as it is use dependant and prevents automatic firing of AP
26
Give examples of b-blockers (class II antiarrhythmics)
- Propranolol
| - Atenolol
27
What is the function of b-blockers?
-Block sympathetic action of b1-Adrenoreceptors in the heart and thus decrease HR and reduce the force of contraction
28
How do b-blockers decrease the HR and reduce force of contraction?
- NA acts on b1 adrenoreceptors which have Gas-> Gas stimulates AC and increases cAMP -> cAMP increased opening of HCN channels increasing slope -> increases HR
- Also increasing cAMP activates PKA which increases Ca entry during AP plateau, b1 adrenoreceptor activation also increases Ca uptake into SR and increases sensitivity of contractile machinery to Ca -> increases force of contraction
- blocking sympathetic activity will therefore reduce HR and contraction
29
When are B-blockers used?
- Heart failure to reduce workload
- Following MI to prevent ventricular arrhythmias -> MI causes an increase in sympathetic activity which can partly cause arrhythmias
- To reduce O2 demand of the heart following MI
- Slow AV conduction to prevent supraventricular tachycardias
30
How do b-blockers decrease the O2 demand of the heart?
-Reduced force of contraction -> reduced myocyte workload -> reduced O2 demand
31
Why are class III antiarrhythmic drugs used?
-To prolong AP and lengthen the absolute refractory period to prevent another AP occuring too soon
32
What are class III antiarrhythmic drugs?
-K+ channel blockers
33
Why are potassium channel blockers not generally used?
-Can be pro-arrhythmic
34
Why and when is amiodarome used even though it is a K channel blocker?
- It has other actions in addition to blocking K+ channels
| - Used to treat tachycardia associated with WPW syndrome
35
What is an example of a Ca channel blocker? (class IV antiarrhythmic)
-Verapamil
36
What is the aim and mechanism of action of verapamil?
- Blocks Ca channels to:
- Decreases slope of pacemaker action potential at SA node (takes longer to reach threshold) (decreasing HR)
- Decreases AV nodal conduction
- Decreases force of contraction
37
What do dihydropyridine Ca channel blockers act on?
-Vascular smooth muscle
38
What is the ultimate aim of diuretics?
-To reduce blood volume
39
What is the mechanism of adenosine when administered pharmacologically?
- Acts on A1 receptors of SAN to inhibit AC and decrease cAMP which decreases Ca channel opening and HCN channel opening -> slows conduction
- Slows AV node conduction
- Vasodilates coronary and systemic vessels
40
When is adenosine used and why?
-Rapid treatment of supraventricular tachycardias as it suppresses AV conduction
41
What is heart failure?
-Chronic failure of the heart to provide sufficient output to meet the bodys requirements
42
What are the features of heart failure?
- Reduced force of contraction
- Reduced cardiac output
- Reduced tissue perfusion
- Oedema
43
What are the two possible aims of drugs used in heart failure?
- Increase cardiac output (positive inotropes)
| - Reduce the workload
44
What two groups of drug are used to increase cardiac output in heart failure?
- Cardiac glycosides
| - B-adrenergic agonists
45
What is the aim of cardiac glycosides, in terms of treatment?
- Improve symptoms
| - Not a long term outcome
46
What is digoxin? What is it's mechanism of action?
-A cardiac glycoside -> blocks NaKATPase -> rise in intracellular Na-> Decreases activity of NCX as Na gradient depleted -> Ca not pumped out so accumulates in cell -> increase in SR store -> increases inotropy
47
Why can cardiac glycosides also be used in tachycardia?
-Increases vagal activity of the heart slows AV conduction and thus the HR
48
How do b-adrenoreceptor agonists increase cardiac output?
- Acts on b1 receptors by mimicing noradrenaline -> Gas -> AC-> increased cAMP-> acts on HCN channels -> increased inotropy
- Increased cAMP activates PKA-> PKA phosphorylates Ca2+ channels increasing opening and increasing Ca during plateau phase
- Activating b1 also increase Ca uptake into SR and increases sensitivity of contractile machinery to Ca -> increased chronotropy
49
-When are b1 adrenoreceptor agonists used?
- Cardiogenic shock
| - Acute but reversible heart failure (eg after surgery)
50
Why arent cardiac glycosides a long term soluteion?
-The heart is already damaged, making it work harder is not a long term solution
51
When does angina occur?
-When the o2 supply to the hear does not meet its need
52
What is angina?
-Ischaemia of the heart tissue due to narrowing of the arteries (atheromatous disease) causing chest pain
53
When is angina most commonly seen? why?
- Upon exertion
- Heart already under decreased blood supply as arteries narrowed -> increased exertion -> increases heart rate-> shortens diastole -> decreased filling of coronary arteries with increased o2 demand (do not fill properly due to increased resistance)-> o2 demand not met
54
What are the aims of treatment in angina?
- Reduce the workload of the heart to reduce o2 demand
| - Improve the blood supply to the heart
55
What drugs catagories can be used to decrease the workload of the heart?
- B-adrenoreceptor blockers (b-blockers)
- Ca2+ channel antagonists
- Organic nitrates
- ACE inhibitors
56
What drugs can be used to increase the blood supply to the heart?
- Organic nitrates (vasodilator)
| - Ca2+ channel antagonists
57
How do organic nitrates work?
- Organic nitrates react with thiold in vascular smooth muscle and cause NO2• to be released
- NO2• is reduced to No which is a powerful vasodilator
58
Name an organic nitrate
- Glyceryl trinitrate
| - Isosorbide dinitrate
59
How does NO cause vasodilation?
-NO activates guanylate cyclase-> increases cGMP -> lowers intracellular Ca -> relaxation of vascular smooth muscle
60
How do organic nitrates relieve symptoms of angina?
Primary action -> act on venous system to cause venodilation -> reduces venous pressure-> lowers preload of the heart as heart fills less and thus force of contraction decreased -> lowers O2 demand
Secondary action -> Acts on coronary arteries and improves o2 delivery to ischaemic myocardium (NB acts on collaterals to improve circulation rather than arterioles)
61
What heart conditions carry an increased risk of thrombus formation?
- Atrial fibrillation
- Acute myocardial infarction
- Mechanical prosthetic heart valves
62
What are the two groups of antithrombotic drugs?
- Anticoagulants
| - Antiplatelet
63
What is heparin?
-An anticoagulant which inhibits thrombin
64
What is warfarin?
- An anticoagulant which is used long term to antagonise the action of vitaminK
- Vit K is necessary for the synthesis of prothrombin in the liver
65
What is aspirin?
- An antiplatelet drug which inhibits platelet function by inhibiting the production of thromboxane (inhibits platelet aggregation)
- Used to prevent thrombus formation following an MI, or in high risk MI pts
66
What are the two causes of hypertension?
- Increased blood volume
| - Increased TPR
67
What are the possible aims to treat hypertension?
- Lower blood volume
- Lower cardiac output directly
- Lower peripheral resistance
68
Why can diuretics be used to treat hypertension?
-Reduce blood volume by preventing Na and water reabsorption
69
Why can ACE inhibitors be used to treat hypertension?
- Decrease Na and water retention by kidney
| - Decrease total peripheral resistance (vasodilation)
70
Why can b-blockers be used to treat hypertension?
-Reduce cardiac output
71
Why can Ca channel blockers selective for vascular smooth muscle be used to treat hypertension?
-Cause vasodilation by reducing intracellular calcium
72
Why can an a1-adrenoreceptor antagonist be used to treat hypertension?
-Blocks a1-adrenoreceptor activity -> reduces vasoconstriction
