Cardiac-related pharmacology Flashcards
(137 cards)
1
Q
What are the two most important types of arrhythmia?
A
Supraventricular
Ventricular
2
Q
What does the QRS complex refer to?
A
The electrical activity of the heart
Nothing to do with the mechanical activity of the heart
3
Q
What does the P wave of the QRS complex represent?
A
Atrial depolarisation
4
Q
What does the QRS complex represent?
A
Ventricular depolarisation
5
Q
What does the T wave of the QRS complex represent?
A
Ventricular repolarisation
6
Q
What does the PR interval represent?
A
The beginning of atrial depolarisation to the onset of ventricular depolarisation
7
Q
Why is atrial repolarisation not shown in the QRS complex?
A
Hidden by the wave caused by ventricular depolarisation
8
Q
What is the most common form of arrhythmia?
A
Atrial fibrillation
Occurs in 5-10% of patients over 65 years of age
9
Q
What are the characteristics of atrial fibrillation?
A
Chaotic atrial activity
All atrial cells become independent pacemakers that fire at different times
Causing small areas to contract at the same time
10
Q
What are the causes of atrial fibrillation?
A
Chronic distention of atria
Systemic inflammation
11
Q
How does chronic distention of atria cause atrial fibrillation?
A
Mechanical pressure causes fibrosis, causing changes to the electrical connectivity
12
Q
How is atrial fibrillation spotted?
A
Lack of a P wave
Palpitations - chance findings
13
Q
How are is fibrillation normally discovered?
A
Through chance discoveries
Secondary morbidities like hypertension and CHF are normally the reason AF is detected
14
Q
What is the reason atrial fibrillation is so dangerous?
A
Thromboembolism
Stroke
Blot clot formation in the atria
Due to the stasis of blood
15
Q
Why do strokes develop in atrial fibrillation?
A
The irregular contraction of atria means the rate of successful contractions is decreased, and not enough force is created to move the clot
However, if the rhythm becomes normal and synchronised for a short period of time, the clot can travel and cause deadly consequnces
16
Q
What are the two main ways to inhibit blood clot formation?
A
Anticoagulants
Antiplatelets
17
Q
What is the primary anticoagulant used for inhibition of clot formation?
A
Heparin
18
Q
Where is heparin found?
A
Endogenously
19
Q
What is the primary anticoagulant used for inhibition of clot formation?
A
Warfarin
Vitamin K inhibitor
20
Q
Where is Warfarin found?
A
In nature
21
Q
When are wafarin and heparin respectively used?
A
Warfarin acts slow, and is used for long term monitoring of blood clots
Heparin is fast acting and is used in a thromboembolism crisis
22
Q
What is the major side effect of clot inhibitors?
A
Bleeding
23
Q
Why is there no natural receptor for warfarin in the body?
A
It is not endogenously produced
24
Q
How do we treat a warfarin overdose?
A
Injection of fresh frozen plasma
Contains all the coagulation factors you need
25
Why is it not advised to inject vitamin K upon warfarin overdose?
Takes a long time before the effect is observed
26
How do we treat heparin overdose?
Protamine, a positively charged nuclear protein, binds to the negatively charged heparin
Forms a complex which inhibits it from entering the circulation
27
How was the importance of platelets discovered?
Hiroshima victims presented with spontaneous bleeding without having low coagulation factors
Low platelet counts however
28
What is an important antiplatelet agent?
Aspirin
29
How does aspirin work?
Inhibits platelet aggregation
Blocks COX through irreversibly binding to it
30
Aspirin works at high concentrations more effectively than low concentrations
TRUE or FALSE
FALSE
Aspirin only works effectively in low concentration
31
Why does aspirin only work at low concentration?
COX inhibitors cause different effects in two different cells
In platelet cells, aspirin blocks the formation of TXA2, a molecule which stimulates platelet aggregation and vasoconstriction
In epithelial cells, aspirin blocks the formation of PGI2, a molecule which inhibits platelet aggregation and causes vasoconstriction
In high concentration of aspirin, the epithelial cells cannot replenish COX and less PGI2 is produced. Therefore, even though the harmful TXA2 from platelets is inhibited, the positive effect of PGI2 is also, so the aspirin is not beneficial
In low concentrations of aspirin, the epithelial cells can produce new COX which produces more PGI2. The beneficial effect of PGI2 complements the effect of aspirin in platelets
32
What is the role of COX in epithelial cells?
Catalyses the formation of PGI2
33
What is the role of COX in platelets?
Catalyses the formation of TXA2
34
How does clopidrogel inhibit platelet aggregation?
Platelets release ADP to stimulate other platelet cells around them in a positive feedback loop
Clopidrogels inhibits these ADP molecules and prevent them from working effectively
35
How does Clopidrogel mimic the effect of endothelial cells?
Endothelial cells also inhibit the positive feedback loop between platelets by transforming ADP into AMP
36
What did George Mines discover?
Vulnerable period in the action potential of the heart
Where electrical stimulation at this point can cause ventricular fibrillation
37
What is ventricular fibrillation?
Desynchronisation of ventricular myocytes
Very rapid and irregular ventricular activation leads to no cardiac output
38
What is the most lethal arrhythmia?
Ventricular fibrillation
39
What are triggers of ventricular fibrillation?
Myocardial ischaemia
Some drugs
Electrical imbalance
Genetic predisposition
40
What are the two main ways in which ventricular fibrillation is treated?
Pharmacological approach
Cardioversion
41
Describe the pharmacological approach of ventricular fibrillation
Inhibits phase O
Through sodium channel antagonists
42
Describe how cardioversion treats ventricular fibrillation
DC shock synchronises the heart
During P wave or QRS complex
AED makes sure it is not firing during the vulnerable period
43
What is the funny current?
The unique current seen in pacemaker cells
Responsible for propagating diastole
44
Describe the funny current
1. Sodium channels open upon diastole
2. Sodium enters and changes the voltage to -40mV
3. This is the threshold for voltage-gated calcium channels
4. Calcium enters and at +10mV, the calcium channels close
5. Potassium channels open and decrease the voltage of the cell
6. Sodium channels open again and the diastolic voltage is returned
45
What is the characteristic feature of funny currents?
They have no resting potential
46
What is after-depolarisation?
Pathological wave were ventricular myocytes become spontaneously active
Phase 2/3 = early afterdepolarisation
Phase 4 = delayed afterdepolarisation
Early after-depolarisation requires pacemaker cells, late after-depolarisation occurs in non-pacemaker cells
Repolarisation is delayed and the action potential is abnormally long
47
What is extrasystole?
After-depolarisation in a small area
Normal
48
What is ventricular tachycardia?
Premature beats are one after the other and rapid
49
What is ventricular fibrillation?
Premature beats happen in all myocytes
50
What is a characteristic of ventricular action potentials?
Prolonged calcium influx
Allows the heart to contract well
51
What are arhythmias?
Disorders of the heart rate and rhythm
52
What is the cause and importance of the refractory period?
Caused by the prolonged opening of calcium channels
Induced prolonged contraction required for effective ejection of blood during systole
53
What are the two clinically important arrhythmia?
Tachycardia
Bradycardia
54
What are the types of atrial tachycardia?
Supraventricular tachycardia
Paroxysmal tachycardia
Atrial fibrillation
55
What are the types of ventricular tachycardia?
Torsades de pointes
Ventrical fibrillation
56
What is another name for bradycardia?
Heart block
57
What are the features of heart block?
Ventricles beat slower and irregularly
Caused by damage to the AVN
Driven by pacemaker activity in the ventricular conducting tissue
Pacemaker required rather than drug therapy
58
What is meant by abnormal pacemaker activity?
Pacemaker activity that is initiated at an ectopic focus in the atria and ventricles
59
What is re-entry?
The refractory period normally prevents the action potential re-invading the tissue
In re-entry there is unidirectional propagation of action potentials
Provides abnormal site for cardiac excitation
More likely to happen in calcium channels due to longer refractory periods
60
What drugs van be used to target arrhythmias?
Class I - IV antiarrhythmic drugs
61
What are class I drugs?
Bind to Na+ channels
Block is more pronounced at rates above normal or in depolarised tissues
62
Why should calcium channel blockers be avoided in heart failure patients?
Reduce contractility
63
Which patient population should not use class II drugs?
Asthmatic patients
Exacerbate bronchoconstriction
64
What do class II drugs do?
B-adrenoceptor antagonism
65
What do class III drugs do?
K+ channel block
66
What do class IV drugs do?
Ca2+ channel block
67
What is the main driving force for the flow of blood through the systemic circulation?
Arterial blood pressure
68
What are the principle homeostatic factors controlling arterial pressure?
Arterioles
Cardiac output
Kidneys
Vasoconstriction
Vasodilation
69
Describe the importance of arterioles in controlling arterial pressure
Major role in controlling peripheral resistance
Regulate the relative blood flow through individual organs
70
Describe the importance of cardiac output in controlling arterial pressure
CO = SV X HR
Main factors affecting SV are plasma volume and venous return
Main factors affecting HR is sympathetic and parasympathetic innervation
71
How is vasocontriction controlled?
Increase in intracellular calcium
Through noradrenaline released by sympathetic acting on a1-adrenoceptors
72
How is vasodilation controlled?
Increase in cAMP
Brought by adrenaline acting on B2-adrenoceptors
73
What are causes of hypertension?
Renal disease
Endocrine disorders
Pheochromocytoma
74
What is essential hypertension?
Cases of hypertension with no known cause
75
What are the main antihypertensive drugs?
Agents affecting the renin-angiotensin system
Thiazide diuretics
Calcium antagonists
B-adrenoceptor antagonists
76
What are the main antihypertensive drugs?
Agents affecting the renin-angiotensin system
77
Which system is preferrably targetted in young patients with hypertension?
Renin-angiotensin system
78
Which system is preferrably targeted in older patients with hypertension?
Thiazides
Calcium antagonists
79
How do thiazide diuretics work?
Increase salt and water excretion
Decrease cardiac output through reduced plasma volume
Reduce peripheral resistance
Decrease renin release
80
What stimulates renin release?
Decreased blood flow to the kidneys
Reduced Na+ concentration in the distal tubule
B-adrenoceptor agonist
81
Which drugs decrease the effect of the renin-angiotensin system?
ACE inhibitors
AT1 receptor antagonists
82
How do AT1 receptor antagonists work?
Antagonise the effect of angiotensin II on the AT1 receptor
83
How do calcium antagonists relieve hypertension?
Block calcium entry
Inhibit depolarisation-induced calcium entry into cardiac and vascular smooth muscle
Reduces arterial pressure
84
How do B1-receptor antagonists alleviate hypertension?
Decrease cardiac output
Decrease sympathetic activity
Decrease renin release
85
Give an example of a vasodilator used for antihypertension
Minoxidil
K+ channel activator
Relaxes smooth muscle by hyperpolarising the plasma membrane
Prevents Ca2+ influx through voltage-dependent calcium channels
86
What does heart failure mean?
Chronic failure of the heart to provide sufficient cardiac output
87
What does congestive mean?
Abnormal accumulation of venous blood and oedema
88
What are the two types of congestive heart failure?
Fast - rare
Slow - chronic
89
Why is CHF important to tackle?
Most common reason for hospitalisation of patients over 65 years of age
90
What are the main causes of CHF?
Cardiomyopathy
Excessive afterload
91
What is afterload?
Pressure against which the heart muscle must work to eject blood during systole
92
What causes cardiomyopathy?
MI
Cardiotoxins
Myocarditis
93
What causes excessive afterload?
Hypertension
Valvular heart defects
94
What determines the presentation of CHF?
The side of the heart affected by heart failure
95
What is the presentation of left sided heart failure?
Positional dyspnea
Due to the build-up of water in the lungs
96
What are possible causes of left sided heart failure?
Cor pulmonale
Atherosclerosis
97
How does cor pulmonale/ atherosclerosis cause left sided heart failure?
Backflow of blood into the atrium due to narrowed blood vessels
The pressure in the lung vasculature increases
The exchange of fluids in the hydrostatic and oncotic pressure changes
This leads to a build-up of water in the lungs
98
What is the presentation of right-sided heart failure?
General venous congestion
Increased venous pressure and peripheral oedema
Prominent jugular vein
99
Describe the pathophysiology of heart failure
Low cardiac output causes low perfusion of organs
Compensatory mechanisms come into place to reduce this
100
What compensatory mechanisms are activated upon the decreased CO seen in heart failure?
Activation of the renin angiotensin system in the kidneys
Vasoconstriction due to the activation of the sympathetic nervous system
101
Why do the compensatory mechanisms that form as a response of decreased CO worsen the heart failure?
Renin angiotensin system is activated, which causes volume retention and vasoconstriction
Sympathetic stimulation causes vasoconstriction
102
How does Laplace's law relate to CHF?
The radius of the heart increases because of the increased afterload
The heart also increases its wall tension because of the increased radius
The heart is therefore working harder and has a higher metabolic and oxygen demand
This leaves the heart more susceptible to things like MI
103
What are the major complications of CHF?
Pump failure characterised by tiredness, shortness of breath and oedema
Atrial fibrillation due to the distention of the muscle walls
104
What are the aims of CHF treatment?
Reduce congestion
Increase cardiac output
105
Which drugs aim at increasing cardiac output for CHF sufferers?
Digoxin - increases vagus activity and inhibits Na+/K+ ATPase
Dobutamine
Beta 1 blockers
Phosphodiesterase inhibitors
106
How does digoxin act on CHF patients?
Inhibits the sodium potassium pumps
Increases the Na+ concentration in the cell, so the Na+-Ca2+ pump does not work so effectively
The concentration of calcium inside the cell increases
This leads to increased inotropy = increase the rate of muscular contraction
107
What are the problems of Digoxin in CHF?
Narrow TI
Does not reduce mortality
108
How does Dobutamine act on CHF sufferers?
Beta-1 agonist
109
How was the use of beta blockers in CHF sufferers revolutionary?
Beta blockers work through decreasing heart contractility
Therefore, they were speculated as not being useful for CHF sufferers
However, it was shown that patients on beta blockers had increased survival
This was the birth of evidence medicine
110
How do beta-blockers have a positive impact on CHF sufferers?
Stop the vicious cycle produced by the stimulation of the sympathetic system and the renin-angiotensin system
Decreased the metabolic and oxygen demand of the heart
Give time for the heart stem cells to start the repair process
111
What are the long-term aims of treating heart failure?
Reduce mortality
Increase quality of life
112
What are the long-term treatments for CHF?
ACE inhibitors
Beta blockers
Low salt diet
113
What is more successful than beta blockers in the treatment of CHF?
Combination therapy
Beta 1 blockers and ACE inhibitors
114
Which blood vessels supply blood to the heart muscle?
Coronary arteries
115
What affects the blood supply to the heart?
Metabolites
Sympathetic nerves
Circulating catecholamines
Mediators from neurons
116
When does blood flow to the heart occur?
During diastole
117
What is the main pathological condition of the coronary circulation?
Atheroscletosis
118
Describe the development of atherosclerosis
Platelets, macrophages and low-density lipoproteins adhere to the damaged endothelium
Macrophages release free radicals causing lipid peroxidation of the LDL, which the macrophages ingest
Macrophages release inflammatory cytokines and growth factors causing proliferation of smooth muscle and fibroblasts
119
What two conditions are caused as a consequence of atherosclerosis?
Angina pectoris
Myocardial infarction
120
What causes the pain of angina?
Action of nociceptors of chemicals released from the ischaemic muscle
121
What are the three main types of angina?
Stable angina - gets better with rest
Unstable angina - does not get better with rest, indication that thrombus has formed in the plaque
Variant angina - caused by coronary artery spasm
122
What is myocardial infarction?
Complete block of the coronary artery
123
What are the therapeutic aims of antianginal therapy?
Prevent MI
Reduce cardiac work and metabolic demand
Increase perfusion of heart muscle
124
Which drugs prevent MI?
Statins
Aspirin
Platelet glycoprotein receptor antagonist
125
How do statins prevent MI?
Inhibit plaque formation
126
How does aspirin prevent MI?
Reduce possibility of thrombosis
127
Which drugs reduce cardiac work and metabolic demand?
Organic nitrates
Calcium antagonists - decreases the excitation of the atrium and ventricles
B-adrenoceptor antagonists - inhibits activity of the sympathetic nervous system
128
Which drugs increase perfusion of the heart muscle?
Organic nitrates
Calcium antagonists
129
How do calcium antagonists reduce MI chances?
Block voltage-dependent L-type channels in vascular smooth muscle and cardiac muscle
Cause relaxation and vasodilation in blood vessels
Slow the heart rate of the heart by acting on SAN and AVN through inhibiting the inward Ca2+ movement during the plateu phase of the cardiac action potential
130
What are the therapeutic aims of MI?
Alleviate the pain
Improve oxygenation of the myocardium
Open the blocked artery by reducing thrombus size
Improve survival
Reduce the possibility of re-infarction
131
Which drugs are used to alleviate pain during MI?
Opioids
132
Which drugs are used to open the blocked artery in MI?
Thrombolytic drugs
Anticoagulants
Antiplatelets
133
Which drugs improve the survival in MI?
Angiotensin-converting enzyme inhibitors
134
Which drugs reduce the possibility of reinfarction?
Aspirin
B-antagonists
135
What is a side effect of ACE inhibitors?
Dry cough
ACE is involved in the metabolism of bradykinin
Without ACE, bradykinin builds up systemically and causes a cough
136
How do PDE inhibitors increase heart contractility in CHF?
Stops the breakdown of cAMP to AMP
Increasing the concentration of cAMP in the heart increases the contractility
137
Why are PDE not used for treatment of heart failure?
They increase mortality
