Cardio Flashcards
1
Q
Which risk factor has the highest proportion of attributable deaths associated with it globally?
A
High blood pressure
2
Q
What is the demographic transition?
A
If deaths from infectious diseases and pregnancy are reduced
Life expectancy rises
The population undergoes the ‘demographic transition’
People are a lot more likely to develop chronic diseases
3
Q
Describe difference in population structure between countries with high and low mortality rates
A
High mortality: pyramid structure with high numbers of young people and few older people
Low mortality: population spread more evenly distributed over all age ranges
4
Q
What effects are increasing levels of acculturation, urbanization and affluence having on the epidemiological transition of cardiovascular disease?
A
Increased rates of smoking, fat intake and salt intake
Resulting in higher rates of hypertension and atherosclerosis
5
Q
What is primordial prevention?
A
Focuses on causes of unequal distribution of health damaging exposures, susceptibilities and health protective resources across social groups
Addresses questions of why socioeconomic position is oassociated with health
Prevent appearance of the mediating risk factor in the population,
Focus on social organisation
6
Q
What is primary prevention?
A
Reduction of incidence of disease among healthy individuals by
Removing primary causative agent
Interrupting transmission of an infective agent
Protecting individual from environmental hazards
Improving host resistance
7
Q
What is secondary prevention?
A
Early detection of pre-clinical disease (screening)
Treatment to prevent progression or recurrence
8
Q
What is tertiary prevention?
A
Treatment of established disease to prevent complications or relieve distress
9
Q
What is the population strategy for disease prevention?
A
Decreasing occurrence of risk factors
Population mean shifted left on bell curve
So overall reduction in number of cases of disease
10
Q
What is the high risk strategy for disease prevention?
A
People thought to be at high risk of disease are targeted to reduce risk factors
Cases of disease are treated
11
Q
What are advantages and disadvantages of the population strategy of disease prevention?
A
Attempts to control determinants of incidence rather than cases
Population based
More radical
More permanent
12
Q
What are advantages and disadvantages to the high risk strategy of disease prevention?
A
Extension of traditional clinical approach
Does not produce lasting population changes
Needs to be repeated from generation to generation
13
Q
What factors are driving the increase in incidence of ischaemic heart disease?
A
Diet: Shift from simple to processed foods, Rise of fat production and consumption, Rise of soft drinks
Physical Inactivity: Rise of cars, Rise of obesity (alongside underweight)
Cultural change: Supermarketisation, Lifestyle, Advertising
14
Q
What is the nutrition transition?
A
People eat more: Meat, Fats, Sugar, Salt, Soft drinks, Energy dense foods
People eat less: Staples, Fruit and vegetables, Fibre, Water
15
Q
What are the components of the recent strategy to reduce population salt intake?
A
Communication: Public Awareness Campaigns, Consumers, Food industry, Decision makers, Media, Health Professionals
Reformulation: Setting Targets, Benchmarking food categories, Labelling, Industry Engagement, Motivation, Costs & Benefits, Consumer awareness, Wider support, Corporate responsibility, Voluntary vs Regulatory
Monitoring: Population salt intake, Urinary sodium, Dietary surveys! Reformulation progress, Salt content of foods (databanks; self-reporting by industry; market surveys), Effectiveness of communication, Measuring awareness of campaigns, Measuring attitudes and behaviour changes
Research: Epidemiology, Nutrition, Public Health, Food technology, Behavioural, Evaluation, Policy
16
Q
What downstream changes can be made to reduce population salt intake?
A
Legislative and fiscal changes
Mandatory reformulation – effective and reducing inequalities
17
Q
What upstream interventions can be put into place to reduce population salt intake?
A
Social marketing, awareness, health promotion, behavioural
Politically more likely but fewer benefits and potentially widen inequalities
18
Q
What different imperatives are there for implementing a population reduction in salt intake?
A
Preventative: Population salt reduction programs are both feasible and effective
Economic: Salt reduction programs are cost-saving
Political: Policies are powerful, rapid, equitable, cost-saving
19
Q
What are the top 3 leading causes of death for males and females globally?
A
Male: ischaemic heart disease, stroke, COPD
Female: stroke, ischaemic heart disease, lower respiratory tract infections
20
Q
Where do thiazide diuretics have their effects? And what are these effects?
A
Act at distal convoluted tubule Inhibit Na+/Cl- co-transport from lumen Increase sodium & water excretion Increase potassium loss Vasodilate by potassium channel activation
21
Q
What are some adverse effects of thiazide diuretics?
A
Gout
Low potassium & low sodium
Raised glucose & cholesterol
22
Q
Name 2 thiazide diuretics
A
Bendroflumethiazide
Hydrochlorothiazide
23
Q
Name 4 potassium sparing diuretics
A
Aldosterone antagonists: Spironolactone, Eplerenone
Epithelial Na+ channel blocker (ENaC): Amiloride, triamterene
24
Q
How are potassium sparing diuretics used?
A
Weak agents
Useful in combination with other drugs
Useful against aldosterone excess
25
What are side effects of potassium sparing diuretics?
High serum potassium and low sodium
| Gynaecomastia (spironolactone)
26
What effect does B1 receptor stimulation have on the heart?
```
Inotropic effect (contraction)
Chronotropic effect (rate)
AV nodal conduction (velocity)
```
27
What effect does B2 receptor stimulation have?
Smooth muscle relaxation
| GI, vascular, bronchial, ciliary
28
Describe the signalling cascade that occurs on stimulation of B1 receptors
Coupled to Gs protein
Leads to increased adenylate cyclase activity, so increased cAMP
This activates protein kinase A which phosphorylates L type calcium channels resulting in increased expression at cell surface
This leads to increased contractility and pacemaker activity
29
Describe the signalling cascade that occurs on stimulation of B2 receptors
Coupled to Gs protein
Leads to increased adenylate cyclase activity, so increased cAMP
This leads to activation of protein kinase A which phosphorylates:
sarcolemma so decreased calcium influx, sarcolplasmic reticulum so increased calcium uptake, myosin light chain kinase so decreases contraction
30
Name a cardio selective beta blocker
Atenolol
| B1 specific
31
What are beta blockers used to prevent?
Heart attacks and strokes
32
What are side effects of beta blockers?
```
Bronchospasm
Lethargy
Heart failure
Raynaud’s
Bad dreams
Explosive diarrhoea
Reduced HDL-cholesterol
```
33
Name some calcium channel blockers
Nifedipine
Diltiazem
Verapamil
34
Where does digoxin exert its effects?
Na/K ATPase
35
Where are L type calcium channels located? And what is their function?
Vascular smooth muscle
Cardiac myocytes & sinoatrial & atrioventricular nodes
Renal tubules
Regulate influx of calcium into cells
Stimulate smooth muscle and cardiac myocyte contraction
Contribute to pacemaker currents and action potentials
36
What effects do calcium channel blockers have?
Vascular smooth muscle relaxation
Decreased myocardial force generation
Decreased heart rate
Natriuresis & diuresis
37
Which calcium channel blockers are used to decrease blood pressure? And which are used primarily to reduce cardiac work?
BP: nifedipine, amlodipine, lercanidipine
Cardio: verapamil, diltiazem
38
What are side effects of verapamil?
```
Heart failure
Heart block
Peripheral oedema
Constipation
Facial flushing
Headaches
```
39
What are side effects of diltiazem?
```
Facial flushing
Headaches
Peripheral oedema
Heart failure
Heart block
```
40
What are Dihydropyridines?
Arterio-selective dilator & natriuretic
| E.g. nifedipine, amlodipine
41
What are side effects of nifedipine and amlodipine?
Marked facial flushing
Headaches
Peripheral oedema
Polyuria (exacerbate prostatism)
42
In what pathological states might the RAAS system be activated?
Heart failure
Sepsis
Severe blood loss
43
Give 4 examples of ACE inhibitors
Captopril, enalapril, lisinopril, ramipril
44
What are side effects of ACE inhibitors?
Cough,
Angio-oedema
Caution in renal artery stenosis
Hyperkalaemia
45
Name 3 angiotensin receptor blockers
Losartan, valsartan, candesartan
46
Name some side effects of angiotensin receptor blockers
Caution in renal artery stenosis
Hyperkalaemia
Myalgia
Raised CPK
47
Name 2 alpha blockers
Prazosin
| Doxazosin
48
Describe the signalling cascade of alpha 1 receptors
Act via Gq which leads to increased activity of phospholipase c
This leads to production of IP3 and DAG from PIP2
This leads to increased calcium release from stores and therefore smooth muscle contraction
49
What is Phenoxybenzamine?
Non selective irreversible alpha blocker
| Used to treat hypertension, particularly caused by phaeochromocytoma
50
What are side effects of alpha blockers?
First dose hypotension
| Postural hypotension
51
What are contraindications to ACE inhibitor use?
Pregnancy, renovascular disease
52
What are contradictions to use of rate limiting calcium channel blockers?
Heart block, CHF
53
What is a contraindication to use of diuretics?
Gout
54
What are contraindications to beta blocker use?
Asthma, COPD, Heart block
55
What are contraindications to alpha blocker use?
Incontinence
56
What are blood pressure targets for patients under 80 years old?
57
What would be a first choice antihypertensive for a patient under 55?
ACE inhibitor or ARB
58
What would be a first choice antihypertensive for a patient over 55 or black patient, African/Caribbean origin of any age?
Calcium channel blocker
59
What is the step 2 choice of antihypertensive if mono therapy is not successful at reducing blood pressure to an acceptable level?
ACE inhibitor/ARB and calcium channel blocker combined
60
What is the step 3 choice of antihypertensive if step 2 combination has failed to control blood pressure adequately?
ACE inhibitor/ARB and calcium channel blocker and thiazide diuretic
61
If steps 1-3 antihypertensive son have failed to control blood pressure, what condition is present? What do you do about it?
Resistant hypertension
| Consider further diuretic, alpha/beta blocker, expert advice
62
What did the sprint trial show relating to blood pressure?
More intensive management of high blood pressure (SBP
63
What should be attempted before starting antihypertensive therapy in patients with high blood pressure?
Moderate reduction in dietary salt intake
64
What long term effects can hypertension have on the heart?
Increased LV mass, with or without chamber dilatation (left
ventricular hypertrophy, LVH)
Left atrial abnormalities
Myocardial ischaemia
Systolic and diastolic LV dysfunction (heart failure)
Atrial and ventricular arrhythmias
Sudden death
65
What are clinical consequences of hypertensive heart disease?
```
Angina pectoris
Asymptomatic heart failure
Cardiac dysrhythmias
Acute Coronary Syndromes
Symptomatic heart failure
Myocardial infarction
Sudden death
```
66
What neurohormonal factors contribute to cardiac damage in hypertension?
Activation of RAAS
Enhanced adrenergic activity
Increased production/reduced catabolism of biologically active molecules (cytokines, growth factors)
67
What haemodynamic factors contribute to cardiac damage in hypertension?
Increased peripheral resistance
Increased wall stress
Decreased coronary reserve
68
What vascular factors contribute to cardiac damage in hypertension?
```
Endothelial dysfunction
Vascular remodelling
Decreased vascular compliance
Increased vascular reactivity
Coronary and Peripheral vascular atherosclerosis
```
69
What myocardial changes contribute to cardiac damage in hypertension?
eft ventricular remodelling
Foetal gene expression
Myocyte hypertrophy
Alteration in extracellular matrix
70
How does hypertensive heart disease lead to oedema?
Passive venous congestion due ventricular dysfunction and high arterial pressure
This leads to increased aldosterone production and thus Na and water retention and therefore oedema
71
How does hypertensive heart disease result in dyspnoea?
Increased pulmonary venous pressure due to ventricular dysfunction leads to increased ventricular filling pressure and increased atrial pressure
This results in increased pulmonary capillary pressure which leads to interstitial oedema
This decreases lung distensibility and increases O2 consumption, therefore leading to shortness of breath
72
Name some common presenting symptoms of congestive heart failure
```
Dyspnoea at rest
Dyspnoea on exertion
Effort intolerance
Fatigue and weakness
Orthopnoea
Paroxysmal nocturnal dyspnoea
GI complaints
```
73
Name some signs of congestive heart failure
```
Resting tachycardia
Third heart sound
Vascular congestion
Peripheral oedema
Hypotension
Organomegaly (e.g. liver)
Pleural effusion
Cachexia
```
74
Describe management steps for hypertensive heart disease
Effective management of high BP to regress LVH
ACE-I or ARB for LV systolic dysfunction
ARB for LV diastolic dysfunction
Beta-blockers in presence of IHD and arrhythmias (AF)
Heart failure: ACE-I first line (ARBs alternative), beta-blockers (3rd gen, nebivolol) prolong survival, if congestive symptoms, loop diuretics or anti-aldosterone
Manage other CV risk factors (statins, aspirin, anti-diabetics)
AF: combine anti-coagulation (vitamin K antagonists, apixaban, dabigatran, rivaroxaban)
Ventricular arrhythmias, specialist input for diagnosis and management
75
What is hypertensive kidney disease?
Hypertensive nephrosclerosis is a blood pressure-related pathologic process marked by a progressive decline in renal function
76
What are some modifiable risk factors for the progression of renal disease?
```
Hypertension
Albuminuria/Proteinuria
Dyslipidemia
Hemoglobin A1C
Smoking
Anemia
Ca and P04
```
77
What are some non modifiable risk factors for the progression of renal disease?
Age
Ethnicity
Gender
78
How do ACE inhibitors effect renal filtration?
Efferent arteriole dilation due to combined effect of bradykinin and a decrease in angiotensin II leads to decrease in GFR
79
What is hypertensive retinopathy?
Spectrum of microvascular signs in the retina pathophysiologically related to elevated blood pressure
80
What are the grades of hypertensive retinopathy?
Mild (grade I-II): arteriolar narrowing, arteriovenous nicking, arteriolar wall opacity (silver-wiring)
Moderate (grade III): Mild retinopathy and one or more of: retinal haemorrhage (blot, dot, or flame-shaped), microaneurysms, cotton-wool spot, hard exudates
Malignant (grade IV): Moderate retinopathy and optic disc swelling and macular oedema (papilloedema)
81
What calibration should an ECG be set to?
1 mV = 10mm calibration
| Paper speed 25mm/second
82
Describe QRS waveform nomenclature on an ECG
```
Initial negative wave = Q (q)
First positive wave = R (r)
Negative wave after R = S (s)
Any second positive wave = R’ (r’)
Entirely negative wave = QS (qs)
LARGE DEFLECTIONS =UPPER CASE
small deflections = lower case
```
83
Which areas of the myocardium are represented by the precordial leads V1-6?
V1, V2: RV wall
V3, V4: IV septum (transition zone)
V5, V6: LV wall
84
What causes the progressive increase in positive deflection of the QRS complex from V1-V6?
Increasing muscle thickness
85
What are the normal dimensions of a QRS complex?
Min height: 8mm
| Max height: R
86
What drug may cause ST depression?
Digoxin
87
What may cause t wave inversion?
Left ventricular hypertrophy
88
Describe normal p wave morphology
Always +ve V3-6
+ve or biphasic V1-2, If biphasic +ve > -ve
Duration
89
What is a normal PR interval?
3-5 small squares
90
In an MI, how quickly should percutaneous coronary intervention be performed? And how quickly should thrombolysis be given?
90 mins from medical contact for PCI
| 30 mins for thrombolysis
91
What is Virchows triad for determining risk of deep vein thrombosis?
Abnormal blood flow
Endothelial injury
Hypercoagulability
92
Which leg is a dvt more likely to occur in?
Left - right common iliac artery crosses origin of left common iliac vein
93
What factors in a history would make you suspicious of a dvt?
Paralysis, paresis or recent orthopedic casting of lower limb
Recently bedridden (over 3 days) or major surgery within past 4 weeks
Localised tenderness in deep vein system
Swelling of entire leg
Calf swelling 3 cm greater than other leg
Pitting edema greater in symptomatic leg
Collateral non varicose superficial veins
Active cancer or cancer treated within 6 months
94
What are differential diagnoses for a dvt?
```
Baker's cyst
Cellulitis
Muscle damage
Superficial venous thrombosis
Post phlebitic syndrome
External venous compression
```
95
What is the wells criteria?
Calculates risk of PE
Clinical signs and symptoms of DVT (3 points)
PE is number 1 diagnosis (3 points)
Heart Rate >100 (1.5 points)
Immobilisation (>3 weeks) or surgery within 4 weeks (1.5 points)
Previous objective PE/DVT diagnosis (1.5 points)
Haemoptysis (1 point)
Malignancy, treatment within 6 months (1 point)
96
What are differences between a VQ scan and a CTPA for imaging PE?
CTPA: Fast and fairly accurate. Often not a perfect scan in real life. Very unlikely to pick up amniotic fluid embolism. CTPA picks up other causes. High radiation dose
VQ scan: higher negative predictive value, good for peripheral defects. Chest radiograph needs to be normal
97
What precautions should be used when imaging women of child bearing age?
ALARA: As low as is reasonably achievable
High dose test: use 10 day rule if possible. Image within 10
days of commencing period. Radiation damage to fetus in early pregnancy is an all or nothing response
Do a pregnancy test or be sure that they are not pregnant
In a true emergency the priority may be to do the scan
98
What may be presenting signs and symptoms of an aortic aneurysm?
Severe back pain
| Hypotensive
99
How can you tell if a patient has a critically ischaemic leg?
Cold, pulseless
Short distance claudication
Rest pain
Gangrene
100
What are options for assessing an ischemic leg?
Doppler ultrasound
MRA
CTA
101
What are indications for renal artery intervention?
Resistant hypertension
Worsening renal function. No point if glomerular sclerosis has already set in (kidneys less than 9cm or obviously echogenic and scarred)
Flash pulmonary oedema
102
What is a resting membrane potential?
Potential difference that exists across the membrane of excitable cells
103
What are the most important ions in determining membrane potential?
Sodium, potassium and chloride ions
104
What are ion concentrations outside of cells?
Na: 140
K: 4
Cl: 115
Ca: 2
105
What are ion concentrations inside cells?
Na: 10
K: 160
Cl: 3
Ca: 0.0001
106
Which ions are membranes permeable to during resting membrane potential?
Membrane is relatively permeable to K+ and Cl-
| Membrane is relatively impermeable to Na+ and Ca++
107
Which ion pump is key to resting membrane potential?
Sodium (pumps outside) and Potassium (pumps inside)
Electrogenic: 3 sodium for 2 potassium, therefore deficit of positive ions inside cell
Generates large concentration gradients for the ions
108
Which ion channels are key to the action potential?
Fast Na channels: When open there is rapid influx of sodium, Close when MP is less negative that -55mV for a few
milliseconds
L-type Ca channels (slow sodium-calcium channels): Take longer to open and cause influx of positive ions
K channels: Large amounts of potassium diffuse out of cell
109
What is Wolff-Parkinson-White syndrome?
Pre excitation syndrome
Abnormal accessory connection pathway between the atria and ventricles (bundle of Kent) which stimulate premature ventricular contraction - supraventricular tachycardia
110
In diastole, what determines the resting membrane potential?
Selective membrane permeability to K+
| K+ concentration gradient (inside > outside)
111
Describe the sino atrial nodal action potential
Phase 4: inward Na pacemaker funny current
Phase 0: upstroke inward Ca current
Phase 3: downstroke outward K current
112
Describe the atrial and ventricular action potential
Phase 4: resting membrane potential
Phase 0: upstroke inward Na current
Phase 1: Na inactivation, K and Cl outward current
Phase 2: plateau, inward Ca current L type
Phase 3: repolarisation, K outward current
113
What is Brugada syndrome?
Reduction in Na+ channel activity
Inherited loss of function mutation of Na-channel, leading to altered spread of heart beat and ventricular fibrillation
Also reduction in Ca2+ channel activity, altering length of plateau of the cardiac action potential
114
What is cardioplegia?
Intentional and temporary cessation of cardiac activity, primarily for cardiac surgery
Depolarisation opens Na+ channels in short term, long term
depolarisation reduces number of Na+ channels available
As a result action potential may be reduced or fail if external [K+] is raised
115
What is excitability in relation to a cardiac myocyte?
Amount of inward current required to bring a myocardial cell to threshold potential
116
What is the basis for the refractory period?
Na+ inactivation gates close with depolarisation
Na+ channels are closed so there can be no inwards current
The cell is thus refractory
117
What happens if a cardiac action potential is too short?
Re-entrant excitation may occur, with risk of ventricular fibrillation
118
How does B1 stimulation lead to increased heart rate? Which receptor has the opposing effect?
Pacemaker potential sped up so action potentials fire more quickly
Acetyl-choline acting at M2 muscarinic receptors
119
How does an action potential lead to myocyte contraction?
Ca2+ entry during plateau phase through L-type voltage gated Ca2+ channels (enhanced by adrenaline and noradrenaline)
Releasing Ca2+ from intracellular stores in sarcoplasmic reticulum (also enhanced by adrenaline and noradrenaline)
Ca2+ activates contraction by binding to troponin C on myofilaments of contractile apparatus, permitting cross bridge formation
120
What are some causes of conduction disease in the heart?
Intrinsic: Idiopathic degenerative fibrosis, Ischaemia, Cardiomyopathies, Infiltrative diseases e.g. sarcoidosis, haemochromatosis, Congenital abnormalities
Extrinsic Causes: Autonomic dysfunction, Hypothyroidism, Electrolyte abnormalitites e.g. hyperkalaemia, Drugs e.g. digoxin, beta-blockers, calcium channel blockers, Cardiac surgery
121
What types of sino atrial nodal bradycardias are there?
Sinus bradycardia
Sinus arrest
Sinus node exit block
Junctional escape rhythm
122
How might you see a junctional escape rhythm on an ECG?
Look for p waves in inferior leads and V1
| Retrograde p wave after QRS complex
123
What are the different types of atrioventricular nodal bradycardias are there?
1st degree AV block: PR interval over 0.2ms
Mobitz 1/Wenkebach: Each beat, pr interval lengthens until one beat is not conducted
Mobitz 2: 2:1 3:1 4:1 patterns of conduction, pr interval is fixed
Complete heart block
124
What are the types of tachycardias?
```
Supraventricular tachycardia (SVT): narrow complex
Ventricular tachycardia (VT): wide complex
```
125
What are the different types of supraventricular tachycardias?
```
Sinus tachycardia
AV nodal re-entrant tachycardia (AVNRT)
AV re-entrant tachycardia (AVRT)
Atrial tachycardia – focal or re-entrant
Atrial fibrillation
```
126
How do you spot an atrioventricular nodal re entrant tachycardia on an ECG?
Retrograde atrial activity
127
Describe the mechanism of re entrant loop tachycardias
2 pathways for electrical activity, slow and fast through AV node
Slow has a short refractory period
If fast is still refractory, slow pathway conducts and then retrograde activity goes back up the fast which then reactivates the atria
128
What does atrial flutter look like on an ECG?
Macro re entrant tachycardia
Sawtooth appearance between QRS complexes
No clear isoelectric line
129
What types of ventricular tachycardias are there?
Normal heart: Right ventricular outflow tract - monomorphic
Torsades: Brugada/CPMVT (catecholaminergic polymorphic VT)
Structural heart disease: IHD – monophormic, HCM (hypertrophic cardiomyopathy)/ARVC (arrythmogenic right ventricular cardiomyopathy)
130
What different mechanisms can underly arrhythmias?
Enhanced automaticity: ectopy or focal tachycardias from atria or ventricles. Elevated extracellular potassium, Low intracellular pH, Catecholamine excess, Ischaemia
Triggered activity: impulse initiation caused by after-depolarizations which occur in presence of a previous AP. When they reach threshold potential, new AP is generated, source of a new triggered response, leading to self-sustaining triggered activity
Re-entry: electrical wave front in heart gets caught in a loop. At least two pathways or presence of barrier which may be anatomic, pathologic or functional. Unidirectional Block: block can be physiologic (premature depolarization or increased heart rate) or pathologic (changes in repolarization). Slow conduction must be present to prevent collision of leading edge of wave front into the trailing edge
131
What is phase 4 of a cardiac ventricular action potential?
Resting phase (resting membrane potential)
Phase cardiac cells remain in until stimulated
Associated with diastole portion of heart cycle
132
What is phase 0 of the cardiac action potential?
Opening of fast Na channels and rapid depolarization
Drives Na+ into cell (inward current), changing membrane potential
Transient outward current due to movement of Cl- and K+
133
What is phase 1 of the cardiac action potential?
Initial rapid repolarization
Closure of fast Na+ channels
Phase 0 and 1 together correspond to the R and S waves of the ECG
134
What is phase 2 of the cardiac action potential?
Plateau phase sustained by balance between the inward movement of Ca+ and outward movement of K +
Has long duration compared to other nerve and muscle tissue
Normally blocks any premature stimulator signals
Corresponds to ST segment of ECG
135
What is phase 3 of the cardiac action potential?
Repolarization, K+ channels remain open, Allows K+ to build up outside cell, causing the cell to repolarize
K + channels finally close when membrane potential reaches certain level
Corresponds to T wave on ECG
136
What disorders of cadiac impulse formation are there?
No signal from pacemaker site
Development of ectopic pacemaker: May arise from conduction cells (most are capable of spontaneous activity), Often a result of other injury (ischemia, hypoxia)
Development of oscillatory after depolarisations: Can initiate spontaneous activity in non pacemaker tissue, May be result of drugs (digitalis, norepinephrine) used to treat other cardiopathologies
137
What is the biggest problem in using anti arrhythmic drugs?
Anti-arrhythmics are pro-arrhythmic as well
Eg: Treatment of a non-life threatening tachycardia may cause fatal ventricular arrhythmia
Must be vigilant in determining dosing, blood levels, and in follow-up when prescribing antiarrhythmics
138
What are different mechanisms of action of anti arrhythmic drugs?
```
Na+ channel blockade
β-adrenergic receptor blockade
Prolong repolarisation
Ca2+ channel blockade
Adenosine
Digitalis glycosides
```
139
What is the mechanism of action of class 1 anti arrhythmic drugs?
Na channel blockers
1A: Mod.block Ph.0; slow conduction; increase APD
1B: Min.block Ph.0; slow conduction; shorten Ph3 repolarisation
1C: Marked block Ph.0; slow conduction; no change APD or repolarisation. Increased suppressionof Na channels
140
Give examples of class 1 anti arrhythmic drugs
1A: Quinidine, Procainamide
1B: Lidocaine, Phenytoin
1C: Flecainide, Encainide
141
Give an example of a class 2 anti arrhythmic drug
Propranolol
142
What is the mechanism of again of class 2 anti arrhythmic drugs?
Beta blockers; decrease adrenergic input
| No effect APD, suppress Ph.4 depolarisation
143
What is the mechanism of action of class 3 anti arrhythmic drugs?
Prolong repolarisation/refractory period
| Mainly K+ channel blockade
144
Give examples of class 3 anti arrhythmic drugs
Bretylium
| Amiodarone
145
What is the mechanism of action of class 4 anti arrhythmic drugs?
Ca channel blockers. Slow conduction and increase effective refractory period in normal tissue (A-V node) and Ca dependent slow responses of depolarised tissue (atria, ventricle, Purkinje)
146
Give examples of class 4 anti arrhythmic drugs
Verapamil
| Diltiazem
147
Give examples of anti arrhythmic drugs which don't fit into the 4 classes
Adenosine, Digoxin, Anticoagulants
148
What is quinidine?
```
1st antiarrhythmic used, treat both atrial and ventricular arrhythmias, increases refractory period
Fast Na channel blocker - class 1A
```
149
What is Procainamide?
Fast Na channel blocker anti arrhythmic
Increases refractory period but side effects
Class 1A
150
What is Disopyramide?
Fast Na channel blocker anti arrhythmic
Extended duration of action, used only for treating ventricular arrthymias
Class 1A
151
How does lidocaine work as an anti arrhythmic drug?
Blocks Na+ channels mostly in ventricular cells, also good for digitalis-associated arrhythmias
Class 1B
152
How does phenytoin work as an anti arrhythmic drug?
Anticonvulsant that also works as antiarrhythmic similar to lidocane - Na channel blockade
Class 1B
153
What is Mexiletine?
```
Oral lidocaine derivative, similar activity
Can be used as class 1B anti arrhythmic
```
154
What is Flecainide?
Slows conduction in all parts of heart
Inhibits abnormal automaticity
Class 1C anti arrhythmic - Na channel blocker
155
What is propafenone?
Class 1C anti arrhythmic drug, Na channel blocker
Also slows conduction
Weak β – blocker
Also some Ca2+ channel blockade
156
How do beta blockers work as anti arrhythmic drugs?
Class 2
Blockade of myocardial β–adrenergic receptors
Direct membrane-stabilizing effects related to Na+ channel blockade
Slows SA node and ectopic pacemaking
Can block arrhythmias induced by exercise or apprehension
157
What is the mechanism of action of Amiodarone?
Class 3 anti arrhythmic
| Prolongs action potential by delaying K+ efflux but many other effects characteristic of other classes
158
What is the mechanism of action of ibutilide?
Class 3 anti arrhythmic drug, K channel blocker
| Slows inward movement of Na+ in addition to delaying K+ influx
159
What is bretylium?
Class 3 anti arrhythmic drug, k channel blocker
First developed to treat hypertension but found to suppress ventricular fibrillation associated with myocardial infarction
160
What is the mechanism of action of verapamil as an anti arrhythmic drug?
Ca channel blocker
Slow rate of AV-conduction in patients with atrial fibrillation
Blocks Na+ channels in addition to Ca2+; also slows SA node in tachycardia
161
What is the mechanism of action of Flecainide?
Class 1C anti arrhythmic
Depress rate of rise of AP without change in refractoriness or APD in normally polarised cells
Decreases APD, decreases automaticity, conduction in depolarised cells
Marked block of open Na channels (decreases Ph. 0); no change
repolarisation
Used primarily for ventricular dysrhythmias but effective for atrial too
Suppresses premature ventricular contractions
Associated with significant mortality; thus, use limited to last resort applications like treating ventricular tachycardias
162
How do beta blockers affect the heart to act as class 2 anti arrhythmics? Metoprolol, Esmolol (short acting), Sotalol (also Class III), Acebutolol, Bisoprolol, Nebivelol
Slow A-V conduction
Prolong A-V refractory period
Suppress automaticity
163
How does propranolol act as an anti arrhythmic?
Main mechanism of action is block of beta receptors
Decrease Ph 4 slope which decreases automaticity
Local anesthetic effect by block of Na channels (membrane stabilisation) at higher doses
Increases refractory period in depolarised tissues
Increases A-V nodal refractory period
164
In which arrhythmic conditions is propranolol used?
Blocks abnormal pacemakers in cells receiving excess catecholamines (pheochromocytoma) or up-regulated beta-receptors (Hyperthyroidism)
Blocks A-V nodal reentrant tachycardias, inhibits ectopic foci
Treat supraventricular tachydysrhythmias
Contraindicated in ventricular failure, also can lead to A-V block
165
Give uses of beta blockers
Angina (non-selective or beta 1-selective): decrease O2 demand more than O2 supply, Exercise tolerance increase in angina patients
Arrhythmia (beta 1-selective, LA-action): catecholamine-induced increases in conductivity and automaticity
Congestive Heart Failure: caution with use
Glaucoma (non-selective): decrease aqueous humor formation (Timolol)
Block of tremor of peripheral origin (beta 2-AR in skeletal muscle)
Migraine prophylaxis
Hyperthyroidism: decrease cardiac manifestation (propranolol)
Panic attacks, stage fright
166
What is beta blocker supersensitivity?
Rebound increase in sympathetic response after stopping beta blocker treatment
Effect with beta-blockers, less with beta-blockers with partial agonist activity (ie. pindolol). Gradual withdrawal
167
What are contraindications to beta blocker use?
Asthma: Blockade of pulmonary beta 2-receptors increase in airway resistance (bronchospasm)
Diabetes: Compensatory hyperglycemic effect of exocrine pancreatic insufficiency in insulin-induced hypoglycemia is removed by block of beta 2-ARs in liver. Beta 1-selective agents preferred
168
What is the mechanism of action of Amiodarone? When is it used?
Prolongs refractory period by blocking potassium channels
Also member of Classes IA,II,III,IV since blocks Na, K, Ca channels and alpha and beta adrenergic receptors
Serious side effects related to iodine core. Used frequently in emergency situation (ITU, A&E)
Effective against atrial, A-V and ventricular arryhythmias
Very long acting (>25 d)
169
What are adverse effects of Amiodarone?
Cardiac: heart block, QT prolongation, bradycardia, cardiac failure, hypotension
Pulmonary: pneumonitis (leading to fibrosis)
Bluish discolouration skin, corneal microdeposition
GI tract disturbances, hepatotoxicity
Thyroid discturbances: both hypo- or hyperthyroidism
170
What are mechanisms of action of verapamil?
Blocks active and inactivated Ca channels, prevents Ca entry
More effective on depolarized tissue, tissue firing frequently or areas where activity dependent on Ca channels (SA node; A-V node)
Increases A-V conduction time and refractory period; directly slows SA
and A-V node automaticity
Suppresses oscillatory depolarising after depolarisations due to digitalis
171
What extracardiac effects does verapamil have?
Peripheral vasodilatation via effect on smooth muscle
Used as antianginal / antihypertensive
Hypotension may increase HR reflexively
172
What are some adverse effects of verapamil?
Cardiac: Too negative inotropic for damaged heart, depresses contractility - Can produce full A-V block. Can't use in HF
Extracardiac:Hypotension, Constipation, Nervousness, Gingival hyperplasia
173
How does adenosine act as an anti arrhythmic?
Activates P1 purinergic receptors (A1) coupled to K channels, decrease CV, increase refractory peroid
Diagnosing and/or terminating PSVT or AVNRT
Activation of ACh sensitive K+ channel. Leading to hyperpolarisation of SA node, depressing the SA node
Slowing AV conduction and shortening action potential in atrium
In PSVT: reduces Calcium current in AV node, leading to depression of re-entry in PSVT
174
How can potassium ions act as anti arrhythmics?
Depress ectopic pacemakers
175
How does digoxin work as an anti arrhythmic?
Used to treat atrial flutter and fibrillation
AV node decreased conduction
Myocardium decreased refractory period
Purkinje fibers increased refractory period, decreased conduction
176
What are side effects of adenosine?
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Chest tightness
Dyspnoea (especially in asthmatic pt – contraindicated)
Sudden fall in blood pressure
Flushing
Headache
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177
How does magnesium act as an anti arrhythmic drug?
Influneces Na/K ATPase, Na channels, K channels, Ca channels
| Used in variety of arrhythmias to stabilise action potential
178
In which arrhythmias might magnesium be the treatment of choice?
Torsade de pointes
| Refractory VTs
179
Describe how pacemakers are inserted
Leads are inserted via subclavian vein and advanced to chambers on right side of the heart
Two leads used, one for right atrium, other for right ventricle
Pulse generator containing microcircuitry and battery are attached to leads and placed into a pocket under skin near clavicle
Pulse generator sends signal down leads in programmed
sequence to contract atria, then ventricles
