Pharmacology arrythmias Flashcards
1
Q
Why is conduction through the AV node slow (0.15s)
A
To allow Atrial contraction to propel blood into ventricles
2
Q
Arrythmias caractéristics
A
Abnormal site of origin of impulse
Abnormal raté or regularity of impulse
Abnormal conduction
3
Q
Fréquence of electrical pulse at sino atrial node
A
60-100 bpm
4
Q
Only conduction pathway between the atria and the ventricles
A
The atrioventricular node
5
Q
P wave
A
Generated by atrial depolarization
6
Q
QRS
A
Ventricular muscle depolarization
7
Q
T wave
A
Ventricular repolarization
8
Q
PR interval
A
Conduction time from atrium to ventricle
9
Q
QT interval
A
Duration of ventricular action potential
10
Q
Aim of Therapy of arrhythmias
A
Reduce Ectopic pacemaker activity more than the one of SA node
Modification of conduction and refractories in reentry circuits
11
Q
Pharmacologic mechanisms available
A
Sodium channel block
Sympathetic block in the heart
Prolongation of effective refractory period
Calcium channel block
12
Q
What is the consequence of blocking Na or Ca channel of depolarized cells
A
Decrease conduction and excitability
Increase refractory period only in depolarized cells and not in polarized cells
13
Q
To what type of channels the channel blockers impact ?
A
Activated channel in phase 0
Inactivated channel in phase 2
14
Q
What happens if a drug binds to a normal cell
A
Will lose the drug rapidly from the receptors during resting portion of the cycle
15
Q
What happens if a drug binds to cell that is constantly depolarized
A
Gisele will recover slowly from the block or not at all
16
Q
In cells with abnormal automaticity how do drugs reduce the phase 4 slope
A
Block ca and Na channel which brings equilibrium close to potassium
17
Q
What are the two targets by drugs on reentry arrhythmias to completely prevent extra systole and reduce late propagation
A
Slow conduction by reducing the number of available unblocked channels
Prolong the recovery time of channels which increases the effective refractory period
18
Q
How is drug-induced arrhythmias possible
A
When dosage increases , normal tissue are also targeted by the drugs
19
Q
How can an anti arrhythmic drug become proarrythmic
A
If there’s fast heart rate, acidosis hyperkalemia , ischaemia
20
Q
Classes of drugs
A
Class I sodium channel blockade
Class 2 sympatholytic
Class 3 prolongation of Action potential duration
Class 4 blockade of cardiac calcium current
21
Q
Which drug share all four classes of action
A
Amiodarone
22
Q
What drug do not fit in any classes
A
Adenosine , magnesium
23
Q
Class 1A drugs
A
Procainamide
Quinidine
Disopyramide
24
Q
Class 1B drugs
A
Lidocaine
Mexiletine
Tocainide
25
Class IC drugs
Flecainide
Encainide
Propafenone
Moricizine
26
Class I drug with weak anti cholinergic effect
Procainamide
27
Class I drug with moderate anti cholinergic effect
Quinidine
28
Class I drug with strong anti cholinergic effect
Disopyramide
29
Actions of procainamide
Slows upstroke of action potential
slows conduction
prolongs the QRS
prolongs the APD ( class 3 action )
30
Is procainamide more effective than quinidine at suppressing ectopic pacemaker activity
No , less effective
| More effective in blocking NA channel tho
31
Extra cardiac effects of procainamide
Ganglion block => Reduced peripheral vascular resistance => hypotension especially when IV
32
Procainamide toxic effects
Cardiotoxicity ( excessive AP prolongation leading to torsades de pointes arrythmia and syncope. Too slowed conduction leads to new arrythmias )
lupus erythematous like syndrome when long term therapy ( arthritis, arthralgia)
Serologic abnormalities which shouldn’t make you stop treatment if no symptoms
Pleuritis
Pericarditis
Parenchymal pulmonary disease
Nausea
```
Diarrhea
Rash
Fever
Hepatitis
Agranulocytosis
```
33
Route of administration of procainamide
Per os
IV
IM
34
Procainamide elimination
Hepatic metabolism to NAPA
NAPA ( has class III activity ) eliminated by kidney
So should pay attention in renal failure
Reduced dosage of low distribution and renal clearance ( risk of heart failure)
35
When should use procainamide
Atrial and ventricular arrythmias
36
Would you pick procainamide as first choice in treatment of sustained ventricular arrythmias due to Acute MI
No
| It’s drug of second or third choice after lidocaine and amiodarone
37
Cardiac effects of quinidine
Slows upstroke of action potential
slows conduction
prolongs the QRS
prolongs the APD ( class 3 action )
38
Toxic cardiac effects of quinidine
Excessive QT interval leads to torsade de pointes
Slowed conduction in heart if toxic concentration.
39
Extra cardiac effects of quinidine
1/3 to 1/2 of patients have GI effect (diarrhea , nausea )
Cinchonism At toxic drug =>headache, dizziness, tinnitus
Immunologic rxns ( thrombocytopenia, hepatitis, angioneurotic edema, fever)
40
Elimination of quinidine
Hepatic metabolism
41
How often is quinidine used
Rarely because of adverse effects
42
Disopyramide cardiac effects
Slows upstroke of action potential
slows conduction
prolongs the QRS
prolongs the APD ( class 3 action ) => more pronounced
43
Why should you administer a drug that slows AV with dysopiramide in atrial flutter/ fibrillation or add B blockers/CCB
Because disopyramide has high antimuscarinic activity
44
Toxic effects of disopyramide
Heart failure ( negative inotropic effect)
Atropine like effects ( urinary retention, dry mouth, blurred vision, constipation, glaucoma worsening)
diarrhea , nausea
Cinchonism At toxic drug =>headache, dizziness, tinnitus
Immunologic rxns ( thrombocytopenia, hepatitis, angioneurotic edema, fever)
45
Is disopyramide a first line antiarrythmic agent ?
No
| And should avoid it in heart failure patients
46
Route of administration of disopyramide
Oral
47
In what type of patient should you reduce dose of disopyramide
Renal failure patient
48
In what type of condition is dysopiramide used as treatment t
Ventricular arrythmias
Some supraventricular arrythmias
49
Route of administration of lidocaine
Only IV
50
Cardiac effects of lidocaine
activated and inactivated NA Channel
51
Least cardiotoxic NA channel blocker
Lidocaine
52
When can lidocaine cause hypotension
In large doses
| If preexisting heart failure patients
53
Most common adverse effects of lidocaine
```
Paresthesias
Tremor
Nausea
Lightheadedness
Hearing disturbances
Slurred speech
Convulsions
```
54
I’m case of seizures due to lidocaine , what drug can you give IV
Diazepam y
55
Why is lidocaine only given IV
Extensive first pass metabolism -97%
56
Why can patient with MI tolerate and require higher lidocaine dose
Because they have increased a1-acid glycoproteins which normally binds lidocaine
So there would be less drug available for distribution
57
Why should you reduce lidocaine dose in heart failure patient
volume of distribution and total body clearance are decreased
58
In liver disease, why should you reduce lidocaine maintenance dose but can keep usual loading dose ?
Plasma clearance is reduced but volume of distribution increased
59
Drugs that can reduce lidocaine clearance
Propranolol
| Cimetidine
60
Therapeutic use of lidocaine
Agent of choice for ventricular tachycardia
Prevention of ventricular fibrillation after cardio version ( can increase mortality)
Arrythmias
61
Mexiletine route of administration
Oral
62
Therapeutic use of mexiletine
Ventricular arrythmias
Pain due to diabetic neuropathy and nerve injury
63
Dose related toxic effects of mexiletine
Tremor
blurred vision
Lethargy
Nausea
64
Mexiletine action ressembles action of ...
Lidocaine
65
Na Channel blocker who has also k channel blocking activity
Flecainide
66
Therapeutic use of flecainide
Normal hearts with supraventricular arrythmias
Auprès premature ventricular contraction
67
Fleicanide elimination
Hepatic metabolism
Kidney
68
Propafenone action is similar to ...
Quinidine but does not prolong AP
69
Therapeutic use of propafenone
Supraventricular arrythmias
70
Propafenone adverse effects
Metal taste
Constipation
Arrythmias exacerbation
71
Moricizine therapeutic use
Was used for Ventricular arrythmias
72
Class II DRUGS ( beta adrenoreceptor blocking drugs)
Propranolol
Esmolol
Sotalol
73
Are class II drugs more effective in in suppression of ventricular ectopic depolarization than class I drug
No , less effective
74
Esmolol short acting b blocker therapeutic use
Antiarrythmic drug for jntraoperative and acute arrythmias
75
Which b blocker has class 3 action
Sotalol (non selective beta blocker )
76
Class III drugs ( prolong effective refractory period by prolonging action potential)
Amiodarone
Dronedarone
Celivarone
Vernakalant
Sotalol
Dofetilide
Ibutilide
77
When are class III drugs putting at risk of torsades de pointes
When slow heart rate
78
Amiodarone route of administration
IV
| ORAL
79
Amiodarone therapeutic use
```
Serious Ventricular arrythmias
Supraventricular arrythmias ( atrial fibrillation)
```
Récurent ventricular tachycardia
80
Dronedarone is an analog of
Amiodarone
81
Dronedarone therapeutic use
Atrial flutter
| Atrial fibrillation
82
Celivarone therapeutic use
Prevention of ventricular tachycardia recurrence
83
Amiodarone cardiac effects
IK blocked
AP prolonged
Block Na channel
Weak class Iv and class II action
84
Amiodarone extra cardiac effects
Peripheral vasodilation ( when IV )
85
Amiodarone toxicity
Bradycardia and Heart block ( if sinus or AV node disease)
Can accumulate in heart, lung, liver, skin, tears
Dose related pulmonary toxicity
Abnormal liver function
Hypersensitivity hepatitis
Photodermatitis and gray blue skin discoloration
Corneal micro deposits
Optic neuritis which can progress to blindness
High iodine
Hypo or hyperthyroidism
86
How long can effect of amiodarone be present after discontinuation
1-3 months
Can still be found in tissues in a 1y
87
If cyp3A4 Is inhibited, amiodarone level ...
Increases
88
If cyp3A4 is induced, amiodarone level ..
Decreases
89
Drugs affected by amiodarone inhibiting CYP450
Increased statins, digoxin, warfarin
90
Why was dronedarone manufactured
To avoid thyroid issues like in amiodarone
91
Dronedarone block...
```
IKs
IKr
ICa
INa
B adrénergic receptor
```
92
How does food intake impact dronedarone
Absorption of dronedarone increased 2-3fold
93
Elimination of dronedarone
Non rénal
94
Why can’t you give dronedarone with cyp3A4 inhibitor
Because also has inhibitory action even tho it is its substrate
95
Vernakalant therapeutic use
Atrial fibrillation
96
Vernakalant cardiac effect
Multi ion channel blocker
Slows conduction over AV node
No QT interval change
Increase only atrial effective refractory period
97
Adverse effect of vernakalant
Dysgeusia
Sneezing
Paresthésia
Cough
Hypotension
98
Enzyme that metabolize vernakalant
CYP2D6
99
Sotalol action
Class 2 and class 3 action
100
Excretion of sotalol
Kidney in unchanged form
101
Cardiac toxic effect of sotalol
Torsade de pointes
Further left ventricle dépression in patients with heart failure
102
Sotalol therapeutic use
Ventricular arrythmias
Maintenance of sinus rythm
Used in children for supraventricular and ventricular arrythmias
103
Dofetilide action
Class 3 block Ikr
104
Which drug treatment should start in hospital after measuring QT
Dofetilide
105
Dofetilide therapeutic use
Maintenance of restoratioof normal sinus rhythm in patients with atrial fibrillation
106
Ibutilide action
Slow cardiac depolarization by blocking IKr
107
Route of administration of ibutilide
IV
108
Clearance of ibutilide
Hepatic metabolism
Metabolites cleared by kidneys
109
Ibutilide therapeutic use
Conversion of atrial flutter/ fibrillation to normal sinus rythm
110
Adverse effects of ibutilide
Excessive QT PROLONGATION
Torsade de pointes
111
Class IV - calcium channel blockers
Verapamil
Diltiazem
112
Cardiac effects of verapamil
Block activated and inactivated L type ca channel
Av node conduction and refractory period increased
113
Verapamil extra cardiac effects
Peripheral vasodilation ( good in hypertension
114
Verapamil toxicity
Hypotension and ventricular fibrillation if patient has ventricular tachycardia but was misdiagnosed with supraventricular tachycardia
Large dose can lead to AV block in AV diseases patient ( atropine and B agonist can help)
Comstipation
Nervousness
lassitude
Peripheral edema
115
Bioavailability of verapamil
20%
116
Verapamil therapeutic use
Supraventricular tachycardia (this and adenosine preferred )
Reduce ventricular rate in atrial fibrillatikn and flutter
Sometimes useful in ventricular arrythmias
117
Diltiazem therapeutic
As useful as verapamil in supraventricular arrythmias
118
Diltiazem adverse effects
Hypotension
| Brady arrythmias
119
Drugs that do not fit any class
Digitalis
Adenosine
Magnesium
Potassium
RAAS drugs
Fish oil
Statins
120
Adenosine action
Activation inward rectifier K+
Inhibits calcium current
When given as bolus , will inhibit AV node conduction and increase AV refractory period
121
For what condition is adenosine drug of choice
Conversion of paroxysmal supraventricular tachycardia tonsinus rythm
122
Adenosine receptor blocker that reduce its activity
Theophylline
| Caffeine
123
Adenosine reuptake inhibitor that increase its activity
Dipyridamole
124
Adenosine toxicity
Flushing
```
Shortness of breath
Chest burning
Av block
Atrial fibrillation
Headaches
Hypotension
nausea
Paresthesia
```
125
Magnesium therapeutic use
Digitalis induced arrythmias if hypomagnesemia
Torsades de pointes even if mg normal
126
Potassium action
Resting potential depolarizing action
Stabilize membrane potential
Hyperkalemia depresses ectopic pacemakers , slows conduction
127
Pretreatment evaluation steps
Eliminate cause ( hypoxia, electrolyte abnormalities, drug therapy, cardiac disease etc)
Make diagnosis
Determine baseline condition
Question need for therapy
128
Only drugs associated with reduced mortality in asymptotic patients
B blockers
