Pharmacology Anti-Arrhythmic 2 Flashcards
(159 cards)
1
Q
what are the cardiac effects of quinidine?
A
same as procainamide
slows the upstroke of the AP
slows conduction
prolongs the QRS duration ECG
prolongs the APD - class 3 action
direct depressant actions on SA and AV nodes
all 1A show reverse use dependence
has vagolytic properties
2
Q
what is the dosage form of quinidine?
A
oral - tablet
Iv - injecton
3
Q
what are the pharmacokinetics of quinidine
A
absorbed in the GI tract
eliminated by hepatic metabolism - CYP3A4
4
Q
what are the adverse effects of quinidine
A
qt interval prolongation
induction of torsades de pointes arrhythmia
excessive sodium channel blocked with slowed conduction throughout the heart
GI - NVD
CINCHONISM - HA dizzy tinnitus
immune - thrombocytopenia, hepatitis, angioneurotic edema, fever
5
Q
does quinidine have DDI effects?
A
substrate of CYP3A4 - strong inhibitors and inducers
6
Q
are there any contraindications for quinidine?
A
drugs causing QT prolongation and electrolyte imbalance
7
Q
which drug from class IA has immediate release and controlled release capsules ?
A
disopyramide
8
Q
how is disopyramide metabolized?
A
CYP3A4
9
Q
T or F disopyramide needs dose adjustment in patients with renal impairment
A
T - decrease dose in renally impaired patietns
10
Q
what is a major CI of disopyramide
A
may cause or worsen CHF - or produce severe hypotension as a consequence o its negative inotropic properties
11
Q
disopyramide is given with
A
drugs slowing ventricular arrhythmia
12
Q
what is a major adverse effect of disopyramide
A
atropine like activity - urinary retention, dry mouth, blurred vision, constipation and worsening of preexisting glaucoma
13
Q
what is the mechanism of action of lidocaine
A
blocks activated and inactivated sodium chanells with rapid kinetics
exerts an antiarrhythmic effect by increasing the electric stimulation threshold of the ventricle during diastole
highly effective in arrhythmias associated with acute MI
greater effects on cells with long action potentials such as purkinje and ventricular cells compared with atrial cells
14
Q
lidocaine is available as what dosage form
A
IV
15
Q
how is lidocaine metabolized
A
extensive first pass metabolism
90% drug metabolized in liver - CYP1A2, 3A4 dealkylation
16
Q
what is the half life of lidocaine
A
1-2 hours - loading and maintenance dose
17
Q
lidocaine has high binding to _______
A
alpha acid glycoprotein
18
Q
due to lidocaine high binding to alpha acid glycoprotein it is important to
A
measure plasma concentration for dose adjs - need higher dose
19
Q
lidocaine dose should be decreased in patients who
A
have CHF
liver disease
take drugs that decrease liver perfusion - propanolol, cimetidine
20
Q
therapeutic use of lidocaine
A
acute management of VA occurring during cardiac manipulations such as cardiac surgery
life threatening arrhythmias which are ventricular in origin occurring during acute MI
21
Q
what are the CI of lidocaine
A
hypersensitivity to amide type anesthetics - lidocaine
stokes adams syndrome
wolf parkinson white syndrome
severe degrees of sinoatrial, atriovetricular or intraventricular block
22
Q
which drug is the least cardiotoxic of the currently used Na+ channel blockers
A
lidocaine
23
Q
what are the toxicities of lidocaine
A
may cause hypotension - partly by depressing myocardial contractility
CNS adverse effects - paresthesia, tremor, nausea of central orgin, lightheadedness, hearing disturbances, slurred speech, and convulsions
24
Q
plasma levels of lidocaine need to be monitored and kept ______- to avoid side effects
A
9 ug/ml
25
what is the appropriate dosage form of mexiletine
oral, capsules
26
what are the similarities between mexiletine and lidocaine
structural similarities - local anesthetic properties
cardiac effects and properties
27
how is mexiletine metabolized?
hepatically by CYP2D6 - 10% unchanged
28
what is the mechanism of action of mexiletine
blocks the fast sodium channel in cardiac tissues, especially the purkinje network without involvement of the autonomic system
29
mexiletine treats
life threatening ventricular arrhythmias such as sustained vtach
30
T or F mexiletine needs dose adjustment in patients with hepatic impairment
T - acidic pH increases clearance
31
what are the adverse effects of mexiletine
neurologic - tremor, blurred vision, lethargy
32
what is the mechanism of action of flecainide
potent blocker of sodium and potassium channels with slow unblocking kinetics
33
T or F flecainide prolongs APD
F
Flecainide does not prolong APD
34
flecainide treats what condition
supraventricular arrhythmias with normal heart
35
what is the dosage form of flecainide
oral - tablet
36
what are the effects of flecainide
decreases ventricular conduction
effective in suppressing premature ventricular contractions and vtach
no antimuscarinic effects
37
what is the pharmacokinetic profile flecainide
well absorbed
half life - 20 hours
hepatic metabolis m- CYP2D6
eliminated by kidneys
38
class 1C drugs cannot be given to
previous MI or Vtach - leads to higher mortality
39
flecainide is used for therapeutic treatment of
life threatening vtach, PSVT, pAF
40
which class IC drug is Proarrhythmogenic
flecainide
41
PSVT stands for
paroxysmal supraventricular tachyvardia
42
propafenone is indicated for patients who
have documented life threatening ventricular arrhythmias
43
what is the mechanism of action propafenone
prolongs teh time to recurrence of symptomatic atrial fibrillation in patients with episodic AF who do not have structural heart disease
of PSVT associated with disabling symptoms in pts who do not have structural heart disease
44
propafenone is similar to propranolol due to
both have weak beta blocking action
45
propafenone is similar in effects to quinidine except
action potential prolongation
46
propafenone has ______ channel kinetics similar to flecainide
sodium / Na+
47
what is the dosage form of propafenone
tablet - oral
48
how is propafenone metabolized
hepatic metabolism
49
what are the CI of propafenone
heart failure
cardiogenic shock
hypotension
disorders of impulse generation and conduction
COPD
bradycardia
electrolyte imbalance
brugada syndrome
50
propafenone should be avoided in pts using
a CYP2D6 inhibitor and CYP 3A4 inhibitor
51
propafenone increase plasma concentrations of
digoxin, warfarin and proponalol
52
what are the AE of propafenone
provoke HF
conduction issues
sudden death - exacerbate arrhythmias
agranulocytosis
exacerbation of myasthenia gravis
53
class III drugs are K+ channel blockers also known as
multichannel blockers
54
class 3 drugs increase
APD and ERP
55
what are the five Class 3 drugs
amiodarone
dronedarone
dofetilide
sotalol
ibutilide
56
patients who fall into the category of underlying structure heart disease are patients who
have HF, LVEF less than 35, CAD, valvular heart disease, LVH
57
what are the key characteristics of class 3 drugs
they block potassium channels in phase 3, or enhance inward current
prolong effective refractory period ERP
increases action potential duration APD
reverse use dependence - high APD slows rates - causing torsade de pointes
low effects when high rates
ALL CAUSE QT PROLONGATION
58
T or F amiodarone is widely used, useful against most arrhythmias
T
59
key components of amiodarone structure is
T4/ thyroxine , two iodine on ring
60
what are the foru types of arrhythmias that can be treated with amiodarone
recurrent ventricular fibrillation
recurrent hemodynamically unstable ventricular tachycardia
afib
ventricular tachy as adj therapy to decrease the freq of uncomfortable cardioverter defibrillator discharges
61
what are the cardiac effects of amiodarone
prolongs APD
* blocks Ikr K+ channels - delayed rectifier
no reverse use dependence
blocks inavativated Na+ channels *
weak adrenergic inhibition and Ca++ bock
slows heart rate and AV node conduction
causes significant QT prolongation - low TdP incidence
62
what are the extra cardiac effects of amiodarone
peripheral vasodilation - IV
63
what dosage form is amiodarone available as
oral and iv
64
what is the bioavailability of the oral dosage form of amiodarone
tablet - 50
65
what is the onset of action of amiodarone
1-3 weeks
66
T or F Amiodarone is not effected by food
F, increased absorbtion with food
67
T or F amiodarone is lipophillic
T
68
where does amiodarone accumulate
in the adipose and thyroid tisseu
69
how is amiodarone metabolized
hepatically, in liver,
CYP3A4, CYP2C8
70
what is a major metabolite of amiodarone
desethylamiodarone
bioactive
71
how is amiodarone excreted?
biliary excretion
72
what is the half life of amiodarone
rapid component - 3-10 day , half the drug
slow component - several weeks
73
how can one achieve rapid effects of amiodarone
via IV administration
74
amiodarone has many DDI concerns, which drugs inhibit CYP3A4 and increase toxicity of amiodarone
protease inhibitors
loratidine
cimetidine
antidepressant - trazodone
grapefruit juice
75
amiodarone has many DDI concerns, it can cause toxicity of which drugs due to enzyme and transporter inhibiton
cyclosporine
atorvastatin, simvastatin
digoxin
quinidine, procainamide, disopyramide
verapamil, propranolol
warfarin
clopidogrel
76
amiodarone has many DDIs, including CYP3A4 inducers which decrease amiodarones efficacy
rifampin
st john wort
77
what are miscellaneous substrates that amiodarone effects
increases fenatanyl , lidocaine
dextromethorpan increases
cholestyramine reduces amiodarone levels
78
amiodarone and which drugs cause QT prolongation and lead to the higher risk of TdP
fluoroquinolones
macrolide abx
azoles
79
what are the toxicities of amiodarone
pulmonary toxicity
bradycardia and heart block
worsened arrhythmia
thyrotoxicosis - blocks T4 to T3, large iodine in the body
liver injury
skin gray blue deposits
loss of vision - corneal microdeposits
80
amiodarone may result in hypothyroidism which is known as
wolff chaikoff effect
81
what is a structural analog of amiodarone
dronedarone
82
how is dronedarone different from amiodarone
the iodine is removed, methanesulfonyl group on bezofuran
83
what does the structural modification of amiodarone to dronedarone cause
there is no effect on the thyroxine metabolism but there is a decrease in half life
84
what are key similarities between amiodarone and dronedarone?
cardiac effects
drug drug interactions
liver toxicity
absorption increases with food
85
what are the key differences between amiodarone and dronedarone
no thyroid effects
no pulmonary toxicity
86
what is the half life of dronedarone
24 hours
87
T or F dronedarone is both a substrate and inhibitor of CYP3A4
T
88
T or F dronedarone is renally eliminated
F
89
what is the black box warning for dronedarone
DO NOT USE IN HEART FAILURE PATIENTS
90
what is a side effect of dronedarone?
it increases tubular secretion of creatinine which leads to 10-20% increase in creatinine
91
what is the mechanism of action of sotalol
beta adrenergic receptor blocking Class 2 and action potential prolonging Class 3 actions
92
what are the therapeutic uses of sotalol
life threatening ventricular arrhythmias and the maintenance of sinus rhythm in patients with afib
pediatric arrhythmias
decreases threshold for cardiac defib
WPW syndrome
93
in what dosage forms is sotalol available
oral, IV
94
what is the distribution of sotalol
well absorbed with a 100% bioavailability
95
T or F sotalol binds to 50% of plasma proteins
F, no binding to plasma proteins
96
how is sotalol metabolized
NO METABOLISM
97
how is sotalol excreted
unchanged during eliminiation in urine
98
what is the half life of sotalol
12 hours
99
what are the toxicities of sotalol
dose related incidence of torsafes de pointes
can cause serious ventricular arrhythmia
caution in using with drugs that prolong QT interval
caution in patients with HF
BRONCHOSPASM
anaphylaxis
caution in patients with heart block
100
what is the mechanism of action of dofetilide
class 3 purely
dose dependent blockade of the delayed rectifier potassium current
blockade of IKr increases hypokalemia
101
T or F Dofetilide shows moderate reverse use dependence
T
102
what is the bioavailability of dofetilide
100%
103
what is the metabolism of dofetilide
20% metabolized, metabolites are inactive
104
how is dofetilide eliminated
in the urine
105
what drug increases the peak plasma concentration of dofetilide
verapamil
106
does dofetilide need to be adjusted for renally impaired patients
yes
107
drugs like cimetidine which inhibit the renal cation secretion mechanism cause what effect when taken with dofetilide
prolong the half life of dofetilide
108
what are the therapeutic uses of dofetilide
effective in restoring the normal sinus rhythm in patients with afib
second to amiodarone in arrhythmia with HF
109
what are the toxicities of dofetilide
ventricular arrhythmia
QT prolongation
Tdp
TdP risk higher with k depleting diuretics
caution with drugs that prolong QT and antiarrhythmic agents
110
Dofetilide is CI in
Qt prolongation
bradycardia
hypokalemia
111
Ibutilide is a therapeutic agent for patients with
atrial flutter
afib
112
what is the mechanism of action of ibutilide
class 4 - blocks Ikr and activation of slow inward sodium current
113
what is the dosage form of ibutilide
IV
114
how is ibutilide metabolized
rapidly by the liverh
115
how is ibutilide excreted
excreted by KIDNEYs
116
what is the half life ibutilide
6 hrs
117
what are the adverse effects of ibutilide
qt prolongation
tdp
moitor ECG for 4 hours after IV administration till QT returns to normal
118
what are the calcium channel blockers for antiarrhythmia
verapamil
diltiazem
119
T or F DHP like nifedipine also share antiarrhythmic efficacy
F, they do not and may precipitate arrhythmias
120
what is the mechanism of action of class IV drugs
block both activated and inactivates L type calcium channels
decreases SA node and AV node rate
121
______ can decrease both early and delayed after depolarization
verapamil
122
what are the misc agents that have anti-arrhythmic properties
adenosine
ranolazine
ivabradine
magnesium
123
_____ is a naturally occuring nucleoside
adenosine
124
what is the mechanism of action of adenosine
activates GPCR in the heart, Gi coupled which leads to the activation of inward rectifier K current leading
inhibition of calcium curent
125
what is the therapeutic use of adenosine
acute termination of reentrant supraventricular arrhythmias
126
what are the cardiac effects of adenosine
activates ach sensitive K+ current in the atrium, snius and av nodes
this leads to shortened action potential duraton, hyperpolarization and slowing of automaticity
slow HR, slow AV conduction
DECREASES INTRACELLULAR EFFECTS OF CYCLIC AMP decreases ca++currents
127
what is the dosage form of adenosine
IV bolus only
128
what is the half life of adenosine
seconds, rapid uptake
129
how is adenosine metabolized
deamination
130
what are the adverse effects of adenosine
safer - rapid clear
transient asystole
chest fullness and dyspnea when therapeutic doses
afib bronchospasm is rare
131
DDI of adenosine
potentiation with dipyridamole
caffeine and theophylline have antagonising effects
132
what is the dose of magnesium typically used
1g as sulfate given IV for 20 minutes
133
what is the mechanism of action of magnesium
unknown, influences na K atpase, na channels , some k channels and ca channels
134
magnesium is used to treat patients with
digitalis induced arrhythmias if hypomg
torsades de pointes even if normal mg
135
which antianginal and anti-arrhythmic agent is a piperazine derivative
ranolazine
136
ranolazine is a ____ and blocks late __ current
metabolic modulator
Na+
137
what is the moA of ranolazine
inhibits late inward sodium current in heart muscle
138
what is the result of the moa of ranolazine
leads to reductions in elevated intracellular calcium levels which leads to reduced tension in the heart wall leading to o2 requirements reducing for the muscle
139
the effects of ranolazine are
increased glucose oxidation
increasing cardiac atp prod
prolongs APD an QT interval
decreasing edematous end products
decreases FA oxidation
DECREASES MYOCARDIAL O2 REQUIREMENTS
DECREASE CELL CONTRACTURE AND RUPTURE BY BALANCING NA CA CHANNEL
DECREASE MYOCARDIAL CELL SWELLING
140
what is the normal adult dosage form of ranolazine and dose
extended release tablets
500 mg orally twice daily
141
how is ranolazine metabolized
CYP3A4
142
how is ranolazine excreted
urine, monitor renal function
143
DDI of ranolazine
cyp3a4 inducers and inhibition
144
what is the CI of ranolazine
liver cirrhosis
strong CYP3A4 inhibitors and inducers
145
what are the ADR of ranolazine
constipation
nausea
dizzy
asthenia - weakness loss of energy
qt prolongation but no Tdp
146
what is the mechanism of action of ivabradine
selective blocker of hyperpolarization - activated HCN ion channels - called class 0 action
147
with ivabradine , __ node function is regulated
SA
148
what is the caridac effect of ivabradine
decreases heart rate and thus oxygen demand
149
what drug is a parasympatholytic
atropine
150
what is the therapeutic use of atropine
symptomatic bradycardia
bradycardia with malignant escape rhythms and asystole
151
how is atropine administered
IV
152
what is a caution to be aware of giving pts atropine
there is a paradoxical decrease in HR in AV block patientswha
153
what are the AE of atropine
dry mouth
blurred vison
urinary retention
higher doses lead to CNS effects
154
what is a general problem with anti arrhythmic drugs
can cause cardiac arrest at high doses by inhibiting all pacemaker activity
155
many anti arrhythmic drugs are _____ especially at high doses by slowing conduction (RE ENTRY)
pro arrhythmic
156
T or F some of the side effects of anti arrhythmic drugs are IRREVERSIBLE
T
157
what are the general adverse effects of anti arrhythmic drugs
torsades
cinchonism
lupus
cholinergic
seizures
ataxia
nystagmus
sudden death
pulmonary fibrosis
158
what is a key thing to remember when determining use of anti arrhythmic drugs
must determine whether the benefit of treatment outweights the liabiliteis of drug administration
159
