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Etiology
Etiology
DEFINITION
DEFINITION
o Torsade de pointes, often referred to as torsade,
is associated with a prolonged QT interval,
which may be congenital or acquired. Torsade
usually terminates spontaneously but frequently
recurs and may degenerate into ventricular
fibrillation.
QTc (msec)
Normal
Borderline
Prolonged
Male
<430
431-450
>450
Female
<450
451-470
>470
QT Correction Formulae
Formula
Mathematical
Expression for QTc
Original Cohort
Mean Age
(Range) (years)
N
Log-Linear
Bazett
QT / (RR)
0.5
39
26 (<14-53)
Fridericia
QT / (RR)
0.33
50
26 (2-81)
Baseline correction
QT / (RR)
0.37
NA
NA
Linear
Framingham
QT + 0.154 (1 RR)
5,018
44 (28-62)
Hodges
607
(20s-80s)
Patophysiology
Torsades De Pointes
Prolonged
QT
Clinical Presentation
o Patients with torsade usually present with
recurrent episodes of palpitations, dizziness, and
syncope; however, sudden cardiac death can
occur with the first episode. Nausea, cold sweats,
shortness of breath, and chest pain also may
occur but are nonspecific and can be produced
by any form of tachyarrhythmia.
Etiology
o Congenital Prolonged QT
o Acquired Prolonged QT :
o Electrolyte Abnormalities : Hipokalemia,
Hipomagnesemia,
o Anty Arythmic Drugs : Quinidine, Procainamide,
Amiodarone, Sotalol
o Antibiotics : Eryhtromicin, Azythromicin, Levofloxacin,
Cotrimoxazole
o Antifungal : Ketoconazole, Itraconazole
o Anti Psychotic : Haloperidol, phenothiazines,
thioridazine
o Anticonvulsants : phenytoin, carbamazepine
(possible)
o Tricyclic and tetracyclic antidepressants
Loperamide
Use of Loperamide
Mechanism of Loperamide
o Loperamide binds to the opiate receptor in gut
wall,
reducing
propulsive
peristalsis
and
increasing intenstinal transit time
o Half Life Loperamide 9-14 hours, well absorbed
from the gut but almost completely extracted
and metabolized by liver and excreted to bile
ducts
o Due to its high affinity fot gut wall and its high
first pass metabolism, very little loperamide
reachs the systemic circulation
Etiology
Discussion
So What was the cause of Torsades de
Pointes in this patient??
Does 8mg/day loperamide can contribute in
this arrhythmia ??
Or Possible Hipomagnesemia / Hipocalcemia
is the reason of this arrhythmia due to his
diarrhea??
Or Possible Drug Interaction from
Loperamide and Amiodarone who contribute
to this TdP??
Or Possible Underlying CAD is the cause?
Loperamide
Loperamide is a derivative of
phenylpiperidine with a chemical
structure similar to the opiate
receptor agonist
Loperamide is a substrate for Pglycoprotein transporter
membranes in the blood and a
highly lipophilic
Pharmacodynamic
Loperamide is an opioid receptor
agonist and act on the -opioid
receptors in the myenteric plexus large
intestines.
On low doses, it does not affect the CNS
like other opioids
It work by decreasing the activity of the
myenteric plexus which decreased
motility smooth muscles
Pharmacokinetic
loperamide metabolized by
cytochrome P450 (CYP) system and a
substrate for CYP3A4 isoenzyme.
Onset of action : 1 hour, maximum effect
16-24 hours
time to peak plasma concentration of 2
hour
plasma half-life: 11 hours
duration: up to 3 days half-life of 7-14
hours, bioavailability <2%
Absorption
following oral dosing, loperamide is
absorbed rapidly with plasma
concentrations in 4 hours
metabolism first to loperamide has
biovabilitas only 0.3%
Distribution,metabo
lism, and excretion
Distribution: loperamide is a substrate that
penetrates the P-glycoprotein that is in the
blood brain barrier and the wall of the
gastrointestinal tract
Metabolism: Loperamide extensively
metabolism in the liver by N-desmethyl
loperamide which is the main metabolic
not yet active through N-demethylation
excretion: loperamide mainly excreted
through the feces but drugs or metabolism
has not changed
Dose
The recommended initial dose is 4mg
(two capsules) followed by 2 mg (one
capsule) after each unformed stool.
Daily dose should not exceed 16mg
(eight capsules).
urinary
retention,
respiratory
depression,
cardiac
Summary
Patient male 72 years old with
palpitation and diagnosed atrial
fibrillation with hipovolemic shock
due to acute gastroenteritis and
treated with loperamide and
digoxin
At 3rd day patient developed
decrease of conciusness with ecg :
Multiple VES leading to VT with
Summary
VT and Torsade de Pointes treated
with amiodarone IV
After that ECG become junctional
bradycardia with CRBBB
Next day ECG become Sinus
Bradycardia
Conclusion
We Cant Exclude cause of Torsade
de Pointes between Loperamide
and Acute Coronary Syndrome
Loperamide may contribute in to
this arryhtmia, but we cant also
exclude acute coronary syndrome
because the history and risk factor
Planning
Thank You