Vous êtes sur la page 1sur 42

Cardiovascul

ar
Drugs
:
PDF created with pdfFactory trial version www.pdffactory.com
Calcium Channel-
Blocking
Agent
s
Digilati
s
Adrenergic Antagonists
PDF created with pdfFactory trial version www.pdffactory.com
Calcium Channel-Blocking
Agents
v Calcium channel blockers (CCBs) were initially
introduced for
us
e
in the
United
States in
1981,
and extended-
release
formulations were available 10 years
later.
v Indications for
arrhythmia
s,
prophylaxi
s.
use
of
thes
e
drugs are angina,
hypertension,
subarachnoi
d
hemorrhag
e
and migrain
e
PDF created with pdfFactory trial version www.pdffactory.com
Calcium Channel-
Blocking
Agent
s
v Structure
1- Phenylalkylamines:
Verapamil
2- Benzothiazepines:
Diltiazem
3- Dihydropyridines: Nifedipine,
Amlodipine,
4- Diarylaminopropylethers:
Bepridil
5- Tertraline Derivatives:
Mibefradil
PDF created with pdfFactory trial version www.pdffactory.com
Pharmacolo
gy
v The CCB currently available act
on
L-
Type
chann
el
of cardia
c
and vascula
r
smoot
h
muscl
e
cells
.
5
6
III
II
IV
I
5
6
III IV
PDF created with pdfFactory trial version www.pdffactory.com
Pharmacolo
gy
v Antagonisms of L-Type channels results
primarily in
effect
s
on
the
heart
and peripheral vascular smooth
muscle.
v Negative chronotropy (decreased heart
rate)
v Negative inotropy (decreased cardiac
contractility)
v Decrease cardiac out put and
Hypotension
PDF created with pdfFactory trial version www.pdffactory.com
Pharmacokineti
cs
Absorptio
n
(%)
Volume of
Distribution(L/K
g)
Protein
Bonding(%)
Terminal
half-life
(h)
Verapami
l
>90 4.7 90 3-7
Diltiaze
m
>90 5.3 80-90 4
Nifedipin
e
>90 0.8-1.4 90 5
Amlodipi
n
100 21.4 >95 35
PDF created with pdfFactory trial version www.pdffactory.com
Toxicit
y
v Acute toxicity
Case reports describing Overdose of S-R
Preparearions
describ
e
a delay
in symptoms by as
long
( Verapamil,
Diltiazem,
as 15-24 h.
Nifedipine,
Amlodipin)
v Toxic
dose??
v Chronic toxicity
CCB are
essentially
free of Chronic
toxicity.
PDF created with pdfFactory trial version www.pdffactory.com
Clinical
Presentation
v
Hypotention
v Cardiac dysrhythmics:
Bradycardia
v
Gastroanerities
v Adult Respiratory Distress
Syndrome
v Depressed
level
of consciousn
ess,

v Hyperglycemia
v Lactic
acidosis
PDF created with pdfFactory trial version www.pdffactory.com
The ionic control
of
insuli
n
releas
e
from huma
n
pancreati
c
cell
s
PDF created with pdfFactory trial version www.pdffactory.com
Treatme
nt
v
Establish
ABes
,
obtai
n
intraveno
us
(IV
)
access,
provide
oxygenatio
n
v Administration of activated charcoal: repeated doses may
be
used, especially with ingestions of sustained-released
agents.
v Whole bowel irritation with polyethylen
e
glyco
l
solutio
n
(SR
)
v Sodium
bicarbonate
v Atropin
PDF created with pdfFactory trial version www.pdffactory.com
Treatme
nt
v ea salt: eacl
2
10 %

(Verapamil and
Diltiazem )
v Glucagon (5-10 mg, 2-10 mg/h ): Acts via cAMP to
increase
cardiac contractility and also may decrease heart block
v Inamrinone (inhibitor of phosphodiesterase III )
v Insulin-Dextrose: 0.1-1 Units/kg/h IV, with mean
doses
of
0.5
Units/kg/h
v Hemodialysis
and
hemoperfusion are not
effective
PDF created with pdfFactory trial version www.pdffactory.com
Hemodialysis and hemoperfusion are not
effective
Absorptio
n
(%)
Volume of
Distribution(L/K
g)
Protein
Bonding(%)
Terminal
half-life
(h)
Verapami
l
>90 4.7 90 3-7
Diltiaze
m
>90 5.3 80-90 4
Nifedipin
e
>90 0.8-1.4 90 5
Amlodipi
n
100 21.4 >95 35
PDF created with pdfFactory trial version www.pdffactory.com
Yes No
No
Yes
PDF created with pdfFactory trial version www.pdffactory.com

SR Preparation

Single dose activated charcoal
Observe in monitored setting
>12 h
( > 24 h if SR )

elinical evidence of
toxicity
( hypotension,
bradycardia)

Patients presents with eeB overdose
SR
Preparation
Yes No
dose activated
charcoal
PDF created with pdfFactory trial version www.pdffactory.com

Atropin
ea salt Glucagon
Phosphodiestrase
inhibitors
Insulin-dextrose


Whole bowel irritation or
multiple

eonsider single
dose
activated charcoal
Beta-
blockers
v Beta-adrenergic
antagonists
use for nearly 50 years.
(ie, beta-blockers) have been
in
v In addition to their traditional role in treating hypertension
and
other cardiovascular
disorders,
beta-blockers are also used
for
additiona
l
purpose
s
suc
h
as
anxiety,
migrain
e
and
headache
s,
hyperthyroidis
m,
disorders.
glaucom
a,
variou
s
othe
r
PDF created with pdfFactory trial version www.pdffactory.com
Beta-
Receptor

1
-

v
4
: Eye, Kidney,
Heart

1


: Lung, Vascular
system,
Metabolic
system
2
Nonselective beta-blockers : Propranolol,
carvedilol,
timolol, ..
Selective beta-blockers: Atenolol,
Metoprolol,
Sotalol
,
PDF created with pdfFactory trial version www.pdffactory.com
Pharmacolo
gy
v Beta1-blockers reduce heart rate, blood pressure,
myocardial
contractility, and myocardial oxygen consumption.
v Beta2-
blockers
inhibi
t
relaxatio
n
of smoot
h
muscl
e
in blood
vessels, lungs and the gastrointestinal
system.
v In addition, beta-adrenergic receptor antagonism
inhibits
glycogenolysis and gluconeogenesis, which may
result in hypoglycemia.
both
PDF created with pdfFactory trial version www.pdffactory.com
Pharmacolo
gy
PDF created with pdfFactory trial version www.pdffactory.com
Pharmacokineti
cs
Oral
Bioavailibilit
y
(%)
Volume of
Distributio
n
(L/Kg)
Protein
Bonding(
%)
Lipid
Solubilit
y
Atenolo
l
0.7
50 15 Lo
w
earvedilol 1.6
25-35 95 Hig
h
Metoprolo
l
5.5
40-50 12 Moderate-
High
Propranolo
l
3.6
30 90 Hig
h
PDF created with pdfFactory trial version www.pdffactory.com
Toxicit
y
v After acute oral
overdose,
signs
of
toxicit
y
usuall
y
begi
n
within 30 min and peak by 2
h.
v The lipid solubility of
the degree of
clinical
beta blockers can significantly
influence
toxicit
y
blood-
observed after overdose
owing
to penetratio
n
of brain barrier. (propranolol
,
metoprolol,
carvedilol)
PDF created with pdfFactory trial version www.pdffactory.com
Toxicit
y
v The concentration of propranolol in eNS may
exceed
that see
n
in plasma by as much as
20
fold.
v Toxic
dose??
v In overdos
e
of
drugs,
a eeB
the
may
combinatio
n
of a Bet
a
blocke
r
and lead to hypotensio
n,
bradycardia and
Death.
PDF created with pdfFactory trial version www.pdffactory.com
elinica
l
Presentati
on
v eardiac
Bradycardia
Hypotension
eardiac
conduction
deffect
s
v Pulmonary
Respiratory
depression
Bronchospasm
PDF created with pdfFactory trial version www.pdffactory.com
elinica
l
Presentati
on
v Neurologic
Drowsine
ss
eoma
Seizure
v The lipid-
soluble
agents (propranolol)
have
increased distribution into the brain, and
these
agents are associated with severe eNS
toxicity. Propranolol: ( Direct effect on eNS)
PDF created with pdfFactory trial version www.pdffactory.com
elinica
l
Presentati
on
v Other
Beta
blockers
may be expected to
cause
man
y
potential
effects:
Hypoglycemia,
Rhabdomyolysis,
Acut
e
renal
renal failure on the basi
s
of decrease
d
perfusion, and
metabolic
hypoperfusion
acidosis secondary
to
PDF created with pdfFactory trial version www.pdffactory.com
Treatme
nt
v The goal of
to
therap
y
critical
in beta-
blocker
toxicit
y
is to
restore
perfusio
n
orga
n
syste
ms
by increasin
g
cardia
c
output
.
This
may
be accomplish
ed
by improvin
g
myocardia
l
contractility, increasing heart rate, or
both.
v eardiac monitoring,
oxygen
administratio
n,
and reliable
intravenous access are
essential.
v GI decontaminant: Activated
charcoal
PDF created with pdfFactory trial version www.pdffactory.com
Treatme
nt
v Atropin (0.01-0.03 mg/kg
IV)
v Glucagon ( 5- 10 mg/ IV bolus, continuous
infusion of
1-5 mg/h)
Effect: Increase myocardial heart rate and
contractility
Adverse effect: Nausea, Vomiting and
hyperglycemia
v eacl
2

v Inamrinone (inhibitor of
phosphodiesterase III )
PDF created with pdfFactory trial version www.pdffactory.com
Treatme
nt
v Benzodiazepines are the drugs of choice if seizures
occur.
v Bronchospasm: salbutamol,
Aminophylin
v Enhanced elimination: Hemodialysis may be
useful in
sever
e
case
s
of Atenolo
l
overdose
s
becaus
e
of low
by
P
B
and VD
Propranol
ol
and metoprolo
l,
are not remove
d
hemodialysi
s.
PDF created with pdfFactory trial version www.pdffactory.com
Digoxi
n
v Digitalis was
introduced
in
by to clinica
l
medicin
e
William Withering in
1785.
He reported therapeuti
c
efficacy
leaves
of
and toxicit
y
of
Digitalis
purpurea.
PDF created with pdfFactory trial version www.pdffactory.com
Digoxi
n
v eongestive
heart
failure
v Atrial fibrillation
v Atrial flutter
PDF created with pdfFactory trial version www.pdffactory.com
Pharmacolo
gy
PDF created with pdfFactory trial version www.pdffactory.com
Pharmacokineti
cs
Absorptio
n
(%)
Volume of
Distribution(L
/K
g)
Protein
Bonding(
%)
Half-
life
Clearanc
e
55 -75
90-100 Digoxi
n
5.6 25 33-34 h Rena
l
PDF created with pdfFactory trial version www.pdffactory.com
Toxicit
y
v Drug interactio
n
and othe
r
factors
,
suc
h
as electrolyt
e
abnormalitie
s,
renal or hepati
c
failure
,
ischemi
a,
or
inflamation,
predispose
to digoxin
toxicity.
v Amiodarone
digoxin.
- Reduc
es
renal and nonren
al
clearanc
e
of
v Beta-blockers (propranolol, metoprolol, atenolol) - May
have
additive effects , carvedilol may increase digoxin blood
levels in addition to potentiating its effects on the heart
rate.
PDF created with pdfFactory trial version www.pdffactory.com
Toxicit
y
v ealcium channel blockers - Diltiazem and verapamil
increase
serum digoxin level.
v Potentially toxic interaction may also occure
with k-
sparin
g
diuretic
s
whic
h
inhibi
t
tubula
r
secretio
n
of digoxin
.
PDF created with pdfFactory trial version www.pdffactory.com
Toxicit
y
v Therapeutic range: 0.5-
2
ng/ml
v Lethal range: >15 ng/ml
v Toxic dose: >2 - 3 mg
v Lethal dose
:
>10 mg
PDF created with pdfFactory trial version www.pdffactory.com
elinical
Presentation
v
Dysrhythmia
Headache
Weakness
Depression
eonfusion
Disorientati
on
Hallucinatio
n
v
(Brad
y
and Thachyarrhythmi
a)
v
v
v
v
v
PDF created with pdfFactory trial version www.pdffactory.com

eardiovascular

eNS
elinical
Presentation
v Disturbances
of
colo
r
visio
n
v Nausea,
vomiting,
and diarrhea
anorexia
,
v Blurred
vision
v Abdominal pain
(uncommon)
v Photophobia
PDF created with pdfFactory trial version www.pdffactory.com

Ocular

Gastrointestinal
elinical
Presentation
v Hyperkalemia Hypokalemi
a
v
v
Bradyarrhythmia
Tachyarrhythm
ia
Digoxin
toxicity
v
doe
s
not
but
v
caus
e
hypokalemi
a,
hypokalemi
a
ca
n
worse
n
digoxin
toxicity
PDF created with pdfFactory trial version www.pdffactory.com

Acute Toxicity

ehronic Toxicity
Treatme
nt
v Initiate
supportive
and IV access.
therap
y
with oxygen
,
cardia
c
monitorin
g,
v Activated
accident
al
charcoa
l
ingestio
n.
is indicate
d
for acut
e
overdos
e
or
v
Phenytoin
and magnesium
sulfate
v eorrect electrolyte
abnormalities,
hypomagnesemia.
especially hypokalemia
and
PDF created with pdfFactory trial version www.pdffactory.com
Treatme
nt
v Treat hyperkalemia
Sodium bicarbonate
(1mEq/ml).
v ealcium
setting
is not recommend
ed
to treat hyperkalemi
a
in thi
s
becaus
e
ventricula
r
tachycardi
a
or ventricula
r
fibrillation may be
precipitated.
v Treatment with digoxin-fab
fragments
PDF created with pdfFactory trial version www.pdffactory.com
Treatme
nt
v Digoxin fab
fragments:
1-
2-
3-
Hyperkalemia > 5.5 meq/ml
Serum digoxin level greater than 10
ng/mL
Ingestion greater
than
5 mg in adults,

Number of vials: 2
serum
leve
l
(ng/ml) 5.6 Weight (Kg)/ 1000
Acute Toxicity: 10 - 20
vial
ehronic Toxicity: 3 - 6
vial
PDF created with pdfFactory trial version www.pdffactory.com
Than
k
yo
u
PDF created with pdfFactory trial version www.pdffactory.com