Date post: | 30-Apr-2017 |
Category: |
Documents |
Upload: | rama-mulyadi |
View: | 218 times |
Download: | 0 times |
Cardiovascular
Drugs:
PDF created with pdfFactory trial version www.pdffactory.com
Ika Yulia Rizki11110122053
Calcium Channel- Blocking
Agents
Digilatis
β Adrenergic Antagonists
PDF created with pdfFactory trial version www.pdffactory.com
Calcium Channel-Blocking Agentsv Calcium channel blockers (CCBs) were initially introduced forus
ein the
UnitedStates in 1981,
and extended-releaseformulations were available 10 years
later.
v Indications for
arrhythmias,
prophylaxis.
use of
these
drugs are angina, hypertension,subarachnoi
dhemorrhage
and migraine
PDF created with pdfFactory trial version www.pdffactory.com
Calcium Channel-Blocking
Agents
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
Pharmacology
v The CCB currently available act on
L-Type
channel
of cardiacand vascula
rsmooth
muscle
cells.
5 6 IIIII
IVI
56III IV
PDF created with pdfFactory trial version www.pdffactory.com
Pharmacologyv Antagonisms of L-Type channels results primarily in
effects
onthe 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
Pharmacokinetics
Absorption(%)
Volume ofDistribution(L/Kg)
Protein Bonding(%)
Terminalhalf-life (h)
Verapamil
>90 4.7 90 3-7
Diltiazem
>90 5.3 80-90 4
Nifedipine >90 0.8-1.4 90 5
Amlodipin
100 21.4 >95 35
PDF created with pdfFactory trial version www.pdffactory.com
Toxicityv Acute toxicity
Case reports describing Overdose of S-R Preparearions
describe
a delayin symptoms by as long( Verapamil, Diltiazem,
as 15-24 h.Nifedipine, Amlodipin)
v Toxic dose??
v Chronic toxicityCCB are essentially
free of Chronic toxicity.
PDF created with pdfFactory trial version www.pdffactory.com
Clinical Presentationv
Hypotentionv Cardiac dysrhythmics: Bradycardiav Gastroanerities
v Adult Respiratory Distress Syndromev Depressed level
of consciousness,
…
v Hyperglycemia
v Lactic acidosis
PDF created with pdfFactory trial version www.pdffactory.com
The ionic control of
insulin
release
from
humanpancrea
ticcells
PDF created with pdfFactory trial version www.pdffactory.com
Treatmentv Establish ABes
,obtain
intravenous
(IV) access, provide
oxygenation
v Administration of activated charcoal: repeated doses may be
used, especially with ingestions of sustained-released agents.
v Whole bowel irritationwith
polyethylene
glycol
solution
(SR)
v Sodium bicarbonatev Atropin
PDF created with pdfFactory trial version www.pdffactory.com
Treatmentv ea salt: eacl2 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
Absorption(%)
Volume ofDistribution(L/Kg)
Protein Bonding(%)
Terminalhalf-life (h)
Verapamil
>90 4.7 90 3-7
Diltiazem
>90 5.3 80-90 4
Nifedipine >90 0.8-1.4 90 5
Amlodipin
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 PreparationSingle 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
YesNo
dose activated charcoal
PDF created with pdfFactory trial version www.pdffactory.com
Atropinea salt Glucagon Phosphodiestrase inhibitors Insulin-dextrose…
Whole bowel irritation or multiple
eonsider single dose activated charcoal
Beta-blockersv Beta-adrenergic antagonists
use for nearly 50 years.
(ie, beta-blockers) have been in
v In addition to their traditional role in treating hypertension andother cardiovascular
disorders,beta-blockers are also used foradditiona
lpurposes
such
asanxiety,
migraine
and
headaches,hyperthyroidis
m,disorders.
glaucoma,
various
other
PDF created with pdfFactory trial version www.pdffactory.com
Beta- Receptor
β 1- βv 4
: Eye, Kidney, Heart
β 1
β : 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
Pharmacologyv Beta1-blockers reduce heart rate, blood pressure, myocardial
contractility, and myocardial oxygen consumption.
v Beta2-blockers inhibit
relaxation
of smooth
muscle
in bloodvessels, 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
Pharmacology
PDF created with pdfFactory trial version www.pdffactory.com
Pharmacokinetics
OralBioavailibility(%)
Volume ofDistribution(L/Kg)
ProteinBonding(%)
LipidSolubility
Atenolol
0.750 15 Low
earvedilol 1.625-35 95 High
Metoprolol
5.540-50 12 Moderate- High
Propranolol
3.630 90 High
PDF created with pdfFactory trial version www.pdffactory.com
Toxicityv After acute oral
overdose,signs of
toxicity
usually
beginwithin 30 min and peak by 2 h.
v The lipid solubility of
the degree of clinical
beta blockers can significantly influencetoxicityblood-
observed after overdose owing
to penetration
of brain barrier.
(propranolol,
metoprolol, carvedilol)
PDF created with pdfFactory trial version www.pdffactory.com
Toxicityv The concentration of propranolol in eNS may exceed
that
seenin plasma by as much as
20fold.
v Toxic dose??
v In overdose
of drugs,
a eeB
themay
combination
of a Betablocker
and lead to hypotension,
bradycardia and Death.
PDF created with pdfFactory trial version www.pdffactory.com
elinical
Presentation
v eardiacBradycardiaHypotension eardiac conduction
deffects
v PulmonaryRespiratory depressionBronchospasm
PDF created with pdfFactory trial version www.pdffactory.com
elinical
Presentation
v NeurologicDrowsiness eoma Seizure
v The lipid-soluble
agents (propranolol) haveincreased distribution into the brain, and
theseagents are associated with severe eNS toxicity. Propranolol: ( Direct effect on eNS)
PDF created with pdfFactory trial version www.pdffactory.com
elinical
Presentation
v Other
Beta blockers
may be expected to cause
many
potential effects:Hypoglycemia, Rhabdomyolysis,
Acute
renalrenal
failure on the
basis
of decreased
perfusion, and metabolichypoperfusion
acidosis secondary to
PDF created with pdfFactory trial version www.pdffactory.com
Treatmentv The goal of
to
therapycritical
in beta-blocker
toxicity
is to restoreperfusio
norgan syste
msby increasin
gcardiacoutput
.This may
be accomplished
by improving
myocardialcontractility, increasing heart rate, or
both.
v eardiac monitoring, oxygen
administration,
and reliableintravenous access are essential.
v GI decontaminant: Activated charcoal
PDF created with pdfFactory trial version www.pdffactory.com
Treatmentv 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 contractilityAdverse effect: Nausea, Vomiting and hyperglycemiav eacl2
v Inamrinone (inhibitor of phosphodiesterase III )
PDF created with pdfFactory trial version www.pdffactory.com
Treatmentv Benzodiazepines are the drugs of choice if seizures occur.
v Bronchospasm: salbutamol, Aminophylin
v Enhanced elimination: Hemodialysis may be useful in
severecase
sof Atenolo
loverdoses
because
of lowby
PB and VDPropranolol
and metoprolol,
are not
removed
hemodialysis.
PDF created with pdfFactory trial version www.pdffactory.com
Digoxinv Digitalis was
introducedinby
to clinical
medicine
William Withering in 1785.He reporte
dtherapeutic
efficacyleaves of
and toxicity
ofDigitalis purpurea.
PDF created with pdfFactory trial version www.pdffactory.com
Digoxinv eongestive heart
failure
v Atrial fibrillation
v Atrial flutter
PDF created with pdfFactory trial version www.pdffactory.com
Pharmacology
PDF created with pdfFactory trial version www.pdffactory.com
Pharmacokinetics
Absorption(%)
Volume ofDistribution(L/Kg)
ProteinBonding(%)
Half-life
Clearance
55 -7590-100
Digoxin
5.6 25 33-34 h Renal
PDF created with pdfFactory trial version www.pdffactory.com
Toxicityv Drug interactio
nand othe
rfactors,
such
as electrolyteabnormalitie
s,renal or hepati
cfailure,
ischemia,
orinflamation, predispose
to digoxin toxicity.
v Amiodaronedigoxin.
- Reduces
renal and nonrenal
clearance
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
Toxicityv ealcium channel blockers - Diltiazem and verapamil increase
serum digoxin level.
v Potentially toxic interaction may also occure with k-
sparing
diuretics
which
inhibit
tubular
secretion
of digoxin.
PDF created with pdfFactory trial version www.pdffactory.com
Toxicityv Therapeutic range: 0.5-2
ng/ml
v Lethal range: >15 ng/ml
v Toxic dose: >2 - 3 mgv Lethal dose
:>10 mg
PDF created with pdfFactory trial version www.pdffactory.com
elinical Presentation
v
DysrhythmiaHeadacheWeakness Depression eonfusion Disorientation Hallucination
v
(Brady
and Thachyarrhythmia)
v
v
v
v
v
PDF created with pdfFactory trial version www.pdffactory.com
eardiovascular eNS
elinical Presentation
v Disturbances of
color
vision
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 Hypokalemia
v
v
BradyarrhythmiaTachyarrhythmiaDigoxin toxicity
v
does notbut
v
cause
hypokalemia,hypokalemi
acan
worsendigoxin
toxicity
PDF created with pdfFactory trial version www.pdffactory.com
Acute Toxicity ehronic Toxicity
Treatmentv Initiate supportive
and IV access.
therapy
with
oxygen,
cardiac monitoring,
v Activatedaccidental
charcoal
ingestion.
is indicated
for acute
overdose
or
v Phenytoin and magnesium sulfate
v eorrect electrolyte abnormalities,
hypomagnesemia.
especially hypokalemia and
PDF created with pdfFactory trial version www.pdffactory.com
Treatmentv Treat hyperkalemia
Sodium bicarbonate (1mEq/ml).
v ealciumsetting
is not
recommended
to treat hyperkalemia
in thisbecaus
eventricular
tachycardia
or ventricularfibrillation may be
precipitated.
v Treatment with digoxin-fab fragments
PDF created with pdfFactory trial version www.pdffactory.com
Treatmentv Digoxin fab fragments:1-2-3-
Hyperkalemia > 5.5 meq/mlSerum digoxin level greater than 10 ng/mLIngestion greater than
5 mg in adults, …
Number of vials: 2 ×serum
level
(ng/ml)
×5.6 × Weight(Kg)/ 1000
Acute Toxicity: 10 - 20 vialehronic Toxicity: 3 - 6 vial
PDF created with pdfFactory trial version www.pdffactory.com