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• Arquivo
• Arritmias e insuficiência cardíaca congestiva

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Electrocardiograms
Isoelectric point
R
T
P
S
Q
Normal ECG
Ventricular premature beat
Ventricular tachycardia
Ventricular fibrillation
Int. Pharmacology Chapter 18
4
Normal electrocardiogram
Textbook of Medical Physiology Guyton Hall
Fig11.1
5
Above, Monophase action potential from a
ventricular muscle fiber during normal cardiac
function, showing rapid depolarization and then
repolarization occurring slowly during the
plateau stage but rapidly toward the end. Below,
Electrocardiogram recorded simultaneously
Textbook of Medical Physiology Guyton Hall
Fig11.3
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Normal electrocardiograms recorded from the three
standard electrocardiographic leads
Textbook of Medical Physiology Guyton Hall
Fig11.7
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Normal electrocardiograms recorded from the six
standard chest leads
Textbook of Medical Physiology Guyton Hall
Fig11.9
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Normal electrocardigrams recorded from the three
augmented unipolar limb leads
Textbook of Medical Physiology Guyton Hall
Fig11.10
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A Normal 12-leadECG recording. The recording were
obtained synchronously, tree leads at a time ( I,
II and III simultaneously) A 1-mV, 200-msec
calibration pulse is visible in the three top
recordings
Medical Physiology Boron Boupaep fig.20-10
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A Normal 12-leadECG recording. The recording were
obtained synchronously, tree leads at a time (
aVR, aVL, and aVF simultaneously) A 1-mV,
200-msec calibration pulse is visible in the
three top recordings
Medical Physiology Boron Boupaep fig.20-10
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A Normal 12-leadECG recording. The recording were
obtained synchronously, tree leads at a time (V1,
V2, and V3 simultaneously) A 1-mV, 200-msec
calibration pulse is visible in the three top
recordings
Medical Physiology Boron Boupaep fig.20-10
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A Normal 12-leadECG recording. The recording were
obtained synchronously, tree leads at a time (V4,
V5, V6 simultaneously) A 1-mV, 200-msec
calibration pulse is visible in the three top
recordings
Medical Physiology Boron Boupaep fig.20-10
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Pathological ECGs
A- Normal Sinus Rhythm
Medical Physiology Boron Boupaep fig.20-13
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Pathological ECGs
B- First-Degree Block
Medical Physiology Boron Boupaep fig.20-13
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Pathological ECGs
C- Second-Degree BlockMöbitz Type I
Medical Physiology Boron Boupaep fig.20-13
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Pathological ECGs
C- Second-Degree BlockMöbitz Type II
Medical Physiology Boron Boupaep fig.20-13
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Pathological ECGs
E- Bundle Branch Blocks
Medical Physiology Boron Boupaep fig.20-13
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Pathological ECGs
F- Third-Degree Block
Medical Physiology Boron Boupaep fig.20-13
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Pathological ECGs
G- Delta Wave (Wolf-Parkinson-White Syndrome)
Medical Physiology Boron Boupaep fig.20-13
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Pathological ECGs
H- Atrial Fibrillation
Medical Physiology Boron Boupaep fig.20-13
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Pathological ECGs
Ventricular Fibrilation
Ventricular tachycardia
Ventricular Fibrillation
Sinus rhythm
Medical Physiology Boron Boupaep fig.20-13
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Main mechanisms of arrhythmogenesis
Int. Pharmacology Chapter 18
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Vaughan Williams classification of antiarrhythmic
drugs
Electrophysiologic actions
Class
Type of drug
Examples
I a Na channel Blocks conduction Quinidine
blocker increases ERP Disopyramide I b
Na channel Blocks conduction Lidocaine
blocker decreases ERP Mexiletine I c
Na channel Blocks conduction Flecainide
blocker no effect on ERP, Encainide
Int. Pharmacology Chapter 18
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Vaughan Williams classification of antiarrhythmic
drugs
Electrophysiologic actions
Class
Type of drug
Examples
II ß Adrenoceptor Decreases sinus
Propranolol antagonist node
automaticity Sotalol Sympatholytic acti
vity III A drug that No effects
on Bretylium prolongs the conduction,
delays Amiodarone action potential repolariz
ation Sotalol duration IV Ca2
antagonist Slow conduction Verapamil velocity
in the Diltizem atrioventricular node
Int. Pharmacology Chapter 18
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Quinidina

• Primeiro antiarrítmico utilizado (1918)
• Classificando como Ia
• Bloqueia canais de Na e K
• Aumenta intervalo QT (bloqueio dos canais de K)
• Aumenta concentrações de digoxina
• Aumenta morte súbita no tratamento de arritmias
• Pode causar taquicardia paroxística
• Uso terapêutico na síndrome do QT curto

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Adverse effects of quinidine
? Nausea ? Fever ? Syncope
? Blood dyscrasia ? Torsades de
pointes
Int. Pharmacology Chapter 18
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Vaughan Williams classification of antiarrhythmic
drugs
Electrophysiologic actions
Class
Type of drug
Examples
I a Na channel Blocks conduction Quinidine
blocker increases ERP Disopyramide I b
Na channel Blocks conduction Lidocaine
blocker decreases ERP Mexiletine I c
Na channel Blocks conduction Flecainide
blocker no effect on ERP, Encainide
Int. Pharmacology Chapter 18
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Procainamida

• Propriedades similares a quinidina
• Mais rapidamente absorvida por via oral
• Profilaxia de taquicardia ventricular
• Não há evidência de redução de morte súbita na FV
  ou no IAM

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Vaughan Williams classification of antiarrhythmic
drugs
Electrophysiologic actions
Class
Type of drug
Examples
I a Na channel Blocks conduction Quinidine
blocker increases ERP Disopyramide I b
Na channel Blocks conduction Lidocaine
blocker decreases ERP Mexiletine I c
Na channel Blocks conduction Flecainide
blocker no effect on ERP, Encainide
Int. Pharmacology Chapter 18
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Lidocaína

• Antiarrítmico Ib
• Administrado por via intravenosa (alto
  metabolismo hepático)
• Não melhora sobrevida no IAM
• Utilizada em taquiarritmias ventriculares
• Utilizada como anestésico e analgésico (local ou
  sistêmico)

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Vaughan Williams classification of antiarrhythmic
drugs
Electrophysiologic actions
Class
Type of drug
Examples
I a Na channel Blocks conduction Quinidine
blocker increases ERP Disopyramide I b
Na channel Blocks conduction Lidocaine
blocker decreases ERP Mexiletine I c
Na channel Blocks conduction Flecainide
blocker no effect on ERP, Encainide
Int. Pharmacology Chapter 18
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Flecainide

• Clássico Ic
• Alargamento do QRS
• Utilizado somente para tratamento de TSV
• Aumenta o risco de morte súbita no IAM

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Survival of patients in the Cardiac Arrhythmia
Suppression Trial
100 95 90 85 0
Survival ()
P 0.0006
0 50 100 150 200 250 300
350 400 450 500
Days after randomization to treatment group
Placebo (number of patients 725)
Encainide or flecainide (number of patients 730)
Study terminated on ethical grounds
Int. Pharmacology Chapter 18
34
Vaughan Williams classification of antiarrhythmic
drugs
Electrophysiologic actions
Class
Type of drug
Examples
II ß Adrenoceptor Decreases sinus
Propranolol antagonist node
automaticity Sotalol Sympatholytic acti
vity III A drug that No effects
on Bretylium prolongs the conduction,
delays Amiodarone action potential repolariz
ation Sotalol duration IV Ca2
antagonist Slow conduction Verapamil velocity
in the Diltizem atrioventricular node
Int. Pharmacology Chapter 18
35
Molecular mechanism of action of ß1adrenoceptor
antagonists
catecholamine
ß1 adrenoceptor
Adenylyl cyclase
Cell membrane
as
ß
?
cAMP
ATP
Kinase (inactive)
Kinase (active)
phosphorylation
Contraction of heart muscle
Int. Pharmacology Chapter 18
36
Sotalol

• Bloqueia canais de K
• Utilizado na profilaxia de fibrilação atrial
  pós-operativa
• d-Sotalol não apresenta atividade beta bloqueadora

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Vaughan Williams classification of antiarrhythmic
drugs
Electrophysiologic actions
Class
Type of drug
Examples
II ß Adrenoceptor Decreases sinus
Propranolol antagonist node
automaticity Sotalol Sympatholytic acti
vity III A drug that No effects
on Bretylium prolongs the conduction,
delays Amiodarone action potential repolariz
ation Sotalol duration IV Ca2
antagonist Slow conduction Verapamil velocity
in the Diltizem atrioventricular node
Int. Pharmacology Chapter 18
38
Amiodarona

• Causa aumento de intervalo QT
• Classe III, entretanto bloqueia canais de Na e
  CA, assim como alfa adrenoceptores
• Diminui expressão de receptores beta1
• Eficaz no tratamento de TSV e TV

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Adverse effects of amiodarone
? Thyroid abnormalities ?
Corneal deposits ? pulmonary disorders
? Skin pigmentation
Int. Pharmacology Chapter 18
40
Vaughan Williams classification of antiarrhythmic
drugs
Electrophysiologic actions
Class
Type of drug
Examples
II ß Adrenoceptor Decreases sinus
Propranolol antagonist node
automaticity Sotalol Sympatholytic acti
vity III A drug that No effects
on Bretylium prolongs the conduction,
delays Amiodarone action potential repolariz
ation Sotalol duration IV Ca2
antagonist Slow conduction Verapamil velocity
in the Diltizem atrioventricular node
Int. Pharmacology Chapter 18
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Verapamil

• Classe IV
• Diminui a frequência no SA
• Diminui a condução do nódulo AV
• Efeito inotrópico negativo
• Vasodilatação coronária
• Utilizado no tratamento de TSV

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Adverse effects of verapamil
? Bradycardia ? Nausea and
vomiting ? Constipation
Adverse effects of adenosine
? acceleration of tachycardia in
Wolff-Parkinson-White syndrome
? Atrial fibrillation in Wolff-Parkinson-White
syndrome ? Bronchospasm and hypotension

Int. Pharmacology Chapter 18
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Adverse effects of Ca2 antagonists
Nifedipine Verapamil / diltiazem
? Dizziness ? Bradycardia ? Flushing
? Hypotension ? Hypotension ?
Congestive heart failure ? Skin rash ?
Heart block ? Peripheral edema ? Skin
rash ? Tachycardia ? Constipation
Int. Pharmacology Chapter 18
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Common diseases that contribute to the
development of congestive heart failure
? Cardiomyopathy ? Myocardial ischemia and
infarction ? Hypertension ? Cardiac valve
disease ? Congenital heart disease ? Coronary
artery disease
Clinical features of congestive heart failure
? Reduced force of cardiac contraction ? Reduced
cardiac output ? Reduced tissue perfusion ?
Increased peripheral vascular restance ? Edema
Int. Pharmacology Chapter 18
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Types of cardiomyopathies involving both the
right and the left ventricle
Dilated (congestive) heart
Normal heart
Hypertrophic heart
Int. Pharmacology Chapter 18
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Mechanism of action of digitalis glycosides
Int. Pharmacology Chapter 18
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Heart Failure Treatment
Bronchus
Pulmonary circulation
Alveolus
Defoaming agents (alcohol)
Antihistaminics
Cerebrum
Sedation, reserpine
Diuretics
Oxygen
Medulla
Spinal anesthesia
Nitrates
Spinal cord
Left Heart
Ganglionic blockers
Right Heart
Digitalis
Tourniquets
Thrombolytics
Venesection
Digitalis (a glycoside)
ACE inhibitors
Adrenolytics sympatholytics
Sugar
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Adverse effects of drugs used in the treatment
of congestive heart failure
? Cardiac glycosides have a narrow
therapeutic index and may precipitate
arrhythmias ? Short-term treatment with
phosphodiesterase inhibitors can cause
thrombocytopenia and arrhythmias ? ß1
Agonists may precipitate tachyarrhythmias, and
long-term use may worse myocardial function
? Diuretics produce serious electrolyte
imbalances such as hypokalemia, which may
produce ventricular arrhythmias ?
Angiotensin-converting enzyme (ACE) inhibitors
produce few adverse effects, andgenerally only
hypotension ? Nitrovasodilators have few
adverse effects
Int. Pharmacology Chapter 18
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Hypertension Treatment Angiotensin-Converting
Enzyme Inhibitors
ACE inhibitors
Liver
Adrenal
Renin substrate (angiotensinogen)
Angiotensin I
Angiotensin II
Medulla
Angiotensin-converting enzyme (ACE)
Cortex
Renin
Angiotensin promotes output of aldosterone
Vasoconstruiction
Aldosterone promotes Na and H2O retention, K
excretion, and arteriolar constriction
Compression of extrarenal or intrarenal vessels
promotes output renin by juxtaglomerular cells
Captopril (an ACE inhibitor)
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Effects of angiotensin-converting enzyme (ACE)
inhibitors
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ß Adrenoceptor antagonists classified according
to cardioselectivity and partial agonist activity
ß adrenoceptor antagonists
Drugs with additional a1 antagonist activity
cardioselective
nonselective
Acebutolol Atenolol Betaxolol Bevantolol Bisopro
lol Celiprolol Esmolol Metoprolol Practolol
Alprenolol Carteolol Nadolol Oxprenolol
Penbutolol Pindolol Propranolol Sotalol Timo
lol
Bucindolol Carvedilol labetalol
possess ß1 partial agonist activity
Int. Pharmacology Chapter 18
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Angiotensin-converting enzyme inhibtors
Elimination plasma half-life (h)
Usual doses (mg/day)
Drug
Elimination
Adverse effects
Main uses
Captopril Congestive heart failure 50-100
4 Renal hepatic Hypotension
Hypertension (aggravated by NSAIDs)
, cough Enalapril Congestive heart failure
2.5-30 30-35
Renalhepatic Similar to captopril Hypertensio
n Gl cancer (low risk) Benazepril Hypertens
ion 10-40 24
Renalhepatic Similar to captopril Lisinopril C
ongestive heart failure 2.5-10 gt30
Exclusively renal Similar to
captopril Hypertension Cilazapril Congestive
heart failure 1.25-20 30-50
Renal Similar to captopril Hypertension
Ramipril Congestive heart failure 2.5-10
85-190 Renalhepatic Simi
lar to captopril Hypertension (1.25 in
renal impairment) Quinapril Congestive heart
failure 10-20 30-50
Renalhepatic Similar to captopril Hypertensio
n Fosinopril Essential hypertension
20-40 12
Renalhepatic Milder than captopril Moexipril H
ypertension 7.5-30 12
Renalfecal Similar to captopril Trandolapril
Hypertension 2-8 up to 8 days
Renal Similar to captopril left
ventricular hypertrophy
Int. Pharmacology Chapter 18
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Dose-response relatioship for thiazide
antihypertensive agents and blood pressure
(antihypertensive action) and as a diuretic
(shown here as effect on K excretion, the
Kaliuretic action)
Response
Dose of thiazide
Antihypertensive action Kaliuretic action
Int. Pharmacology Chapter 18
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Pharmacotherapeutic approach to congestive heart
failure
Problem Approach Fatigue rest, positive
inotropes Edema Diet (salt restriction),
diuretics, digitalis Poor cardiac
contractility Positive inotropes Dyspnea Diuret
ics (thiazides / loop) Congestion Nitrovasodila
tors Increased cardiac preload Angiotensin-conver
ting enzyme and afterload inhibitors,
venodilators, vasodilators Irreversible heart
failure Heart transplantation
Int. Pharmacology Chapter 18
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Drugs used in the treatment of the various stages
of congestive heart failure
Normal
Mild
Moderate
Diuretics ACE inhibitors Nitrovasodilators
Systolic ventricular function
Severe
Digoxin ACE inhibitors Combination diuretics
Digoxin Diuretics ACE inhibitors Nitrovasodilators
Increasing age
Int. Pharmacology Chapter 18
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EPHESUS - The occurrence of death from any cause
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The occurrence of death from cardiovascular-relate
d causes or hospitalization for cardiovascular
events
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The occurrence of sudden death from cardiac causes
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Eventos Adversos

• RALES ginecomastia e dor na mama (10 dos
  homens, 8 vs 5).
• EPHESUS hiperkalemia (5.5 vs. 3.9)
• Hiperkalemia foi maior em pacientes com CR
  lt50mL/min

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Positive inotropes that improve cardiac
contractility ? Cardiac glycosides (e.g.
digoxin) ? Phosphodiesterase inhibitors
(e.g. inamrinone) ? ß1 Agonists (e.g.
dobutamide)
Int. Pharmacology Chapter 18
66
Adverse effects of cardiac glycosides
? Toxicity because the therapeutic dose
ratios are narrow ? May promote cardiac
K loss and hypokalemia which precipitate
life-threatening arrhythmias when used with
diuretics ? Abdominal disconfort,
emesis, and anorexia ? Arrhthmias with
cardioversion, which should therefore be used
with extreme caution
Int. Pharmacology Chapter 18
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Additional drugs used in congestive heart failure
to reduce edema and cardiac preload and afterload
? Diuretics (e.g., furosemide) ?
Angiotensin-converting enzyme (ACE) inhibitors
(e.g. captopril) ? Nitrovasodilators (e.g.
intravenous nitroprusside oral hydralazine,
topical nitroglycerin
Int. Pharmacology Chapter 18
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Classification of cardiomyopathies based upon
anatomic, pathophysiologic, and etiologic
considerations
Cardiomyopathy
etiologic
Anatomic / pathophysiologic
cardiac / systemic disease
Congestive (dilated)
hypertrophic
Restrictive (constrictive)
idiopathic
Int. Pharmacology Chapter 18
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The major extrinsic neurohumoral compensatory
mechanisms involved in congestive heart failure
(CHF)
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ß Adrenoceptor antagonists should be avoided in
patients with
? Asthma ? Diabetes mellitus
with hypoglycemic reactions ? Severe
intermittent claudication
Adverse effects of propranolol
? Bradycardia ? Depression
? Fatigue ? Cold extremities
Int. Pharmacology Chapter 18
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The main calcium antagonists used in
cardiovascular disease
Usual dose (mg/day)
Plasma half-life (h)
Metabolism and elimination
Adverse effects
Drug
Main uses
Verapamil Essential hypertension
160-480 p.o. 2-7 Hepatic metabolism
Constipation Hypertensive emergency
5 i.v. By CYP3A/CYPIA2 (most common)
Angina pectoris 160-480 p.o. Urinary
excretion Hypotension Acute
myocardial infarction 360 p.o.
secondary prevention Supraventricular
tachycardia 2.5 i.v. repeated Diltizem
Angima pectoris 180
p.o. 2-6 Hepatic metabolism Hypotension
Myocardial infarction up to 360 p.o.
prolonged Hight first-pass Edema
Variant angina 306 p.o.
In elderly urinary excretion Headache
Hypertension 180-360 p.o. Of
metabolites (all rare)
Supraventricular tachycardia 20i.v. over
2min Raynaud phenomenon Nifedipine
hypertension (all forms) 15-30 or sublingual
5 Hepatic metabolism Hypotension
Ischemia heart disease 0.2 intracoronary by
CYP3A4 (all forms) or 10-60
p.o. Hight first pass Raynaud
phenomenon Urinary excretion of Heart
failure metabolites
Int. Pharmacology Chapter 18
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The main calcium antagonists used in
cardiovascular disease (cont)
Usual dose (mg/day)
Plasma half-life (h)
Metabolism and elimination
Adverse effects
Drug
Main uses
Nicardipine Angina pectoris 30-120
p.o. 1-2 Similar to nifedine
Hypotension Hypertension 60-120 p.o.
(30-60 sustained release) Felodipine
Arterial hypertension 10-20 p.o. 24
Similar to nifedipine Similar to
(but slower)
ditizem Amlodipine Essential
hypertension 10 in single 30-60 Hepatic
metabolism Hypotension daily dose
(slow, no first pass) Bradycardia
Int. Pharmacology Chapter 18
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Main mechanisms of arrhythmogenesis
50
50
EAD
0
0
mV
mV
-50
-50
DAD
-100
msec
-100
msec
0
0
500
1000
1500
500
1000
1500
Early afterdepolarization
Delayed afterdepolarization
Int. Pharmacology Chapter 18
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Mean vector through the partially depolarized
ventricles
Textbook of Medical Physiology Guyton Hall
Fig. 12.1
75
Vectors drawn to represent potentials for several
different hearts, and the axis of the potential
for each heart
Textbook of Medical Physiology Guyton Hall
Fig. 12.2
76
Determination of a projected vector B along the
axis of lead I when vector A represents the
instantaneous in the ventricles
Textbook of Medical Physiology Guyton Hall
Fig. 12.4
77
Axes of three bipolar and three unipolar leads
Textbook of Medical Physiology Guyton Hall
Fig. 12.3
78
Determination of the projected vector B along the
axis of lead I when vector A represents the
instantaneous potential in the ventricles
Textbook of Medical Physiology Guyton Hall
Fig. 12.5
79
Determination of the projected vector in leads I,
II and III when vector A represents the
instantaneous potential in the ventricles
Textbook of Medical Physiology Guyton Hall
Fig. 12.6
80
Colored areas of the ventricles are depolarized
(-) white areas are still polarized ().
Textbook of Medical Physiology Guyton Hall
Fig. 12.7
81
Mechanisms of arrhythmogenesis
Abnormal impulse generation
Automatic rhythms Enhanced normal
automaticity Abnormal automaticity Triggered
rhythms Early after-depolarizations Delayed
after-depolarizations
Abnormal impulse conduction
Conduction block First -,second- or third-degree
block Re-entry Circus movement Reflection
Int. Pharmacology Chapter 18