Академический Документы
Профессиональный Документы
Культура Документы
Global Overview/Review
Topics discussed:
Autonomic Nervous System
and
Blood Pressure Control
eNotes:
Cardiovascular
Pharmacology
Antihypertensive Drugs
Drugs for Angina
ACE Inhibitors
Calcium Channel
Blockers
Prepared and presented by:
Marc Imhotep Cray, M.D.
Adrenergic Blockers
Cardiac Glycosides
Blood Pressure
Blood Pressure(2)
Hormonal
Renin-angiotensin-aldosterone system
Local transmitters
Nitric Oxide (NO)
Carotid Sinus
Brain Stem
Parasympathetic
(Vagus)
-Adrenoceptor
Spinal Cord
Sympathetic
-Adrenoceptor
Arteriole
Baroreceptor Reflexes
in BP Control
BP
Parasympathetic
Sympathetic
Baroreceptor Reflexes
in BP Control
2
BP
Carotid sinus
senses BP
Parasympathetic
Sympathetic
Baroreceptor Reflexes
1 BP
in BP Control
Vasomotor Center responds
with Symp. NS activity
3
and Parasymp. activity
Carotid sinus
senses BP
Parasympathetic
Sympathetic
Baroreceptor Reflexes
in BP Control
3
BP
Carotid sinus
senses BP
Parasympathetic
Sympathetic
Heart rate
and contractility
4
PVR
9
Baroreceptor Reflexes
in BP Control
Vasomotor Centre responds
with Symp. NS activity
3 and Parasymp. activity
BP
Carotid sinus
senses BP
Parasympathetic
Sympathetic
Heart rate
and contractility
4
PVR
BP
10
Hormonal
Renin-angiotensin-aldosterone system
Local transmitters
Nitric Oxide (NO)
11
End-diastolic volume
Determined by venous filling pressure (distensible
ventricle)
13
Stroke Volume
Overdistended,
output falls
15
Hormonal
Renin-angiotensin-aldosterone system
Local transmitters
Nitric Oxide (NO)
16
Renin-Angiotensin System
Liver
SENSOR IN
KIDNEY
Angiotensin Precursor
(Circulating)
Renin
(Circulating)
Angiotensin I
OUTCOMES
Angiotensin II
Vasoconstriction
Na+ Retention
K+ Excretion
Aldosterone from
adrenal cortex
AT1 Receptor
17
BP Control
Mechanisms
Summary
18
Antihypertensive Drugs
Membrane
Ca2+ Channels
Ca2+
Plasma Membrane
Trigger
Sarcoplasmic
Reticulum
Ca2+
Ca2+
Vascular selective
dihydropyridines
nifedipine
felodipine
amlodipine
24
1 Adrenoceptor Antagonists
Beta-adrenoceptor antagonists (beta-blockers)
Cardiac 1 Adrenoceptor
Stimulation
Heart rate
contractility
blood pressure
heart work
27
Cardiac 1 Adrenoceptor
Blockade
Heart rate
contractility
blood pressure
heart work
28
Cardiac 1 Adrenoceptor
Blockers
Metoprolol
Atenolol
29
Cardiac 1 Adrenoceptor
Blockers: Clinical Uses
Antiarrhythmic (slows some abnormal fast
rhythms)
Antihypertensive
Antiangina: via reduced heart work
30
31
Renin-angiotensin system
Liver
Renal Blood
Flow
Na+ load
Angiotensin Precursor
Renin
Angiotensin I
Angiotensin Converting Enzyme
Angiotensin II
Vasoconstriction
Na+ Retention
K+ Excretion
Aldosterone
AT1 Receptor
32
33
34
Uses
Antihypertensive
Heart failure
35
1 Adrenoceptor Blockers
Alpha-adrenoceptor antagonists (alpha-blockers)
36
Carotid Sinus
Brain Stem
Parasympathetic
(Vagus)
-Adrenoceptor
Spinal Cord
Sympathetic
1-Adrenoceptor
37
1 Adrenoceptor Blockers
Peripheral vasodilator vascular resistance
Agents:
Prazosin
38
Volume Reduction
Reduces cardiac filling pressure (LVEDV/P)
Thus reduces stroke volume and cardiac
output
Independent vascular relaxation with long
term use
Clinical Use of
Antihypertensives
Consequences of chronic high blood pressure
heart failure
arterial disease
kidney failure
strokes
myocardial infarction (heart attack)
Aim of treatment
prevent consequences of high BP
40
42
43
Nitrates
Glyceryl trinitrate
(GTN)
Isosorbide (di)nitrate
45
GTN
OrganicNitrate
NO2
R-SH
NO
Nitrosothiols
(R-SNO)
Ester Reductase
+
See : Nitrates, Digoxin and Calcium Channel Blockers
Dr. Paul Forrest
Royal Prince Alfred Hospital
cGMP
RELAXATION
Guanylate Cyclase
GTP
Protein Kinase G
46
47
Use of Nitrates
Very fast, short-lived vascular dilatation (Greater
in venules than arterioles)
lower vascular resistance means less heart work
less heart work means less need for coronary
artery blood flow
therefore, nitrates help chest pain (angina) that
happens during exercise when there is coronary artery
obstruction.
Not used for managing chronic high blood pressure
48
Medicines from foxgloves are called "Digitalin". The use of Digitalis purpurea extract
containing cardiac glycosides for the treatment of heart conditions was first described
in the English speaking medical literature by William Withering, in 1785. It is used to
increase cardiac contractility (it is a positive inotrop) and as an antiarrhythmic agent to
control the heart rate, particularly in the irregular (and often fast) atrial fibrillation. It is
therefore often prescribed for patients in atrial fibrillation, especially if they have been
diagnosed with heart failure. From: http://en.wikipedia.org/wiki/Digitalis
49
Cardiac Glycosides:
Digoxin
50
Digoxin
Mechanism of Action
Na+/K+ ATPase
Outside
Na+ Ca2+
Na+
Na+
Inside
K+
Channels
K+
Pump
Ca2+
Exchanger
51
Digoxin blocks
Na+/K+ ATPase
P
Mg2+
ATPase
K+
Mg2+
ATPase
Dig
Digoxin increases
intracellular Ca2+
Na+
K+
Pump
Na+
Ca2+
Exchanger
53
Effect of [Ca2+]i
Na+/Ca2+ antiporter
Na+/K+ ATPase
+
+
K
NaNa
+
+
Ca2+
K
Na+
Ca2+ channel
Ca2+
Trigger
Sarcoplasmic
Reticulum
Ca2+
Ca2+
contractility
Actin & Myosin
54
Toxic
Various abnormal rhythms
55
Uses of Digoxin
Atrial fast arrhythmias: slows rate
Heart Failure: increases contractile
strength
56
Reference Resource
57