2010 Page 1

Antihypertensive Drugs
Diuretic drugs
Anti-anginal drugs
Drugs in treatment of heart failure
Cardio-Vascular
2010 Page 2
Angina
- Myocardial ischemia: imbalance in myocardial
oxygen supply and demand that may result
O
2
Supply O
2
demand
=
Normal:
Angina pectoris is caused by transient myocardial ischemia
2010 Page 3
Angina
- Myocardial ischemia: imbalance in myocardial
oxygen supply and demand that may result
O
2
Supply O
2
demand
=
Ischemia:
Angina pectoris is caused by transient myocardial ischemia
2010 Page 4
Angina
- Angina Pectoris:
- Severe Chest pain (angere" meaning "to choke" +
"pectus" meaning "chest") due to Ischemia, felt beneath
the sternum, radiating to the left arm and shoulder
2010 Page 5
Angina
Angina Types
Stable/
Exertional
Unstable/
Crescendo
Variant/Prinzmetal
Vasospastic
2010 Page 6
Angina
Angina Types
Stable/
Exertional
Unstable/
Crescendo
Variant/Prinzmetal
Vasospastic
coronary artery has
been severely
narrowed due to the
buildup of plaque
(atherosclerosis)
Pain occurs with
exercise/Stress
(exertion)
Most common
disruption of a coronary
plaque platelet
aggregation thrombosis
at the arterial wall
occlusion (NOT complete)
of the vessel
Pain occurs more
frequently and with less
effort
Less common
coronary
vasospasm
reduced blood flow
and ischemic pain
Pain occurs
Spontaneously
and at rest
Least common
2010 Page 7
Angina
2010 Page 8
Angina
2010 Page 9
Anti-anginal drugs
O
2
Supply O
2
demand
=
Treatment
Coronary blood flow
Regional distribution
to ischemic area
Heart Rate
Contractility
Preload
After load
2010 Page 10
Filling Pressure
and volume/
Venous return
Arterial Resistance
Anti-anginal drugs
2010 Page 11
Anti-anginal drugs
- Organic Nitrates
Glyceryl trinitrate (Nitroglycerin)
Isosorbide dinitrate
Isosorbide mononitrate
2010 Page 12
Anti-anginal drugs
NO
GC
GTP cGMP
PKG
Myosin Myosin-P
(active)
MLCK
Contraction
NO
Nitrates
Reduction
Tissue-SH
v. endothelium
v. Smooth
muscle
Ca-Calmodulin
[Ca
2+
]
i
2010 Page 13
Anti-anginal drugs
O
2
Demand O
2
Supply
Venodilatation Arteriodilatation
Pre-load After-load Coronary VD
Regional distribution
to ischemic area
Anti-anginal Effects
Organic Nitrates
2010 Page 14
Anti-anginal drugs
- Tolerance
- Frequently repeated or continuous exposure to high doses of
organic nitrates EFFECT...HOW?
- Theory 1: cellular depletion of sulfahydryl groups no NO!
- Theory 2: ROS peroxynitrite formation no NO!
- Prevention:
- Eccentric dosing ( 2 b.i.d interval 7 hrs)
- Omit night dosing
Organic Nitrates
2010 Page 15
- Therapeutic use:
- Acute attack: Glyceryl trinitrate (sublingual tablet/spray),
Isosorbide Dinitrate
- Prophylaxis: Isosorbide mononitrate tablet /Transdermal Glyceryl
trinitrate
- S.E
- Headaches
- Flushing
- Postural Hypotension
- HIGH DOSE: BP and TC
- C.I
- Phosphodiestrase inhibitors (Sildenafil , Viagra) cGMP degradation
Anti-anginal drugs
Organic Nitrates
2010 Page 16
Anti-anginal drugs
Arteriodilatation
After-load Coronary VD HR contractility
O
2
Demand
O
2
Supply
Calcium channel blockers
Caution: Nifedipine (not alone)
Clinical studies: most effective in Variant angina
Anti-anginal Effects
2010 Page 17
Anti-anginal drugs
Beta blockers
HR contractility
O
2
Demand
In Vasospastic angina NEVER given alone
Sudden STOPAngina attack/ MI
Especially during exercise/ Stress
O
2
Supply
perfusion to subendocardium
ischemic area
Anti-anginal Effects
2010 Page 18
Anti-anginal drugs
Controlled!
Treat CVS disease
FATS
2010 Page 19
Anti-anginal drugs
- Antiplatelet:
Adjuvant therapy
Against Atherosclerotic plaque
Acetyl salicylic acid
Clopidogrel
Anti-thrombin:
Heparin
2010 Page 20
Anti-anginal drugs
- Nitrates + -blockers
- Synergistic effect+ Prevent reflex TC
- Nitrates can alleviate the -blockers induced coronary VC
- Dihydropyridines + -blockers
- Synergistic effect + Prevent reflex TC
- DHP can alleviate the -blockers induced coronary VC
- CCB + Nitrates
- Synergistic effect
- Not Dihydropridines
- Deltiazem and Verapamil prevent reflex TC
- Nitrates +CCB+ -blockers
Combination Therapy
2010 Page 21
Anti-anginal drugs
- Acute attack :
- Nitroglycerin sublingual
- Variant:
- CCB (or + Nitrates)
- Step 2 with caution(+ Beta-blocker)
- Stable:
- Beta-blocker (or + Nitrates)
- Step 2 add CCB
- Unstable:
- Beta-blocker (usually + Nitrates)
- Step 2 add CCB
2010 Page 22
Anti-anginal drugs
NO Yes Yes Raynaud's
syndrome
Yes Yes Not
preferred
Hypertension
NO YES YES Asthma
-blockers CCB Nitrates
ACEI