DRUGS USED FOR

TREATMENT STABLE ANGINA

PECTORIS

IKE HUSEN
DEP. OF PHARMACOLOGY & THERAPY
Medical School- Universitas Padjadjaran
 LEARNING OBJECTIVE
Learning Objectives:
 Describe Mechanism of action (MoA)
related to its pathophysiology
 Describe MoA related to its effects leading
to indications & related to adverse effects
leading to contraindications
 Describe its specific pharmacokinetics that
impact to clinical usage

References:
 Katzung
 Lippincott’s
 ANGINA PECTORIS

Clinical manifestation that result from myocardial

ischemia

The clinical manifestation

Chest pain left arm
jaw or neck
Duration < 20 minutes

ECG : ?
 TYPE OF ANGINA PECTORIS

1. PRINZMETALS
 Vasospasm
 Precipitating factor (-)
2. CLASSIC ANGINA
 Atherosclerosis
 Precipitating factor (+)
3. UNSTABLE
 An acute coronary
syndrome
- frequent and intense of
angina pain
 PATHOGENESIS OF ANGINA PECTORIS

Risk factor
Age Hypertension, DM,
Genetics smoking, dyslipidemia

O2 demand
O2 supply

Ischemia Chest Pain

 THE PRINCIPLES OF TREATMENT AP
Drugs
Risk factor Captopril
Statin
others

Antiplatelet aggregation :
Aspirin

β blocker
O2 demand CCB
ON
O2 supply
O2 supply
ON Ischemia Chest Pain
CCB
 THE PRINCIPLES IN THE TREATMENT OF MI-
UNSTABLE AP
Risk factor Drugs

Antiplatelet
Trombolysis
Anticoagulant

O2 demand Sedative
others
O2 supply

O2 supply
necrosis Chest Pain Analgesic :
ON
Morphine
Others drugs
THE PRINCIPLES OF TREATMENT AP
1. Improve perfusion of myocardium (  O2
supply ) :
I. Organic Nitrates
II. Calcium Channel Blockers

2. Reduced the myocardial metabolic demand.

3. Reduced (treat) the risk factors:

Anti hypertension
Drugs lowering lipid
Anti diabetic drugs
 CASE
A 65 years old man is being evaluated for
elevated blood pressure. He occasionally has
Angina pectoris precipitated by physical
exertion and rapidly controlled by sublingual
nitroglycerine (NG).
His blood pressure is 160/100 mmHg. He is
advice to take Nifedipine. He is develops
flushing, dizziness and nervousness shortly
after taking the drug, and the number of
angina episode increase during the period.
 Questions
How
How can
can NG NG controlled
controlled the
the angina
angina attack?
attack?
How
How is
is the
the MOA
MOA of of NG
NG in
in controlling
controlling the
the angina
angina attack?
attack?
SE
SE and
and contraindication?
contraindication?
Why
Why the
the SESE occurs?
occurs?
What
What is
is the
the difference
difference ofof sublingual-transdermal
sublingual-transdermal
preparation?
preparation?
ORGANIC NITRATE

Nitroglycerine
Isosorbid dinitrate
Isosorbid mononitrate
Erythrityl tetranitrate
Pentaerythritol tetranitrate
 MECHANISM OF ACTION OF NITROGLYCERINE
= ISDN

Activated Guanylcyclase Muscle relaxant

GTP

NO Activated Guanyl
cyclase
SH
Nitrosothiol
CAMP
NO2-
NG
ISDN
ONO2 ONO2 Vasodilation
others
 EFFECTS :

1. Collateral Vessels  ↑ O2 supply

2. Venodilation  ↓ Preload

↑ O2 demand

What if it is given to hypotensive patient?

to tachycardia patient?
 SIDE EFFECTS = Adverse Drug Reaction

Drug tolerance

NO Vasodilation
Met-Hb
SH
Nitrosothiol
V meningial Heart

Hb + NO2-
NG Headache
ISDN
ONO2 ONO2
others BP

Tachycardia Syncope
SIDE EFFECTS

1. Headache
2. Tachycardia/Syncope
3. Pseudocyanosis
4. Tolerance

Contraindication

1. Hypotension
2. Dysrrhithmia (Tachycardia)
3. Severe Anemia
4. Brain Injury
Drugs &dosage form Usual dose Onset of action Duration go action
(mg) (min) (hr)
Nitroglycerine

Sublingual 0,3-0,6 2-5 0,16-0,50

Oral 3-20 20-45 2-8

Transdermal 5-30 (per 24 30-60 12-24

hr)
Intravenous 5-300 Immediate Transient
mEq/min
Isosorbide dinitrate

Sublingual 2,5-10 3-20 1-2

Oral, chewable 5-60 30-60 2-10

Oral, sustained release 40 30-60 6-10

 LEARNING OBJECTIVE
 To describe the pharmacological properties of
diltiazem (CCB)
 Mechanism of action
 Effects Heart Coroner

Vascular Peripheral
 Side effects
 To differentiate the pharmacodynamics and
pharmacokinetics among CCB
 CALCIUM CHANNEL BLOCKER

DILTIAZEM
NIFEDIPINE
AMLODIPINE, NICARDIPINE, FELODIPINE
VERAPAMIL
 CCB : MECHANISM OF ACTION
Block calcium channel found in the heart and
vascular smooth muscle
 EFFECT OF CCB
1. On vascular (vasodilatation)
Collateral flow
After load
2. On heart
Contraction
Heart rate
Conduction

What if it is given to CHF patient? Which one is

tolerable for the patient?
What if it is given to hypotensive patient?
 PHARMACODYNAMIC EFFECT
Nifedipine Diltiazem Verapamil
Vasodilatation
Coronary +++ +++ ++
Peripheral +++ + +++

Heart :
Frequency
Contractility
SA node -
AV node -
 SIDE EFFECT OF CCB
1. Hypotension
2. Cardio depression (AV node block)
3. Peripheral edema Why
Why do
dothe
the
4. Constipation SE
SEoccurs?!
occurs?!
5. Gingival swelling
 PHARMACOKINETICS OF CCB

Drug A D M E
(%)
Diltiazem - - - 70 (liver)

Nifedipin - - - 90 (renal)

Verapamil - - - 70 (renal)
 LEARNING OBJECTIVE

 Describe the role of beta adrenergic blocker

in coronary Arterial Disease

 Describe the pharmacokinetics of beta

adrenergic blocker
 BETA ADRENERGIC BLOCKER (BB)
Adrenergic receptor :

Selective
Heart
BB
Bronchus
Atenolol Non selective
Glucose met
BB
Uterine
Propranolol
Vascular
Nadolol

 adrenergic
 THE ROLE OF BB in

  O2 demand
Heart :  rate
 contraction

 Prevent Infarct Size

 PHARMACOKINETICS PROPERTIES

Drug Lipid soluble Note Elimination

Propranolol High Hepatic

Nadolol Low Kidney

Atenolol Low Unchanged

Labetolol Moderate Kidney