Dr Ahmadou M. Jingi.

Professor G. Ashuntantang
FHS-UBa

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Course Oblectives
1. List the class of medicines used in treating Ischemic
Heart Disease

2. Briefly describe the mechanism of action of each

drug class

3. List 4 common side effects

4. List 4 contra-indications

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What is Ischemic Heart Disease?
 Reduced blood supply to the heart

 Caused by blockage or narrowing in the coronary

arteries

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Presentation (Classification) of IHD
1. Sudden death

2. Acute coronary syndrome

i. Myocardial infarction

ii. Unstable angina

3. Stable angina pectoris

4. Ventricular arrythmias

5. Heart failure

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 Pericardium
Epicardial Vessel
(Epicardium)

Subepicardium

Myocardium

Subendocardium

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 Metabolic
Control Extravascular
Neural Compressive
Control Forces
Vascular
Resistance
Endothelial
Control Diastolic
Phase
Heart Rate
Auto-regulation
Coronary
Blood
Flow Contractility

SUPPLY DEMAND

O2- Systolic Wall

Carrying Tension (pre-
Capacity load and
afterload)
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Factors Increasing
Myocardial Oxygen Consumption
1. Increased Heart Rate
2. Increased Inotropy (Contractility)
3. Increased Afterload
4. Increased Preload

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Pharmacologic agents
Therapy is aimed in restoring balance between myocardial

oxygen supply and demand:

1. Increase oxygen delivery

2. Decrease cardiac oxygen demand or consumption

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Pharmacologic agents
Drugs

1. Nitrates

2. Beta blockers

3. Calcium channel blockers

4. Potassium channel openers

5. Specific sinus node inhibitors

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 Nitrates
 All organic nitrates share the same action. Differ only in time
course. The only major action is direct on specific smooth muscle
relaxation

 Short acting:

 Glyceryl trinitrate (GTN, Nitroglycerine)

 Long acting:

1. Isosorbide dinitrate (short acting by sublingual route),

2. Isosorbide mononitrate,

3. Erythrityl tetranitrate,

4. Pentaerythritol tetranitrate
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 Mechanism of action
 Organic nitrates lead to the formation of the reactive
gaseous free radical NO and related NO-containing
compounds

 NO can activate guanylyl cyclase, increase the cellular level

of cyclic GMP, activate PKG, and modulate the activities of
cyclic nucleotide phosphodiesterases

 In smooth muscle, the net result is reduced phosphorylation

of myosin light chain, reduced Ca2+ concentration in the
cytosol, and relaxation
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Mechanism of action

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 Pharmacokinetics
 Absorbtion
 Bioavailability
 Oral: generally low
 Sub-lingual: 10-60%
 Transdermal: 50-90%
 Distribution
 In all body tissues including the brain
 Biotransformation
 >99% mainly in the liver (by high capacity nitrate reductase)
 Extensive first pass metabolism
 Therapeutic effect is apparent within 1-3 minutes of use of
sublingual tablets, sublingual spray, or buccal tablets.
 Within 1-2 minutes after intravenous dose
 Half life: very variable
 Sub-lingual nitroglycerine : 2-3 minutes
 Oral isosorbide mononitate: 4-5 hours
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Effects of Nitrates
Promote relaxation of vascular smooth muscle
1. Low concentrations of nitroglycerin :
 Preferentially dilate veins more than arterioles
 Decreases venous return, leading to a fall in left and right
ventricular chamber size and end-diastolic pressures
thus, Decreased preload
 Systemic arterial pressure may fall slightly
2. Higher doses of organic nitrates cause:
 Further venous pooling and may decrease arteriolar
resistance as well, thereby decreasing blood pressure and
cardiac output

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 Nitrates side effects
1. Headache (due to meningeal vasodilation),
2. Dizziness
3. Reflex Tachycardia (baroreceptor mediated due to a fall in
arterial BP produced by higher doses of NTG)
4. Orthostatic hypotension

5. Flushing
6. Weakness

7. Rashes
8. Syncope

9. Palpitations
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Contra-indications of Nitrates
1. Severe hypotension

2. Severe hepatic disease

3. Increased intra-cranial pressure

4. Hypovolemic states

5. Cerebral hemorrhage

6. Sildenafil (viagra)

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Therapeutic uses
Mainly used in:

1. Stable angina pectoris

2. Congestive heart failure

3. Unstable angina pectoris and NSTEMI

4. Acute myocardial infarction

5. Prinzmetal angina

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 Mechanism of action
They bind to beta receptors in the heart:
1. Reducing heart rate

2. Reducing contractility

3. And blood pressure thus reducing myocardial oxygen

demand

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 Pharmacokinetics
 Bioavailability

 Well absorbed , high lipid solubility

 Variable: 25-90%

 Distribution

 Rapidly and widely distributed

 Biotransformation

 Majority of beta blockers are metabolized in the liver

 Many undergo first pass metabolism

 Excretion
 Majority are excreted through urine 28
Some beta blockers
1. Metoprolol

2. Atenolol

3. Bisoprolol

4. Carvedilol

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Some beta blockers

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Adverse effects
1. Heart Block
2. Bradycardia
3. Erectile dysfunction
4. Hypoglycemia
5. Bronchoconstriction (asthma)
6. Depression
7. Insomnia
8. Raynaud phenomenon
9. Hypotension
10. Heart failure exacerbation

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Contra-indications
1. Asthma

2. High grade AV block: Mobitz II, 3rd degree AV block

3. Peripheral vascular disease

4. Acute decompensated heart failure

5. Severe bradycardia (HR<50)

6. Active Raynauds disease

7. Cardiogenic shock

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 Mechanism of action
 Inhibit the influx of calcium into cardiac and smooth
muscle cells by blocking voltage dependent L-type calcium
channels thereby reducing smooth muscle and cardiac
contractility
 Reducing cardiac contractility will reduce myocardial
oxygen demand
 Reducing smooth muscle contractility will lead to
vasodilation

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 Pharmacokinetics
 Calcium channel blockers are given orally and are generally
well absorbed

 They are metabolized in the liver

 Excretion is through the urine

 The drugs cross the placenta and enter breast milk

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Therapeutic uses
1. Drug of choice for prinzmetal angina

2. Chronic stable angina

3. Other uses

i. Hypertension

ii. Supraventricular arrhythmias

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Adverse effects
1. Headache

2. Constipation

3. Dizziness

4. Nausea

5. Flushing

6. Peripheral oedema

7. Palpitations

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Contra-indications

1. Hypotension

2. Sinus bradycardia

3. Severe heart failure

4. Hypotension

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Some Calcium Calcium blockers

1. Non dihydropyridine
i. Verapamil
ii. Diltiazem

2. Dihydropyridine
i. Nifedipine
ii. Nicardipine
iii. Amlodipine

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 Nicorandil
 Causes arterial vasodilation coupled with venodilation
decreasing preload as well as afterload
 No cardiac effects
Use
 Stable angina
 Prinzmetal angina
Side effects
1. Flushing
2. Palpitation
3. Headache
4. Dizziness
5. Ulcers in the mouth 41
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 Ivabradine
 Specific inhibitor of If current (Na/K current) in sino-atrial
node

 No other known action on other channels

 Does not modify myocardial contractility and intra-cardiac

conduction

 Indicated for angina pectoris refractory to standard

treatment

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