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Antianginal Drugs

Claro M. Isidro M.D.


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Definition of terms

Angina Pectorisis the principal symptoms

of patient with ischemic heart disease.

Manifested by sudden, severe, pressingsubsternal pain that often radiates to the left

shoulder and along the flexor surface of the

left arm.

Usually precipitated by exercise,

excitement or a heavy meal.


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Types of Angina

Typical Angina ( Classical Angina )

pain is commonly induced by exercise,

excitement or a heavy meal secondary to advanced atherosclerosis of

the coronary vessels

associated with ST-segment depression onECG


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Variant Angina ( Prinzmetal Angina)

pain is induced while at rest

associated with ST-segment elevation onECG

secondary to vasospasm of the coronary

vesselsUnstable angina

may involve coronary spasm and may also

have the component of atherosclerosis the duration of manifestation is longer than

the first two and has the manifestation ofMyocardial infarction


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* Myocardial ischemia which producesangina results from imbalances in

myocardial oxygen supply & demand

relationship such as decreased oxygen

supply and/or increased oxygen demand.

Etiology

1. Decrease oxygen supply

2. Increase demand for oxygen


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Determinant of Myocardial Oxygen Supply

1. Coronary blood flow

Determined by: perfusion pressure

duration of diastole

coronary bed resistance

2. Arterio-venous oxygen difference


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Determinant of Myocardial Oxygen demand

Major Determinants

1. Wall stress

intraventricular pressure

ventricular volume

wall thickness

2. Heart rate

3. Contractility


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Determinants of Vascular Tone

Relaxation of vascular smooth muscle by:

1. Increase cGMP

2. Decrease intracellular calcium

3. Increase cAMP

4. Stabilizing or preventing depolarization of

the vascular smooth muscle cell

membrane


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Treatment Plan:

A. decrease the risk factor like

atherosclerosis, hypertension, smokingB. increase oxygen supply

C. decrease oxygen demand


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ANTIANGINAL DRUGS

I. AGENTS WHICH O2 DEMAND & O2

SUPPLY

A. NITRATES

B. CALCIUM CHANNEL BLOCKERS

II. AGENTS WHICH O2 DEMANDC. BETA BLOCKERS


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NITRATES AND NITRITES

Classification of nitrates:

1. Rapidly acting nitrates* used to terminate acute attack of angina

* e.g.- Nitroglycerin and Amyl nitrate

* usually administered sublingually2. Long acting nitrates

* used to prevent an attack of angina

* e.g. -Erythrytyl tetranitrate, Isosorbide

dinitrate, Pentaerythrytol tetranitrate

* administered orally or topically


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Nitrates

Coronary artery dilatation

Decrease coronary bed resistance

(Relieved coronary vasospasm)

Increase coronary blood flow

Increase oxygen supply


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Nitrates

Reduction on peripheral resistance

(Secondary to dilatation of aorta)

Decrease blood pressure

Decrease after load

Decrease workload

Decrease oxygen consumption


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Nitrates

Reduced venous return(Due to dilatation of the veins)

Decrease left ventricular volume

Decrease preload

Decrease workload



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Effects

1. Coronary artery dilatation

2. Reduction of peripheral arterial

resistance

decrease after load

3. Reduce venous returndecrease

preload


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Potential Beneficial Effects of Nitrates.

Beneficial effects Results

Decrease Ventricular vol. Decrease myocardial oxygenrequirement

Decrease arterial pressure

Decrease ejection time

Venodilatation of epicardial coronaryart.

Relief of coranary artery spasm

Increase collateral flow due to

venodilatation

Increase perfusion to ischemic

myocardium

Decrease left ventricular pressure> decrease preload due to dilatation

of the vein

> decrease after load due to

dilatation of the arteries

Improved subendocardial perfusion


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Deleterious Effects Results

Reflex tachycardia Increase myocardial

oxygen requirement

Reflex increase incontractility

Decrease diastolic

perfusion

Decrease myocardial

perfusion

Potential Deleterious Effects


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ROUTES OF ADMINISTRATION

1. Sublingual route

rational and effective for thetreatment of acute attacks of angina pectoris. Half-life

depend only on the rate at which they are delivered to the

liver.

2. Oral route

to provide convenient and prolongedprophylaxis against attacks of angina

3. Intravenous Route useful in the treatment of

coronary vasospasm and acute ischemic syndrome.

4. Topical route

used to provide gradual absorption ofthe drug for prolonged prophylactic purpose.


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Drug Usual single dose Route of

administration

Duration of action

Short acting

Nitroglycerin

0.15-1.2 mg sublingual 10 - 30 min

Isosorbide dinitrate 2.5-5 mg sublingual 10

60 min

Amyl nitrite 0.183 ml inhalation 35 min

Long acting

Nitroglycerin sustained

action

6.513 mg q 6-8 hrs oral 68 hrs

Nitroglycerin 2%ointment

1

1.5 inches q hr topical 3

6 hrs

Niroglycerin slow

released

12 mg per 4 hrs Buccal mucosa 36 hrs

Nitroglycerin slow

released

1025 mg /24hrs (one

patch/day}

transdermal 810 hrs

Isosorbide dinitrate 2.510 mg per 2 hrs sublingual 1.52 hrs

Isosorbide dinitrate 1060 mg per 4-6 hrs oral 46 hrs

Isosorbide dinitrate

chewable

510 mg per 2-4 hrs oral 23 hrs

Isosorbide mononitrate 20 mg per 12 hrs oral 6

10 hrs


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Adverse Effects

1. Throbbing headache

2. Flushing of the face

3. Dizziness

especially at the beginning oftreatment

4. Postural Hypotensiondue to pooling of

blood in the dependent portion of the body


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Contraindication

1. Renal ischemia

2. Acute myocardial infarction

3. Patients receiving other

antihypertensive agent


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B-Blockers

Hemodynamics Effects

1. Decrease heart rate

2. Reduced blood pressure and cardiac

contractility without appreciable

decrease in cardiac output


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B-Blockers

Decrease heart rate & Contractility

Increase duration of diastole

Decrease workload


Decrease O2consumption



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Contraindication

1. Congestive heart failure

2. Asthma

3. Complete heart block


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Ca - Channel Blockers

Effects

1. Coronary artery dilatation

2. Reduction on peripheral arterial

resistancedecrease after load


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Ca Channel Blockers

Coronary artery dilatation

Decrease coronary bed resistance(Relieved coronary vasospasm)




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Ca channel Blockers

Reduction on peripheral resistance(Secondary to dilatation of aorta)

Decrease blood pressure

Decrease after load

Decrease workload



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Most commonly used Ca Channel Blockers

1. Nifedipine

2.Verafamil

3. Diltiazem

Pharmacokineticss

Drugs Onset of action Peak of action Half-life

Nifedipine 20 minutes 1 hour 3-4 hours

Verafamil 1-2 hours 5 hours 8-10 hours

Diltiazem 15 minutes 30 minutes 3-4 hours

Nicardifine 20 minutes 45 minutes 2-4 hours

Felodipine 2-5 hours 6-7 hours 11-16 hour


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Unwanted effect

Nausea and vomiting

Dizzyness Flushing of the face

Tachycardiadue to hypotension

Contraindications

Cardiogenic shock

Recent myocardial infarction

Heart failure

Atrio-ventricular block


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Combination Theraphy

1. Nitrates and B-blockers

* The additive efficacy is primarily aresult of one drug blocking the adverseeffect of the other agent on net myocardialoxygen consumption

* B-blockersblocks the reflextachycardia associated with nitrates

* Nitratesattenuate the increase in the

left ventricular end diastolic volumeassociated with B-lockers by increasingvenous capacitance


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2. Ca channel blockers and B-blockers

* useful in the treatment of exertional

angina that is not controlled adequatelywith nitrates and B-blockers

* B-blockersattenuate reflex

tachycardia produce by nifedipine

* These two drugs produce decrease blood

pressure


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3. Ca channel blockers and Nitrates

* Useful in severe vasospastic orexertional angina (particularly in patient

with exertional angina with congestive

heart failure and sick sinus syndrome)

* Nitrates reduce preload and after load

* Ca channels reduces the after load

* Net effect is on reduction of oxygendemand


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4. Triple drugsNitrate +Ca channel

blockers +B-blockers*Useful in patients with exertional anginanot controlled by the administration of two

types of anti-anginal agent

* Nifidipinedecrease after load

Nitratesdecrease preload

B-blockers

decrease heart rate &myocardial contractility


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Type of

Angina

Other Names Description Drug Therapy

STABLE Classic

Exertional

Fixed

Atherosclerotic

Obstruction

coronary artery

Nitrates

CCB

B-blockers

VARIANT Prinzmetals

Vasospasmic

Vasospasm at

any time

Nitrates

CCB

UNSTABLE Crescendo Combined effect

Pre= MI

Nitrates

CCB

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