Angina pectoris

DRUGS USED IN ANGINA PECTORIS & MYOCARDIAL

INFARCTION

WIWIK RAHAYU, dr., M.Kes

Depart.of.Pharmacology & Therapy

Faculty Of Medicine – Riau University

WIWIK RAHAYU, dr., M.Kes

Depart.of.Pharmacology & Therapy

Faculty Of Medicine – Riau University

ANGINA PECTORISA syndrome of inadequate oxygen delivery to

the myocardium relative to the oxygen

requirement of this tissue• Symptom

Severe, transient retrosternal pain radiated to the left arm, back or jaw

• Duration:

0,5 – 30 minute• ECG:

ANGINA PECTORIS

O2 Supply

Ischemic

PAIN

TYPE OF ANGINA PECTORIS

1. CLASSIC ANGINA– Atherosklerosis– Precipitating factor (+)

2. PRINZMETALS– Vasospasm– Precipitating factor (-)

3. UNSTABLEA rapid increase in frequency and intensity of anginal pain occurs, which is thought to herald imminent myocardial infection.

PATHOPHYSIOLOGY (I)

• Age

• Smoking

• DM

• Genetic ?

• Hypertension

• Hypercholesterolemia

• Oral contraception

atherosklerosis

OBSTRUCTION (a.coronary)

Decreased 02 supply

RISK FACTOR

Angina Pectoris

PATHOPHYSIOLOGY II

O2 supply O2 demand&

ISCHEMIA

PAIN

Precipitating factors

Angina Pectoris

PRINCIPLES IN THE TREATMENT OF ANGINA PECTORIS

1. O2 supply to the tissue

2. O2 demand of the tissue

3. Risk Factor

ANTI ANGINAL DRUGS1. ORGANIC NITRATES

– AMIL NITRIT

– NITROGLYCERIN

– ISOSORBIDE DINITRATE

2. Ca ++ CHANNEL BLOCKERS (CCB)– NIFEDIPINE, AMILODIPINE

– DILTIAZEM

– VERAPAMIL

3. ADRENERGIC BLOCKERS– PROPANOLOL cs

NITROGLYCERINENitroglycerine – the prototype nitrate drug.

All nitrates have the same mechanism of Action.

MECHANISM OF ACTION

Administrated nitrates

Nitrites

Nitric oxide (NO)

cGMP

Dephosphorylation of myosin light chain

Vascular smooth muscle relaxation

EFFECT

Venodilatation

PreloadRelief of

coronary a spasm Collateral flow

O2 demand O2 supply O2 supply

Inotropic ?Chronotropic ?

Nitroglycerin

EFFECTHigh Dose

Vasodilatation

BP

tachycardia

O2 demandParadoxal effect

Nitroglycerin

EFFECT

1. Increased O2 supply

2. Decreased O2 demand

Preload

Afterload

3. Contractility (N)

4. Heart rate

5. Decreased in platelet aggregation (?)

Nitroglycerin

Dosage

INDICATION

• ANGINA PECTORIS

•Acute

•Prophylaxis

• ACUTE MYOCARDIAL INFARCTION

• CONGESTIVE HEART FAILURE

Nitroglycerin

ADVERSE DRUG REACTIONS• Common side – effects

Headaches• Serious SE

– Hypotension – Syncope ( cause cerebral ischemia) tachycardia

• Others Edema Methemoglobinemia SL: Burning sensation

• Withdrawal symptoms• Tolerance

Nitroglycerin

ADVERSE DRUG REACTIONS

Tolerance

• Appears within 12 hours

• Long acting preparationContinuous infusion

Caused: - BM depletion

• Avoid by a nitrate free interval

• Cross tolerance

Nitroglycerin

CONTRAINDICATION

• Hypotension

• Severe anemia

• Brain injury

• Tachyaritmia

Nitroglycerin

CALCIUM CHANNEL BLOCKERS (CALCIUM ANTAGONIST)

I. NIFEDIPINE AMLODIPINE, FELODIPINE,

NICARDIPINE, NIMODIPINE, ETC

II. DILTIAZEM

III. VERAPAMIL

MECHANISM OF ACTION

• Inhibit the influx of Calcium into CARDIAC & VASCULAR cells MUSCLE TONE

CCB

EFFECTS (I)CCB

Vascular Effects Cardiac Effects

Vasodilatation

O2 supply After load BP

O2 demand

Heart Rate Conduction

Contraction

O2 demand

EFFECTS (II)CCB

Phenylalkylamines A (Verapamil)

Dihydropyridines

B(Nifedipine) C(Nimodipine)

Benzothiazepines

D (Diltiazem)

VasodilatationPeripheral

Coronary

Cerebral

Heart Rate

SA Node

AV Node

Contractility

++

++

+

+++

+++

+

-

-

+

+

+++

-

-

-

-

+

+++

+

Pharmacokinetics

Drug Absorption Bioavailability Active Metabolites

Half Life (hr)

Onset of Action after Oral Dosing

Peak Effect after oral Dosing

Verapamil

Nifedipine

Diltiazem

>90%

>90%

>80%

10%-35%

60%-70%

40%

+

-

+

5

2

3,5

<1hr

<20min(2-3 min)*

<1hr

1-2hr

30min

2-3hr

CLINICAL PROBLEMS AND SIDE EFFECTSVERAPAMIL

Problems in 8% to 10% of patientsMajorModerate

Minor

NIFEDIPINEProblems in 17% to 20% of patientsMajor

DILTIAZEMProblems in 2% to 5% of patientsMinor

CardiodepressionHypotensionAV node blockPeripheral edemaHeadacheConstipation

HypotensionHeadachePeripheral edema

Hypotension -AV Node BlockPeripheral edema -Cardiodepression

NIFEDIPINE

• Effects (?)

• SE: VD flushing, dizziness, headache, palpitation, peripheral edema

rare myalgia, hypokalemia, gingival swelling

• Drug InteractionCimetidine

Prazosin

• Indication1.PRINZMETAL,S (VASOSPASTIC) ANGINA

Monotherapy, 40-80 mg

More effective when combined with Isosorbid

2.CHRONIC STABLE ANGINA

Combined with Beta Blocker

3.UNSTABLE ANGINA

Monotherapy is contraindication

Combined with Beta Blocker

Nifedipine

SECOND GENERATION DHP

AMLODIPIN: Dosage: 5-10 mg, once daily

NICARDIPINE: Dosage: 20-40 mg, every 8 hours

NIMODIPINE : Subarachnoid Hemorrhage

Migraine

Nifedipine

BETA BLOCKER

• CARDIOSELECTIVE– Acebutolol– Atenolol *– Metoprolol *

• NON CARDIOSELECTIVE– Propanolol *– Nadolol *– Carteolol – Sotalol

• VASODILATOR NONSELECTIVE– Labetolol– Pindolol– Carvedilol

PROPANOLOL

Is the prototype adrenergic blocker

Adrenergicblocker

Inotropic chronotropic domotropic

Renin Ag peripheral BP resistance

aldosteron

Sodium, water retention

BP

O2 demand

INDICATION

I. ANGINA PECTORISFor Chronic management of stable angina

II. MYOCARDIAL INFARCTIONReduces infarct size and has tens recoveryReduce the incidence f sudden arrhythmic death after myocardial infarct

III. HYPERTENSIONIV. ARRYTHMIAV. MIGRAINEVI. GLAUCOMAVII. HYPERTHYROIDISM

SIDE EFFECTSPropanolol

SELECTION OF DRUGS

Drugs ESR Liposoluble FPE Elimination T 1/2

Propanolol +++ ++ L 1-6

Nadolol 0 0 0 K 20-24

Atenolol + 0 0 K 6-7

Metoprolol + + ++ L 3-7

CONTRAINDICATION

• Severe bradycardia, heart block

• Asthma or bronchospasm

• Severe depression

• Peripheral vascular (gangrene, skin, necrosis, Raynaud’s phenomenon)

• DM

• Renal failure

ACUTE MYOCARD INFARCT

O2 Supply

Infarct

PAIN

THERAPY

1. Oksigen2. Morfin3. Metaklopramide4. Nitrogliserin5. Aspirin6. Streptokinase7. Heparin8. Laksativ (bila perlu)

Other Drugs

ACE INHIBITORReduce:

1. Remodeling ventricle2. Haemodinamic3. Reduce heart failure

BETA BLOCKER1. Reduce O2 myocard demand2. Reduce size of infarct

Kasus:

Seorang laki-laki 56 tahun, datang dengan

keluhan sering nyeri dada (khas)

PD: TD= 200/100 mmHg

Diagnosis: Angina Pectoris Klasik

Pertanyaan:

- Bagaimana terapi akut, kronis, lainnya

Seorang wanita 62 tahun, datang dengan

keluhan nyeri dada terutama pagi hari.

PD: TD=180/90, Riwayat DM (+)

Diagnosis: Angina Pectoris Vasospastik

Pertanyaan:

- Bagaimana terapi akut, kronis, lainnya ?

Seorang laki-laki, 60 tahun datang ke UGD

dengan keluhan nyeri dada hebat, muntah,

keringat dingin

PD: TD= 180/100

Diagnosis: Acute Myocard Infarct

Pertanyaan:

- Bagaimana penanganan pasien tersebut?

Wassalam,