DRUGS USED IN ANGINA PECTORIS & MYOCARDIAL INFARCTION WIWIK RAHAYU, dr., M.Kes Depart.of.Pharmacology & Therapy Faculty Of Medicine – Riau University
May 11, 2015
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,