Curriculum Vitae

Nama : Prof. Dr. dr. Rozaimah Zain-Hamid, MS, SpFK

Fakultas Kedokteran, USU, Medan * Staf Pengajar Program S2 Biomedik & Program Administrasi Kebijakan Kesehatan; Program S3 Kedokteran, Sekolah Pascasarjana, USU, Medan * Wakil Ketua Komisi Nasional Etika Penelitian Kesehatan (KNEPK), Indonesia

Pekerjaan : * Guru Besar Tetap Departemen Farmakologi dan Terapeutik,

Riwayat Pendidikan: * Dokter (dr), dari Fakultas Kedokteran, USU. Medan * Magister Sains (MS), Ilmu Kedokteran Dasar (Basic Medical Sciences), dari Fakultas Pascasarjana, Universitas Indonesia, Jakarta * Doktor (Ph.D), Farmakologi Klinik (Clinical Pharmacology), dari Institute of Post-graduated Studies, Universiti Sains Malaysia, Malaysia * Spesialis Farmakologi Klinik (Sp.FK), dari Dewan Penilai Kepakaran Persatuan Dokter Ahli Farmakologi Klinik Indonesia (PERDAFKI) Pusat, Jakarta.

ROZAIMAH ZAIN-HAMID

Department of Pharmacology and Therapeutics Faculty of Medicine Universitas Islam Sumatera Utara

Angina pectoris

Severe chest pain that occurs when coronary blood flow is inadequate to supply the oxygen required by the heart

Zain-Hamid, R; Department of Pharmacology & Therapeutics Faculty of Medicine - UISU.

Angina pectoris
Most common condition involving tissue ischemia

Vasodilators
Zain-Hamid, R; Department of Pharmacology & Therapeutics Faculty of Medicine - UISU.

The most frequent cause of angina

Atheromatous obstruction of the large coronary vessels

Atherosclerotic or classic angina

Zain-Hamid, R; Department of Pharmacology & Therapeutics Faculty of Medicine - UISU.

Transient spasm of localized portions of coronary vessels, which is usually associated with underlying atheromas

Significant myocardial ischemia & pain

Variant or vasospastic angina
Zain-Hamid, R; Department of Pharmacology & Therapeutics Faculty of Medicine - UISU.

The primary cause of angina pectoris

Imbalance between the oxygen requirement of the heart & the oxygen supplied to it via coronary vessels

Zain-Hamid, R; Department of Pharmacology & Therapeutics Faculty of Medicine - UISU.

Atherosclerotic or classic angina

The imbalance occurs when myocardial oxygen requirement (during exercise) & coronary blood flow does not proportionately

Ischemia pain
Zain-Hamid, R; Department of Pharmacology & Therapeutics Faculty of Medicine - UISU.

Variant angina

Oxygen delivery as a result of reversible coronary vasospasm

(usually superimposed on chronic obstruction)

Zain-Hamid, R; Department of Pharmacology & Therapeutics Faculty of Medicine - UISU.

Variant angina

Oxygen delivery as a result of reversible coronary vasospasm

(usually superimposed on chronic obstruction)

Zain-Hamid, R; Department of Pharmacology & Therapeutics Faculty of Medicine - UISU.

Imbalance between oxygen delivery & myocardial oxygen demand

Can be corrected

delivery ( coronary flow) oxygen demand ( cardiac work)

Zain-Hamid, R; Department of Pharmacology & Therapeutics Faculty of Medicine - UISU.

Variant angina

Spasm of coronary vessels can be reversed by nitrates or calcium channel blockers

Zain-Hamid, R; Department of Pharmacology & Therapeutics Faculty of Medicine - UISU.

 Not all vasodilators are effective in angina

Conversely, that some agents useful in angina are not vasodilators (-blockers)
Zain-Hamid, R; Department of Pharmacology & Therapeutics Faculty of Medicine - UISU.

Treatment of angina
coronary artery blood flow
vasodilators (NO donors, Calcium channel blockers)

oxygen demand on the heart

adrenoceptor- blocking drugs

treat coronary artery diseases

cholesterol: statins surgical procedures (stents, angioplasty) lifestyle changes
Zain-Hamid, R; Department of Pharmacology & Therapeutics Faculty of Medicine - UISU.

Drugs used to treat angina

1. Nitrates & nitrites
2. Calcium channel blocker 3. - adrenoceptor blocking drugs 4. Antiplatelets 5. Statins
Zain-Hamid, R; Department of Pharmacology & Therapeutics Faculty of Medicine - UISU.

1. Nitrates & nitrites

Zain-Hamid, R; Department of Pharmacology & Therapeutics Faculty of Medicine - UISU.

Organic Nitrates
1. nitroglycerin (TNT)
delivered in all forms sublingual (cheap, prophylactic) longer duration of action
(active metabolite: 5-isosorbide mononitrate)

2. isosorbide dinitrate

3. isosorbide mononitrate 4. long-acting transdermal patches 5. tetranitrates

differ in onset and duration of actions
Zain-Hamid, R; Department of Pharmacology & Therapeutics Faculty of Medicine - UISU.

Pharmacokinetics of nitrates
High lipid solubility
sublingual absorbed across skin

Rapidly absorbed from anywhere Extensive first pass metabolism Bioavailability is very low Older forms shorter T Newer tetranitrites have longer T Sublingual route is a preferred
Zain-Hamid, R; Department of Pharmacology & Therapeutics Faculty of Medicine - UISU.

Effects of nitrate on the circulation

Zain-Hamid, R; Department of Pharmacology & Therapeutics Faculty of Medicine - UISU.

Pharmacological mechanism
Organic nitrates NO guanylyl cyclase
cGMP cGMP dependent protein kinase intracellular Ca2+ vascular smooth muscle relaxation
Zain-Hamid, R; Department of Pharmacology & Therapeutics Faculty of Medicine - UISU.

Beneficial effects of nitrates in the treatment of angina

1. ventricular volume 2. arterial pressure 3. ejection time myocardial oxygen requirement
Zain-Hamid, R; Department of Pharmacology & Therapeutics Faculty of Medicine - UISU.

Beneficial effects of nitrates in the treatment of angina

Vasodilatation of epicardial coronary arteries

Relief of coronary artery spasm

Zain-Hamid, R; Department of Pharmacology & Therapeutics Faculty of Medicine - UISU.

Beneficial effects of nitrates in the treatment of angina

collateral flow

Improved perfusion to ischemic myocardium

Zain-Hamid, R; Department of Pharmacology & Therapeutics Faculty of Medicine - UISU.

Beneficial effects of nitrates in the treatment of angina

left ventricular diastolic pressure

Improved subendocardial perfusion

Zain-Hamid, R; Department of Pharmacology & Therapeutics Faculty of Medicine - UISU.

Deleterious effects of nitrates in the treatment of angina

Reflex tachycardia Reflex in contractility

myocardial oxygen requirement

Zain-Hamid, R; Department of Pharmacology & Therapeutics Faculty of Medicine - UISU.

Deleterious effects of nitrates in the treatment of angina

Diastolic perfusion time due to tachycardia

myocardial perfusion
Zain-Hamid, R; Department of Pharmacology & Therapeutics Faculty of Medicine - UISU.

Therapeutic use of nitrates

All types of angina

Acute myocardial infarction

Congestive heart failure: isosorbide dinitrate used in prophylaxis attack and congestive heart failure after myocardial infarction
Zain-Hamid, R; Department of Pharmacology & Therapeutics Faculty of Medicine - UISU.

Adverse drug reaction & tolerance of nitrates Headache Orthostatic hypotension

faint when stand-up decreased venous return

Tachycardia
baroreceptor reflex

Conversion to nitrites at high concentrations

oxidizes ferrous iron converts hemoglobin to methemoglobin reduces O2 supply
Zain-Hamid, R; Department of Pharmacology & Therapeutics Faculty of Medicine - UISU.

2. Calcium channel blockers

Zain-Hamid, R; Department of Pharmacology & Therapeutics Faculty of Medicine - UISU.

Calcium channel blockers

1. Derivat DIHYDROPYRIDINE
Short acting : nifedipine Long acting : amlodipine, felodipine

2. Derivat BENZOTHIAZEPINE (diltiazem)

3. Derivat DIPHENYLALKYLAMINE (verapamil, gallopamil)

Basic actions of calcium channel blockers on CVS

Drug
Vasodilation
contractility Nifedipine Diltiazem Verapamil 5 3 4 1 2 4

Suppression
Automaticity (SA)
1 5 5

Conductivity (AV)
0 4 5

Zain-Hamid, R; Department of Pharmacology & Therapeutics Faculty of Medicine - UISU.

Anti-ischemic effects of Calcium channel blockers

Zain-Hamid, R; Department of Pharmacology & Therapeutics Faculty of Medicine - UISU.

3. -adrenoceptor - blocking drugs

Zain-Hamid, R; Department of Pharmacology & Therapeutics Faculty of Medicine - UISU.

Beta Blockers

Zain-Hamid, R; Department of Pharmacology & Therapeutics Faculty of Medicine - UISU.

Mechanism of action -adrenoceptor blocking drugs

activation of 1 receptor in heart CO

Beta Blocker

Renin

angiotensin II

PR

BP

aldosteron Na and water retention blood volume

Zain-Hamid, R; Department of Pharmacology & Therapeutics Faculty of Medicine - UISU.

Anti-ischemic effects of -blocker

Zain-Hamid, R; Department of Pharmacology & Therapeutics Faculty of Medicine - UISU.

Effects of nitrovasodilators alone and in combination with beta-blockers or calcium channel blocker
Hemodynamic Parameter Heart Rate Afterload Preload Contractility Ejection Time Nitrates Alone
Reflex Reflex

Beta-Blockers Nitrates Plus Betaor CC B Alone Blockers or CCB

* None or None

None

Undesirable effects are shown in italics * Dihydropyridines have little direct effect on cardiac contractility but may cause an increase in contractility due to a reflex increase in sympathetic tone.

Zain-Hamid, R; Department of Pharmacology & Therapeutics Faculty of Medicine - UISU.

Adverse drug reaction of - blockers

myocardial performance Combination with calcium channel blockers Suppression of cardiac contractility AV block
Zain-Hamid, R; Department of Pharmacology & Therapeutics Faculty of Medicine - UISU.

Contra indication to - blockers

Asthma, bradycardia, Diabetes Mellitus, A-V block 3rd degree, severe cardiac dysfunction, except caused by hypertension, arrhythmia or tachycardia which respons to - blockers

Zain-Hamid, R; Department of Pharmacology & Therapeutics Faculty of Medicine - UISU.

Conclusions
Drugs for angina pectoris treatment :

coronary artery blood flow

oxygen demand on the heart

treat coronary artery diseases

Zain-Hamid, R; Department of Pharmacology & Therapeutics Faculty of Medicine - UISU.

Zain-Hamid, R; Department of Pharmacology & Therapeutics Faculty of Medicine - UISU.