ISCHEMIC HEART DISEASE

(IHD)

Jainuri Erik Pratama, M.Farm.Klin., Apt

Anatomy
 Ischemic Heart Disease (IHD)

- Coronary Artery Disease (CAD)

- Atherosclerosis of the epicardial vessels
- Begins early in life, often not being clinically
manifest until the middle-aged years and
beyond
Ischemic Heart Disease (IHD)
Three main coronary arteries:
1. Left anterior descending artery
2. Circumflex artery
3. Right coronary artery

Coronary arteries are blood vessels

that carry blood, oxygen and
other nutrients to the heart
tissue to help it work effectively.
Getting older – hardened coronary
arteries & build up fatty deposits
on the inner lining of the vessel
(atherosclerosis) - narrowing of
the coronary arteries- blood
supply to heart muscle is
reduced  symptoms of
coronary artery disease
 Ischemic Heart Disease (IHD)

Acute coronary syndrome (ACS)

• Unstable angina,
• Non–ST-segment-elevation myocardial
infarction (NSTEMI), and ST-segment-
elevation myocardial infarction (STEMI), and
MI diagnosed by biomarkers only,
• Chronic stable exertional angina pectoris,
• Ischemia without clinical symptoms or owing to
coronary artery vasospasm (variant or
Prinzmetal’s angina)
Normal
 Epidemiology
- Annual Incidence Rate 1.5% (0.1 to 5 per 1000).
- More than 2600 Americans die of CVD each day, or on
average of 1 death every 33 seconds. The death rates
from CVD were 532.0 (per 100,000) for black males, 419.3
for white males, 400.7 for black females, and 294.9 for
white femal
- Framingham Study  prevalence was about 1.5% for
women and 4.3% for men aged 50 to 59 yearses (US,
1998)
- Other factors that increase the risk of death include the
presence of heart failure (or markers such as poor
ventricular wall motion and low ejection fraction), smoking,
diabetes, and prior MI
 Etiology & Pathophysiology

1. Atheroscheloris
Faktor risiko a.l. kolesterol, dislipidemia, DM, riwayat keluarga, obat -
obatan (kokain)
2. Spasm
Spasme arteri koroner pd semua ras (Jepang)
Spasme krn mediator ex : endotelin ; terjadi setiap saat , sering tdk
terkait dg latihan fisik
3. Embolism
Jarang terjadi krn arteri koroner pendek ; dpt terjadi pd pasien dengan
riwayat endokarditis
4. Congenital
Prevalensi kecil (1-2%)
 Etiology & Pathophysiology

Atheroschelorsis

Spasm
 Atherosclerosis*

A lesion begins as a fatty streak (a) and can develop into an

intermediate lesion (b), and then into a lesion that is vulnerable to
rupture (c) and, finally, into an advanced obstructive lesion (d)

*Rader DJ & Daugherty A. Nature. Vol. 451, February 2008

 MANIFESTASI KLINIK

Nyeri dada (chest discomfort) > 30 menit dg

rasa nenekan, diremas, tercekik dan
heavy pain (berat)
Diaporesis (berkeringat)
Berdebar
Nausea, vomiting
Nafas pendek
 Treatments

- Desired Outcome
- Short term: reduce & prevent anginal symptoms
- Long term: prevent CHD events (MI, arrhytmias, HF, life)
- Risk Factor Modification
- Unalterable: gender, age, family history or genetic composition
- Alterable: smoking, HTN, hyperlipidemia, obesity, sedentary life
style.
 Treatments

Non Pharmacology Therapy

Revascularization
- Percutaneous Coronary Intervension (PCI) –
Percutaneous Transluminal Coronary Angioplasty
(PTCA)
- Coronary Artery Bypass Grafting (CABG)
 Treatments
PCI
 Treatments
CABG
 Treatments

Pharmacology Therapy

1. Beta Adrenergic Blocking Agents

2. Nitrates
3. Calcium Channel Antagonists
4. Investigational Agents
Treatments
 Treatments

1. Beta Adrenergic Blocking Agents

- Decreased HR, Contractility, BP  reduce O2 demand
- Benefit in Px with
- limited physical activity due anginal attack,
- HTN,
- anxiety associated w/ angina
- Side Effects
hypotension, heart failure, bradycardia, heart block,
bronchospasm, peripheral vasoconstriction & intermittent
claudication, altered glucose metabolism, lipid abnormalities
 Treatments

1. Beta Adrenergic Blocking Agents

- Discontinuation: due to CNS adverse effect of fatigue,
malaise & depression
- Abrupt withdrawal – tapering down for 2 days
- Drug of choice for chronic exertional angina, chronic
angina due to reduce silent ischemia, early morning
peak of ischemic activity & improving mortality after MI
- CCB as substitute – monotherapy or combination
- Prototype drug: metoprolol, propanolol, atenolol
 Treatments
2. Nitrates
- Reduction of O2 demand secondary to venodilation &
arterial-arteriolar dilation leading to reduction wall
stress from reduce ventricular volume & pressure
- Large first pass effect, short to very short t1/2, high CL,
large interindividual variability
- Used for acute anginal attack, prevent effort or stress
induced attacks, or for long-term prophylaxis (combine
w/ beta blocker or CCB).
 Treatments

2. Nitrates
- Side effects:
- postural hypotension, headache, flushing, nausea, tachycardia,
rash
- Repeated use is not harmful or addicting
- Nitrate tolerance – reduction of tissue cyclic GMP due to
decreace production & increase breakdown of guanylate
cyclase, and increase superoxide level
- Lack of cGMP – depletion of intracellular sulfhydryl
cofactor (cystein)
Nitrate Products

Product Onset (min) Duration Initial Dose

Nitroglycerin
IV 1–2 3–5 min 5 µg/min
Sublingual/lingual 1–3 30–60 min 0.3 mg
PO 40 3–6 h 2.5–9 mg tid
Ointment 20–60 2–8 h 1/2–1 in
Patch 40–60 >8h 1 patch
Erythritol tetranitrate 5–30 4–6 h 5–10 mg tid
Penterythritol 30 4–8 h 10–20 mg tid
tetranitrate
Isosorbide dinitrate
Sublingual/chewable 2–5 1–2 h 2.5–5 mg tid
PO 20–40 4–6 h 5–20 mg tid
Isosorbide mononitrate 30–60 6–8 h 20 mg qd, bida

aProduct-dependent.
 Treatments

3. Calcium Channel Antagonist

- Modulation of calcium entry into vascular smooth muslce
and myocardium, as well as variety of other tissue
- Reduce MVO2
- Pt w/ contraindication or intolerance to beta blockers,
Prinzmetal’s angina, PVD, severe ventricular
dysfunction, HTN
- HOPE study – suggest ACEI for preventing long-term
consequenses of IHD
Terima Kasih