Angina Pectoris Students 3

7/28/2019 Angina Pectoris Students 3

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anginapectoris

= ischemic heart

disease (IHD)


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anginapectoris

Definition

ankhon= strangling

pectis= chest

coronary blood flow fails tomeet myocardial oxygenrequirements (myocardialischemia):

basic cause:

O2 demand (physical activity)

O2 supply (blood flow obstructed)


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Pathophysiology

anginapectoris

O2 supply O2 demand


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Pathophysiology

anginapectoris

O2 supply

O2 demand


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Anginapectoris

Clinical presentation

chest discomfort:

pressure/tightness

burning

choking/breathlessness

pain discomfort at other sites:

epigastrum

shoulders/arms

neck/jaw

nausea

diaphoresis

duration:

typically 1-5 minutes

range 15sec-15min


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Angina classification

1. stable (typical) angina

the most common form of angina consequence of coronary atherosclerosis

presents in physical activity, emotional stress etc.

predictable, reproducible (exertion)

worse in cold conditions and after meals

anginapectoris


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2. unstable angina (crescendo/pre-infarction angina)

intermediate state between stable angina and MI

a presentation of acute coronary syndromes(ACS)

may appear unexpectedly, at rest

often not associated with physical activity

usually a consequence of severe coronaryatherosclerosis possibly complicated by a

rupture and thrombus formation

management similar to that of MI

anginapectoris


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3. Prinzmetal angina (variant/vasospastic angina)

an uncommon form of angina

consequence of coronary artery spasm

occurs at rest

patients may be younger, with lower risk

typical ECG profile

anginapectoris


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coronary artery

obstruction

angina

50% potential

70% stable (exercise-induced)

90% unstable (at rest)

anginapectoris


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Risk factors

smoking

HTN

hyperlipidemia

diabetes

overweight

sedentary lifestyle

family history

male gender

anginapectoris


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Non-pharmacological Tx

lifestyle modifications

increased, controlled physical activity (exercise training)

smoking cessation

weight management, balanced diet

invasive interventions

PCI - percutaneous coronary intervention:

- balloon angioplasty

CABG - coronary artery bypass grafting

EECP - enhanced external counter-pulsation

- stent placement

anginapectoris


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Pharmacotherapy

Three major drug classes:

organic nitrates

CCBs

anginapectoris

-blockers


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Pharmacotherapy


organic nitrates

CCBs

anginapectoris

-blockers


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Pharmacotherapy

-blockers

relief of angina

symptoms

cardiac 1 receptorantagonism

blood

pressure

myocardial

contractility

myocardial O2demand

anginapectoris


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Pharmacotherapy

-blockers - clinical considerations

1st line in stable angina

anti-anginal effect is dose-dependent

titrate dose to alleviate symptoms and HR=50-60,considering ADEs

very effective in prevention of exertional angina

ineffective, potentially harmful in Prinzmetal angina

(induction of vasospasms)

long-acting 1-selective preferred (atenolol, metoprolol)

reduce morbidity and mortality (post-MI)

anginapectoris


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Pharmacotherapy


organic nitrates

CCBs

anginapectoris

-blockers


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Pharmacotherapy

Organic nitrates:

nitroglycerin (NTG)

NTG

anginapectoris


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Pharmacotherapy

Organic nitrates:

nitroglycerin (NTG)

isosorbide dinitrate (ISDN)

isosorbide mononitrate (ISMN)

ISMN ISDN NTG

prodrugs

anginapectoris


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PharmacotherapyOrganic nitrates - mechanism of action

arginine + O2

Endogenoussources

nitric oxide (NO)

vascular smoothmuscle relaxation

venous and coronary

vasodilation

nitrite

nitrate

NTGISDN

ISMN

minor effect onarteries

small

hypotensive effect

anginapectoris


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PharmacotherapyOrganic nitrates:

nitroglycerin (NTG):

Nitroderm, Deponit, Nitrolingual, Nitrocin

isosorbide dinitrate (ISDN):

Isoket

(spray), Cordil

, Isolong

isosorbide mononitrate (ISMN):

Monolong, Mononit, Monocord

anginapectoris


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PharmacotherapyOrganic nitrates - ADEs:

headache facial flushing

hypotension

bradycardia

excessivearterioarteriodilation

excessive

venovenodilation

Organic nitrates - DDIs:

PDE-5 inhibitors (sildenafil = Viagra, severe hypotension)

alcohol (hypotension)

anginapectoris


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PharmacotherapyOrganic nitrates - use:

nitrate clinical use mode ofadministration

onset ofeffect

durationof effect

NTG

acute angina sublingual/IV rapid short

chronic angina transdermal rapid long

ISDN

acute angina sublingual rapid short

chronic angina oral delayed medium

ISMN chronic angina oral delayed long

anginapectoris


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PharmacotherapyOrganic nitrates - tolerance:

reduced effect following long-term use

effect restored after nitrate-free interval

presentation:

decrease in NO formation

decrease in NO effect

proposed mechanisms:

activation of vasoconstricting RAAS

anginapectoris


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PharmacotherapyOrganic nitrates - tolerance:

asymmetrical dosing allowing for 8-12hr

nitrate-free intervals:

prevention:

nitrate dosage form recommended dosing regimen

ISDNIR BID: 7/12; TID: 7/12/17

SR BID: 8/14; OD: morning

ISMN IR BID: 8/15SR OD: morning

IR/SR: immediate/sustained release; OD - 1/d; BID - 2/d; TID - 3/d

anginapectoris


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PharmacotherapyOrganic nitrates - clinical considerations:

sublingual NTG/ISDN for acute angina and forprophylaxis (prior to physical activity known toinduce acute angina

ISDN/ISMN for chronic angina: daytime for exertional

angina, nighttime for nocturnal angina

prevention of nitrate tolerance

improve exercise duration; not shown to mortality

anginapectoris


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PharmacotherapyThree major drug classes:

organic nitrates

CCBs

anginapectoris

-blockers


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ischemia

hypoxia

depletion ofenergy stores

Ca++ influx

Pharmacotherapy

Ca++ in ischemia

anginapectoris

CCBs

smooth muscle

coronary vasodilation

negative chronotropic effect

negative inotropic effect

peripheral vasodilation


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Pharmacotherapy

CCBs - subclasses

Dihydropyridines (nifedipine, amlodipine)

arterial vasodilation

minimal effect on cardiac rate/conduction

verapamildiltiazemnifedipinerelative affinity to

++++++cardiac Ca++ channels

++++++vascular Ca++ channels

avoid short acting (BP drop, reflex tachycardia, mortality)

anginapectoris


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Pharmacotherapy

CCBs - subclasses

Non-dihydropyridines: verapamil (phenylalkylamine)

cardiac conduction effect > vasodilating effect

negative chronotrope/inotrope




anginapectoris

avoid in cardiacdepression

avoid in cardiacdepression

lessheadache,edema

lessheadache,edema

i


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Pharmacotherapy

CCBs - subclasses

Non-dihydropyridines: diltiazem (benzothiazepine)

intermediate properties

coronary vasodilator (mild arterial vasodilator);

negative chronotrope (not negative inotrope)




anginapectoris

useful in variant angina (relieves coronary artery spasm)

i


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Pharmacotherapy

anginapectoris

angina


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PharmacotherapyACEIs in stable angina?

some ACEIs have been shown to M&M

- anti-inflammatory effect in plaque?

mechanism of benefit unclear

consider adding in non-responders

- reduction of LV hypertrophy

no clinical evidence regarding ARBs

anginapectoris

angina


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PharmacotherapyAnti-platelet Tx in stable angina?

for prevention of thrombus formation

aspirin generally accepted for 1/ 2 prevention

also indicated in unstable angina

addition of clopidogrel

anginapectoris

angina


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PharmacotherapyStable angina

1st-line: -blocker (prevent progression to MI)

- nitrates advantageous in LV dysfunction

combine as needed with nitrate/CCB

triple therapy as needed

- CCBs advantageous in HTN

consider ACEI

anginapectoris

angina


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PharmacotherapyUnstable angina (non-acute Tx)

1st-line: -blocker (prevent progression to MI)

CCB - for refractory cases

nitrate

aspirin +/- clopidogrel

anginapectoris

statin

ACEI (ARB)

aldosterone antagonist in some

angina


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PharmacotherapyPrinzmetal angina

1st-line: CCBs (antispastic effect)

-blockers not indicated (may induce vasospasms)

if uncontrolled - combine a nitrate

anginapectoris

angina


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Myocardial infarctionPathophysiology

deterioration of unstable angina

complete occlusion of coronary artery

atherosclerotic thrombus formation

rarely caused by vasospasms w/o atherosclerosis

massive cellular necrosis/death

anginapectoris

angina


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Myocardial infarctionPresentation

chest pain, may radiate to arms/neck/jaw etc.

diaphoresis

shortness of breath

~20% silent MI

nausea

a g apectoris

angina


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Myocardial infarctionDiagnosis

symptoms

cardiac enzymes

ECG

gpectoris

angina


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Myocardial infarctionPharmacotherapy

thrombolytics

-blockers

antiplatelet/anticoagulant Tx

CCBs

anti-arrhythmics

nitrates

analgesics

stool softeners

gpectoris

angina


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pectoris

DRUGS FOR EXAM

isosorbide mononitrate

Angina Pectoris Students 3

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