Antianginal Drugs

Dr Navyashree R
Asst Professor
Dept of Pharmacology
 Angina pectoris

 Pain syndrome due to induction

of an adverse O2 supply /
demand situation in a portion of
the Myocardium
 Chief symptom of IHD
 Classification

 Classical angina – stable angina

→ common form, predictably provoked
→ lesion – atherosclerotic affliction of larger coronary
artery

→ SUBENDOCARDIAL CRUNCH
–during diastole
→ acutely developing but reversible LVF
 Variant/Prinzmetal angina
→ unpredictable - attack occurs at rest / during
sleep
→ localized coronary Vasospasm

 Unstable angina
 Antianginal Drugs

 Nitrates
1. Short acting: GTN
Isosorbide dinitrate

2. Long acting: Isosorbide dinitrate

Isosorbide mononitrate
Erythrityl tetranitrate
Penta erythritol tetranitrate.
 Beta Blockers: Propranol, Metoprolol, Atenolol, etc

 Calcium channel blockers:

 Phenylalkylamines – Verapamil

 Benzothiazepines – Diltiazem

 Dihydropyridines – Nifedipine, Amlodipine

 K+ channel openers: Nicorandil, Pinacidil

 Others: Dipyridamole
Trimetazidine , Ranolazine, Ivabradine
Oxyphedrine
 Nitrates

1. Preload Reduction
Heart 2. Afterload reduction
3. Redistribution of coronary blood flow

1. Dilatation of Bronchi
Other
2. Dilatation of Biliary tract & esophagus
 Concepts of Preload and Afterload.
• The degree of tension on the muscle when it begins to
contract, is called the preload, the load against which
the muscle exerts its contractile force, is called the
afterload.
• For cardiac contraction, the preload is usually
considered to be the end-diastolic pressure when the
ventricle has become filled.
• The afterload of the ventricle is the pressure in the
artery leading from the ventricle. (Sometimes the
afterload is loosely considered to be the resistance in
the circulation rather than the pressure.)
 Preload reduction
 Mainly exerted on vascular smooth muscle.

 Nitrates dilate veins more than arteries →

peripheral pooling of blood → decreased
venous return, i.e. preload on heart is reduced
→ end diastolic size and pressure are reduced
→ decreased cardiac work
 Afterload reduction
 also produce some arteriolar dilatation →
slightly decrease total peripheral resistance
(t.p.r.) or afterload on heart
 BP falls somewhat - systolic more than
diastolic
Molecular MOA
Nitrates
↓
Nitric oxide (NO)
↓
Activation of Guanylyl cyclase
↓
GTP → cGMP
↓
Myosin LCK →Myosin LCK PO43+
↓
reduced MLCK interferes with myosin activation
fails to interact with actin

Relaxation of smooth muscles

 Pharmacokinetics

 All are lipid soluble

 Well absorbed from buccal mucosa, GIT and skin

 Extensively metabolized in liver

– except Isosorbide mononitrate
 ADRs

 Fullness in head, throbbing headaches

 Sweating, palpitation, dizziness, fainting

 Methemoglobinemia

 Rashes – penta erythritol tetranitrate

 TOLERANCE
 Cross tolerance to nitrates
 Attenuation of anti-ischemic effects if the drug

is continuously present in the body.

 Drug dependence
 Sudden withdrawal after prolonged use can
result in coronary and peripheral vasospasm

 Drug interaction
 Dangerous hypotension with SILDENAFIL
 Glyceryl trinitrate: volatile liquid
plasma t1/2 – 2 minutes

Routes of administration:
transdermal
oral dose – 5 -15 mg
sublingual dose – 0.5mg
iv route – 5mcg/min
 Clinical uses
 Angina pectoris – both, classical and variant
 Acute coronary syndromes
 CHF and acute LVF
 Myocardial infaction
 Interventional cardiac procedures
Do not administer if
• Systolic BP is < 90 mm Hg
• Heart rate is < 50 or > 100
beats/min
• Right ventricular infarction is
suspected
• Hypotension caused by GTN
limits use of beta blockers
• If sildenafil has been taken in
the past 24hrs

 Biliary colic, esophageal spasm

 Cyanide poisoning – Na+ nitrite with Na+ thiosulphate

Alternatives : HYDROXOCOBALAMIN and
DICOBALT EDETATAE
 Beta blockers
 Do not dilate coronaries or other blood vessels & act
by reducing cardiac work and O2 consumption
 Cardioselective agents (atenolol, metoprolol) are
preferred
 To be taken on a regular schedule; not on ‘as and
when required’ basis.
 The dose has to be individualized.
 Abrupt discontinuation after chronic use may
precipitate severe attacks, even MI
 Calcium channel blockers
 Calcium channel blockers: they block the voltage
gated L type calcium channels and reduce frequency
of opening of these channels in response to
depolarisation

 Phenylalkylamines – Verapamil

 Benzothiazepines – Diltiazem

 Dihydropyridines – Nifedipine, Amlodipine

 ACTIONS
 The two most important actions of CCBs are:
(i) Smooth muscle (especially vascular)
relaxation.
(ii) Negative chronotropic, inotropic and
dromotropic action on heart.
 Drug interactions: Verapamil

 Beta-blockers: Depression of SA & AV nodes. Negative

inotropic effect-HF

 Digoxin: V. decreases the renal & non renal elimination of

digoxin

 Amiodarone: Depression of SA & AV nodes

 BZDs: increased sedation

 Increases the levels of quinidine & oral anticoagulants

Uses
1. Angina pectoris : reduce frequency and severity of
classical as well as variant angina.
 Exercise tolerance is increased.

2. Hypertension

3. Cardiac arrhythmias

4. Hypertrophic cardiomyopathy

5. Others - Nifedipine is an alternative drug for premature labour ,

Verapamil has been used to suppress nocturnal leg cramps, The DHPs reduce
severity of Raynaud’s episodes.
 Potassium channel openers
 Nicorandil, Pinacidil
 dual mechanism
 activates ATP sensitive K+ channels (KATP)
 hyperpolarize vascular smooth muscle
 also acts as a NO donor—relaxes blood vessels
by increasing cGMP.
 NICORANDIL
Activates ATP sensitive K+channels
↓
Hyperpolarizes vas. Sm.muscles
↓
↑ cGMP due to NO
↓
Relaxes bl. vessels
 ADRs
 Flushing
 Palpitation
 Weakness
 Headache
 Dizziness
 Vomiting
 Mouth Ulcers
 USES
1. Angina pectoris
 useful in resistant angina when combined with other
drugs.
 Administered i.v. during angioplasty for acute MI, it
is believed to improve outcome.
 Miscellaneous - Trimetazidine

 Anti anginal drug

 No effect on HR/BP

 Angina frequency is reduced and exercise

capacity is increased

 Added to nitrate/β-blocker/CCB
 Dipyridamole
 Coronary vasodilator

 Prevents uptake and degradation of adenosine

 Dilates resistance vessels & no effect on conducting vessels

 Does not afford symptomatic benefit

 Inhibits platelet aggregation by ↑ PGI2 & ↑ cAMP in

platelets
 Coronary steal phenomenon-dilates resistance
vessels in non-ischaemic zone as well

 Tab 25, 75, 100mg(persantin, cardiwell)

 Dose : 25-100mg t.i.d

 Uses :

1. Post MI & post stroke

2. Prosthetic heart valves

 RANOLAZINE
 Metabolic modifier

 Reduces myocardial oxygen demand and has

cardioprotective property

 Inhibits the late sodium current and prevents calcium

overload in the myocardium

 Approved for prophylaxis of angina as add on therapy in

patients who do not respond to first line drugs
 Ivabradine
 Bradycardiac drug

 Selectively blocks If sodium channel blocker

 May be used as alternative to betaz blockers

 Choice of drug

 Exertional Angina

• Acute attack

• Acute prophylaxis

• Chronic prophylaxis
Combinations of drugs in angina
 Nitrates + Beta blockers
 Nifedepine + Beta blockers
 Nitrates + CCBs
 CCBs + Beta blockers + Nitrates
 Drug therapy in
MYOCARDIAL INFARCTION
 Acute coronary syndromes
 Unstable angina (UA):
• Vascular obstruction is incomplete,
• myocardial necrosis is absent—biochemical markers
of ischaemia do not appear in blood,
• ST segment is not elevated in ECG.
 Non ST segment elevation myocardial
infarction(NSTEMI):
 Vascular obstruction is incomplete, attended by
relatively smaller area of myocardial necrosis;
 biochemical markers appear in blood, but ST segment
is not elevated.
 ST segment elevation myocardial infarction
(STEMI):
• Vascular obstruction is complete,
• larger area of myocardium is necrosed,
• biochemical markers are prominent
• ST segment in ECG is elevated.
 Myocardial infarction (MI) is ischaemic
necrosis of a portion of the myocardium due to
sudden occlusion of a branch of coronary
artery.
1. Pain, anxiety and apprehension
2. Oxygenation
3. Maintenance of blood volume, tissue perfusion
and microcirculation
4. Correction of acidosis
5. Prevention and treatment of arrhythmias
6. Pump failure :increase c.o. and/or decrease
filling pressure without unduly increasing
cardiac work or lowering BP.
(a) Furosemide: indicated if pulmonary wedge
pressure is > 20 mm Hg. decreases cardiac preload.
(b) Vasodilators: venous or combined dilator is selected
according to the monitored haemodynamic parameters.
Drugs like GTN (i.v.), or nitroprusside have been
mainly used.
(c) Inotropic agents: dopamine or dobutamine i.v.
infusion (rarely digoxin if AF present) may be needed to
augment the pumping action of heart and tide over the
crisis.
7. Prevention of thrombus extension,embolism,
venous thrombosis
 Aspirin(162–325 mg) should be given for
chewing and swallowing as soon as MI is
suspected, continued at 80–160 mg/day.
 Anticoagulants (heparin followed by oral

anticoagulants
 Any benefit is short-term; anticoagulants are
not prescribed on long-term basis now
8. Thrombolysis and reperfusion
 Fibrinolytic agents, i.e. plasminogen

activators—streptokinase/ urokinase/alteplase
to achieve reperfusion of the infarcted area
 primary percutaneous coronary intervention

(PCI) with stenting is nowthe preferred

revascularization procedure,wherever
available.
 9. Prevention of remodeling and subsequent
CHF
 10. Prevention of future attacks
 (a) Platelet
 (b) β blockers
 (c) Control of hyperlipidaemia