Treatment of Angina

Anti-anginal drugs: Drugs that prevent, abort, terminates attack of angina pectoris.
Angina Pectoris: Is a pain syndrome due to induction of an adverse oxygen supply/demand
situation in a portion of the myocardium.
Types:
(a) Classical angina (common form): Attacks are predictably provoked (stable angina) by
exercise, emotion, eating and subside when the increased energy demand is withdrawn.
Etiology: Severe arteriosclerotic affliction of larger coronary arteries (conducting vessels)
which run epicardially into deeper tissue. The coronary obstruction is ‘fixed’; blood flow fails
to increase during increased demand → ischaemic pain.
During classical angina → end diastolic left ventricular pressure raises from 5 mm Hg to 25
mm Hg → Produce sub endocardial crunch during diastole → Aggravate the ischemia →
Left ventricular failure →Which is reduced by taking rest and reducing myocardial work
load.
b) Variant Angina / Uncommon / Prinzmetal’s Angina:
Attacks occur at rest or during sleep → unpredictable → due to recurrent localized coronary
vasospasm.
c) Unstable Angina: Rupture of an atherometous plaque (sclera) → Attracting platelet
deposition.
CLASSIFICATION
1. Nitrates
(a) Short acting: Glyceryl trinitrate (GTN, Nitroglycerine)
(b) Long acting: Isosorbide dinitrate, Isosorbide mononitrate, Erythrityl tetranitrate,
Pentaerythritol tetranitrate
2. β Blockers: Propranolol, Metoprolol, Atenolol
3. Calcium channel blockers
(a) Phenyl alkylamine: Verapamil
(b) Benzothiazepine: Diltiazem
(c) Dihydropyridines: Nifedipine, Felodipine, Amlodipine
4. Potassium channel opener: Nicorandil
5. Others: Dipyridamole, Trimetazidin
Classification:
1) Nitrates (GTN as prototype) :
i) Preload reduction : Nitrates dilate veins more than arteries → peripheral pooling of blood
→ decreased venous return → preload on heart is reduced → end diastolic size and pressure
are reduced → decreased cardiac work → ↓ O2 consumption → abolishes the subendocardial
crunch by restoring the pressure gradient across ventricular wall due to which subendocardial
perfusion occurs during diastole.
ii) Afterload reduction: Nitrates also produce some arteriolar dilatation → slightly decrease
total peripheral resistance (t.p.r.) → ↓ after load
iii) Redistribution of coronary flow: Nitrates preferentially relax bigger conducting
coronary arteries than arterioles or capillaries. Dilation of conducting vessels all over by
nitrates along with ischemia induced dilation of autoregulatory resistance vessels only in the
ischemic zone → ↑ blood flow to this ischemic zone while in nonischaemic zone resistance
vessel maintains their tone → flow does not increase.
Mechanism of relief of Angina:
a) Classical Angina:
i) ↑ Blood supply to ischaemic zone (Redistribution zone)
ii) ↓ Cardiac work by vasodilation
b) Variant Angina:
By counteracting coronary vasospasm.
Mechanism of action:
Organic nitrates are rapidly denitrated enzymatically in the smooth muscle cell to release the
reactive free radical nitric oxide (NO) which activates cytosolic guanylyl cyclase →
increased cGMP → causes dephosphorylation of myosin light chain kinase (MLCK) through
a cGMP dependent protein kinase. Reduced availability of phosphorylated (active) MLCK
interferes with activation of myosin → it fails to interact with actin to cause contraction.
Consequently relaxation occurs. Raised intracellular cGMP may also reduce Ca2+
entry—contributing to relaxation.
a) GTN (glyceryl trinitrate):
Volatile liquid → adsorb onto inert material of tablet → stored into airtight container .
Sublingual route → terminating the attack of angina with 1-2 min.
Transdermal patch: steady delivery for 24 hrs
b) Isosorbide dinitrate:
Sublingually at the time of anginal attack
Orally for chronic prophylaxis
c) Isosorbide mononitrate:
Active metabolite of Isosorbide dinitrate. If given orally undergoes first pass metabolism →
given parenterally
Adverse effects:
These are mostly due to vasodilatation.
1. Fullness in head, throbbing headache;
2. Flushing, weakness, sweating, palpitation, dizziness and fainting
3. Methemoglobinemia:
4. Rashes.
USES:
1. Angina pectoris
2. Acute coronary syndromes (ACS)
3. Myocardial infarction (MI)
4. CHF and acute LVF
5. Biliary colic
6. Esophageal spasm
7. Cyanide poisoning: Nitrates generate methaemoglobin which has high affinity for cyanide
radical and forms cyanomethaemoglobin.
Haemoglobin
↓ Nitrates
Methaemoglobin
↓ Cyanide
Cyanomethaemoglobin
↓ Sod. Thiosulfate
Methaemoglobin + Sod. thiocyanate
↓
Excreted in urine
2. β Blockers:
Act by reducing the cardiac work (↓ HR)
↓ Inotropic state
β Blockers limit increase in modalities that occur during exercise or anxiety → Increase in
cardiac tolerance.
3. K+ channel openers:
Eg: Nicorandil, Pencidil
Activates ATP sensitive K+ channels → Hyperpolarising vascular smooth mucles → Dilation
of vascular smooth muscles.
Also NO donor → ↑ cGMP → relaxes blood vessels → arterial dilatation is coupled with
venodilatation → Coronary flow is increased.
Dipyridamole: It is a powerful coronary dilator.
Increases total coronary flow by
a) preventing uptake of adenosine
b) Preventing degradation of adenosine
Adenosine is a local mediator involved in auto regulation of coronary flow in response to
ischaemia.
Dipyridamole inhibits platelet aggregation. By potentiating PGI2 and increasing cAMP in
platelets → employed for prophylaxis of coronary and cerebral thrombosis in post-MI and
post stroke patients.