DRUGS AFFECTING ANGINA PECTORIS

ORGANIC NITRATES
1. Isosorbid dinitrate – Inc cGMP – MOA: All the drugs are de-nitrated to form nitric oxide which activate guanylate cyclase enzyme that
vascular smooth muscle increases cGMP which leads to vascular smooth muscle relaxation
relaxation Action: Nitroglycerine Dilatation of large veins Pooling of venous blood
2. Isosorbid mononitrate – solid at Decrease preload Decreased heart work Dilatation of coronary vasculature
room temperature Increase cardiac perfusion.
3. Nitroglycerine – mod. Volatile Kinetics: OOA <1 min (nitroglycerine) and 1 hour (ISMN). Undergo significant first pass effect
4. Amylnitrate – mod. volatile therefore is administered by sublingual route or transdermal patch. Oral ISDN 1 undergo extensive
metabolism in liver and is converted into ISMN 2.
ADR: Headache (most common). High dose leads to postural hypotension, facial flushing, and
tachycardia. * Throbbing headache d/t meningeal vasodilation
NB: (1) Development of rapid desensitization to vasodilation (Natural physiological effect). (2) Can be
used as antidote to treat cyanide poisoning 3.
BETA BLOCKERS
Propranolol (non- MOA: Lowers the rate and force of contraction, thereby decreasing myocardial oxygen demand. It blocks the action of
selective β blocker), β1 receptors.
Metoprolol Uses: To reduce the severity and frequency of angina attack. Also used to treat MI, HT, Arrhythmias, anxiety, tremors
(Selective β1 and glaucoma
blocker) Kinetics: Absorbed orally, Extensive first pass effect, 90% plasma bound, T 1/2 is 4 hours, Hepatic excretion, 3 hours for
metoprolol.
ADRs: Bradycardia, sedation, worsening of pre-existing asthma (broncho-constriction) lesser risk with metoprolol,
cardiac failure, fatigue, depression, hypoglycemia
Contraindication: Asthma, Diabetes, bradycardia, PVD4, COPD5
NB: Dose should be tapered out to prevent the rebound angina or HT. (2) Agent with intrinsic sympathomimetic activity
like pindolol should be avoided as they do not prove helpful
CALCIUM CHANNEL BLOCKERS
1
Iso-sorbid dintrate
2
Iso-sorbid mononitrate
3
Nitrite induces methemoglobinemia which binds to free cyanide producing less toxic cyanomethemoglobin.
4
Peripheral vascular disease
5
Chronic obstructive pulmonary disease
Calcium is essential for cardiac contraction but in case of ischemia Ca +2 entry into to cardiac cell increases b/c hypoxia produces depolarization.
This continuous depolarization increases ATTP activity leading to energy depletion resulting in further worsening of ischemia.
MOA: All the Ca+2 channel blockers protect this phenomenon by inhibiting Ca +2 entry in cardiac and smooth muscles thereby decreasing muscle
tone and vascular resistance.
Kinetics: Extensive metabolism in liver, repeated administration may lead to increases bioavailability, T 1/2 d/t saturation of hepatic enzymes. In
case of liver cirrhosis bioavailability and half-lives may increase, as well as in older patients
ADRs: Major effects are due to vasodilation (dizziness, hypotension, headache, flushing and nausea), constipation, peripheral edema, cough,
wheezing, pulmonary edema,
Uses: All types of angina, MI
Nifedipine MOA: Relaxes smooth muscles of peripheral vasculature. Causes reflex tachycardia
(dihydropyridine) ADRs: Worsened myocardial ischemia, decreased coronary perfusion; ankle edema, flushing, headache,
hypotension,
Kinetics: Administered orally in the form of extended release tablets, i.v is only given in sub-arachnoid heamorrhage,
extensive metabolism. Elimination by stool and urine, T 1/2 4 hour. Oral bioavailability 45 – 75%. Onset of action is
within an hour
Contraindication: Coronary artery disease
Verapamil MOA: Relaxes the Ca+2 channels of heart. AV blocking effect leading to cardiac slowing
(Phenylalkylamine) Kinetics: Extensively metabolized in the liver and is converted into norverapamil by N-demethylation (T1/2 ~ 10 hours
but less potent than the parent compound). T 1/2 6 hour. Oral bioavailability 25 – 35%. Onset of action is within an
hour. 15 min after i/v administration. >80% protein bound, Hepatic excretion
ADRs: Constipation, Inc. risk of heart failure or heart block. Bradycardia, transient asystole,
Contraindication: Heart failure d/t negative inotropic effect
Interaction: Precaution should be taken when given with digoxin
Diltiazem MOA: Affect vascular smooth muscle and cardiac muscle intermediately. AV blocking effect leading to cardiac
(Benzothiazepines) slowing. Decrease the pace of SA node
Kinetics: Extensively metabolized in the liver, and transformed into desacetlydiltiazem, which have half of the
vasodilator activity of the parent compound. T 1/2 3 – 4 hour. Oral bioavailability 45 – 65%. Onset of action is within an
hour
NEWER ANTI-ANGINA AGENTS
Ranolazine MOA: Act by inhibiting late sodium current that contributes in Na +/Ca+2 exchanger. This helps in fall in intracellular
calcium thereby decreasing cardiac muscle contractility and cardiac work
NB: Approved for angina treatment in USA
Metabolic Trimetazidine MOA: During ischemia myocardial metabolism shifts from CHO metabolism to fatty acid metabolism thus
modulators increasing myocardial oxygen demand. Trimetazidine is also known as pFOX inhibitors b/c they partially
 blocks fatty acid oxidation in myocardium thereby decreasing myocardial oxygen demand
NB: Not approved in USA
MOA: In body tissues hypoxanthine in converted into xanthine which is in turn converted into uric acid.
During this reaction reactive oxygen species are formed which contributes in endothelial dysfunction.
Allopurinol inhibits the conversion of xanthine to uric acid. It is said that prolonged treatment with the
drug increases the exercise time in patients with atherosclerotic angina.
Kinetics: 80% bioavailability after oral administration. T1/2 1 – 2 hours. Metabolite is alloxanthine which is
produced by xanthine oxidase but the metabolite retains the property to inhibit the enzyme with long
Allopurinol duration of action
ADRs: GI disturbances (Nausea, vomiting and diarrhea) Neuritis, vasculitis, bone marrow suppression,
with rare aplastic anemia. Hepatotoxicity
Interaction: Azathioprine (chemotherapeutic purine) dose is decreased to 75%. Cyclophosphamide effect
is increased. Probenecid and oral anti-coagulant (Inhibition of )
NB: Safety not established in children and pregnancy
Bradycardiac drugs MOA: Reduces cardiac rate by hyperpolarization activated Na+ channel in the SA node. It inhibit angina comparable to
(ivabradine) Ca+2 channel blockers and β blockers.
NB: It do not deal with GI and bronchial smooth muscle therefore they lack ADRs of calcium channel and β blockers
Rho kinases (Fasudil) Rho kinases is a family of enzymes that inhibits vascular relaxation. Excessive activity of these enzymes is involved in
coronary spasm, pulmonary hypertension, apoptosis and other conditions.
MOA: Inhibits rho kinases of smooth muscles in heart thereby reducing coronary vasospasm. Proved efficient in CAD
and improved stress induced test in clinical trial.
NB: Belongs to investigational group.
Co-morbidity Long acting nitrates β - blockers Ca+2 channel
blockers
None
Recent Myocardial infarction
Asthma, COPD
Hypertension
Diabetes
Renal disease
Migraine