ANTI- ANGINAL DRUGS

Prashiddha Dhakal MBBS (KUSMS, 11th)

What Is Angina?

Central chest discomfort or pain due to transient ishemia of the myocardium

Pain may radiate to one arm OR to both arms OR to neck OR to jaw OR to the epigastrium

Duration- Less than 20min

Types Of Angina

Classical/Typical/Stable/Exertional Angina• Due to fixed and stable plaque

Prinzmetal/Variant Angina• Due to spasm of coronary artery

Unstable Angina• Due to unstable plaque (± thrombus)

Pharmacological Goals & Drugs Classification

↓ Preload (Venodilation)• Nitrates, Potassium Channel Openers ↓ Afterload (Arteriolodilation)• Calcium Channel Blockers, Potassium

Channel Openers ↓ Heart Rate• Beta Blockers, Calcium Channel Blockers Dilate Coronary Artery• Dipyridamole

NITRATESNitroglycerine, Isosorbide Dinitrate, Isosorbide Mononitrate

Release Nitric Oxide in smooth muscles of Veins(mainly) & Arterioles

Stimulate Guanylyl Cyclase & ↑cGMP

Stimulate Protein Kinase G

Dephosphorylation & inactivation of MLCK

Relaxation of vascular smooth muscle

NITRATES Venodilation → ↓ Venous Return → ↓Preload

Venodilation → ↓intraventricular pressure → less compression on vessels supplying subendocardial myocardium → ↑ Perfusion

Arteriolodilation → ↓ TPR → ↓ Afterload

Dilates collateral pathways & provides blood to ischemic area

NITRATES

BETA BLOCKERS

Non-selective - Propanolol

Cardioselective (β1) - Atenolol, Metoprolol Have following actions :

-ve Chronotropy (SA Node)

-ve Dromotropy (AV Node)

-ve Inotropy (Contractile myocardium)

-ve Clinotropy (Velocity of contraction & relaxation)

BETA BLOCKERS Adverse Effects Fatigue (Blockade of β2 receptors in blood

vessels supplying skeletal muscles) Bradycardia (Blockade of β1 receptors in

heart)

Precaution Abrupt withdrawal can ↑heart rate,

↑contractility & cause arrythmia & even MI.

(Upregulation of receptors)

BETA BLOCKERS

Contraindications

Prinzmetal Angina COPD, Asthma,Bronchiectesias (β2 in lungs) Diabetes Mellitus(β2 in liver & pancreas) Raynaud’s Disease(β2 in peripheral blood

vessels) Bradyarrythmias (β1 in heart) Depression

CALCIUM CHANNEL BLOCKERS Phenyl Alkylamines- Verapamil

Benzothiazepines- Diltiazem

Dihydropyridines- Nifedipine, Amlodipine, Felodipine

Blocks voltage gated L-type Ca channels present in cardiac & vascular smooth muscles

CALCIUM CHANNEL BLOCKERS Depending upon their types, they can have

following actions :

-ve Chronotropy (SA Node)

-ve Dromotropy (AV Node)

-ve Inotropy (Contractile myocardium)

-ve Clinotropy (Velocity of contraction & relaxation)

↓Afterload (Arteriolodilatation)

CALCIUM CHANNEL BLOCKERS

HEART ARTERIOLES

Verapamil ++++ +

Diltiazem ++ ++

Dihydropyridines - ++++

Adverse Effects

•Verapamil- similar to Beta Blockers•Dihydropyridines- similar to Nitrates•Diltiazem- common to above two

POTASSIUM CHANNEL OPENERS

Nicorandil, Pinacidil Opens Potassium channels in vascular

smooth muscles & causes K efflux resulting into the hyperpolarization of the cell.

Venodilation- ↓Preload

Arteriolodilation- ↓Afterload

PHARMACOTHERAPY FOR ANGINA

Stable Angina Acute attack- NTG 0.5mg S/L

Prophylaxis-

Nitrates- Isosorbide Mononitrate, Transdermal NTG

β Blockers- Propanolol, Atenolol, Metoprolol

CCB-Amlodipine, Verapamil SR & Diltiazem SR

PHARMACOTHERAPY FOR ANGINA

Variant Angina

Acute- NTG S/L or I/V

Prophylaxis-

Nitrates- Isosorbide Mononitrate

CCB-Amlodipine, Diltiazem SR

Potassium Channel Openers- Nicorandil, Pinacidil

β BLOCKERS ARE CONTRAINDICATED

PHARMACOTHERAPY FOR ANGINA

Unstable Angina NTG S/L

Antiplatelets agent- Aspirin, Clopidogrel

β Blockers- Atenolol, Metoprolol

CCB- Amlodipine or Nifedipine SR

LMW Heparin