Skip to main content

Renin Angiotensin Mechanism.

AntiAnginal Drugs

  • The Drugs used in treatment of Angina pectoris are called as antianginal drugs.

Classification:

  1. Nitrates:
  • a) Short acting (10 minutes): Glyceryl tri nitrate. (Nitroglycerine, GTN)
  • b) Long Acting (1 hour): Isosorbide di nitrate, Isosorbide mono nitrate.
      2. Calcium channel blockers:
  • a) Phenyl alkyl amine: Verapamil.
  • b) Benzothiazepin: Diltiazem.
  • c) Dihydropyridines: Nifedipine, Amlodipine, Nimodipine, felodipine.
       3. Beta Adrenergic Blockers:  Propranolol, Atenolol, Metoprolol, Alprenolol.
       4. Potassium Channel Openers: Nicorandil.
       5. Miscellaneous: Dipyridamole, Trimetazidine, Ranolazine, Oxyphedrine etc.

Nitrates

1) Glyceryl Tri Nitrate:

  • It is heavy colorless explosive liquid.
  • It as an organic nitrate compound and is synthesized by nitration of glycerin.
  • Nitroglycerine was first used in treatment of angina pectoris by William Murrell in 1878.
IUPAC Name: 1,3-dinitrooxypropan-2-yl nitrate.

Mechanism of Action:

  • Nitroglycerin is converted into nitric oxide (NO) in smooth muscle and activates guanylyl cyclase, thereby increasing cGMP concentration, and resulting in smooth muscle relaxation.
  • Dilatation of the veins results in decreased venous return to the heart, thereby decreasing left ventricular volume (reduced preload) and decreasing myocardial oxygen requirements.
  • Arteriolar relaxation reduces arteriolar resistance (reduced afterload), thereby decreasing myocardial oxygen demands. In addition, nitroglycerine causes coronary artery dilatation, thereby improving myocardial blood distribution.

Therapeutic Uses:

  1. In treatment of angina attacks.
  2. As a tocolytic agent (Used in prevention of premature abortion)

Side effects / Toxic effects:

  1. Tachycardia.
  2. Orthostatic Hypotension.
  3. Throbbing headache.
  4. Can react with Sildenafil citrate and a like drugs to induce profound hypotension leading to death.

2) Isosorbide Mono Nitrate:

IUPAC Name: [(3S,3aR,6R,6aS)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl] nitrate
  • Isosorbide-5-mononitrate, the long-acting metabolite of isosorbide dinitrate, is used as a vasodilatory agent in the management of angina pectoris.
  • By dilating the vessels, it lowers the blood pressure and reduces the left ventricular preload and afterload, therefore, leads to a reduction of myocardial oxygen requirement.

Calcium Channel Blockers.

  • The drugs which block calcium ion channels and are employed as vasodilators are called as Calcium Channel blockers.

Mechanism of Action:

  • These class of drugs block the voltage gated “L Type” of calcium ion channels and hence reduce intracellular calcium concentration and muscle contractility.

1) Verapamil:

  • It belongs to the “Phenyl Alkyl Amines” class of the calcium ion channel blockers.
IUPAC Name:  2-(3,4-dimethoxyphenyl)-5-[2-(3,4-dimethoxyphenyl)ethyl-methylamino]-2-propan-2-ylpentanenitrile;hydrochloride

Mechanism of Action:

  • Verapamil inhibits the transmembrane influx of extracellular calcium ions into myocardial and vascular smooth muscle cells, causing dilatation of the main coronary and systemic arteries and decreasing myocardial contractility.

 

  • This class of drug has following essential chemical features,
  1. The benzene ring,
  2. A tertiary amino nitrogen charged at physiological pH.
  3. The isopropyl group and other ring substituents are not found essential for the activity.

Therapeutic Uses:

  1. Angina pectoris.
  2. Management of hypertension.
  3. AV nodal cardiac arrhythmia.

Side Effects / Toxic effects:

  1. Heart failure.
  2. AV node depression.
  3. SA node depression.

2) Amlodipine:

  • Amlodipine is a synthetic “dihydropyridine” and a calcium channel blocker with antihypertensive and antianginal properties.
IUPAC Name: 3-O-ethyl 5-O-methyl 2-(2-aminoethoxymethyl)-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate.

Mechanism of Action:

  • Amlodipine inhibits the transmembrane influx of extracellular calcium ions into myocardial and vascular smooth muscle cells, causing dilatation of the main coronary and systemic arteries and decreasing myocardial contractility.

Essential structural features for  activity:1-4 dihydropyridines

  1. The 1-4 dihydropyridine ring.
  2. The secondary nitrogen remaining uncharged at physiological pH.
  3. A bulky substituent at 4 position of the 1-4 dihydropyridine ring.
  4. NO2 and other ester moieties are not essential.

Therapeutic Uses:

  1. Angina pectoris.
  2. Management of hypertension.
  3. In certain cardiac arrhythmias.

Side Effects / Toxic effects:

  1. Hypotension.
  2. Swelling of ankles.
  3. Vertigo.

3) Diltiazem:

  • It belongs to the “Benzothiazepin” class of Calcium ion channel blockers.
IUPAC Name: [(2S,3S)-5-[2-(dimethylamino)ethyl]-2-(4-methoxyphenyl)-4-oxo-2,3-dihydro-1,5-benzothiazepin-3-yl] acetate;hydrochloride.

Mechanism of Action:

  • Diltiazem hydrochloride inhibits the transmembrane influx of extracellular calcium ions into select myocardial and vascular smooth muscle cells, causing dilatation of coronary and systemic arteries and decreasing myocardial contractility.

Structure Activity Relationship:

  1. The tertiary basic nitrogen is essential for action.
  2. N demethylation and quaternarization of nitrogen reduces the activity or abolishes the activity.

Side effects/ Toxic effects:

  1. Hypotension.
  2. Bradycardia.
  3. Dizziness.

Therapeutic Uses:

  1. Stable angina.
  2. Unstable angina.
  3. Variant angina.
  4. Supraventricular tachycardia.
  5. Atrial fibrillation.
  6. Atrial flutter.

Adrenergic Beta Blockers.

1) Atenolol:

  • It is well known beta blocker used in several cardiac conditions.
IUPAC Name:  2-[4-[2-hydroxy-3-(propan-2-ylamino)propoxy]phenyl]acetamide

Mechanism of Action:

  • Atenolol acts as a peripheral, cardio selective beta blocker specific for beta-1 adrenergic receptors, without intrinsic sympathomimetic effects.
  • It reduces exercise heart rates and delays atrioventricular conduction, with overall oxygen requirements decreasing.

Therapeutic uses:

  1. Hypertension.
  2. Angina.
  3. Myocardial infraction.
  4. Supraventricular Tachycardia.
  5. Ventricular tachycardia.
  6. Alcohol withdrawal symptoms.

Side effects / Toxic Effects:

  1. Hypotension.
  2. Bradycardia.
  3. Hypoglycemia.

Potassium channel openers:

1) Nicorandil:
  • Its a potassium channel opener drug used in treatment of angina pectoris.
IUPAC Name: 2-(pyridine-3-carbonylamino)ethyl nitrate.

Mechanism of action:

  • Nicorandil is a potassium channel opener with nitro vasodilator (NO donor) actions, making it both an arterial and a venous dilator.
  • It causes sustained dilation of both the arterial resistance and conductive vessels that increases coronary blood flow.

Therapeutic Uses:

  • In treatment of various angina.

Side effects / Toxic effects:

  1. Flushing.
  2. Palpitations.
  3. Perianal ulcerations.
Labels:

Popular posts from this blog

Rate of Drying Curve.

  Definition Drying is defined as the removal of liquid from a product usually with application of heat. Rate of Drying Curve. Drying process can be divided into three periods Initial Adjustment Period. Constant drying rate period. First falling drying rate period. Second falling rate period. Initial Adjustment Period (A-B): Also called the “ Heating up” period . In this period the substance gets heat and increases in temperature. Drying has not yet started. Constant drying rate period (B-C): During this period the temperature of the solid and the rate of drying remain constant. The moisture evaporating from the surface is replaced by water diffusing from the interior of the solid at a rate equal t o the rate of evaporation.  The moisture content at the end of constant rate (point C) is referred to as the critical moisture content (CMC).  At CMC, dry spots start appearing and drying rate starts falling . First falling drying rate period (C-D): This period is also called the period of
Read more

Heat Exchangers and Heat Interchangers.

  In pharmaceutical industries many types of equipments are used for transfer of heat, they can be classified as follows, Heat Exchangers. Heat Interchangers. Heat Exchangers: These devices are used for transferring heat from a fluid (Hot Gas or Steam) to another fluid (Liquid) through a metal wall. Heat Interchangers: These devices are used for transferring heat from a One liquid to another liquid or one gas to another gas through a metal wall. HEAT EXCHANGERS; The equipment used for heat transferring are known as heat exchangers. Some of the processes that involves heat transfer in pharmaceutical industries are: Preparation of starch paste (in steam jacketed kettle). Crystallization. Evaporation. Distillation.  Classification of heat exchangers On the basis of transfer of heat, heat exchangers are classified as: Direct transfer type:  The hot and cold fluids are separated by a metal wall through which the heat is transferred from hot fluid to cold fluid. E.g. shell and tube heater, 
Read more

Flash Distillation.

  Principle: When a hot mixture is allowed to enter from a high-pressure zone into a low pressure zone, the entire liquid mixture is suddenly vaporized. This process is known as flash vaporization .  During this process, the chamber is cooled.  The less volatile fraction is condensed and the more volatile component remains in the vapor phase .  This process requires time, hence liquid and vapor are kept in intimate contact until equilibrium is achieved. Flash distillation is also called equilibrium distillation because separation of two liquids takes place when liquid and vapor phases are at equilibrium. Equipment used for Flash Distillation: Construction: It consists of a pump, which is connected to a feed reservoir.  Pumps help in pumping the feed into the heating chamber.  The heating chamber is heat supplied by steam.  The other end of the pipe is directly introduced into the vapor-liquid separator through a reducing valve.  The vapor outlet is provided at the top of the separato
Read more