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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5265_Библиотеки_им_академика_М_И_Перельмана.pdf
Drugs Acting on Cardiovascular System 227
7.2.7 Nifedipine
Generic Name: Nifedipine
Brand Names: Adalat, Afeditab CR, Nifediac, Nifedical, Procardia
Nifedipine is a first generation dihydropyridine calcium channel blockers used to treat
hypertension and angina pectoris. It decreases arterial smooth muscle contractility and subsequent
vasoconstriction by inhibiting the influx of calcium ions through L-type calcium channels
IUPAC Name: dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
Properties: It appears as odorless yellow, crystalline crystals or powder, tasteless with melting
point 172°C to 174°C. It is practically insoluble in water and soluble in acetone, methylene
chloride, chloroform, ethyl acetate, methanol and ethanol.
Uses:
➢ Nifedipine is used to treat hypertension (high blood pressure).
➢ It is used to treat angina (chest pain).
➢ It is used for the management of chronic stable angina (effort-associated angina).
➢ It is used in Raynaud’s phenomenon (it is a problem that causes decreased blood flow to
the fingers. In some cases, it also causes less blood flow to the ears and toes).
➢ It is used in premature labor.
Dosage Forms and Strengths: Capsule: 10 mg, 20 mg, tablet, extended release: 30 mg, 60 mg,
90 mg.
➢ Angina: Conventional orally (10 mg) every 8 hours or 30-60 mg (extended release)
orally once daily initially; may be increased every 7-14 days as needed.
➢ Hypertension: Extended release (30-60 mg) orally once daily; may be increased every
7-14 days as needed; not to exceed 90 mg/day.
Storage Conditions: Nifedipine liquid-filled capsules should be stored at a temperature of 15°C
to 25°C; protected from light and moisture; and stored in tight, light-resistant containers. The
extended-release tablets of the drug should be protected from light and moisture, and stored in
tight, light-resistant containers at a temperature less than 30°C.
Officials:
➢ Nifedipine, I.P.
➢ Nifedipine Capsule, I.P.
➢ Nifedipine Injection, I.P.
228 Text Book of Pharmaceutical Chemistry
7.3 ANTIANGINAL AGENTS
Angina is chest pain or feeling of discomfort when there is not sufficient blood flow to the
heart muscle. The medical term used for chest pain is angina pectoris. It is a symptom of coronary
artery disease (CAD), the most common heart disease. Coronary artery disease occurs when
plaque (a sticky substance deposition) builds up in the arteries that supply blood to the heart,
reducing blood flow.
Anginal pain usually occurs in the centre of the chest, behind the breastbone, a feeling of pain
in the chest, shoulders, arms, neck, jaw or back. There are mainly three types of angina:
1. Stable angina: It is the most common type and happens when heart is working harder
than usual, e.g., physical activity or stress can trigger it.
2. Unstable angina (most serious): It does not follow a pattern and can happen without
physical exertion. It does not go away with rest or medicine. It is a sign that you could
have a heart attack soon.
3. Prinzmetals or variant angina: Prinzmetals is an uncommon pattern of episodic angina
that occurs at rest and is due to coronary artery spasm (vasospasm). It is also referred to
as “variant” angina.
Classification of Antianginal Agents
7.3.1 Isosorbide Dinitrate
Brand Names: Dilatrate-SR, Isochron, Iso Ditrate, Isordil Titradose, Sorbitrate
Isosorbide dinitrate is an organic polycyclic compounds containing an isosorbide (1,4-
Dianhydrosorbitol) moiety, which consists of two-oxolan-3-ol rings. It is the dinitrate salt form of
isosorbide, an organic nitrate with vasodilator activity.
Drugs Acting on Cardiovascular System 229
IUPAC Name: 1,4,3, 6-dianhydro-2,5-di-o-nitro-D-glucitol
Properties: Isosorbide dinitrate occurs as white crystalline powder, and is odorless. It is soluble
in water; and freely soluble in acetone, alcohol ether and chloroform.
Mechanism of Action: Isosorbide dinitrate is converted to nitric oxide (NO), an intermediate
active compound that activates the enzyme guanylate cyclase. This stimulates the synthesis of
cyclic guanosine 3',5'-monophosphate (cGMP) which then activates a series of protein kinase-
dependent phosphorylations within the smooth muscle cells, eventually leading to
dephosphorylation of the myosin light chain of the smooth muscle fiber. The subsequent
sequestration of calcium ions leads to vasodilation and relaxation of the smooth muscle cells.
Storage: Isosorbide dinitrate injections are colorless and stable in the intact ampoules or bottles
when stored at room temperature. Isosorbide dinitrate tablets should be stored in tight, light-
resistant containers at room temperature (25°C) and should not be exposed to extremes in
temperature. Loss of potency is accelerated by exposure to heat and moisture.
Pharmaceutical Formulations: It is available as an oral tablet both in extended release and slow
release (sublingual or chewable) tablet. It is effective for the treatment of acute angina attack,
congestive heart failure, and for oesophageal spasms.
➢ Sublingual tablets: 2.5 and 5 mg
➢ Chewable oral tablets: 5 and 10 mg
➢ Oral tablets: 5, 10 and 20 mg
➢ Time-release tablets: 40 mg
Officials:
➢ Isosorbide Dinitrate Tablet, I.P.
➢ Diluted Isosorbide Dinitrate, I.P.
➢ Isosorbide Dinitrate Injections
7.4 EXERCISE
A. Long Answer Type Questions
1. Write chemical name, structure and medicinal uses of:
(a) Amiodarone
(b) Sotalol
2. What are antiarrythmic agents? Classify them and give the structure, properties and uses
of Quinidine Sulphate.
3. Write about the types of arrhythmia.
4. Give the properties, storage condition and brand name of the following drugs:
(a) Hydralazine hydrochloride
(b) Nifedipine
230 Text Book of Pharmaceutical Chemistry
5. What are antihypertensive agents? Write the structure, properties and uses of
Propranolol.
6. What are antianginal drugs? Classify antianginal drug, and write the structure and uses
of Isosorbide Dinitrate.
7. Write the structure, properties and therapeutic uses of Phenytoin sodium.
8. Write the structure, properties and therapeutic uses of Verapamil.
B. Short Answer Type Questions
1. Define the term hypertension.
2. Define the term angina pectoris.
3. Write about the different types of Angina.
4. Write the structure and uses of Captopril.
5. Write the difference between primary and secondary hypertension.
6. Write the uses of:
(a) Procainamide hydrochloride
(b) Verapamil
(c) Phenytoin sodium
7. Differentiate between systolic and diastolic pressure.
8. Write the structure and uses of clonidine hydrochloride.
C. Fill in the Blanks
1. Brand name of Nifedipine is _____________.
2. Methyldopa is used in the treatment of _____________.
3. Lidocaine hydrochloride is used in the treatment of _____________.
4. Chemically propranolol is a _____________.
5. Source of Quinidine is _____________.
6. A brand name of Captopril is _____________.
7. Hydralazine belongs to _____________ class
8. Procainamide is structurally related to _____________.
9. Normal blood pressure is _____________ mmHg.
10. The antihypertensive drug Losartan is _____________ antagonists.
11. The drug Ramipril is indicated for the treatment of _____________.
12. Atenolol is the drug of class _____________.
Drugs Acting on Cardiovascular System 231
Answers:
1. Nifediac
2. Hypertension
3. Hypertension
4. 1-naphthalen-1-yloxy-3-(propan-2-ylamino) propan-2-ol
5. Cinchona alkaloid
6. Capoten
7. Hydrazinophthalazine
8. Procaine
9. 120/80
10. Angiotensin II subtype I (AT1) receptor
11. Hypertension
12. β-Adrenergic blockers
Chapter
8
DIURETICS
STRUCTURE
8.1 Introduction
8.2 Exercise
OBJECTIVE
➢ Diuretics: Acetazolamide, Frusemide, Bumetanide, Chlorthalidone, Benzthiazide,
Metolazone, Xipamide, Spironolactone
8.1 INTRODUCTION
Diuretics are a group of drugs that increase the amount of water and salt expelled from the
body as urine. These medications, often known as water pills, help the body get rid of excess fluid
and salt. They are used to treat disorders such as high blood pressure, edema (extra fluid in the
tissues), and others. These drugs work by eliminating salt and chloride from the body through the
urine, which then removes excess water out of the body.
Types of Diuretics
There are different types of diuretics which work in different ways. They are thiazides, loop
diuretics, and potassium-sparing diuretics.
1. Thiazide Diuretics: Thiazide diuretic includes hydrochlorothiazide, benzthiazide,
hydroflumethiazide bendroflumethiazide, polythiazide, indapamide, clopamide,
xipamide, metolazone, etc. These diuretics are mainly used to treat high blood pressure
(hypertension). They are occasionally also used for heart failure. Thiazide diuretic is a
bicyclic structure that contains adjacent sulfur and nitrogen atoms on one ring.
2. Loop Diuretics: Loop diuretics, e.g., furosemide, bumetanide, torasemide and ethacrynic
acid are used in the treatment of pulmonary edema, high blood pressure, kidney problems
and heart failure. These drugs work by inhibiting the sodium-potassium-chloride
(Na
+
/K
+
/2Cl) co-transporter in the thick ascending Loop of Henle.
3. Potassium-sparing Diuretics: Potassium-sparing diuretics are the drugs that increase
diuresis (urination) without the loss of potassium. There are various potassium-sparing
diuretics. They are Spironolactone, Eplerenone, Triamterene and Amiloride. Potassium-
sparing diuretics are used to:
Diuretics 233
➢ treat heart failure
➢ prevent low levels of potassium (hypokalaemia) occurring when other diuretics are
used
➢ treat high blood pressure (hypertension).
Carbonic Anhydrase Inhibitors
Carbonic anhydrase inhibitors are mainly used for the treatment of glaucoma. These drugs
reduce the reabsorption of bicarbonate from the proximal tubule in the kidneys. Acetazolamide,
dichlorphenamide and methazolamide are carbonic anhydrase inhibitors. Acetazolamide is also
used as an anticonvulsant to control certain seizures in the treatment of epilepsy.
Osmotic Diuretics
Osmotic diuretics mainly act on the proximal convoluted tubule and the descending limb of
the Loop of Henle. They can be used to reduce intracranial and intra-ocular pressure. These
different classes of diuretic drugs act on different site of nephrone. Structure of nephrone and site
of diuretic drug actions is shown in Fig. 8.1.
Fig. 8.1: Structure of Nephrone (Site of Diuretic Drug Action)
Classification of Diuretics
1. Loop diuretics
➢ Furosemide
➢ Bumetanide
➢ Torasemide
➢ Ethacrynic acid (only historical)
234 Text Book of Pharmaceutical Chemistry
2. Thiazide diuretics
➢ Hydrochlorothiazide
➢ Benzthiazide
➢ Hydroflumethiazide
➢ Bendroflumethiazide
➢ Polythiazide
3. Thiazide-like diuretics
➢ Chlorthalidone
➢ Indapamide
➢ Clopamide
➢ Xipamide
➢ Metolazone
4. Potassium-sparing Diuretics
➢ Spironolactone
➢ Eplerenone
➢ Triamterene
➢ Amiloride
5. Carbonic Anhydrase Inhibitors
➢ Acetazolamide
➢ Methazolamide
➢ Dichlorphenamide
6. Osmotic Diuretics
➢ Mannitol
➢ Isosorbide
➢ Glycerol
Drugs and their Site of Action:
Type
Drug
Site of Action
Osmoic diuretics
Mannitol
Proximal convoluted tubule
Descending limb
Collecting duct
Carbonic anhydrase inhibitors
Acetazolamide
Proximal tubule
Thiazides
Hydrochlorothiazide,
Chlorthiazide, Metolazone
Distal convoluted tubule
Loop diuretics
Ethacrynic acid, Furosemide,
Bumetanide, Toresamide
Loop of Henle
Potassium-sparing diuretics
Spironolactone, Triamterene,
Amiloride, Eplerenone
Collecting tubule
Diuretics 235
8.1.1 Acetazolamide
Brand Name: Diamox, Diamox Sequels
Acetazolamide is a sulfonamide, a member of thiadiazoles and a monocarboxylic acid amide.
It is a conjugate acid of an acetazolamide(1-) and derives from a hydride of a 1,3,4-thiadiazole.
It is a non-competitive inhibitor of carbonic anhydrase, an enzyme found in cells in the proximal
tube of the kidney, the eye, and glial cells.
Nomenclature: N-(5-Sulfamoyl-1,3,4-thiadiazol-2yl)-acetamide
Properties: Acetazolamide appears as white to faintly yellowish-white fine crystalline, odorless,
tasteless powder. Its melting point is 260.5°C. It is sparingly soluble in cold water; slightly
soluble in alcohol; insoluble in chloroform, diethyl ether, and carbon tetrachloride; slightly
soluble in acetone; and readily soluble in 1N sodium carbonate solution.
Uses:
➢ Acetazolamide is used to lower intraocular pressure in the treatment of malignant (ciliary
block) glaucoma, which may occur after inflammation surgery, trauma, or use of miotics.
➢ It is used to lower intraocular pressure prior to surgery.
➢ It has a role as a diuretic.
➢ It is used as an anticonvulsant drug.
Dosage Forms: Oral capsule, extended release (500 mg); oral tablet (125 mg; 250 mg)
Glaucoma:
➢ Closed-angle (acute congestive) glaucoma
500 mg PO/IV, followed by 125-250 mg PO q4hr
Sustained-release – 500 mg PO q12hr
➢ Open-angle (chronic simple) glaucoma
250 mg-1 g PO/IV q day or divided q6-12hr
Sustained-release – 500 mg PO q12hr
Storage: Acetazolamide tablets and extended-release capsules should be stored in a well-closed
container at 15°C to 30°C. Reconstituted solutions retain their physical and chemical properties
for 12 hours at room temperature 20°C to 25°C.
Officials:
➢ Acetazolamide, I.P.
➢ Acetazolamide Tablet, I.P.
236 Text Book of Pharmaceutical Chemistry
8.1.2 Furosemide
Brand Names: Lasix, Diaqua-2, Lo-Aqua
Furosemide is a derivative of sulfamoylanthranilic acid. It is also known as frusemide, and
belongs to a group of medicines called loop diuretics (also known as water pills). It works by
acting on the kidneys to increase the flow of urine.
Chemistry and Structure: Chemically furosemide is a chlorobenzoic acid that is 4-
chlorobenzoic acid substituted by a (furan-2-ylmethyl) amino and a sulfamoyl group at positions
2 and 5 respectively. It is a diuretic used in the treatment of congestive heart failure.
IUPAC Name: 4-chloro-2-(furan-2-ylmethylamino)-5-sulfamoylbenzoic acids.
Properties: Furosemide occurs as an odorless, almost tasteless white to slightly yellow
crystalline powder. It is slightly soluble in water, chloroform and ether; soluble
in acetone, methanol and DMF; soluble in methanol, acetone and dilute NaOH; and freely soluble
in alkali hydroxide.
Uses: Furosemide is used for the treatment of edema (fluid retention; excess fluid held in body
tissues) caused by various medical problems, including heart, kidney, and liver disease. It is also
used in edema caused by congestive heart failure because of its antivasoconstrictor and diuretic
effects. It is used in liver cirrhosis, kidney impairment and nephrotic syndrome. It has a role as a
xenobiotic, an environmental contaminant and a loop diuretic.
Dosages of Furosemide: Furosemide is available in the solution and tablet dosage form.
➢ Injectable solution: 0 mg/mL
➢ Oral solution: 10 mg/mL
➢ Tablet: 20 mg, 40 mg, 80 mg
Storage: Keep the medicine in tightly closed container. Store it at room temperature and away
from excess heat and moisture. Furosemide injection should be stored at a temperature of 15°C to
30°C and protected from light; injections having a yellow color should not be used. Furosemide
tablets should be stored and dispensed in well-closed, light-resistant containers at a controlled
room temperature of 15°C to 30°C.
Stability: Dispose of unused furosemide solution after 90 days. It is stable under recommended
storage conditions. When heated to decomposition, it emits very toxic fumes of hydrogen
chloride, nitrogen oxides and sulfur oxides.
Officials:
➢ Furosemide, I.P.
➢ Furosemide Injection, I.P.
➢ Furosemide Tablet, I.P.