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Drugs Acting on Autonomic Nervous System 207
Capsule contains the active ingredients 5 mg chlordiazepoxide hydrochloride and 2.5 mg
clidinium bromide.
Storage and Stability: Store the drug at room temperature 25°C; excursions permitted to 15°C to
30°C, Keep containers securely sealed, and store in a cool, dry, well-ventilated area. Store it away
from incompatible materials and foodstuff containers. Protect containers against physical damage
and check regularly for leaks. Observe manufacturer’s storing and handling recommendations. It
is stable under normal temperatures and pressures. Avoid prolonged or repeated exposure.
6.5.4 Dicyclomine Hydrochloride
Brand Names: Bentyl, Dibent, Dicyclocot
Dicyclomine is a tertiary amine and a carboxylic ester. It derives from a
2- diethylaminoethanol and a 1,1'-bi(cyclohexyl)-1-carboxylic acid. Dicyclomine hydrochloride is
the hydrochloride salt form of dicyclomine, a synthetic analog of acetylcholine with
antimuscarinic activity.
Chemical Name: 2-(diethylamino) ethyl 1-cyclohexylcyclohexane-1-carboxylate; hydrochloride
Properties: Dicyclomine hydrochloride occurs as a fine, white, crystalline powder, practically
odorless and has very bitter taste. Melting point is 164-166°C.
Uses:
➢ It is used to treat spasms of the intestines such as occur in irritable bowel syndrome.
➢ It is used to treat or prevent spasm in the muscles of the gastrointestinal tract.
➢ It helps to reduce the symptoms of stomach and intestinal cramping.
➢ It slows the natural movements of the gut and relax the muscles in the stomach and
intestines.
Dosage Forms: Dicyclomine is available as an oral tablet capsule or solution that you take by
mouth and by injection. It is available as a brand name Bentyl drug.
➢ Intramuscular solution (10 mg/mL)
➢ Oral capsule (10 mg)
➢ Oral syrup (10 mg/5 mL)
➢ Oral tablet (20 mg)
Storage: Keep it away from light. Protect from freezing. Do not store this medication in moist or
damp areas. Dicyclomine tablets and capsules: store at room temperature between (15°C and
30°C). Dicyclomine oral solution: Store between 68°F and 77°F.
208 Text Book of Pharmaceutical Chemistry
Officials:
➢ Dicyclomine Hydrochloride, I.P.
➢ Dicyclomine Hydrochloride Tablet, I.P.
➢ Dicyclomine Hydrochloride, Oral Solution, I.P.
6.6 EXERCISE
A. Long Answer Type Questions
1. Write the structure, chemical name and medicinal uses of:
(a) Tropicamide
(b) Cyclopentolate hydrochloride
2. What are alpha-adrenergic blockers? Give the structure, properties and uses of
Tolazoline and Phentolamine.
3. Define direct acting agents. Write the properties, chemical name and uses of
Acetylcholine and Carbachol.
4. Give the properties, storage condition and brand name of the following drugs:
(a) Epinephrine
(b) Atenolol
(c) Dicyclomine hydrochloride
5. What are sympathomimetic agents? Write the classification with examples of
sympathomimetic agents.
6. Classify beta-adrenergic blockers. Write the structure, uses and marketed preparations
of Propranolol.
7. What are cholinergic blocking agents? Write the properties and uses of Atropine
Sulphate.
B. Short Answer Type Questions
1. Write the structure and properties of Dopamine.
2. Define adrenergic drugs.
3. Give the structure of Propranolol.
4. Write the uses of:
(a) Neostigmine
(b) Edrophonium chloride
(c) Tacrine hydrochloride
5. Define cholinergic drugs.
6. Give the structure and chemical name of any two sympathomimetic agents.
7. Write the structure and uses of Norepinephrine.
8. Write the structure, properties and uses of Tropicamide.
Drugs Acting on Autonomic Nervous System 209
C. Fill in the Blanks
1. Brand Name of Prazocin is _______________.
2. Salbutamol (Albuterol) is used to treat _______________.
3. Brand name of Tropicamide is _______________.
4. Neostigmine is used for the treatment of _______________.
5. Brand name of Biperidine is _______________.
6. Cyclopentolate structure consists of a _______________ structure.
7. Chemical name of Dopamin is _______________.
8. Tolazoline is a drug of the class _______________.
9. Brand name of Propanolol is _______________
10. _______________ is the brand name of dopamine.
11. Chemical name of the drug Phenoxybenzamine is _______________.
12. The drug Prazosin is a _______________ derivative.
13. Atropine is a naturally occurring tertiary amine (alkaloid) extracted from ____________.
Answers:
1. Minipress
2. Asthma
3. Minims Tropicamide, Mydriacyl, Paremyd
4. Mysthanea gravis
5. Dyskinon
6. carboxylic ester
7. 4-(2-aminoethyl)benzene-1,2-diol
8. Imidazoles
9. Inderal
10. Intropin
11. N-benzyl-N-(2-chloroethyl)-1-phenoxypropan-2-amine
12. Piperazine
13. Atropa belladonna
Chapter
7
DRUGS ACTING ON
CARDIOVASCULAR SYSTEM
STRUCTURE
7.1 Antiarrhythmic Drugs
7.2 Antihypertensive Agents
7.3 Antianginal Agents
7.4 Exercise
OBJECTIVES
➢ Antiarrhythmic Drugs: Quinidine Sulphate, Procainamide Hydrochloride, Verapamil,
Phenytoin Sodium, Lidocaine Hydrochloride, Lorcainide Hydrochloride, Amiodarone
and Sotalol
➢ Antihypertensive Agents: Propranolol, Captopril, Ramipril, Methyldopate Hydrochloride,
Clonidine Hydrochloride, Hydralazine Hydrochloride and Nifedipine.
➢ Antianginal Agents: Isosorbide Dinitrate
7.1 ANTI-ARRHYTHMIC DRUGS
An arrhythmia (also called dysrhythmia) is a heart rhythm disorder in which the heart beats
irregularly. Cardiac arrhythmia refers to a group of conditions that cause the heart to beat
irregular, too slowly, or too quickly.
The electrical activity in the heart is seen in a normal pathway, the regular heart rhythm
(called normal sinus rhythm) means the electrical pulse from the sinus node is being properly
transmitted throughout the heart muscle. When the electrical signals to the heart that coordinate
heartbeats are disrupted, arrhythmia occurs. In adults, normal sinus rhythm usually accompanies a
heart rate of 60 to 100 beats per minute. There are different kinds of arrhythmias.
Types of Arrhythmias
➢ Tachycardia: Tachycardia is a fast heart rhythm with a rate of more than 100 beats per
minute.
➢ Bradycardia: Bradycardia is a slow heart rhythm with a rate below 60 beats per minute.
Drugs Acting on Cardiovascular System 211
➢ Supraventricular arrhythmias: “Supra” means above. Arrhythmias that begin in the
atria (upper chambers) are called supraventricular arrhythmias.
➢ Ventricular arrhythmias: Arrhythmias that arise in the ventricles (lower chambers).
➢ Bradyarrhythmias: Slow heart rhythms may be caused by disease in the heart’s
conduction system, such as the sinoatrial (SA) node, atrioventricular (AV) node or His-
Purkinje network.
Antiarrhythmic agents are the drugs that are used to prevent and treat irregular heart rate and
heartbeat. Antiarrhythmic drugs are classified into different classes and are used to treat various
types of arrhythmia.
Table 7.1: Classification of Antiarrhythmic Drugs
Class
Mechanism of Action
Drugs
Class I
Block Na channels
Ia
Slows phase 0 depolarization
Quinidine, Procainamide,
Disopyramide
Ib
Shortens phase 3 repolarization
Lidocain, Phenytoin, Tocainide,
Mexiletine
Ic
Marked decrease in phase 0
Encainide, Flecainide
Class II
Beta-adrenergic blockers
(Decrease in heart rate, AV conduction)
Propranolol
Class III
Prolongation of ventricular
repolarization (Phases 1-3)
Amiodarone, Bretylium, Sotalol
Class IV
Calcium channel blockers
Blocks slow inward Ca
2+
channel
Veerapamil, Diltiazem
7.1.1 Quinidine Sulphate
Brand Name: Quinidine Sulfate
Quinidine is a natural cinchona alkaloid extracted from cinchona bark. It consists of
cinchonine with the hydrogen at the 6th position of the quinoline ring substituted by methoxy
group, used to treat certain types of irregular heartbeats. Quinidine comes as a tablet (quinidine
sulfate). Quinidine sulphate is an optical isomer of quinine, extracted from the bark of the
cinchona tree. This alkaloid dampens the excitability of cardiac and skeletal muscles by blocking
sodium and potassium currents across cellular membranes.
212 Text Book of Pharmaceutical Chemistry
IUPAC Name: (5-ethenyl-1-azabicyclo[2.2.2]octan-2-yl)-(6-methoxyquinolin-4-yl)methanol;
sulfuric acid.
Properties: It occurs as fine, odorless, needle-like, very bitter white crystals which frequently
cohere in masses or as a fine, white powder. It is slightly soluble in water and soluble in alcohol.
Stability and Storage: Protect it from light; darkens on exposure to light /dehydrate. It should be
stored in well closed, light-resistant containers. Quinidine salts slowly acquire a brownish tint on
exposure to light. Quinidine gluconate injection should be stored at 15°C to 30°C. When diluted
to a concentration of 16 mg/mL with 5% dextrose injection, quinidine gluconate injection is
stable for 24 hours at room temperature and up to 48 hours when refrigerated.
Uses:
➢ Quinidine sulfate is used to treat or prevent many types of irregular heartbeats (heart
arrhythmias such as atrial fibrillation).
➢ It can also be used to treat malaria.
➢ It can improve the ability to perform normal activities by decreasing the number of
irregular heartbeats.
Dosage Forms:
➢ Tablet – 200 mg (as sulfate), 300 mg (as sulfate)
➢ Extended-release (long-acting) tablet – 300 mg (as sulfate), 324 mg (as gluconate)
➢ Injectable solution – 80 mg/mL (as gluconate)
➢ Atrial fibrillation – 300-400 mg PO q6hr
➢ PSVT – 400-600 mg PO q2-3hr until paroxysm terminated
➢ Atrial/ventricular premature contractions – 200-300 mg PO q6-8hr
Officials:
➢ Quinidine Sulphate, I.P.
➢ Quinidine Sulphate Tablet, I.P.
Drugs Acting on Cardiovascular System 213
7.1.2 Procainamide Hydrochloride
Generic Name: Procainamide
Brand Names: Amidoprocain, Novocamid, Novocainamid, Novocainamide, Novocainamidum,
Novocaine Amide, Procaine Amide, Procaine Amide Hydrochloride
Structure and Chemistry: Procainamide is structurally related to procaine, but in place of an
ester group, procainamide contains an amide group. They belong to aminobenzamides class, and
are aromatic carboxylic acid derivatives consisting of an amide with a benzamide moiety and
a triethylamine attached to the amide nitrogen.
IUPAC Name: p-Amino-N-[2-(diethylamino) ethyl]benzamide hydrochloride
Properties: Procainamide hydrochlorideis is white to yellowish white, crystalline powder and
odorless. It is very soluble in water, freely soluble in ethanol, very slightly soluble in ether, and
practically insoluble in ether and benzene. Melting point is 165°C to 169°C.
Storage Conditions: Store in airtight containers. Store tablets and capsules at room temperature.
Avoid excessive heat. Protect from moisture. All preparations should be protected from light.
Procainamide should not be used in patients with bronchial asthma or myasthenia gravis.
Uses:
➢ Procainamide is a drug used to control and treat ventricular arrhythmias.
➢ It is used in supraventricular arrhythmias.
➢ It is used in atrial flutter/fibrillation.
➢ It is used in Wolf-Parkinson-White syndrome.
Dosage Form: Injectable solution (100 mg/mL; 500 mg/mL)
Officials:
➢ Procainamide Hydrochloride, I.P.
➢ Procainamide Hydrochloride Injection, I.P.
➢ Procainamide Hydrochloride Tablet, I.P.
7.1.3 Verapamil
Brand Names: Isoptin, Verelan, Verelan PM, Calan, Bosoptin, Covera-HS
Verapamil is a phenylalkylamine and a member of the non-dihydropyridine class of calcium
channel blockers.
214 Text Book of Pharmaceutical Chemistry
IUPAC Name: 2-(3,4-dimethoxyphenyl)-5-[2-(3,4-dimethoxyphenyl)ethyl-methylamino]-2-propan-
2-ylpentanenitrile
Verapamil administered, as a racemic mixture, contains equal amounts of the S- and R-
enantiomer, each of which is pharmacologically distinct – the S-enantiomer carries approximately
20 times greater potency than the R-enantiomer.
Properties: Verapamil occurs as white, crystalline powder, practically odorless, with a bitter
taste. It is not chemically related to other antiarrhythmic drugs. It is practically insoluble in water;
soluble in benzene and ether; sparingly soluble in hexane; and freely soluble in the lower
alcohols, acetone, ethylacetate and chloroform.
Therapeutic Uses: Verapamil is the drug of choice for prevention and treatment of PSVT. It is
also used as an alternative treatment for mild or moderate hypertension. It has been shown to be
effective in the treatment of angina pectoris.
Mechanism of Action: Verapamil inhibits the entry of calcium through calcium channels into
cardiac cells. It reduces the magnitude of the calcium current entry and decreases the rate of
recovery of the channel. Channel blockade by Verapamil is enhanced as the frequency of
stimulation increases. Its action on cardiac tissue results in antiarrythmic and negative inotropic
effects.
Dosage Forms: Adult: Oral; as hydrochloride: 120-480 mg daily in 3-4 divided doses according
to the severity of the condition and patient’s response.
Stability and Storage: Verapamil HCl should be stored at room temperature and protected from
light. Store tablets and ampoules at 15°C to 25°C, and protect from light. Dispense in tight, light-
resistant containers.
Drugs Acting on Cardiovascular System 215
Officials:
➢ Verapamil Hydrochloride, I.P.
➢ Verapamil Hydrochloride Injection, I.P.
➢ Verapamil Hydrochloride Tablet, I.P.
7.1.4 Phenytoin Sodium
Brand Names: Dilantin, Phenytek
Phenytoin is classified as a hydantoin derivative, formerly known as diphenylhydantoin.
Phenytoin Sodium is the sodium salt form of phenytoin. It is the most commonly used as
anticonvulsants.
Phenytoin sodium is related of the barbiturates in chemical structure, but has a five-
membered ring. Structure of phenytoin sodium is represented by the following structural formula:
IUPAC Name: 5,5-diphenylimidazolidine-2,4-dione
Properties: Phenytoin appears as fine white or almost white crystalline powder, odorless or
almost odorless, tasteless, and slightly hygroscopic. On exposure to air, it gradually absorbs
carbon dioxide with the liberation of phenytoin. It is soluble in water and alcohol. Practically, it is
insoluble in chloroform, ether and methylene chloride.
Mechanism of Action: Phenytoin is used to protect against seizures by causing voltage-
dependent block of voltage-gated sodium channels and inhibits the positive feedback loop that
results in neuronal propagation of high frequency action potential. In this way, seizures are
prevented.
Uses: Antiepileptic drugs are used in tonic-clonic seizures, focal seizures and status epilepticus. It
is also useful in abnormal heart rhythms; ventricular arrhythmias and sudden episodes of atrial
tachycardia after other antiarrhythmic medications or cardioversion has failed.
Dosage Forms:
Adults: 200-500 mg a day, taken as 1 or 2 doses.
Children (aged 12 to 17 years): 300-400 mg, taken as 2 doses.
Phenytoin Sodium Injection, USP: 50 mg phenytoin sodium per millilitre:
➢ 2 ml (100 mg) Single Dose vials
➢ 5 ml (250 mg) Single Dose vials
Storage: Store at 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C. After
opening, any unused product should be discarded.
216 Text Book of Pharmaceutical Chemistry
Officials:
➢ Phenytoin Sodium, I.P.
➢ Phenytoin Sodium Tablet, I.P.
➢ Phenytoin Sodium Injection, I.P.
7.1.5 Sotalol
Brand Names: Betapace, Sorine, Betapace AF, Sorine
Sotalol is a sulphonamide that is N-phenyl methane sulfonamide in which the phenyl group is
substituted at position 4 by a 1-hydroxy-2-(isopropylamino) ethyl group. It is supplied as a
capsule-shaped tablet for oral administration. The structural of sotalol is:
IUPAC Name: N-[4-[1-hydroxy-2-(propan-2-ylamino)ethyl] phenyl]methanesulfonamide
Properties: Sotalol hydrochloride occurs as a white, crystalline solid hydrophilic. It is soluble in
water, propylene glycol and ethanol, but is only slightly soluble in chloroform.
Uses: Sotalol is the drug used to slow the abnormally fast heart rate in certain arrhythmias, such
as atrial fibrillation and atrial flutter. It is used to prevent paroxysmal supraventricular and also
suppresses ventricular ectopic (an ectopic heartbeat is an irregularity of the heart rate and heart
rhythm involving extra or skipped heartbeats) arrhythmias. The drug also helps to suppress
ventricular tachycardia.
Dosage Forms:
➢ Intravenous solution (15 mg/mL)
➢ Oral solution (5 mg/mL)
➢ Oral tablet (120 mg, 160 mg, 240 mg, 80 mg, AF 120 mg, AF 160 mg, AF 80 mg)
Storage Conditions: Sotalol should be stored at 77°F (25°C). It should be stored for a short time
in temperatures as low as 59°F (15°C) and as high as 86°F (30°C). Sotalol AF should be stored at
a temperature between 68°F and 77°F (20°C and 25°C).
7.1.6 Amiodarone
Brand Names: Pacerone, Cordarone, Nexterone
Amiodarone is a benzofuran derivative. It is one of the most commonly used antiarrhythmic
drugs.