Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5265_Библиотеки_им_академика_М_И_Перельмана.pdf
Drugs Acting on Autonomic Nervous System 197
Chemical Name: (3S,4R)-3-ethyl-4-[(3-methylimidazol-4-yl)methyl]oxolan-2-one
Properties: It occurs as white, hygroscopic, odorless, crystalline solid slightly bitter. Its melting
point is 195°C to 198°C. It is also given as 204°C to 205°C. It is freely soluble in ethanol;
insoluble in diethyl ether; soluble in water, alcohol and chloroform; sparingly soluble in ether
and benzene; and almost insoluble in petroleum ether.
Uses:
➢ Pilocarpine is used to treat glaucoma or ocular hypertension (high pressure inside the
eye).
➢ It is used to treat dry mouth caused by Sjogren’s syndrome or by radiation to treat head
and neck cancer.
Dosage Form: Pilocarpine comes as a tablet, oral tablet (5 mg and 7.5 mg).
➢ Adsorbocarpine/Akarpine/Isopto Carpine/Pilocar/Pilocarpine/Pilocarpine Hydrochloride/
Vuity Ophthalmic Sol: 1%, 1.25%, 2%, 4%.
➢ Pilocarpine/Pilocarpine Hydrochloride/Salagen Oral Tab: 7.5 mg.
Storage and Stability: Stable in air but affected by light Nitrate. On heating to decomposition, it
emits toxic fumes. Store at 20°C to 25°C and excursions permitted between 15°C and 30°C (59°F
and 86°F). Protect from freezing.
Official:
➢ Pilocarpine Nitrate, I.P.
CHOLINESTERASE INHIBITORS
Cholinesterase inhibitors (also known as anti-cholinesterase) are chemical agents that block the
breakdown of the neurotransmitter acetylcholine. This increases the amount of the acetylcholine in
the synaptic cleft that can bind to muscarinic and nicotinic receptors. These drugs used as drugs
for Alzheimer’s and myasthenia gravis.
6.3.4 Neostigmine
Brand Names: Bloxiverz, Prostigmin
Neostigmine is a cholinesterase inhibitor, sold under the brand name Bloxiverz. It is a
quaternary ammonium ion involving an anilinium ion core with three methyl substituents on
the aniline nitrogen, and a 3-[(dimethylcarbamoyl)oxy] substituent at position 3. The chemical
structure of Neostigmine is:
Chemical Name: [3-(dimethylcarbamoyloxy)phenyl]-trimethylazanium
198 Text Book of Pharmaceutical Chemistry
Properties: It occurs as a bitter tasting, white crystalline powder and is very soluble in water and
soluble in alcohol. Neostigmine Methylsulfate Injection, USP is a sterile, non-pyrogenic solution
intended for intramuscular, subcutaneous or slow intravenous use.
Uses:
➢ Neostigmine is used to improve muscle tone in people with myasthenia gravis.
➢ It is used to treat Ogilvie syndrome.
➢ It is used in the conservative management of acute colonic pseudo-obstruction.
➢ It is used to treat the symptoms reversal of non-depolarizing neuromuscular blockade.
➢ It is used in post-operative distention or urinary retention.
➢ Neostigmine injection is also used to prevent or treat certain kidney or intestinal
problems.
➢ It is used in Paralytic Ileus (a condition in which the muscles of the intestines do not
allow food to pass through, resulting in a blocked intestine).
➢ It is used in paroxysmal supraventricular tachycardia.
Storage and Stability: Store the drug at controlled room temperature between 15°C to 30°C
(59°F to 86°F). Protect from light. Store the drug in carton until time of use.
Dosage Forms and Strengths:
➢ Injectable solution (methylsulfate salt; Bloxiverz): 0.5 mg/mL, 1 mg/mL
➢ Tablet (bromide salt; Prostigmin): 15 mg
Officials:
➢ Neostigmine Bromide, I.P.
➢ Neostigmine Bromide Tablet, I.P.
➢ Neostigmine Methylsulphate Injection, I.P.
6.3.5 Edrophonium Chloride
Brand Names: Enlon, Enlon-plus
Edrophonium chloride is the chloride salt of edrophonium, a rapid-onset, short-acting
cholinesterase inhibitor used in cardiac arrhythmias and in the diagnosis of myasthenia gravis.
It prevents breakdown of the neurotransmitter acetylcholine and acts by competitively inhibiting
the enzyme acetylcholinesterase, structure of edrophonium is a quaternary ammonium ion that is
N-ethyl-N, N-dimethylanilinium in which one of the meta positions is substituted by
a hydroxy group. The chemical structure of Edrophonium chloride is:
Drugs Acting on Autonomic Nervous System 199
Chemical Name: ethyl-(3-hydroxyphenyl)-dimethyl azanium chloride
Properties: Edrophonium chloride is available as a crystalline solid, soluble in organic solvents
such as ethanol, DMSO and dimethyl formamide, which should be purged with inert gas.
Uses:
➢ Edrophonium chloride is used to differentiate myasthenia gravis (severe muscle
weakness) from cholinergic crisis and Lambert-Eaton.
➢ It is also used to reverse the effects of certain muscle relaxants (e.g., gallamine and
tubocurarine) during surgery.
➢ It is used for the reversal of neuromuscular blockade in anesthesia.
➢ It is used for the management of poisoning due to tetrodotoxin.
➢ It may be used adjunctively in the treatment of respiratory depression caused by curare
over dosage.
Dosage Form: This product is available in the following dosage forms:
➢ Enlon Intramuscular Inj Sol: 1 mL, 10 mg
➢ Enlon Intravenous Inj Sol: 1 mL, 10 mg
➢ Subcutaneously 0.5 to 1 mg
Storage and Stability: It should be stored at controlled room temperature 15°C to 30°C.
6.3.6 Tacrine Hydrochloride
Brand Name: Cognex
Tacrine is a drug of the class of acridines that is 1,2,3,4-tetrahydroacridine substituted by
an amino group at position 9. It is a member of acridines and an aromatic amine. Tacrine
Hydrochloride is the hydrochloride salt form of tacrine, an amino acridine derivative with
cognitive stimulating property. It is used in the treatment of Alzheimer’s disease. The structural
formula of tacrine hydrochloride is:
Chemical Name: 1,2,3,4-tetrahydroacridin-9-amine;hydrochloride
Properties: Tacrine hydrochloride appears as yellow or white crystalline solid and bitter in
taste. It is freely soluble in distilled water, 0.1 N hydrochloric acid, acetate buffer (pH
4.0), phosphate buffer (pH 7.0 to 7.4), methanol, dimethylsulfoxide (DMSO), ethanol and
propylene glycol. The compound is sparingly soluble in linoleic acid and PEG 400.
200 Text Book of Pharmaceutical Chemistry
Uses:
➢ Tacrine hydrochloride is used in the treatment of mild to moderate dementia of the
Alzheimer’s type.
➢ It is effective in the treatment of dementia of the Alzheimer’s type.
Dosage Form: Tacrine Hydrochloride Capsules, USP. Each capsule of Cognex® contains tacrine
as the hydrochloride.
Storage and Stability: Store at 20°C to 25°C (68°CF to 77°F); excursions permitted to 15°C
to30°C (59°F to 86°F). Protect from moisture.
6.3.7 Pralidoxime Chloride
Brand Names: Atnaa, Duodote, Protopam
Pralidoxime chloride belongs to a family of compounds called oximes that bind to
organophosphate-inactivated acetylcholinesterase and indirect cholinergic agonist
(parasympathomimetic). It contains a pralidoxime; is a pyridinium salt and an organic chloride
salt; and has a role as a cholinesterase reactivator and a cholinergic drug. The structural formula
of Pralidoxime chloride is:
Chemical Name: (NE)-N-[(1-methylpyridin-1-ium-2-yl) methylidene] hydroxylamine chloride
Properties: Pralidoxime chloride appears as white to pale yellow, non-hygroscopic crystalline
powder and odorless. It is freely soluble in water to the extent of 1 g in less than 1 ml. It is stable
in air, melts between 215°C and 225°C with decomposition.
Uses:
➢ Pralidoxime chloride is used for the management of Alzheimer’s disease symptoms.
➢ It is small beneficial effect on cognition and other clinical measures.
Dosage Form: Adults: 30 mg/kg (typically 1-2 g), administered by intravenous therapy over 15-
30 minutes, repeated 60 minutes later. It can also be given as a 500 mg/h continuous IV infusion.
Storage and Stability: Store this drug at room temperature between (20°C and 25°C). Keep the
medication tightly closed and in a light-resistant container. Store it away from moisture. Protect
from moisture.
Drugs Acting on Autonomic Nervous System 201
6.3.8 Echothiopate Iodide
Brand Name: Phospholine Iodide
Ecothiopate iodide is an iodide salt and a quaternary ammonium salt contains an ecothiopate.
It potentiates the action of endogenous acetylcholine by inhibiting acetyl cholinesterase that
hydrolyzes acetylcholine. It is used as an ocular antihypertensive in the treatment of open-angle
glaucoma, particularly when other drugs have proved inadequate. The structural formula of
Ecothiopate iodide is:
Chemical Name: 2-diethoxyphosphorylsulfanylethyl(trimethyl)azanium iodide
Properties: Ecothiopate iodide occurs as a white, crystalline, water-soluble, hygroscopic solid
having a slight mercaptan-like odor. When freeze-dried in the presence of potassium acetate, the
mixture appears as a white amorphous deposit on the walls of the bottle.
Uses:
➢ Ecothiopate iodide is used in the treatment of chronic open-angle glaucoma.
➢ It is used in the treatment of sub-acute or chronic angle-closure glaucoma after
iridectomy or where surgery is refused or contraindicated.
➢ It is used in certain non-uveitic secondary types of glaucoma, especially glaucoma
following cataract surgery.
Dosage Form: Echothiophate iodide for Ophthalmic Solution is available in the following
strengths: [1.5 mg (0.03%), 3 mg (0.06%), 6.25 mg (0.125%), or 12.5 mg (0.25%)].
Storage and Stability: Store under refrigeration (2°C to 8°C). After reconstitution, store at room
temperature (approximately 25°C). Do not refrigerate. Discard any unused solution after 4 weeks.
6.4 CHOLINERGIC BLOCKING AGENTS
Acetylcholine (Ach) is a neurotransmitter that functions in both the central and peripheral
nervous systems, responsible for the transmission of nerve impulses to effectors cells in the
parasympathetic nervous system. A cholinergic receptor binds to acetylcholine and mediates its
effects.
There are mainly two types of cholinergic receptors: nicotinic and muscarinic. This
classification is based on the effects of two chemical agents (nicotine and muscarine) that imitate
the effects of Ach at the receptor sites.
202 Text Book of Pharmaceutical Chemistry
Both classes of cholinergic receptors are implicated in memory. They are activated by
agonists, which are compounds that can stimulate a receptor to produce a biological response, or
antagonists, which are compounds that counter the effect of agonists.
Cholinergic blocking agents or anticholinergic drugs are group of substances that block
the action of acetylcholine (ACh), a neurotransmitter, in synapses of the cholinergic nervous
system. They block acetylcholine from binding to cholinergic receptors, namely the nicotinic and
muscarinic receptors. Anticholinergic drugs are used for the treatment of various conditions such
as gastrointestinal disorders, genitourinary disorders, and respiratory disorders.
Classification of Cholinergic Blocking Agents
6.4.1 Atropine Sulphate
Brand Names: Atropine, Auto-injector, Sal-Tropine, AtroPen, Atreza
Atropine is a naturally occurring tertiary amine (alkaloid) extracted originally from Atropa
belladonna (deadly nightshade). It contains two isomers, d and l hyoscyamine. It is a competitive
antagonist of the actions of acetylcholine and other muscarinic agonists. The structural formula of
atropine sulphate is:
Chemical Name: (8-methyl-8-azabicyclo[3.2.1]octan-3-yl)3-hydroxy-2-phenylpropanoate; sulfuric
acid
Properties: Atropine sulphate occurs as colorless crystals, odorless or white crystalline powder
very bitter in taste. It is freely soluble in water. One gram dissolves in 0.4 ml water. One gram
dissolves in 5 ml cold alcohol, 2.5 ml in boiling alcohol, 2.5 ml glycerol, 420 ml chloroform and
3,000 ml ether. It is almost optically inactive.
Uses: Atropine Sulfate Injection is an antimuscarinic agent used in the treatment of various
conditions:
Drugs Acting on Autonomic Nervous System 203
➢ Atropine sulfate eye drops is used to dilate the pupil before examination of eye.
➢ It is used in the treatment of eye condition called amblyopia (lazy eyes) and other eye
conditions, e.g., cycloplegia and mydriatic.
➢ The eye drops are used in the treatment of iritis and uveitis to immobilise the iris and
ciliary muscle and to prevent or break down adhesions.
➢ It is used in the determination of refraction in children below six years and children with
convergent strabismus.
➢ It is used to treat bradycardia (low heart rate).
➢ It is used to reduce salivation, mucus and bronchial secretions before surgery.
➢ It is used as an antidote for overdose of cholinergic drugs or mushroom poisoning.
Storage and Stability: Atropine sulphate should be stored in single- or multiple-dose containers,
preferably glass, at room temperature, between 20°C to 25°C. Keep tightly closed, protected from
light, freezing should be avoided. The shelf-life is 24 months from the date of manufacturing.
Atropine sulphate effloresces when exposed to dry air. When heated to decomposition, toxic
fumes of oxides of nitrogen and sulphide are emitted.
Dosage Form: Atropine comes as a solution (liquid) to instill in the eyes and an eye ointment to
apply to the eyes. It is available as a sterile solution in normal saline or water for injection. It is
also available in oral forms (tablets). Injectable solution (0.05 mg/mL, 0.1 mg/mL, 0.4 mg/mL,
0.4 mg/mL – NaCl 0.9% and 1 mg/mL); intramuscular solution (2 mg/0.7 mL) and intravenous
solution (0.1 mg/mL and 0.4 mg/mL – NaCl 0.9%).
Officials:
➢ Atropine Sulphate, I.P.
➢ Atropine Sulphate Eye Ointment, I.P.
➢ Atropine Sulphate Injection, I.P.
➢ Atropine Sulphate Tablet, I.P.
➢ Atropine Methonitrate, I.P.
➢ Morphine Sulphate and Atropine Sulphate Injection, I.P.
6.4.2 Ipratropium Bromide
Brand Names: Atrovent, Combivent, Ipravent
Ipratropium bromide is the synthetic derivative of the alkaloid atropine, a quaternary
ammonium compound with anticholinergic properties. It is the anhydrous form of the bromide
salt of ipratropium. It is used in the control of symptoms related to bronchospasm in chronic
obstructive pulmonary disease (COPD). The structural formula of Ipratropium bromide is:
204 Text Book of Pharmaceutical Chemistry
Chemical Name: [(1R,5S)-8-methyl-8-propan-2-yl-8-azoniabicyclo[3.2.1]octan-3-yl]3-hydroxy-
2-phenylpropanoate; bromide
Properties: It is a white crystalline powder with bitter taste and melting point of 232°C to 233°C.
It is soluble in water, slightly soluble in ethanol and insoluble in other organic solvents.
Uses:
➢ Ipratropium bromide is used in the treatment of chronic obstructive pulmonary disease
(COPD) and asthma exacerbation.
➢ It is used in prevention and treatment of bronchial asthma and asthma-type chronic
bronchitis.
➢ It is used in treating symptoms of asthma, colds and allergies.
➢ It is used to treat symptoms associated with chronic lung conditions.
➢ It also reduces mucus (phlegm) production. This effect helps to improve lung function
and reduce breathing difficulty.
➢ Ipratropium blocks the effect of acetylcholine on airways (bronchi) and nasal passages.
➢ It is used to treat and prevent minor and moderate bronchial asthma, especially asthma
that is accompanied by cardiovascular system diseases.
Storage and Stability: Store at room temperature (between 59°F to 86°F) in a cool and dry place.
Ipratropium bromide is fairly stable in neutral and acidic solutions, but is rapidly hydrolyzed in
alkaline solution. Its aerosol formulation should not be stored at temperatures above 30°C (86°F),
or in the presence of excessive humidity.
Dosage Forms: Ipratropium bromide inhalation solution is administered by oral inhalation with
the aid of a nebulizer. Each ml contains ipratropium bromide 0.02% (500 mcg in 2.5 ml); for oral
inhalation, Pratropium Bromide 250 mg/1 mL Nebuliser Solution and Ipratropium Bromide 500
mg/2 mL Nebuliser solution.
6.5 SYNTHETIC CHOLINERGIC BLOCKING AGENTS
6.5.1 Tropicamide
Brand Names: Minims Tropicamide, Mydriacyl, Paremyd
Tropicamide belongs to the class of anticholinergic and antimuscarinic agents. Structurally, it
is an amide with a pyridine, a benzene ring, and an alcohol attached to it. It is the synthetic
derivative of tropic acid. Clinically, it is mainly used to widen (dilate) the pupil for an eye
examination or other diagnostic procedures. The structural formula of tropicamide is:
Drugs Acting on Autonomic Nervous System 205
Chemical Name: N-ethyl-3-hydroxy-2-phenyl-N-(pyridin-4-ylmethyl)propanamide
Properties: Tropicamide occurs as white crystalline powder and is odorless. It is slightly soluble
in water; and easily soluble in ethanol, dilute hydrochloric acid, sulfuric acid and chloroform.
Uses:
➢ Tropicamide is used to dilate the pupil and to help examine the back of the eye.
➢ It is used to allow better examination of the lens, vitreous humor and retina.
➢ It is used to treat anterior uveitis, decreasing risk of posterior synechiae and decreasing
inflammation in the anterior chamber of the eye.
➢ It is used to induce mydriasis (dilation of the pupil).
➢ It is used for cycloplegia (paralysis of the ciliary muscle of the eye) in diagnostic
procedures, such as measurement of refractive errors and examination of the fundus of
the eye.
Dosage Forms: Tropicamide is available in the form of eye drops. Ophthalmic solution (0.5%;
1%).
Storage and Stability: Keep tightly closed, protected from heat, air and light may damage the
drug. Freezing should be avoided. The drug should be kept at room temperature between 68°F
and 77°F (20°C and 25°C). Store in a cool and dry place away from sunlight.
Officials:
➢ Tropicamide, I.P.
➢ Tropicamide Eye Drops, I.P.
6.5.2 Cyclopentolate Hydrochloride
Brand Names: Ak-pentolate, Cyclogyl, Cyclomydril, Minims Cyclopentolate Hydrochloride
Cyclopentolate structure consists of a carboxylic ester, a tertiary amino compound and a
tertiary alcohol. Cyclopentolate hydrochloride is the hydrochloride salt of cyclopentolate, used to
produce mydriasis (excessive dilation of the pupil) and cycloplegia (paralysis of the ciliary
muscle of the eye) for opthalmic diagnostic procedures. The structural formula of Cyclopentolate
hydrochloride is:
206 Text Book of Pharmaceutical Chemistry
Chemical Name: 2-(dimethyl amino) ethyl 2-(1-hydroxycyclopentyl)-2-phenylacetate;
hydrochloride
Properties: It occurs as a crystalline, white and odorless solid that is very soluble in water, easily
soluble in alcohol, and only slightly soluble in ether.
Uses: Cyclopentolate hydrochloride is used to produce dilation of pupils (mydriasis) and paralysis
of the iris muscle in the eye (cycloplegia) for diagnostic procedures.
Dosage Forms: Cyclopentolate is available in solution; cyclopentolate hydrochloride ophthalmic
solution, USP (0.5%, 1%, 2%).
Storage and Stability: Store at 8°C to 25°C (46°F to 77°F). After opening, Cyclogyl can be used
until the expiration date on the bottle.
6.5.3 Clidinium Bromide
Brand Names: Chlorax, Librax
Clidinium bromide is a quaternary ammonium salt and an organic bromide salt. It contains a
clidinium. It derives from a benzilic acid and a 3-quinuclidinol. It is a gastrointestinal muscarinic
receptor antagonist. The structural formula of Clidinium bromide is:
Chemical Name: (1-methyl-1-azoniabicyclo[2.2.2]octan-3-yl)2-hydroxy-2,2-diphenylacetate;
bromide
Properties: Clidinium bromide occurs as a white or nearly white, almost odorless, crystalline
powder that is optically inactive. It is soluble in water and alcohol but only very slightly soluble
in ether and benzene.
Uses:
➢ Clidinium bromide is used for the symptomatic treatment of peptic ulcer disease.
➢ It is used to relieve abdominal or stomach spasms or cramps due to colicky abdominal
pain, diverticulitis and irritable bowel syndrome.
➢ It is suggested for hyperchlorhydria, ulcerative or spastic colon and anxiety states with GI
manifestations.
➢ It is used in inflammation of the colon called acute entero colitis.
Dosage Forms: Available as clidinium bromide; dosage expressed in terms of the salt. Librax
combines in a single capsule formulation of chlordiazepoxide hydrochloride and clidinium
bromide.