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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5265_Библиотеки_им_академика_М_И_Перельмана.pdf
Analgesic and Anti-inflammatory Agents 267
Uses:
➢ It helps to relieve pain, tenderness, swelling, and stiffness caused by osteoarthritis
(arthritis caused by a breakdown of the lining of the joints) and rheumatoid arthritis
(arthritis caused by swelling of the lining of the joints).
➢ It can be used for a number of conditions, including injury, menstrual cramps, arthritis,
and other musculoskeletal problems.
Dosage Forms: Feldene (piroxicam); Oral capsule: 10 mg maroon and blue, 20 mg maroon.
Storage: The drug should be kept at room temperature between 20ºC and 25ºC. Direct contact
with heat, air and light may damage the medicines. Exposure to medicine may cause some
harmful effects. Protect this medication from light.
Officials:
➢ Piroxicam, I.P.
➢ Piroxicam Capsules, I.P.
10.2.5 Celecoxib
Brand Names: Celebrex, Consensi, Elyxyb
Celecoxib is a member of the class of pyrazoles that is 1H-pyrazole which is substituted at
positions 1, 3 and 5 by 4-sulfamoylphenyl, trifluoromethyl and p-tolyl groups, respectively. It is a
non-steroidal anti-inflammatory (NSAID), non-narcotic analgesic drug used in the treatment of
arthritis.
IUPAC Name: 4-[5-(4-methylphenyl)-3-(trifluoromethyl) pyrazol-1-yl]benzenesulfonamide
Properties: Celecoxib is a white to off-white powder with a pKa of 11.1 (sulfonamide moiety). It
is hydrophobic and is practically insoluble in aqueous media at physiological pH range.
Uses: Celecoxib is a non-steroidal anti-inflammatory drug used to reduce pain in several
indications, including:
➢ It is used to relief pain and inflammation in osteoarthritis.
➢ It is used in acute pain in adults.
➢ It is used in rheumatoid arthritis and juvenile rheumatoid arthritis.
➢ It is used to relief pain in ankylosing spondylitis.
➢ It is used in painful menstruation.
➢ It is use to reduce the number of colon and rectal polyps in people with familial
adenomatous polyposis.
268 Text Book of Pharmaceutical Chemistry
Dosage Forms: Celebrex (celecoxib) capsules: 50 mg, 100 mg, 200 mg and 400 mg white, with
reverse printed white on green band with markings of 7767 on the cap.
Storage: It should be stored at room temperature 20°C to 25°C; excursions permitted between
15°C to 30°C.
10.2.6 Mefenamic Acid
Brand Name: Mefenamic Acid
Mefenamic acid is an aminobenzoic acid that is anthranilic acid in which one of the
hydrogens attached to the nitrogen is replaced by a 2,3-dimethylphenyl group. It is analogous
to fenamic acid. This compound may be made from 2-chlorobenzoic acid and 2,3-
dimethylaniline. It is a non-steroidal anti-inflammatory drug (NSAID) with anti-inflammatory,
antipyretic and analgesic activities.
IUPAC Name: 2-(2, 3-dimethylanilino) benzoic acid
Mefenamic acid inhibits both isoforms of the enzyme cyclooxygenase (COX-1 and COX-2),
resulting in a decreased formation of precursors of prostaglandins and thromboxanes. As these
receptors have a role as a major mediator of pain sensitivity, inflammation and fever, but also
in hemostasis (natural reaction to an injury that stops bleeding and repairs the damage), kidney
function, sustaining of pregnancy, and protection of the gastric mucosa. The symptoms of pain
are temporarily reduced.
Properties: Mefenamic acid is a white to greyish-white, odorless, microcrystalline powder with a
melting point of 230°C to 231°C and water solubility of 0.004% at pH 7.1.
Uses:
➢ Mefenamic acid is used to treat pain and inflammation in rheumatoid arthritis and
osteoarthritis.
➢ It is used in post-operative pain and acute pain including muscle and back pain.
➢ It is used in toothache and menstrual pain, as well as being prescribed for menorrhagia.
Storage: Store the medicine in a closed container at room temperature, away from heat, moisture,
and direct light. Keep from freezing.
Dosage Forms: Oral capsule (250 mg)
Officials:
➢ Mefenamic Acid, I.P.
➢ Mefenamic Acid Capsules, I.P.
Analgesic and Anti-inflammatory Agents 269
10.2.7 Paracetamol
Brand Names: Acephen, Acetadryl, Allzital, Apadaz
Paracetamol (Acetaminophen) is a p-aminophenol derivative with analgesic and antipyretic
activities. A member of the class of phenols that is 4-aminophenol in which one of the hydrogen
attached to the amino group has been replaced by an acetyl group.
IUPAC Name: N-(2,3,5,6-tetradeuterio-4-hydroxyphenyl) acetamide
Uses: Paracetamol is used for the treatment of fever. It is also used for pain relief. It provides
relief from headache, toothache, backache, nerve pain, musculoskeletal pain, post vaccination
fever, etc. Taking too much acetaminophen can cause liver damage, sometimes serious enough to
require liver transplantation or cause death.
Properties: Paracetamol is very slightly soluble in cold water but greater soluble in hot water.
It is soluble in methanol, ethanol, dimethyl formamide, ethylene dichloride, acetone and ethyl
acetate whereas, slightly soluble in ether; and insoluble in petroleum ether, pentane and benzene.
Melting point is 169°C to 170.5°C.
Doagse Forms: Paracetamol 500 mg tablet is the most widely used over-the-counter (OTC)
medication.
➢ Missed Dose: Paracetamol 500 mg tablet is normally taken on a needed basis. If you miss
a scheduled dose, take it as soon as possible but do not double the dose to make up for the
missed one.
➢ Overdose: Never take more than the prescribed dose. Seek immediate medical attention
in case of an overdose with Paracetamol 500 mg tablet.
Storage: Keep away from children. Keep in a cool, dry place, away from direct sunlight.
Officials:
➢ Paracetamol I.P.
➢ Paracetamol Tablet, I.P.
➢ Paracetamol Syrup, I.P.
10.2.8 Aceclofenac
Brand Names: Airtal, Gerbin
Aceclofenac is a monocarboxylic acid, a carboxylic ester, a secondary amino compound, an
amino acid and a dichlorobenzene. It derives from a diclofenac. It is an oral non-steroidal
anti-inflammatory drug (NSAID) related to diclofenac, used to treat osteoarthritis, rheumatoid
arthritis and ankylosing spondylitis.
270 Text Book of Pharmaceutical Chemistry
IUPAC Name: 2-[2-[2-(2,6-dichloroanilino)phenyl]acetyl]oxyacetic acid
Aceclofenac works by inhibiting the action of cyclooxygenase (COX) that is involved in the
production of prostaglandins (PG) which is accountable for pain, swelling, inflammation and
fever.
Properties: Aceclofenac occurs as a white to off-white, light tan crystalline solid with a
molecular weight of 354.19. It is practically insoluble in water with good permeability and
soluble in DMSO. It has melting point of 149°C to 153°C.
Uses: It is used for the relief of pain and inflammation in:
➢ Rheumatoid arthritis: It relieves swelling and stiffness of joints and overall pain due to
the Arthritis.
➢ Osteoarthritis: It helps alleviate painful, tender joints and manage pain.
➢ Ankylosing spondylitis: It helps to manage the stiffness and pain in spondylitis.
Storage: Stored in well closed, light-resistant containers at temperature 2°C to 8°C.
10.3 EXERCISE
A. Long Answer Type Questions
1. Classify analgesic and antipyretic drugs. Give a detail account on Morphine.
2. What are anti-inflammatory agents? Give a detail account of NSAIDs drugs.
3. Write the classification of NSAIDS. Give the structure, properties and uses of Aspirin.
4. Write the structure, properties, therapeutic uses and official preparations of Diclofenac
sodium.
B. Short Answer Type Questions
1. Write the structure of Aspirin.
2. Give official preparation of Paracetamol.
3. Give structure of Ibuprofen.
4. Give the pharmaceutical uses of Codein.
5. Write a short note on Narcotic antagonists.
6. Give the pharmaceutical uses and storage of Aspirin.
7. Explain in brief Morphine and its analogues.
8. Write the structure and properties of Morphine.
Analgesic and Anti-inflammatory Agents 271
C. Fill in the Blanks
1. The NSAIDs drug Aspirin belongs to the class of ____________.
2. Morphine is obtained from ____________.
3. O-acetoxy benzoic acid is the IUPAC name of ____________.
4. Pentazocin is a derivative of ____________.
5. Diclomax is the brand name of ____________.
6. IUPAC name of Paracetamol is ____________.
7. Ibuprofen is a derivative of ____________.
8. ____________ is the brand name of Pethidine.
9. Analgesics are the drugs used to relieve ____________.
10. Paracetamol belongs to the chemical group called ____________.
11. Indomethacine is a derivative of ____________.
12. Codeine is the natural plant alkaloids found in extracts of ____________.
Answers:
1. Salicylates
2. Poppy plant (Papaver somniferum)
3. Aspirin
4. 2,6-methannobenzazocin
5. Diclofenac
6. Paracetamol
7. Propionic acid
8. Demerol
9. Pain
10. Para-aminophenol derivatives
11. Indole
12. opium
Chapter
11
ANTI-INFECTIVE AGENTS
STRUCTURE
11.1 Antifungal Agents
11.2 Urinary Tract Anti-infective Agents
11.3 Anti-tubercular Agents
11.4 Antiviral Agents
11.5 Antimalarial Agents
11.6 Sulfonamides
11.7 Exercise
OBJECTIVES
Antifungal Agents: Amphotericin-B, Griseofulvin, Miconazole, Ketoconazole, Itraconazole,
Fluconazole, Naftifine Hydrochloride.
Urinary Tract Anti-infective Agents: Norfloxacin, Ciprofloxacin, Ofloxacin, Moxifloxacin.
Anti-tubercular Agents: INH, Ethambutol, Para-amino Salicylic Acid, Pyrazinamide,
Rifampicin, Bedaquiline, Delamanid, Pretomanid.
Antiviral Agents: Amantadine Hydrochloride, Idoxuridine, Acyclovir, Foscarnet, Zidovudine,
Ribavirin, Remdesivir, Favipiravir.
Antimalarials: Quinine Sulphate, Chloroquine Phosphate, Primaquine Phosphate, Mefloquine,
Cycloguanil, Pyrimethamine, Artemisinin.
Sulfonamides: Sulfanilamide, Sulfadiazine, Sulfamethoxazole, Sulfacetamide, Mafenide Acetate,
Cotrimoxazole, Dapsone.
11.1 ANTIFUNGAL AGENTS
Fungal diseases are called mycoses. Mycoses are common, and a variety of environmental
and physiological factors can play a role in the development of fungal diseases. Inhalation of
fungal spores or localized colonization of the skin may initiate persistent infections. Therefore,
mycoses often start in the lungs or on the skin.
Anti-infective Agents 273
Antifungal agents are the drugs that selectively eliminate fungal pathogens in a host while
causing minimal toxicity to the host. Fungicides or fungistatics are the two types of medications
that are used to treat and prevent fungal diseases like athlete’s foot, ringworm, candidiasis
(thrush), and dangerous systemic infections such as cryptococcal meningitis. The majority of
these medications require a doctor’s prescription, although a few are available over-the-counter
(over-the-counter).
Types of Fungal Infections
1. Superficial mycoses: Superficial mycoses occur to the outermost layers of the skin and
hair; affect skin and mucous membrane; and rarely life-threatening, In some cases, it
spreads to other part of the body or become invasive (systemic). Most superficial fungal
infections are easily diagnosed and can be treated effectively. Superficial mycoses are
caused by Pityrosporum orbiculare, Trichosporon cutaneum (white), Piedraia hortae
(black).
Disease state: Tinea versicolor, Piedra, oral thrushes, and athlete’s foot, nail infections,
etc.
2. Cutaneous Mycoses (Dermatophytoses): Cutaneous mycoses are infections of the
keratinized epidermal appendages that are found on the skin’s surface (include invasive
hair and nail diseases). Unlike the superficial mycoses, the organisms that cause these
diseases are called dermatophytes. Cutaneous mycoses are caused by Microsporum,
Trichophyton and Epidermophyton fungi, candida albicans and related forms.
Disease state: Ringworm of scalp, hairless skin, candidosis of skin, mucous membrane,
etc.
Classification of Antifungal Drugs Based on Structure
1. Antibiotics
(a) Polyenes: Amphotericin B (AMB), Nystatin, Natamycin, Hamycin
(b) Heterocyclic benzofurans: Griseofulvin
2. Antimetabolites: 5-Flucytosine (5-FC)
3. Azoles
(a) Imidazoles:
➢ Topical: Clotrimazole, Econazole, Miconazole, Oxiconazole
➢ Systemic: Ketoconazol
(b) Triazoles: Fluconazole, Itraconazole, Voriconazole, Posaconazole, Ravuconazole
4. Allylamines: Terbinafine, Butenafine, Naftifine, Amorolfine
5. Echinocandins: Caspofungin, Cilofungin, Micafungin, Anidulafungine
6. Other topical agents: Tolnaflate, Undecylenic acid, benzoic acid, Salicylic acid,
Dichlorophen, Ciclopirox olamine, Thiabendazole, Quinidochlor, Sodium iodide.
274 Text Book of Pharmaceutical Chemistry
Polene Antibiotics
Antifungal antibiotics have been isolated from soil bacteria Streptomyces. Polen antibiotics
used clinically to treat fungal infections- nystatin, amphotericin B, and candicidin. All three are
used in the treatment of topical infections, while only amphotericin B is used against sysatemic
infections.
The polyene antibiotics have broad antifungal activity against organisms ranging from yeasts
to filamentous fungi and from saprophytic to pathogenic fungi.
11.1.1 Amphotericin-B
Generic Name: Amphotericin B
Drug Class: Polyenes
Brand Names: Fungizone, Abelcet, Ambisome, Amphotec, Fungizone.
Amphotericin B is a polyene antifungal antibiotic produced by Streptomyces nodosus. It has a
broad spectrum of activity against many fungal species, e.g., Candida (excluding C. lusitaniea),
Aspergillus, Cryptococcus neoformans, Coccidioides species, Blastomyces, Histoplasma,
Fusarium, Scedosporium and Zygomycetes.
The structure of amphotericin B contains a large lactone (macrolide) ring with numerous
conjugated double bonds. The polar hydroxylated portion and the non-polar hydrocarbon
sequence lend an amphiphilic character to the molecule. It interacts with ergosterols, forms pores
that increase membrane permeability and allow leakage of intracellular ions and macromolecules
from fungal cell (cause cell death).
Uses:
➢ Amphotericin B is used to treat serious, life-threatening fungal infections.
➢ It is not used for the treatment of a minor fungal infection such as a yeast infection of the
mouth, esophagus, or vagina.
➢ Amphotericin B is FDA-approved for the opportunistic infections (OIs) of HIV. It is
recommended for the treatment of:
Anti-infective Agents 275
• Candidiasis, including esophageal and invasive candidiasis
• Cryptococcosis
• Histoplasmosis
• Coccidioidomycosis
• Leishmaniasis infections (including visceral leishmaniasis and cutaneous
leishmaniasis)
• Talaromycosis
Properties: Amphotericin B appears as deep yellow prisms or needles from DMF. It is a yellow
to orange, odorless, or practically odorless, powder. It is insoluble in water, dehydrated alcohol,
ether, benzene, and toluene; soluble in dimethyl formamide, dimethyl sulfoxide, and in propylene
glycol, and slightly soluble in methyl alcohol.
Storage/Stability: It should be stored below 8°C in airtight containers and protected from light. It
is stable for 3 days in culture at 37°C. It is stable at 2°C to 8°C for 2-3 weeks. For long-term
stability, solutions should be kept frozen at –20°C.
Dosage Forms: Intravenous powder for injection (50 mg).
Officials:
➢ Amphotericin, I.P.
➢ Amphotericin, B.P.
11.1.2 Griseofulvin
Brand Names: Grifulvin V, Fulvicin P/G
Griseofulvin belongs to the group of medicines called antifungal. It is used to treat fungus,
infections of the body, feet, groin and thighs, scalp, skin, fingernails, and toenails. This medicine
may be taken alone or used along with medicines that are applied to the skin for fungus
infections.
Griseofulvin is a benzofuran derivative which is fungistatic but is fungicidal for young active
cells. It accumulates in the stratum corneum and is highly effective against the dermatophytes.
It has a fungistatic action against Trichophyton, Microsporum and Epidermophyton species. It is
an antibiotic use to treat fungal infections such as ringworm of the body, athlete’s foot, barber’s
itch, and fungal or ringworm of the nails. It inhibits fungal cell mitosis by causing disruption of
the mitotic spindle structure, thereby arresting the metaphase of cell division.
276 Text Book of Pharmaceutical Chemistry
IUPAC Name: (2S,5'R)-7-chloro-3',4,6-trimethoxy-5'-methylspiro[1-benzofuran-2,4'-cyclohex-2-
ene]-1',3-dione
Properties: Griseofulvin appears as white to pale cream-colored crystalline, tasteless powder.
It is odorless or almost odorless, soluble in n,n-dimethylformamide. It is slightly soluble in
ethanol, chloroform, methanol, acetic acid, acetone, benzene, and ethyl acetate; practically
insoluble in water and petroleum ether.
It is practically insoluble in water due to its low water solubility. Griseofulvin has a low
dissolution rate, which leads to low drug bioavailability. It is used orally only for
dermatophytosis. It is ineffective topically and reserved for cases in which topical treatment with
creams is ineffective.
Uses:
➢ Griseofulvin is used in the treatment of fungal infections of the skin and hair.
➢ It is used for the treatment of ringworm infections of the skin, hair, and nails, namely:
tinea corporis, tinea pedis, tinea cruris, tinea barbae and cradle cap.
➢ It is a fungistatic agent used to treat superficial fungal skin infections such as tinea capitis
➢ It is used for the treatment of athlete’s foot.
➢ It is used to treat especially those areas that are difficult to treat locally (eye, mouth), or
those refractory to other therapy.
➢ It is used in fungal infections of the scalp.
Dosage Forms:
➢ Oral suspension: Microcrystalline 125 mg/5 mL
➢ Oral tablet: Microcrystalline 500 mg
➢ Ultra microcrystalline 125 mg
➢ Ultra microcrystalline 250 mg
Storage Conditions: Preparation of Griseofulvin should generally be stored at a temperature less
than 40°C, preferably between 15°C to 30°C. Griseofulvin oral suspension should be protected
from freezing and stored in light-resistant containers. These drugs should be stored in well-closed
containers.
Officials:
➢ Griseofulvin, I.P.
➢ Griseofulvin Tablet, I.P.