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Drugs and Their Classification

Feb 18, 2018

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Page 1: Drugs and Their Classification

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PROJECT REPORT

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ACKNOWLEDEMENT

I take this opportunity to thank several persons who were a great

help in making this project a success.

It is my foremost duty to express my deep regards & gratitude to

my Chemistry teacher Mrs. under whose guidance &

supervision I am able to undertake this project. It is her who has

been my primary source of inspiration and who motivated, guided

and encouraged me at different stages to shape this project.

 !"I#$ %I'%(

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1. DRUGS AND MEDICINES

)rugs are chemicals of low molecular masses *+-- /--u0. hese

interact with macromolecular targets and produce a biological response.

1hen the biological response is therapeutic and useful, these chemicals

are called medicines and are used in diagnosis, prevention and treatment

of diseases. If taken in doses higher than those recommended, most of 

the drugs used as medicines are potential poisons. 'se of chemicals for 

therapeutic effect is called chemotherapy.

. Drugs can be classifie !ainl" #n cri$eria #u$line as f#ll#%s2

.. 3n the basis of pharmacological effect

his classification is based on pharmacological effect of the drugs. It is

useful for doctors because it provides them the whole range of drugs

available for the treatment of a particular type of problem. 4or example,

analgesics have pain killing effect, antiseptics kill or arrest the growth of 

microorganisms.

..5 3n the basis of drug action

It is based on the action of a drug on a particular biochemical process. 4or 

example, all antihistamines inhibit the action of the compound, histamine

which causes inflammation in the body. here are various ways in which

action of histamines can be blocked.

..6 3n the basis of chemical structure

It is based on the chemical structure of the drug. )rugs classified in this

way share common structural features and often have similar pharmacological activity. 4or example, sulphonamides have common

structural feature, given below. 7tructural features of sulphonamides

..8 3n the basis of molecular targets

)rugs usually interact with biomolecules such as carbohydrates, lipids,

proteins and nucleic acids. hese are called target molecules or drug

targets. )rugs possessing some common structural features may have

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the same mechanism of action on targets. he classification based on

molecular targets is the most useful classification for medicinal chemists.

1.& DRUG'TARGET INTERACTION

Macromolecules of biological origin perform various functions in the body.

4or example, proteins which perform the role of biological catalysts in the

body are called en9ymes, those which are crucial to communication

system in the body are called receptors. Carrier proteins carry polar 

molecules across the cell membrane. #ucleic acids have coded genetic

information for the cell. :ipids and carbohydrates are structural parts of 

the cell membrane. 1e shall explain the drug;target interaction with the

examples of en9ymes and receptors.

1.&.1 En("!es as Drug Targe$s

.5..  Catalytic action of en9ymes

4or understanding the interaction between a drug and an en9yme, it is

important to know how do en9ymes catalyse the reaction *7ection /.5.80.

In their catalytic activity, en9ymes perform two major functions2

he first function of an en9yme is to hold the substrate for a chemical

reaction. ctive sites of en9ymes hold the substrate molecule in a

suitable position, so that it can be attacked by the reagent effectively.

7ubstrates bind to the active site of the en9yme through a variety of 

interactions such as ionic bonding, hydrogen bonding, van der 1aals

interaction or dipole;dipole interaction *4ig. <.0.

he second function of an en9yme is to provide functional groups

that will attack the substrate and carry out chemical reaction.

.5..5  )rug ;=n9yme Interaction

)rugs inhibit any of the above mentioned activities of en9ymes. hese

can block the binding site of the en9yme and prevent the binding of 

substrate, or can inhibit the catalytic activity of the en9yme. 7uch drugs

are called en9yme inhibitors. )rugs inhibit the attachment of substrate on

active site of en9ymes in two different ways 2

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)rugs compete with the natural substrate for their attachment on the

active sites of en9ymes. 7uch drugs are called competitive inhibitors

*4ig. <.50.

7ome drugs do not bind to the en9yme>s active site. hese bind to a

different site of en9yme which is called allosteric site. his binding of 

inhibitor at allosteric site *4ig.<.60 changes the shape of the active

site in such a way that substrate cannot recognise it. If the bond

formed between an en9yme and an inhibitor is a strong covalent

bond and cannot be broken easily, then the en9yme is blocked

permanently. he body then degrades the en9yme;inhibitor complex

and synthesises the new en9yme.

1.&.& Rece)$#rs as Drug Targe$s

%eceptors are proteins that are crucial to body>s communication process.

Majority of these are embedded in cell membranes *4ig. <.80. %eceptor 

proteins are embedded in the cell membrane in such a way that their 

small part possessing active site projects out of the surface of the

membrane and opens on the outside region of the cell membrane *4ig.

<.80.

In the body, message between two neurons and that between neurons to

muscles is communicated through certain chemicals. hese chemicals,

known as chemical messengers are received at the binding sites of 

receptor proteins. o accommodate a messenger, shape of the receptor 

site changes. his brings about the transfer of message into the cell.hus, chemical messenger gives message to the cell without entering the

cell *4ig. <./0.

here are a large number of different receptors in the body that interact

with different chemical messengers. hese receptors show selectivity for 

one chemical messenger over the other because their binding sites have

different shape, structure and amino acid composition. )rugs that bind to

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the receptor site and inhibit its natural function are called antagonists.

hese are useful when blocking of message is re?uired. here are other 

types of drugs that mimic the natural messenger by switching on the

receptor, these are called agonists. hese are useful when there is lack of 

natural chemical messenger.

1.* T+ERA,EUTIC ACTION O- DI--ERENT CLASSES O- DRUGS

he therapeutic action of a few important classes of drugs are as follows 2

1.*.1 An$acis

 n antacid is any substance, generally a base or basic salt, which

neutrali9es stomach acidity. hey are used to relieve acid indigestion,

upset stomach, sour stomach, and heartburn.

 ntacids perform a neutrali9ation reaction, i.e. they buffer gastric acid,

raising the p" to reduce acidity in the stomach. 1hen gastric hydrochloric

acid reaches the nerves in the gastrointestinal mucosa, they signal pain to

the central nervous system. his happens when these nerves are

exposed, as in peptic ulcers. he gastric acid may also reach ulcers in the

esophagus or the duodenum.

"yperacidity or acid dyspepsia simply means increase of acidity in the

stomach. he human stomach secretes hydrochloric acid which is

necessary for the digestion of food. 1hen the stomach contains an

excessive amount of hydrochloric acid, then the condition is called as

hyperacidity. 7ometimes, hyperacidity is confused for a simple bellyache.

his is because people with hyperacidity generally get pains in their 

stomach with similar symptoms as bellyaches. his confusion is morerampant in children who cannot differentiate between different kinds of 

stomach ailments. "owever, hyperacidity can be found out with the sour 

belching and after taste of the already eaten food in the mouth.

"yperacidity symptoms are observed a couple of hours after eating, when

the food has been digested and still excess acids are left within the

stomach. t this stage, the following symptoms are seen

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  typical feeling of restlessness

4eeling of nausea *wanting to throw up0 and actual vomiting

7our belching with an after taste of the already;eaten food

7tiffness in the stomach, which is called as atonic dyspepsia

:ack of desire for any other type of food

Indigestion

Constipation

'ntil @A-, only treatment for acidity was administration of antacids, such

as sodium hydrogencarbonate or a mixture of aluminium and magnesium

hydroxide. "owever, excessive hydrogencarbonate can make the

stomach alkaline and trigger the production of even more acid. Metal

hydroxides are better alternatives because of being insolubleB these do

not increase the p" above neutrality. hese treatments control only

symptoms, and not the cause. herefore, with these metal salts, the

patients cannot be treated easily. In advanced stages, ulcers become life

threatening and its only treatment is removal of the affected part of the

stomach. major breakthrough in the treatment of hyperacidity came

through the discovery according to which a chemical, histamine,

stimulates the secretion of pepsin and hydrochloric acid in the stomach.

he drug cimetidine*egamet0, was designed to prevent the interaction of 

histamine with the receptors present in the stomach wall. his resulted in

release of lesser amount of acid. he importance of the drug was so much

that it remained the largest selling drug in the world until another drug,ranitidine *antac0, was discovered.

7ome drugs used as antacids are 2

 luminium hydroxide

Magnesium hydroxide

Calcium carbonate

7odium bicarbonate

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!ismuth subsalicylate

"istamine

Cimetidine

%anitidine

3mepra9ole

:ansopra9ole

OME,RAOLE

1.*.& An$i/is$a!ines

1hen body comes into contact with whatever the allergic trigger is ;;

pollen, ragweed, pet dander, dust mites, for example ;; it makes

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chemicals called histamines. hey cause the tissue in nose to swell

*making it stuffy0, nose and eyes  to run & eyes, nose and sometimes

mouth to itch. 7ometimes there is also an itchy rash on your skin, called

hives.

 ntihistamines  reduce or block histamines, so they stop allergy

symptoms. ntihistamines work well to relieve symptoms of different types

of allergies, including seasonal *hay fever 0, indoor and food allergies, but

they canDt relieve every symptom. o treat nasal congestion, doctor may

recommend taking a decongestant. 7ome drugs combine an

antihistamine and decongestant.

7ynthetic drugs, brompheniramine *)imetapp0 and terfenadine *7eldane0,

act as antihistamines. hey interfere with the natural action of histamine

by competing with histamine for binding sites of receptor where histamine

exerts its effect.

 ntihistamines come in different forms, including tablets, capsules, li?uids,

nasal sprays, and eyedrops. =xamples of prescription antihistamines

include2

 stelin, stepro *a9elastine0 nasal sprays

 tarax, $istaril *hydroxy9ine0

Clarinex *desloratadine0

Cyproheptadine *generic only0

=madine *emadastine0 eyedrops

:ivostin *levocabastine0 eyedrops

3ptivar  *a9elastine0 eyedrops

Ealgic *carbinoxamine0

Fy9al *levocetiri9ine0

=xamples of 3C antihistamines2

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 llegra *fexofenadine0

!enadryl *diphenhydramine0

)imetane *brompheniramine0

Claritin, lavert *loratadine0

avist *clemastine0

Chlor;rimeton *chlorpheniramine0

yrtec *certiri9ine0

=yedrops likes =madine and :ivostin treat symptoms of eye allergies,

including itchy, watery eyes. 7ome medications, like llegra;), Claritin;),

and yrtec;), combine an antihistamine and a decongestant to relieve

congestion.

7ide =ffects of ntihistamines

 ntihistamines can cause side effects, and some cause more side effects

than others. )rugs such as !enadryl, Chlor;rimeton, and avist and

belong to an older group known as Gfirst;generationG antihistamines. hey

tend to cause more side effects, particularly drowsiness.

#ewer;generation antihistamines such as llegra, Clarinex, and yrtec

and have fewer side effects, so they may be a better choice for some

people.

7ome of the main side effects of antihistamines include2

)ry mouth

)rowsiness

)i99iness

#ausea and vomiting

%estlessness or moodiness *in some children0

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rouble urinating or not being able to urinate

!lurred vision

Confusion

  ALLERGA'D

1.*.* Neur#l#gicall" Ac$i0e Drugs

1.3.3.1  ran?uili9ers

ran?uili9ers and analgesics are neurologically active drugs. hese affectthe message transfer mechanism from nerve to receptor. ran?uili9er is a

drug that acts on the central nervous system and is used to calm,

decrease anxiety, or help a person to sleep. 3ften called depressants

because they suppress the central nervous system and slow the body

down, they are used to treat mental illness as well as common anxiety

and sleeplessness.

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here are two types or classes of tran?uili9ers2 major tran?uili9ers and

minor tran?uili9ers. he former are antipsychotic drugs and the latter are

considered antianxiety  drugs. ntipsychotic drugs are used to treat

patients with a severe mental illness, like schi9ophrenia. ntianxiety drugs

are given to patients with emotional problems, like anxiety. here are

various types of tran?uili9ers. hey function by different mechanisms.

#oradrenaline is one of the neurotransmitters that play a role in

mood changes. If the level of noradrenaline is low for some reason,

then the signal;sending activity becomes low, and the person suffers

from depression. In such situations, antidepressant drugs are

re?uired. hese drugs inhibit the en9ymes which catalyse the

degradation of noradrenaline. If the en9yme is inhibited, this

important neurotransmitter is slowly metabolised and can activate its

receptor for longer periods of time, thus counteracting the effect of 

depression. Ipronia9id and phenel9ine are two such drugs.

chlordia9epoxide and meprobamate, are relatively mild tran?uili9ers

suitable for relieving tension.

=?uanil is used in controlling depression and hypertension.

)erivatives of barbituric acid vi9., veronal, amytal, nembutal, luminal

and seconal constitute an important class of tran?uili9ers. hese

derivatives are called barbiturates. !arbiturates are hypnotic, i.e.,

sleep producing agents.

7ome other substances used as tran?uili9ers are valium and

serotonin.

MEPROBAMATE PHENELZINE (NARDIL)

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I,RONIAID ALIUM ERONAL

 

1.3.3.2   nalgesics

 nalgesics reduce or abolish pain without causing impairment of 

consciousness, mental confusion, in coordination or paralysis or some

other disturbances of nervous system.

hese are classified as follows2

#on;narcotic *non;addictive0 analgesics

 spirin and paracetamol belong to the class of non;narcotic

analgesics. spirin is the most familiar example. spirin inhibits the

synthesis of chemicals known as prostaglandins which stimulate

inflammation in the tissue and cause pain. hese drugs are effective

in relieving skeletal pain such as that due to arthritis. hese drugs

have many other effects such as reducing fever *antipyretic0 and

preventing platelet coagulation. !ecause of its anti blood clotting

action, aspirin finds use in prevention of heart attacks.

AS,IRIN

#arcotic drugs

Morphine and many of its homologues like heroin, codeine, when

administered in medicinal doses, relieve pain and produce sleep. In

poisonous doses, these produce stupor, coma, convulsions and

ultimately death. Morphine narcotics are sometimes referred to as

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opiates, since they are obtained from the opium poppy. hese

analgesics are chiefly used for the relief of postoperative pain,

cardiac pain and pains of terminal cancer, and in child birth.

1.*.2 An$i!icr#bials

)iseases in human beings and animals may be caused by a variety of 

microorganisms such as bacteria, virus, fungi and other pathogens. n

antimicrobial tends to destroyHprevent development or inhibit the

pathogenic action of microbes such as bacteria *antibacterial drugs0, fungi

*antifungal agents0, virus *antiviral agents0, or other parasites

*antiparasitic drugs0 selectively. ntibiotics, antiseptics and disinfectants

are antimicrobial drugs.

1.3.4.1  ntibiotics

 ntibiotics are used as drugs to treat infections because of their low

toxicity for humans and animals. Initially antibiotics were classified as

chemical substances produced by microorganisms *bacteria, fungi and

molds0 that inhibit the growth or even destroy microorganisms. he

development of synthetic methods has helped in synthesising some of the

compounds that were originally discovered as products of 

microorganisms. lso, some purely synthetic compounds have

antibacterial activity, and therefore, definition of antibiotic has been

modified. n antibiotic now refers to a substance produced wholly or partly

by chemical synthesis, which in low concentrations inhibits the growth or 

destroys microorganisms by intervening in their metabolic processes.

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he search for chemicals that would adversely affect invading bacteria but

not the host began in the nineteenth century. Eaul =hrlich, a erman

bacteriologist, conceived this idea. "e investigated arsenic based

structures in order to produce less toxic substances for the treatment of 

syphilis. "e developed the medicine, arsphenamine, known as salvarsan.

Eaul =hrlich got #obel pri9e for Medicine in @-J for this discovery. It was

the first effective treatment discovered for syphilis. lthough salvarsan is

toxic to human beings, its effect on the bacteria, spirochete, which causes

syphilis is much greater than on human beings. t the same time, =hrlich

was working on a9odyes also. "e noted that there is similarity in

structures of salvarsan and a9odyes. he s K s linkage present in

arsphenamine resembles the # K # linkage present in a9odyes in the

sense that arsenic atom is present in place of nitrogen. "e also noted

tissues getting coloured by dyes selectively. herefore, =hrlich began to

search for the compounds which resemble in structure to a9odyes and

selectively bind to bacteria. In @65, he succeeded in preparing the first

effective antibacterial agent, prontosil, which resembles in structure to the

compound, salvarsan. 7oon it was discovered that in the body prontosil is

converted to a compound called sulphanilamide, which is the real active

compound. hus the sulpha drugs were discovered. large range of 

sulphonamide analogues was synthesised. 3ne of the most effective is

sulphapyridine.

7:$%7# E%3#37I:

7':E"#I:MI)= 3)L=

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 )espite the success of sulfonamides, the real revolution in antibacterial

therapy began with the discovery of lexander 4leming in @5@, of the

antibacterial properties of a Penicillium fungus. Isolation and purification of 

active compound to accumulate sufficient material for clinical trials took

thirteen years. ntibiotics have either cidal *killing0 effect or a static

*inhibitory0 effect on microbes. few examples of the two types of 

antibiotics are as follows2

!actericidal !acteriostatic

Eenicillin =rythromycin

 minoglycosides etracycline

3floxacin Chloramphenicolhe range of bacteria or other microorganisms that are affected by a

certain antibiotic is expressed as its spectrum of action. ntibiotics which

kill or inhibit a wide range of ram;positive and ram;negative bacteria

are said to be broad spectrum antibiotics. hose effective mainly against

ram;positive or ram;negative bacteria are narrow spectrum antibiotics.

If effective against a single organism or disease, they are referred to as

limited spectrum antibiotics. Eenicillin has a narrow spectrum. mpicillin

and moxycillin are synthetic modifications of penicillins. hese have

broad spectrum. It is absolutely essential to test the patients for sensitivity

*allergy0 to penicillin before it is administered. In India, penicillin is

manufactured at the "industan ntibiotics in Eimpri and in private sector 

industry.

Chl!"m#henicl$ isolated in @8A, is a broad spectrum antibiotic. It is

rapidly absorbed from the gastrointestinal tract and hence can be given

orally in case of typhoid, dysentery, acute fever, certain form of urinary

infections, meningitis and pneumonia. %"ncm&cin and 'l"cin are the

other important broad spectrum antibiotics. he antibiotic &*i"+i!ine is

supposed to be toxic towards certain strains of cancer cells.

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E=#CI::I# C":3%ME"=#IC3:

ofoxacin

.6.8.5  ntiseptics and )isinfectants

 ntiseptics and disinfectants are also the chemicals which either kill or 

prevent the growth of microorganisms. Antiseptic(s) are antimicrobial

substances  that are applied to living tissue/skin  to reduce the

possibility o inection, sepsis, or putreaction. hese are not ingested

like antibiotics.

Some common antiseptics are

Alcohols, most commonly ethanol (6!"#$, %&propanol (6!'#$and &propanol/isopropanol ('!)#$ or mixtures o thesealcohols, are commonly reerred to as *surgical alcohol*, and areused to disinect the skin beore in+ections are given, oten alongith iodine (tincture o iodine$ or some cationic suractants (ben-alkonium chloride .!.#, chlorhexidine .!.# oroctenidine dihydrochloride .%!.#$.

0oric acid is used in suppositories to treat yeast inections o thevagina, in eyeashes, as an antiviral to shorten the duration o

cold sore attacks, in creams or burns, and trace amounts in eyecontact solutions.

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1odine is usually used in an alcohol solution (called tincture oiodine$ or as 2ugol3s iodine solution as a pre& and postoperativeantiseptic.

Sodium chloride (salt$ is used as a general cleanser and as an

antiseptic mouthash. 1ts eak antiseptic e4ect is due tohyperosmolality o the solution above ."#.

Commonly used antiseptic, dettol is a mixture of chloroxylenol and

terpineol.

!ithionol *the compound is also called bithional0 is added to soaps to

impart antiseptic properties.

 Iodine is a powerful antiseptic. Its 5;6 per cent solution in

alcoholwater mixture is known as tincture of iodine. It is applied on

wounds. Iodoform is also used as an antiseptic for wounds.

!oric acid in dilute a?ueous solution is weak antiseptic for eyes.

Disinfectants are antimicrobial agents that are applied to non&living ob+ects to destroy microorganisms that are living on theob+ects.5% 7isinection does not necessarily kill allmicroorganisms, especially resistant bacterial spores8 it is lesse4ective than sterili-ation, hich is an extreme physical and/orchemical process that kills all types o lie.

A wide range of different substances are used as disinfectants, including alcohols (also usedas antiseptics), aldehydes, such as ortho-phthalaldehyde, bleaches based on chlorine

compounds, hydrogen peroxide and also iodine (also another traditional antiseptic) and

 potassium permanganate solution. Phenolic compounds also have anti-bacterial activity and

are often used in disinfectants bought for use in the home, and in disinfectant hand-washes

and soaps.

Different disinfectants wor in different ways. !ydrogen peroxide, which reacts to produce

free oxygen radicals and bleaches that are based on chlorine compounds are very powerful

oxidising agents. "hey oxidise the complex molecules present on the surface of bacteria,

causing their cell walls and cell membranes to disrupt. "he proteins on the surface become

irreversibly damaged and start to stic together forming clumps. "his happens very #uicly $

a strong solution of sodium hypochlorite solution that is used to disinfect a toilet, for

example, ills bacteria within seconds. "he bacterial cell cannot respond to the damage

#uicly enough and the whole cell simply splits open and dies.

7ame substances can act as an antiseptic as well as disinfectant byvarying the concentration.

4or example, -.5 per cent solution of phenol is an antiseptic while itsone percent solution is disinfectant.

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Chlorine in the concentration of -.5 to -.8 ppm in a?ueous solution

and sulphur dioxide in very low concentrations, are disinfectants.

C":3%3FL:=#3: =%EI#=3: !I"I3#3:

1.*.3 An$ifer$ili$" Drugs

 ntibiotic revolution has provided long and healthy life to people. he life

expectancy has almost doubled. he increased population has caused

many social problems in terms of food resources, environmental issues,

employment, etc. o control these problems, population is re?uired to be

controlled. his has lead to the concept of family planning. ntifertility

drugs are of use in this direction.

he basic aim of antifertility drugs is to prevent conception or fertili9ation.hese control the female menstrual cycle and ovulation. he birth control

pills are essentially a mixture of synthetic esterogen and progesterone

derivatives which are more potent than the natural hormones.

It is known that progesterone suppresses ovulation. 7ynthetic

progesterone derivatives are more potent than progesterone.

#orethindrone is an example of synthetic progesterone derivative most

widely used as antifertility drug.

he estrogen derivative which is used in combination with progesterone

derivative is ethynylestradiol *novestrol0.

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NORET+INDRONE ET+4N4LESTRADIOL 5NOESTROL6

Mifepristone is a synthetic steroid which blocks the effects of 

progesterone and is used as a Gmorning after pillG in many countries.

MI-E,RISTONE