Chemicals in medicines

The words ‘medicine’ and 'drug' are often used in our country to mean the same substances: any
substance, manufactured artificially, which can help recovery from sickness, relieve symptoms or
modify a natural process in the body. A medicine is often a mixture of several chemical
compounds. Even if it has only one active component compound often other substances are used
as fillers or binders to give it bulk. Chemistry, the science related to chemical substances,
provides us the tools to make and study the substances that are the constituents of almost all
medicines. The past hundred years or so, ever since the advent of organic chemistry, many
chemical compounds have been discovered in nature that are effective for curing diseases.
Modern chemistry has also made it possible to synthesize several medicines using methods of
organic chemistry.
The most common medicines can be classified into few groups, e.g. antibiotics, antiseptics,
analgesics, tranquillizers, antipyretics, hormonal, steroids etc.
There are very many medicines that come under each of these groups. Often several chemical
compounds that make a particular group of medicines, say antibiotics have similar chemical
structure. Since the medicines in a particular group are effective for treating a particular type of
ailment or disease, their mode of action can also be very similar. But, the methods used to isolate
a medicine from its natural sources or to synthesize it are most often very different.

ANTIBIOTICS
Our body and our domestic animals, can serve as hosts to a wide variety of disease-
causing organisms (pathogens): These are:

• bacteria
• viruses
• fungi
• protozoon’s

An antibiotic (Greek anti, "against"; bios, "life"), is a chemical substance produced by

one organism that is destructive to another. This process traditionally has been called
antibiosis and is the opposite of symbiosis. More specifically, an antibiotic is a type of
chemotherapeutic agent that has a toxic effect on certain types of disease-producing
microorganisms without acting dangerously on the patient. The definition most used for
antibiotics is: any substance produced by a microorganism which harms or kills another
microorganism. However, antibiotics DO NOT harm viruses. Doctors often prescribe
antibiotics when you may have a viral infection because of the possibility that you may
also acquire a bacterial infection because you are so ill with a virus - being ill places a
person at risk for certain bacterial infections that are normally handled without any
problem.

The overwhelming majority of antibiotic substances are natural products that certain
bacteria and fungi (molds) produce and send outside of their cells. About 90% of the
antibiotics in use today, are isolated from bacteria. There are a few antibiotics, however,
which are completely synthetic... that is, are made from scratch in the laboratory. These
particular antibiotics are designed to inhibit some process previously identified to be
completely unique to bacteria, and necessary for the bacterium to remain alive.
An antibiotic can be most often classified into any one of the following categories of
chemical compound:

1. Amino glycosides
2. Glycopeptides
3. Beta Lactams also known as Penicillin’s
4. Tetracycline
5. Quinolines
6. Sulfonamides

Amino glycosides

Amino glycosides are antibiotics that are often administered into veins or muscle to treat
serious bacterial infections. Some amino glycosides are also used orally to treat intestinal
infections or topically to treat eye infections. Some very popular examples of this group
of antibiotics are

• Streptomycin
• Kanamycin
• Neomycin
• Gentamycin

They are the inhibitors of protein synthesis, ↓ 30S ribosomal subunit, but some
abnormal proteins insert in cell membrane & form pores, thus become bactericidal

The chemical structure of this group of antibiotics is:

Glycopeptides

Glycopeptide antibiotics are a class of antibiotic drugs. They consist of a glycosylated

cyclic or polycyclic nonribosomal peptide. Important glycopeptide antibiotics include
vancomycin, teicoplanin, ramoplanin, and decaplanin.

This class of drugs inhibits the synthesis of cell walls in susceptible microbes by
inhibiting peptidoglycan synthesis. Bacterial cell wall contains peptidoglycan strands

• Peptidoglycan is composed of UDP-N-acetyl-muramic acid, UDP-N-acetyl-

glucosamine & a pentapeptide
• Cycloserine, resembles to alanine & inhibits addition of alanine into peptide
chain
• Vancomycin inhibits transglycosidase enzyme & prevents peptidoglycan chain
elongation

Due to their toxicity, their use is restricted to those patients who are critically ill or who
have a demonstrated hypersensitivity to the β-lactams.

The chemical structure of a glycopeptide antibiotic is

Penicillin

Penicillin is one major class of antibiotics. They are used to treat strep throat and
countless other infections. Examples of various kinds of penicillin include

Amoxicillin, Ampicillin, Carbenicillin, Cloxacillin, Dicloxacillin, Flucloxacillin..

They are the inhibitors of cross linking of peptidoglycan strands:

• Inhibit transpeptidase enzyme, involved in cross linking of peptidoglycan

strands
• Also called as transpeptidation reaction & strengthens cell wall.
• Defects in the synthesis of cell wall cause wholes in cell wall & changes in
permeability
• Leading to bacterial swelling & lysis
• Hence cell wall synthesis inhibitors are bactericidal

Common structural features of Beta-Lactams;

Tetracycline

Tetracyclines are another category of antibiotics. In addition to being used to treat

infections, they are often used to manage acne. A few of the tetracyclines frequently used
are:

 Achromycin V (Tetracycline)
 Minocin (Minocycline)
 Vibramycin (Doxycycline)

They are the inhibitors of protein synthesis, ↓ 30S ribosomal subunit & are
bacteriostatic

The chemical structure of most tetracycline is related to the following structure. The
name is derived from the fact that it is made up of four rings (cycles).

Quinolones

The quinolones are a family of broad-spectrum antibiotics. The parent of the group is
nalidixic acid. The majority of quinolones in clinical use belong to the subset of
fluoroquinolones, which have a fluoro group attached the central ring system.
Quinolones and fluoroquinolones are bactericidal drugs, actively killing bacteria.
Quinolones inhibit the bacterial DNA gyrase or the topoisomerase II enzyme, thereby
inhibiting DNA replication and transcription.

They are the inhibitors of DNA replication & mitosis, inhibit bacterial topisomerase-II [
in gram (-) bacteria] & topoisomerase IV [in gram (+) bacteria], inhibit DNA replication
& are bactericidal

The common chemical structure is as follows

Sulfonamides

Sulfonamide drugs (known widely as "sulfa drugs") were the first antibacterial
antibiotics, and paved the way for the antibiotic revolution in medicine. The first
sulfonamide was trade named Prontosil, which is a prodrug. Experiments with Prontosil
began in 1932 in the laboratories of the Bayer Corporation, a component of the huge
German chemical trust IG Farben. The dye-based drug was synthesized by Bayer chemist
Josef Klarer and tested in animals under the direction of physician/researcher Gerhard
Domagk. Domagk quickly won the 1939 Nobel Prize in Medicine and Physiology, an
honor that Hitler forbade him to accept.

They are the inhibitors of DNA & cell division, can affect microbial DNA & cell
division in following ways:

• Inhibit DNA synthesis

a) Inhibitors of folate synthesis- Sulfonamides & sulfones inhibit dihydro-

pteroate synthase (DHPS) enzyme

Trimethoprim inhibits dihydro-folate reductase (DHFR) enzyme (bacterial

DHFR more than human)

b) Inhibitors of thymidylate synthesis- Flucytosine: is a cytosine analogue &

inhibits thymidylate synthase (TS)

• Converted in fungi & GI flora to 5-fluorouracil (5-FU)

• 5-FU converted to 5-FdUMP
• 5-FdUMP incorporated to DNA

Some examples of sulfonamide antibiotics are:

Mafenide, Sulfacetamide, Sulfamethizole, Sulfanilimide, Trimethoprim etc.

How Antibiotics act.

Antibiotics attack a metabolic pathway found in the bacterium but not in the host. This is
not an insurmountable problem for bacterial pathogens because they differ in many
respects from eukaryotes.

Thus pencillins (beta-

lactams) work by interfering
with the synthesis of the
bacterial cell walls — a
structure that is not found in
eukaryotes. The walls of
bacteria are made of a
complex polymeric material
called peptidoglycan. It
contains both amino acids
and amino sugars. The amino
sugars are of two kinds

• N-acetylglucosamine (NAG) and its close relative

• N-acetylmuramic acid (NAM).

These two form a linear polymer of NAG alternating with NAM. They are linked by a
glycosidic bond between the #1 and #4 carbons (this is the linkage attacked by lysozyme)
and are oriented in the same way they are in cellulose. Side chains containing 4 or 5
amino acids are attached to each NAM. These form covalent bonds with amino acids in
adjacent chains. The bonds may

• be direct to the next chain or

• include additional peptide cross bridges (e.g., 5 glycine residues) which
• extend to chains in the same plane
(shown here) as well as to chains
above and below.

This elaborate, covalently cross-linked

structure provides the great strength of the
cell wall. It also leads to the remarkable
conclusion that the bacterial cell wall
meets the definition of a single molecule!

The beta-lactam antibiotics bind to and

inhibit enzymes needed for the synthesis
of the peptidoglycan wall. While they have
little effect on resting bacteria, they are lethal to dividing bacteria as defective walls
cannot protect the organism form bursting in hypotonic surroundings.
The aminoglycosides bind to the 30S subunit of the bacterial ribosome, because the
bacterial ribosome differs in several ways from the eukaryotic ribosome and thus
interferes with the formation of the initiation complex , causing misreading of the
mRNA.

Tetracyclines also bind to the 30S subunit of the bacterial ribosome. They prevent the
transfer of activated amino acids to the ribosome so protein synthesis is halted.

The fluoroquinolones block the action of two bacterial topoisomerases — enzymes that
relieve the coils that form in DNA when the helix is being opened in preparation for
replication or transcription or repair.

block the synthesis of folic acid. Mammals ignore PABA and its analogs and thus can
tolerate sulfa drugs.
The mode of action of Sulfonamides is a bit different. Both bacteria and their human
hosts require folic acid for nucleic acid synthesis (it is converted into prunes and
thymidine) as well as protein synthesis (precursor of the amino acids methionine and
glycine). However, bacteria synthesize their folic acid starting with para-aminobenzoic
acid (PABA), while we must ingest our folic acid already formed; that is, for us it is a
vitamin.

Production of antibiotics

Since the first pioneering efforts of Florey and Chain in 1939, the importance of
antibiotics to medicine has led to much research into discovering and producing them.
The process of production usually involves screening of wide ranges of microorganisms,
testing and modification. Production is carried out using fermentation; a process that is
important in anaerobic conditions when there is no oxidative phosphorylation to maintain
the production of ATP by glycolysis.

ANALGESICS
Analgesics are medicines that help to control pain and reduce fever. An analgesic
(colloquially known as a painkiller) is any member of the diverse group of drugs used to
relieve pain (achieve analgesia). This derives from Greek an-, "without", and -algia,
"pain". Examples of analgesics that are available over the counter are: aspirin,
acetaminophen, ibuprofen, ketoprofen and naproxen sodium. Some analgesics contain a
combination of ingredients in one pill, such as aspirin, acetaminophen and caffeine.

Analgesics act in various ways on the peripheral and central nervous system; they include
paracetamol (acetaminophen), the nonsteroidal anti-inflammatory drugs (NSAIDs) such
as the salicylates, narcotic drugs such as morphine, synthetic drugs with narcotic
properties such as tramadol, and various others. Some other classes of drugs not normally
considered analgesics are used to treat neuropathic pain syndromes; these include
tricyclic antidepressants and anticonvulsants.
Thus acetylsalicylic acid (commonly known as aspirin) is a salicylate with the chemical
structure:

Aspirin is commercially synthesized using a two-step process. First, phenol (generally

extracted from coal tar) is treated with a sodium base generating sodium phenoxide,
which is then reacted with carbon dioxide under high temperature and pressure to yield
salicylate, which is acidified, yielding salicylic acid. This process is known as the Kolbe-
Schmitt reaction.
ANTISEPTICS

Antiseptics are antimicrobial substances that are applied to living tissue/skin to reduce
the possibility of infection, sepsis, or putrefaction. They should generally be
distinguished from antibiotics that destroy microorganisms within the body, and from
disinfectants, which destroy microorganisms found on non-living objects. Some
antiseptics are true germicides, capable of destroying microbes (bactericidal), whilst
others are bacteriostatic and only prevent or inhibit their growth. Antibacterial are
antiseptics that only act against bacteria.

Some chemical compounds/groups of chemical substances that are often used as

antiseptics are:

• Alcohols
Most commonly used is ethanol (60-90%), 1-propanol (60-70%) and 2-
propanol/isopropanol (70-80%) or mixtures of these alcohols. They are commonly
referred to as "surgical alcohol". Used to disinfect the skin before injections are
given, often along with iodine (tincture of iodine) or some cationic surfactants
(benzalkonium chloride 0.05 - 0.5%, chlorhexidine 0.2 - 4.0% or octenidine
dihydrochloride 0.1 - 2.0%).

• Quaternary ammonium compounds

They include the chemicals benzalkonium chloride (BAC), cetyl
trimethylammonium bromide (CTMB), cetylpyridinium chloride ,
cetylpyridinium chloride (CPC) and benzethonium chloride (BZT). Benzalkonium
chloride is used in some pre-operative skin disinfectants (conc. 0.05 - 0.5%) and
antiseptic towels. The antimicrobial activity of Quats is inactivated by anionic
surfactants, such as soaps. Related disinfectants include chlorhexidine and
octenidine.

• Boric acid
Used in suppositories to treat yeast infections of the vagina, in eyewashes, and as
an antiviral to shorten the duration of cold sore attacks. Put into creams for burns.
Also common in trace amounts in eye contact solution. Though it is popularly
known as an antiseptic, it is in reality only a soothing fluid, and bacteria will
flourish comfortably in contact with it.

• Chlorhexidine Gluconate
A biguanidine derivative, used in concentrations of 0.5 - 4.0% alone or in lower
concentrations in combination with other compounds, such as alcohols. Used as a
skin antiseptic and to treat inflammation of the gums (gingivitis). The
microbicidal action is somewhat slow.

Hydrogen peroxide
 Used as a 6% (20Vols) solution to clean and deodorise wounds and ulcers. More
common 1% or 2% solutions of hydrogen peroxide have been used in household
first aid for scrapes, etc. However, even this less potent form is no longer
recommended for typical wound care as the strong oxidization causes scar
formation and increases healing time. Gentle washing with mild soap and water or
rinsing a scrape with sterile saline is a better practice.

• Iodine
Usually used in an alcoholic solution (called tincture of iodine) or as Lugol's
iodine solution as a pre- and post-operative antiseptic. No longer recommended to
disinfect minor wounds because it induces scar tissue formation and increases
healing time. Gentle washing with mild soap and water or rinsing a scrape with
sterile saline is a better practice. Novel iodine antiseptics containing
iodopovidone/PVP-I (an iodophor, complex of povidone, a water-soluble
polymer, with triiodide anions I3-, containing about 10% of active iodine, with the
commercial name Betadine) are far better tolerated, don't affect wound healing
negatively and leave a depot of active iodine, creating the so-called "remanent,"
or persistent, effect. The great advantage of iodine antiseptics is the widest scope
of antimicrobial activity, killing all principle pathogens and given enough time
even spores, which are considered to be the most difficult form of
microorganisms to be inactivated by disinfectants and antiseptics.

• Mercurochrome
Not recognized as safe and effective by the U.S. Food and Drug Administration
(FDA) due to concerns about its mercury content. Another obsolete
organomercury antiseptics include bis-(fenylmercury) monohydrogenborate .

• Phenol (carbolic acid) compounds

Phenol is germicidal in strong solution, inhibitory in weaker ones. Used as a
"scrub" for pre-operative hand cleansing. Used in the form of a powder as an
antiseptic baby powder, where it is dusted onto the belly button as it heals. Also
used in mouthwashes and throat lozenges, where it has a methadone-like
painkilling effect as well as an antiseptic one. Example: TCP. Other phenolic
antiseptics include historically important, but today rarely used (sometimes in
dental surgery) thymol, today obsolete hexachlorophene, still used triclosan and
sodium 3,5-dibromo-4-hydroxybenzenesulfonate (Dibromol).

• Sodium chloride
Used as a general cleanser. Also used as an antiseptic mouthwash. Only a weak
antiseptic effect, due to hyperosmolality of the solution above 0.9%.

• Sodium hypochlorite
Used in the past, diluted, neutralised and combined with potassium permanganate
in the Daquin's solution. Nowadays used only as disinfectant.
DISINFECTANTS

By the middle of the nineteenth century, post-operative sepsis infection accounted for the
death of almost half of the patients undergoing major surgery.

In 1839 the chemist Justin von Liebig had asserted that sepsis was a kind of combustion
caused by exposing moist body tissue to oxygen. It was therefore considered that the best
prevention was to keep air away from wounds by means of plasters, collodion or resins.

Germ Connection with wound sepsis

When, in 1865, Louis Pasteur suggested that decay was caused by living organisms in the
air, which on entering matter caused it to ferment, Lister made the connection with
wound sepsis.

A meticulous researcher and surgeon, Lister recognized the relationship between

Pasteur's research and his own. He considered that microbes in the air were likely causing
the putrefaction and had to be destroyed before they entered the wound.

In the previous year Lister had heard that 'carbolic acid' was being used to treat sewage in
Carlise, and that fields treated with the affluent were freed of a parasite causing disease in
cattle.

Pasteur suggested three methods: filter, heat, or expose them to chemical solutions. The
first two were inappropriate in a human wound, so Lister experimented with the third.

As the germ theory of disease became more widely accepted, it was realized that
infection could be better avoided by preventing bacteria from getting into wounds in the
first place. This led to the rise of sterile surgery. Some consider Lister "the father of
modern antisepsis."

In 1879 Listerine mouthwash was named after him for his work in antisepsis. Also named
in his honor is the bacterial genus Listeria, typified by the food-borne pathogen Listeria
monocytogenes.

The first major development towards modifying basic antimicrobial agents to make them
more specialized, more effective, was in 1906 when Bechhold and Ehrlich synthesized
the bis-phenols. They found that by linking two phenol rings directly or by mean of an
alkaline group, the bactericidal and bacteriostatic effects of the phenols were greatly
enhanced. Further work was done on the bis-phenol (During 1931) leading eventually to
the synthesis of hexachlorophene.
Iodine has also been modified for use as an antiseptic. The Iodine molecules can be added
to other substances which have the ability to increase the antimicrobial qualities of the
elements, whilst reducing the irritancy of iodine.
.
Antiseptics: An agent that inhibits or destroys microorganisms on living tissue including
skin, oral cavities and open wounds.

Chemical disinfectants: A chemical agent used on inanimate surfaces and objects to

destroy infectious fungi, viruses and bacteria but not necessarily their spores. Sporicidal
and antiviral agents may be considered a special class of disinfectants. Disinfectants are
often categorized as high level, intermediate level, and low level by medically oriented
groups based upon their efficacy against various microorganisms.

Decontamination: The removal of microorganisms by disinfection or sterilization.

Disinfectants: A chemical or physical agent that destroys or removes vegetative forms of

harmful microorganisms when applied to a surface.

Sanitizing agents: An agent which reduces microbes on inanimate surfaces, the number
of all forms of microbial life including fungi, viruses and bacteria.

Sporicidal agents: An agent that destroys bacterial and fungal spores when used in
sufficient concentration for a specified contact time. It is expected to kill all vegetative
microorganisms.

Sterilants: An agent that destroys all forms of microbial life including fungi, viruses and
all forms of bacteria and their spores. Sterilants are liquid or vapor-phase agents.

Microorganisms differ greatly in their resistance to disinfecting agents. The order of

resistance of clinically significant microorganisms to chemical disinfectants from most to
least resistant.
The resistance of some clinically important microorganisms to chemical disinfectants:

1) Type of Microorganisms Examples

2) Bacterial spores Bacillus subtilis and Clostridium sporogenes.

3) Mycobacteria Mycobacterium tuberculosis.

4) Non lipid-coated viruses Poliovirus and Rhinovirus.

5) Fungal spores and vegetative molds Trichophyton, Crytococcus and Candida sp.and
yeasts.

6) Vegetative bacteria Pseudomonas.aeruginosa,

Staphylococcus aureus and
 Salmonella etc.

7) Lipid-coated viruses Herpes simplex virus, Hepatitis B virus, HIV

Classification of Disinfectants

Chemical disinfectant is classified by their chemical type. This includes Aldehydes,

alcohol, halogens, and per-oxides, quaternary ammonium compounds and phenolic
compounds.
General classification of Antiseptics, Disinfectants and Sporicidal Agents.

Chemical Entity Classification Examples

1) Aldehydes Sporicidal agents 2% Gluteraldehyde

2) Alcohol General purpose disinfectants, antiseptic, 70% Isopropyl

antiviral agents. alcohol
70% Alcohol.
3) Chlorine and Sporicidal agents 0.5% Sod.
Sod.hypochlorite hypochlorite
4) Phenolics General purpose disinfectant 500µg per gm chloro-
xylenol.
5) Ozone Sporicidal agent 8% gas by weight
6) H2O2 Vapor phase sterilant, liquid sporicidal 4µg per gm H2O2
agent, antiseptic vapor
10-25% solution, 3%
solution.
7) Substituted Antiseptic agents 0.5% Chlorhexidine
Diguanides gluconate.
8) Per-acetic acid Liquid sterilant, vapor phase sterilant 0.2% Per-acetic acid,
1µg per gm per-acetic
acid.
9) Ethylene oxide Vapor-phase sterilnt 660µg per gm
ethylene oxide.
10) Quaternary General purpose disinfectant, antiseptic 200µg per gm
Amm. Benzalkonium
compounds chloride
11) β- Propiolactonic Sporicidal agent 100µg per gm β-
Propiolactone.
Selection of an antiseptic for hand and surgical site disinfection:
Hands and surgical sites are disinfected in a hospital setting to reduce the resident flora
and to remove transient flora (e.g. – Streptococcus pyogenes and methicillin resistant
Staphylococcus aureus and Pseudomonas aeruginosa) that have been implicated in
hospital- associated infection. Use of antiseptic to disinfectant hands has been shown to
be more effective than soap and water in reducing the counts of bacteria on the skin;
repeated antiseptic use further reduces these counts. These principles may be applied to
clean room operation in the pharmaceutical industry.

Mechanism of Disinfectant activity

Target Disinfectants

Cell wall Formaldehyde, hypochlorite’s and

mercurials
1) Cytoplasmic membrane, action on Anilides and hexachlorophene
membrane potential
2) Membrane enzymes, action on Hexachlorophene
electron transport chain
3) Action on ATP Chlorhexidine and ethylene oxide
4) Action on enzymes with –SH group Ethylene-oxide, Gluteraldehyde, Hydrogen
peroxide, hypochlorite’s, Iodine and
mercurial’s
5) Action on general membrane Alcohols, Chlorhexidine and quaternary
permeability ammonium compounds.
6) Cell contents, general coagulation Chlorhexidine, Aldehydes,
Hexachlorphene and quaternary
ammonium compounds
7) Ribosome’s Hydrogen peroxide and mercurial’s
8) Nucleic acids Hypochlorite’s
9) Thiol-groups Ethylene oxide, gluteraldehyde, hydrogen
peroxide, hypochlorite’s and mercurial’s
10) Amino groups Ethylene oxide, gluteraldehyde and
hypochlorite’s
11) General oxidation Ethylene oxide gluteraldehyde and
hypochlorite’s

Microbial Resistance to Disinfectants:

The development of microbial resistance to disinfectant is less likely, as disinfectants are
more powerful biocidal against low population of microorganisms usually not growing
actively, so the selective pressure for the development of resistance is less profound.
However, the most frequently isolated microorganism from an environmental monitoring
program may be periodically subjected to use dilution testing with the agents used in the
disinfection program to confirm their susceptibility.

Neutralizing Agents for common Disinfectant

Disinfectant Neutralizing Agents

1) Alcohols Dilution or polysorbate 80

2) Gluteraldhyde
3) Sodium hypochlorite’s
4) Chlorhexidine
5) Mercuric chloride
6) Quaternaryammonium
compounds
Glycine and Sodium bisulfate
Sodium thiosulfate
Poltsorbate 80 and lecithins
Thioglycolic acid
Polysorbate 80 and lecithins

Because a wide range of different materials of construction are used in clean rooms and
other controlled areas, each material needs to be evaluated separately to validate the
efficacy of a given disinfectant.
Typical surfaces to be decontaminated by disinfectants in a Pharmaceutical
manufacturing Area.

Materials Application
1) Stainless steel Work surfaces, filling equipments and tanks.
2) Glass Windows and vessels.
3) Plastic, Vinyl Curtains.
4) Plastic, Polycarbonate Insulation coating.
5) Lexan(Plexiglas’s) Shields.
6) Epoxy-Coated gypsum Walls and Ceilings.
7) Fiber glass-Reinforced Wall paneling.
plastic
8) Terrazzo tiles Floors.
 APPLICATIONS OF DISINFECTANTS

Disinfectant Uses
Alcohols Ethyl or isopropyl alcohol at 70-80% concentration is a good
general purpose disinfectant; not effective against bacterial
spores.
Phenols Effective against vegetative bacteria, fungi and viruses
containing liquids, unpleasant odor.
Formaldehyde Concentration of 5-8% formalin is a good disinfectant against
vegetative bacteria, spores and viruses; known carcinogen;
irritating odor.
Quaternary Ammonium Cationic detergents are strongly surfaced active; extremely
Compounds effective against lipoviruses; ineffective against bacterial
spores; may be neutralized by anionic detergents (i.e. soaps).
Chlorine Low concentrations (50-500 ppm) are active against vegetative
bacteria and most viruses; higher concentrations (2,500 ppm)
are required for bacterial spores; corrosive to metal surfaces;
must be prepared fresh; laundry bleach (5.25% chlorine) may
be diluted and used as a disinfectant.
Recommended for general use; effective against vegetative
Iodine bacteria and viruses; less effective against bacterial spores;
Wescodyne diluted 1 to 10 is a popular disinfectant for washing
hands.

Factors affecting Disinfection

The following are six primary variables that influence the efficacy of disinfection:
1) Nature of the item to be disinfected:

The rougher the surface, the longer the contact time required for disinfection.

2) Number of microorganisms present:

The number of microorganism present will lengthen the time for effective disinfection to
take place. In general, higher numbers of organisms require more time for disinfection.

3) Resistance of microorganisms:
 Some microorganisms are more resistant to disinfection than others. The generally
accepted order from the most resistance to the least resistant is: bacterial spore,
mycobacteria, hydropjillic viruses, fungi, vegetative bacteria, lipid viruses. Disinfecting a
spill with a small concentration of bacterial spores will require longer disinfection time
than a large concentration of lipid viruses.

4) Type and concentration of disinfectant used:

Resistance of microorganisms depends on the type of disinfectant used. A particular

microorganism may be more resistant to one type of disinfectant than another. For
instance, alcohol (Isopropyl or ethyl) is effective against vegetative bacteria and most
lipophilic viruses. Many disinfectants are broad spectrum; that is, effective against all or
most forms of microbial life. Some non-broad spectrum disinfectants include phenolics and
quaternary ammonium compounds. Some broad spectrum disinfectants include
Gluteraldehydes, sodium hypochlorites, and hydrogen peroxides. Alcohols lie somewhere
in between these two.

The concentration of a particular disinfectant effects disinfection. In most cases, a higher

concentration increases microbial killing power and decreases time necessary for
disinfection.

However, some disinfectants are not as effective in higher concentrations. Iodophors must
be diluted according to the directions on the label; over-diluting or under-diluting may
substantially lower the microbial potency. Alcohols used in concentration above 90% are
less effective because the water added to dilute the alcohol allows it to penetrate better and
reach its target. Optimal concentration range is between 70-90%.

5) Presence of organic material:

The presences of organic soiling matter will compromises disinfection. Blood, blood
product, bodily fluids and feces contain significant amounts of proteins, and protein will
bind and inactivate some disinfectants or slow their action. Therefore, in the presence of
large amounts of protein, a higher concentration of disinfectant and longer contact time
will be necessary to achieve maximal disinfection.

6) Duration of exposure and temperature:

Duration of exposure and temperature influences the disinfection process. The

longer the duration of exposure, the higher the degree of disinfection achieved.
Some disinfectants require a longer contact time to achieve killing, and some
 microorganisms need longer exposures to be killed. Higher temperature increases
the killing power of most disinfectants, where lower temperature may slow the
killing power of most disinfectants. .

General Description of disinfectants used:

1) Incidur:

Incidur is a broad spectrum; Microbiocidal action including HIV, Hepatitis B etc.It

shows long residual effect with sustained release. It is manufactured by Henkel
Germany. It is purposely used for surface disinfection and fumigation.

Range of application:
 High risk areas like Operation theatres, Intensive care Unit (ICU), laboratories
and drug manufacturing units.

 Commonly used for general purpose in laboratories and pharmaceuticals units.

Mode of Action:
 It interferes with enzymes with –SH groups and Thiol group of proteins.

 It is also responsible for general oxidation of cellular components in microbial

cells.

Recommended concentration and contact time (According to manufacturer):

• According to manufacturer (Henkel Germany), Incidur is effective at 1%
concentration for 1 hour exposure or contact time.

2) Levermed:

Levermed is broad spectrum hand disinfectant. It acts as Bactericidal, Sporicidal,

Fungicidal and Virucidal agent. It is manufactured by Universal Healthcare
Silvassa. It is marketed by Johnson Diversy. It is purposely used for hand
disinfection and laboratory practices. Levermed is ready to use prepared hand
disinfectant.

Active Ingredients (w/w):

• n- popanol………………………50%

• Iso-propyl Alcohol...……………20%
 • Benzalkonium chloride………...0.5%

• Emollents.

Range of Application:
• Industrial Quality Control Laboratories, Research Institutes, Academics, Drug
Manufacturing units.

Mode of Action:
• It generally shows action towards membrane permeability. It coagulates cellular
components.

Recommended concentration and contact time (According to manufacturer):

• According to manufacturer (Universal Healthcare, Silvassa), Levermed is
effective at 10 minutes exposure or contact time.

3) Oxivir:

Oxivir is broad spectrum environmental cleaner & disinfectant. It is oxygen based

Bactericidal, Sporicidal, Virucidal, Fungicidal, Yeasticidal. Oxivir is concentrated
oxygen based liquid cleaner disinfectant for cleaning and disinfectant of all water
resistant surfaces. It is manufactured by Johnson Diversy. It is effective against
Bacteria, Fungi, Yeasts, Virus. It is purposely used for Fumigation, Cleaning and
disinfecting equipment. It is compatible with metals and surfaces used in
hospitals. However, material compatibility on a small and inconspicuous place is
recommended before use.

Composition:
Hydrogen peroxide
Alkyl Benzene sulphonic acid
Alcohol ethoxylate (C12-15) 3EO
Hydroxyethene-1-1-diphosphonic acid
2- butoxyethanol

Feature Advantage Benefits

Accelarated hydrogen Higher grade disinfectant Broad spectrum Microbial kill

peroxide

Aldehyde free product No negative occupational Eco-friendly and user friendly

hazards

Cleaner and Single shot product Time and cost effective

disinfectant

Range of Application:
  Oxivir is purposely used in Hospitals, laboratories, Institutes and Drug
manufacturing units.

Recommended Concentration and contact time:

 According to manufacturer (Johnson Diversy), Oxivir is effective at 2.5% for 5
minute contact time.

Mode of Action:
 Oxivir shows action on enzymes with –SH group.

 Oxivir also cause general oxidation of cellular components.

4) Virex II 256:

Virex II 256 is high level instrument & surface disinfectant Bactericidal,

Sporicidal, Virucidal, Fungicidal, Yeasticidal. Virex II 256 is a high level
disinfectant of surfaces and critical instruments (which come in contact with
blood stream or normally sterile areas of the body, such as rigid and flexible
surgical instruments) in healthcare application. . It is purposely used for Cleaning
and disinfecting equipment. It is compatible with metals and surfaces used in
hospitals. However, material compatibility on a small and inconspicuous place is
recommended before use. Virex II 256 is blue colored liquid disinfectant
manufactured by Johnson Diversy. It is effective against Bacteria, Fungi, Yeasts,
Virus.

Composition:
 Didecyl dimethyl ammonium chloride……………………..8.7%
 n-alkyl dimethyl benzyl ammonium chloride………………8.19%
 Lauryl amine amine oxide
 Ethylene diamine tetra acetic acid sodium salt
 Sodium biocarbonate

Feature Advantage Benefits

N-alkyl dimethyl benzyl Combination of most potent Broad spectrum kill

ammonium chloride & Didecyl QAC’s
dimethyl ammonium chloride

Aldehyde free product No negative occupational hazard Eco friendly and user
friendly
 Cleaner and disinfectant Single shot product Time and cost effective

Range of Application:
 Virex II 256 is purposely used for instruments disinfection. It is also used for
surface disinfection. It is also used for washing and other tiled surfaces. It is
compatible with most metals and surfaces used in pharmaceuticals units,
Laboratories and Research Institute.

Recommended Concentration and contact time:

 According to manufacturer (Johnson Diversy), Virex II 256 is effective at 0.4%
for 10 minutes contact time or exposure.

Mode of Action:
 It causes general cell components coagulations.

ANTACIDS
Antacids perform a neutralization reaction, i.e. they buffer gastric acid, raising the pH to
reduce acidity in the stomach. When gastric hydrochloric acid reaches the nerves in the
gastrointestinal mucosa, they signal pain to the central nervous system. This happens
when these nerves are exposed, as in peptic ulcers. The gastric acid may also reach ulcers
in the esophagus or the duodenum.
Other mechanisms may contribute, such as the effect of aluminum ions inhibiting smooth
muscle cell contraction and delaying gastric emptying.

Calcium Carbonate
CALCIUM CARBONATE is a calcium salt. calcium carbonate, CaCO3, white chemical
compound that is the most common nonsiliceous mineral. It occurs in two crystal forms:
calcite, which is hexagonal, and aragonite, which is rhombohedral. Calcium carbonate is
largely insoluble in water but is quite soluble in water containing dissolved carbon
dioxide, combining with it to form the bicarbonate Ca(HCO3)2. Such reactions on
limestone (which is mainly composed of calcite) account for the formation of stalactites
and stalagmites in caves. Iceland spar is a pure form of calcium carbonate and exhibits
birefringence, or double refraction.

It is used as an antacid to relieve the symptoms of indigestion and heartburn. It is also

used to prevent osteoporosis, as a calcium supplement, and to treat high phosphate levels
in patients with kidney disease.
Antacids are usually taken after meals and at bedtime, or as directed by your doctor or
health care professional. Take your medicine at regular intervals. Do not take your
medicine more often than directed.
Need to take care before taking this:
•constipation
•dehydration
•high blood calcium levels
•kidney disease
•stomach bleeding, obstruction, or ulcer
•an unusual or allergic reaction to calcium carbonate, other medicines, foods, dyes, or
preservatives
•pregnant or trying to get pregnant
•breast-feeding

Interaction with medicines

Do not take this medicine with any of the following medications:

•ammonium chloride
•methenamine

This medicine may also interact with the following medications:

•antibiotics like ciprofloxacin, tetracycline
•captopril
•delavirdine
•gabapentin
•iron supplements
•medicines for fungal infections like ketoconazole and itraconazole
•medicines for seizures like ethotoin and phenytoin
•mycophenolate
•quinidine
•rosuvastatin
•sucralfate
•thyroid medicine.

ANTIHISTAMINES
A histamine antagonist is an agent which serves to inhibit the release of histamine.
The term antihistamine usually refers to the classical H1 receptor blockers.
Reversible & competitive H1 receptor antagonists block the binding of histamine to its
receptors.
These compounds do not influence the formation or release of histamine. [Cromolyn
which inhibits the release of histamine from mast cells and is useful in the treatment of
asthma.]

Histamine
 Basic amine autacoid stored in granules of mast cells and basophils.
  IgE-dependent release
 IgE-independent release (C3a and C5a, or drugs (e.g., d-tubocurarine).
 Acts as neurotransmitter in histaminergic nerves

Histamine Synthesis

Histamine Receptors

 3 Receptors
• H1, H2, H3 (H4 suggested)
 All receptors G-protein-coupled
 Signaling pathway
• H1 (PLC - IP3 & DAG)
• H2 (AC – cAMP)
• H3 (decrease in Ca2+ flux).

Physiological Actions of Histamine/Mediating Receptors

Action Receptor Location

Smooth muscle contraction H1 All smooth muscles

Vasodilatation H1 Endothelial cells

Increased Vasc. Permeability H1 (H2?) Endothelial cells

Cardiac stimulation H2 Cardiac muscles

Increased gastric secretion H2 Parietal cells

Pain and itch H1 Sensory nerve endings

Inhibition of transmitter relay H3 Nerve ending

Major Pathological Roles

 Allergic diseases
• allergic rhinitis (hay fever)
• Allergic conjunctivitis
• urticaria (Triple response)
• anaphylactic shock
• Allergic angioedema
 Drug reactions
 Insect bites
 Hyper secretion of acid in peptic ulcers.

Classification
 1st Generation
 2nd Generation

1st Generation

 Key Members
• Diphenhydramine
• Chlorpheniramine
• Doxylamine
• Hydroxyzine

 Characteristics
• High lipophilicity, easily enters CNS
• Highly sedative
• Anti-muscarinic, anti-α-adrenergic, anti-5HT
• Some have anti-motion sickness effect
• Some have local anaesthetic effect
• Generally short-acting
2nd Generation

 Key Members
• Desloratadine (loratadine)
• Fexofenadine (terfenadine)
• Cetirizine
• Azelastine

 Characteristics
• No CNS entry (Low lipophilicity, most ionized; also protein binding)
• Non-sedating
• No significant autonomic receptor blocking effect
• Generally long-acting
• Some are cardio toxic

Clinical Uses of Antihistamines

 Allergy (e.g., any 1st or 2nd generation)

• Allergic rhinitis
• Allergic conjunctivitis
• Urticaria (both acute and chronic)
• Allergic angioedema
• Anaphylactic shock
 Motion sickness (e.g., diphenhydramine)
 As hypnotics (e.g., Doxylamine)

Adverse Effects of Antihistamines

 Sedation (1st gen.)

 Dry mouth, blurred vision (1st gen.)

 Cardio toxicity: prolongation of QT intervals (early 2nd gen. terfenadine,

loratadine)

 Drug interaction (many 2nd gen. metabolized via P450)

TRANQUILLISERS
Tranquillizers also known as sedatives are man-made drugs, they are usually prescribed
by doctors as short-term treatments for depression, anxiety, stress and insomnia
(difficulty in sleeping).

The most commonly prescribed tranquillizers are from the class of drugs called
benzodiazepines (benzos) and are known as minor tranquillizers. There are various
benzos and they are usually known by their brand names, a few of the well known
products include:

• Valium the generic name is diazepam.

• Ativan the generic name is lorazepam.
• Mogadon the generic name is nitrazepam. On the street they may be called
moggies.
• Normison the generic name is temazepam. On the street they may be called jellies
or eggs.
• Rohypnol the generic name is flunitrazepam. On the street they may be called
roofies, rope or the forget-pill.

Drugs of abuse

The easy availability of tranquillizers has made them common as drugs of abuse. Some
drug abusers take tranquillizers to bring them down after using stimulants such as ecstasy
or cocaine. Others take them to enhance the effect of alcohol.

Temazepam has become a street drug as a substitute for heroin and Rohypnol is the
tranquilizer most associated with "date rape" as it has been known to be used to spike
drinks. The victim is often unaware that they have been slipped a drug and while under
the influence they are vulnerable to sexual abuse and rape.

Immediate effects of tranquillizers

Tranquillisers calm the user down and reduce feelings of agitation and restlessness, they
also slow down mental activity and produce drowsiness. Tranquillisers can have a
relaxing effect on the muscles. High doses of tranquillizers can make users forgetful,
dizzy and can induce sleep.
The effects of tranquillizers can begin after 10-40 minutes and can last for 3-6 hours but
this depends greatly on the drug used and the strength prescribed.

There is a high risk of accidents when driving or operating machinery when on

tranquillizers. Some tranquillizers can cause a temporary loss of short-term memory, and
an increase in aggression.

If mixed with alcohol or other depressant drugs tranquillizers can be extremely dangerous
and can cause a fatal overdose.

Long-term effects of taking tranquillizers

A low dosage of tranquillizers prescribed for a short period of time is unlikely to pose
any greater risk to health. However, if you take tranquillizers regularly a tolerance can
develop, so you will need to take more to get the same effect and you may also find you
become dependent on them. Therefore it is recommended that tranquillizers are not used
for long periods, and should not be taken for more than a 2-4 week period. If you are
taking them for insomnia a 2-3 night break from the tranquillizers each week is
recommended.

After 2-3 weeks of continuous use tranquillizers may become ineffective as sleeping pills
and after 4 months ineffective against anxiety.

Long term use of tranquillizers can cause depression, memory loss, mental confusion,
stomach disorders and aggressive behaviour.

The withdrawal effects can be very unpleasant and include sickness, headaches,
irritability, anxiety, nausea and in some cases panic attacks.

ANTI FERTILITY DRUGS/ ORAL CONTRACEPTIVE

PILLS
The combined oral contraceptive pill (COCP), often referred to as the birth-control
pill or simply "the pill", is a birth control method that includes a combination of an
estrogen and progestogen. When taken by mouth every day, these pills inhibit female
fertility.

Mechanism of action

Combined oral contraceptive pills were developed to prevent ovulation by suppressing

the release of gonadotropins. Combined hormonal contraceptives, including COCPs,
inhibit follicular development and prevent ovulation as their primary mechanism of
action.
Progestagen negative feedback decreases the pulse frequency of gonadotropin-releasing
hormone (GnRH) release by the hypothalamus, which decreases the release of follicle-
stimulating hormone (FSH) and greatly decreases the release of luteinizing hormone
(LH) by the anterior pituitary. Decreased levels of FSH inhibit follicular development,
preventing an increase in estradiol levels. Progestagen negative feedback and the lack of
estrogen positive feedback on LH release prevent a mid-cycle LH surge. Inhibition of
follicular development and the absence of a LH surge prevent ovulation.

Estrogen was originally included in oral contraceptives for better cycle control (to
stabilize the endometrium and thereby reduce the incidence of breakthrough bleeding),
but was also found to inhibit follicular development and help prevent ovulation. Estrogen
negative feedback on the anterior pituitary greatly decreases the release of FSH, which
inhibits follicular development and helps prevent ovulation.

A secondary mechanism of action of all progestagen-containing contraceptives is

inhibition of sperm penetration through the cervix into the upper genital tract (uterus and
fallopian tubes) by decreasing the amount of and increasing the viscosity of the cervical
mucus.

Drug interactions

Some drugs reduce the effect of the Pill and can cause breakthrough bleeding, or
increased chance of pregnancy. These include drugs such as rifampicin, barbiturates,
phenytoin and carbamazepine. In addition cautions are given about broad spectrum
antibiotics, such as ampicillin and doxycycline, which may cause problems "by impairing
the bacterial flora responsible for recycling ethinylestradiol from the large bowel"