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What are Pharmaceuticals ?

A pharmaceutical is a drug that is also referred to as

medicine ,medication and can be defined as any chemical substance intended for the use in medical diagnosis, cure , treatment and prevention of disease . It may be also used to enhance the body potential and trying to the best out of the human body . Can also be regarded as supplement .

History of Pharmaceuticals
The word pharma derives from the Greek word

pharmakon meaning drug or medicine . The earliest drugstores date back to the Middle Ages. The first known drugstore was opened by Arabian Pharmacists in Baghdad in 754 and many more began operating in the medical islamic world later spread to Europe. By the 19th century, many of the drugstores in Europe and North America had eventually developed into larger pharmaceutical companies.

 Cancer drugs were a feature of the 1970s. From 1978,

India took over as the primary center of pharmaceutical production without patent protection. Demand for nutritional supplements and so-called alternative medicines created new opportunities and increased competition in the industry.

Classification of pharmaceuticals
Pharmacokinetics it deals with the study of drug and

the rate at which it affects the body and the duration of the effect . Pharmacodynamics It deals with the biochemical and psychological effects of drugs on the body or on microorganisms or parasites within or on the body. Pharmacoepidemiology- it is the study of the use and effects of drugs on large groups of people.

 Pharmacovigilance - science of collecting, monitoring,

researching, assessing and evaluating information of drungs on humans Pharmaceutical formulation- is the process in which different chemical substances, including the active drug, are combined to produce a final medicinal product.

Classification of Pharmaceutical Drugs

1.
2. 3.

4.
5. 6.

Trentyxicyls : reduces headache . Antipyretics: reducing fever. Analgesics: reducing pain (painkillers). Antimalarial drugs: treating malaria. Antibiotics: inhibiting germ growth. Antiseptics: prevention of germ growth near burns, cuts and wounds.

Why we use drugs ?

To repair the damaged part.

To enhance performance . To reduce pain .

To increase the body resistance .

To maintain a stability in our body and nervous system

. To gain physical and mental balance . To get a strong immune system .

Types of medications :
For the digestive system : to faster the metabolism rate

and increase the digestion activity . For the cardiovascular system : to cure the blocks present inorder to increase the blood flow . For pain and consciousness : to reduce the pain or to get unconscious at the time of operations .

 For muscles : To strengthen the muscles and make

them more strong . For skeletons : To reduce the pain in joints and to make the bones stronger . For eye : To protect the eye from infections of dust and air . For skin : To prevent skin from any diseases and allergies . For nutrition : To increase the vitamins and protein content in the body .

Side effects of pharmaceuticals

Lack of sleep High and low blood pressure. Hyper tension . Severe pain . Excessive hunger. Headache. Eye irritation. Anger . Weakness . Dehydration

Injection or Admnistration of drugs in the body

It can be performed in various dosage forms such

as pills, tablets, or capsules. intravenous (into the blood through a vein) and oral administration (through the mouth). all at once as a bolus, at frequent intervals or continuously. By the medium of food and water .

Legal considerations
Approved by International Narcotics Control Board of

United nations . Patented and liscened Drugs . In India approved by FDA ( Food and Drug Assocoation) . Central Drugs Standard Control Organization

Evironmental Impact
Contamination of water .
May also be deposited in the environment through

improper disposal, runoff from sludge fertilizer and reclaimed wastewater irrigation, and leaky sewage. filtered ineffectively by wastewater treatment plants. In the bodies of plants and animals .

What are Biopharmaceuticals

Biologically significant compounds like hormones and proteins useful for treatment of variety of human health disorders, usually called as Biopharmaceuticals or Biotherapeutics or Biologicals, usually obtained from biological source and produced through industrial biotechnology

Important Biotherapeutics
Insulin- hormone which lowers blood

sugar; used by diabetics Interferon- class of cytokines effective vs viral infections Factor VIII- blood protein necessary for clotting; missing in hemophiliacs Streptokinin - bacterial enzyme to dissolve blood clots in coronary arteries Beta endorphins- pain suppressors

More than 30 recombinant therapeutics have been approved globally for commercial use and several are on the way
In India, 12-15 of these are presently being marketed. Many of these are being imported (excepting few

like Hepatitis B vaccine, Insulin etc.) and consumed and now several are underway for indigenous production

Globally approved recombinant therapeutics are broadly categorized into blood factors, hormones, growth factors, interferons, interleukins, vaccines and other miscellaneous therapeutic products

Some approved Therapeutics

The products of rDNA technology Hormones
Growth hormone, Insulin, Calcitonin, FSH

Cytokines
Interferons (Interleukins),

EPO,

CSF,

Neurotrophic factors

Clotting factors
Factor VIII, Factor IX

Vaccines
Hepatitis B, acellular pertussis vaccine

(Bordatella pertussis, whooping cough)

Monoclonal antibodies

Commercial production of Therapeutics

The commercial production of recombinant Biologicals and therapeutics now became an important area in global industralization
The process developed in production of therapeutics has to be taken to industrial scale for implementing these developed process in industrial scale and to get viable industrial production of these therapeutics or biologicals mainly through Fermentation technology

Pilot scale Fermenter

Insulin - first recombinant protein to be produced

Insulin is an important hormone which regulates

sugar metabolism An inability to produce insulin results in a form of diabetes, this disease can be treated by daily injections of insulin Historically, insulin from pigs or cows is used, but known to produce immune reactions in some patients Challenge: how to make human insulin to be used as a drug in cell systems or microbes?

Recombinant Insulin overcome many problems

Idea: take the gene of human insulin, clone into a

plasmid, introduce the plasmid into E. coli or cells, and use them E.coli as Biological Factory for insulin production
Amino acid sequence produced insulin (Contains 51

amino acids) and is identical to that of the natural human protein and it will not cause any immune reactions
Much more economical than attempts to produce

insulin by chemical synthesis

Owen Mumford Ltd., UK

History of Penicillin
- Modern era of antibiotic discovery - Inhibiting the formation of peptidoglycan cross-links in the bacterial cell wall : Inhibition of DD-transpeptidase

Penicillin G (Benzyl penicillin) R = benzyl group

Biosynthesis of Penicillin G in Fungus

Discovery and development

Alexander Fleming was trying to isolate the bacterium, Staphylococcus aureus by growing it on the surface of nutrient at St. Marys Hospital in 1928 : Breakthrough in antibiotic history

- He noticed that no bacteria grew near the invading substance in the contaminated plate. : Meaningful finding, not a failed experiment - He thought the cell killing must be due to an antibacterial agent - Identification of foreign particles as common mold of the Penicillium genus (later identified as Penicillium notatum) - Recovery of a tiny quantity of secreted material using the crude extraction methods - Secreted material : powerful antimicrobial activity and named penicillin - The discovery laid essentially dormant for over a decade
World War II resurrected the discovery : desperate demand an antibiotic

with minimal side effects and broad applicability Howard Florey and Ernst Chain of Oxford : rebuilt on Flemings observation

Human growth hormone (hGH, or Somatotropin)

Secreted by the pituitary gland, and is responsible

for normal body growth and development, by stimulating protein production in muscle cells, energy release from the breakdown of fats and stimulates the development of bones
These processes together are responsible for

longitudinal growth. Inadequate production of GH results in short stature, defined as a below normal height for a given age

 In children and adolescents, the rate of growth in height is primarily determined by the rate at which endogenous GH is secreted The growth spurt during puberty is caused by increased secretion of GH Under normal conditions, GH secretion and growth rate remain increased until final height

is reached, after which GH secretion is reduced to a steady state

Production of hGH
Purification of recombinant human growth hormone (rhGH) from Chinese hamster ovary (CHO) cell culture supernatant by Gradiflow large-scale electrophoresis is described. Production of rhGH in using E. coli as an alternative for using CHO cells, with the advantage that rhGH is secreted into protein-free production media, facilitating a more simple purification and avoiding resolubilization of inclusion bodies and protein refolding. proteins

Erythropoietin
Human Eryhtopoietin is produced in kidney

A glycoprotein, acts on the bone marrow to increase the production of red and white blood cells. Stimuli such as bleeding or moving to high altitudes (where oxygen is scarce) trigger the release of erythropoietin
Known as EPO, MW 30400 Kda, 165 amino acids in human (192 Mouse) Has been widely used development of immunity

in

AIDS

for

Kidney is the principal production site of Erythropoietin

Bones like Femur, Tibia, Vertebra, Sternum, Rib produce most RBC and WBC under the influence of EPO

When EPO is produced When RBC count comes down (Oxygen level decreases) in the blood

It will result in
Kidney cells specifically sense the oxygen deficit in the blood and start producing Erythropoietin

EPO also has therapeutic Abuses

Used in sports to improve endurance Now detected from naturally occurring EPO by protein markers produced during post injection phase

Biotherapeutics are delicate drugs

Much

larger and more complex than traditional pharmaceuticals of unstable with a precise

Composed

proteins structure
Easily

damaged by unfavorable temperature history during storage

Even insulin has temperature problems

Insulin Shelf-life

Insulin

Months

is a very temperature stable biotherapeutic

1000 100 10 1 0.1 -20 0 20 40 60 Temperature (C)

A graph of storage life vs

temperature shows saw tooth peak

The product dies at both

temperature extremes

Effect of temperature storage extremes o o

<0 C >8 C

Freezing Protein denaturation Formation of aggregates Loss of functional activity Formation of potentially hazardous immunogenic byproducts

Chemical side reactions Protein denaturation Formation of aggregates Loss of functional activity Formation of potentially hazardous immunogenic byproducts