Friday, June 13, 2008

Source and Composition of Drugs

Sources and composition of drugs


Most drugs currently used in veterinary practice are synthesized by the organic chemist, screened and tested by the pharmacologist &toxicologist, prepared in suitable dosage form by the pharmaceutical chemist, evaluated by the clinical investigator, and marketed by pharmaceutical company.

Classification of drugs:

1. Drugs classification basing on source (source of drugs).
A. Natural Sources: I. Vegetable/ plant drugs.
II. Animal drugs. .
III. Microbial drugs.
IV. Mineral drugs.
B. Synthetic & semi synthetic drugs.
Vegetable Drugs

Plate kingdom offers a variety of pharmacologically active principles. The ancient Hindu literature and the oldest system of medicine “Ayurveda” recognized the medicinal value of several plant preparations. Important drugs like Digitalis, reserpine, morphine, quinine, atropine, curare, etc., all were originally obtained from plants. Even today, plants continue to remain as one of the major source of drugs. The medicinal value resides in all parts of plant;, however, the concentration of the active principle varies in different parts—seeds, flowers, leaves, bark, roots, rhizomes and bulbs forms important sources of several drugs. Active principles obtained from plants are,

(1) Alkaloids: Basic nitrogenous substances, which are insoluble in water, but form, water soluble salts with acids. Higher concentrations found in seeds & roots, Alkaline in reaction, intensely bitter to taste. Potent poisons leaving no post mortem changes. Salts of heavy metals, Iodine, and tannic acid precipitate these. Name of the alkaloid ends with “ine”, like, Morphine, Atropine, Emetine, Nicotine, strychnine, and reserpine.

(2) Glycosides: are various sugars combined with organic structures through an ether- like linkage. Sugar part is called Glycon and the enzyme hydolysis these two will breakout. Pharmacological action resides in a glycon and the sugar influences the solubility and permeability of the glycosides. These compounds are neutral and will not form salts, soluble in alcohol but not in water. Eg. Digoxin, Ouabain, Linamarin. Amygdalin. Words end with letters “in”.
Some glycosides following enzyme hydrolysis produce HCN—called Cyanogentic glycocides. Jawar, Yougst. Cardiac glycosides: specific action on heart. Digitalis.

(3) Saponins: Non-nitrogenous substances soluble in water and capable of causing foam/ froth when shaken with water. Upon hydrolysis they split into a sugar part and a non-sugar part (sapogenin) quilla senega like glycosides, hence considered as a sub – class of glycosides. Used as emulsifiers (quillaria).

(4) Tannins: are non-nitrogenous substances having a characteristic astringent action upon the mucosa by precipitating the proteins (Astringent action). Tannins are soluble in water Eg. Catechu, Kino, Galls.

(5) Resins: Brittle, amorphous compounds formed from the oxidation or polymerization of terpenes, components of volatile oils. They are insoluble in water, but soluble in organic solvents.Eg., Podophyllum resin, jalap.

(6) Oleoresins: Mixtures of volatile oils and resins. Eg. Terpentine oil, male fern extract.

(7) Neutral Principles: Active principles of plants not conforming to any of above composition not known, bitter in taste. Aloin , santonin.

(8) Oils: Two types (i) Fixed oils (ii) volatile oils
(i) Fixed oils: Are gycerides of oleic, palmitic and stearic acids. These have food values. Stable will not evaporate when exposed to air. Eg. Castor oil, linseed oil, peanut oil.
(ii) Volatile oil: They will evaporate readily and have a characteristic odor. Are also called as aromatic essential, ethereal or flavoring oils. These are used for different purposes.
Carminative: eucalyptus oil, turpentine oil.
Antiseptics: peppermint oil
Counter irritants: turpentine oil,
Analgesics: oil of wintergreen, oil of clove.
Flavoring agent: peppermint oil


Fixed oils
Volatile oils
1. Extracted or expressed from fruits/ seeds
1.Distilled by steam distillation, plants, leaves, flowers are used.

2. Liquids at room temp., solidify on cooling.
2.remain liquid even on cooling. Some are solid on room temp. Camphor, menthol

3. Insoluble in water, soluble in alcohol. Chloroform, ether.

3. Slightly soluble in water, miscible in fixed oils, soluble in alcohol, chloroform.
4. Form soap with alkalis and metallic oxides.

4. No soaps
5. Decompose and becomes rancid on heating

5.no tendency to become rancid
6. Lubricant properties
6. Not
7. Leave a grease spot on paper
7. Not
8. Acts as nutrients & emollientliquid esters of higher fatty acids (oleic, palimitic & stearic and glycerin.

8. No nutrient or emollient properties. Composition of volatile oils consists mostly of liquid hydro- carbon called terpens or pinins.



9. Gums: Polysaccharides secreted by certain trees and capable of forming thick mucilaginous colloids when mixed with water. These are pharmacologically inert and used as suspending or emulsifying agents and stabilize mixtures of other active drugs in liquid dosage forms. Eg. gum acacia, gum arabic, gum tragacanth.

10. Oleo gum resins: mixture of gum, resin & volatile oil. Obtained as exudates from plants asafetida, myrrh.

11.Balsams: Resins containing Benzoic or cinnamon acid. They have agreeable odor. Balsam of Tolu: skin dressings, Balsam of Peru: used in cough.

Animal Drugs

Liver, endocrine glands and secretary organ of animals are used to extract active constituents.

i. Hormones: Posterior pituitary extract Insulin, Thyroxin, Gonadotrophins.
ii. Vitamins: Cod or shark liver oils as rich source of vitamin A&D.
iii. Ontisera: Canine distemper, antisera, antisnake venom.
iv. Others: Heparin, Liver extract.

Microbial Drugs

Bacteria and fungi isolated from soil are the important sources of antibiotics. Eg. Penicillin, streptomycin, gentamicin, neomycin. The viruses and bacteria causing infectious diseases are also valuable in the preparation of vaccines. Dried yeast is an important source of B- complex vitamins.

Mineral Drugs

Many inorganic compounds are used in the treatment of a variety of disease states. Mag. Oxide-Antacid, Mag.Sul- purgative, pot.iodide- expectorant, pot.nitrate- diuretic, Fe.Sulfate- heamatonic.

Synthetic Drugs

Majority of drugs in the present day usage are of synthetic origin. The drugs, which are exclusively included under this source, are anaesthetizes, antiprotozoan drugs, antiseptics, tranquilizers, antiarrhythmies, antiarrhythmies.

With advancement of medical chemistry and the knowledge of structure activity relationship, several drugs of natural origin are chemically altered to produce new compounds with specific pharmacological actions. Such new drugs are called semi- synthetic drugs. Eg. Morphine derivatives, antagonists, Dihydrostreptomycin, semi synthetic penicillins.


Classification of drugs basing on chemical nature (composition of drugs)


A. Inorganic Drugs: a. Acids: Benzoic acid, acetic acid, salicylic acid.
b. Bases: sod. bi.Carb., Mag.hydroxide
c. Salts: NaCl, Mgo, Fe.Sulfate, CuSo4, CoCl.
d. Metals: Cu, Iron, and Zinc.
e. Metalloids: Arsenic, Antimony, and Phosphorus.
f. Non metals: - Halogens& Sulphar, water and oxygen.

B. Organic Drugs: a. Alkaloids: Morphine, atropine, nicotine.
b. Glycosides: digitoxin, gitoxin, amgdalin.
c. Saponin: quillaria.
d. Tanins: catechu,
e. Resin: podophyllum
f. Oleoresins: turpentine oil
and, Gums, Oils, Enzymes and Hormones

Whole herb – chirrata
Root -- gention, asafoetida, aconite
Bark--- cinchona
Stem or modification---- Rhizome – Rubarb, Ginger
Squill -- bulb

Gums & Resins
Leaves—Belladona, Digitalies.
Flowers – Santonin, canmodies indica,
Seeds -- Nurvomica, castor oil.
Fruits-- Citrus, Capsicum, PIPPER.

Lecture Notes

History And Scope Of Pharmacology - Definitions - Pharmacopoeias

The discovery of drugs was undoubtedly through the trial and error as people tried various plant, animal and mineral substances in their environment as potential sources of food. The earliest compilation of drugs was the Chinese herbal The Pen Tsao written by Emperor Shennung in about 2700B.C. Veterinary & human medicine were well developed in Asia-minor during antiquity. The code of Hammurabi (about 2200B.C.) described penalties for malpractitioners.

The oldest record of Egyptian drug codification is the Kahun Papyrus 2000B.C. It deals with veterinary medicine & uterine disease of women and contains a number of prescriptions.

The Ebers Papyrus (1550B.C) is a compilation of a number of disease conditions and 829 Prescriptions for medicaments employed in Egyptian medicine. The codified drug lore of Egypt was transmitted to Greek civilization.

Hippocrates; Foremost among early Greek physicians teacher formed a group of physicians known as Hippocratic school. There were astute diagnosticians and brilliant surgeons and maintained high ethical standards.

They had little use of drugs, as they recognised that sick people usually tended to get well regardless of treatment. This concept of the healing power of nature became known as the “Vis Medicatrix Nature”. A perfect from the Hippocratics school, which still provides an ethical basis for practice of therapeutics is “Above all, do no harm” both these relearned again throughout subsequent history. The four element of natural philosophy were water, fire, air and earth, combinations of these elements gave rise to four humors of the body related to scale of life from most alive to death. Treatment consisted of attempting to balance these humors by replenishment of bleeding, purging (including vomiting and sweating), which continued well into 19th century.

Scientific basis for medicine was begun by Aristotle (384-322B.C.), who made and recorded numerous observations on animals. His student Theophrastus classified medicine plants on the basis of charactristics rather than use in treatment.

Dioscorides: surgeon with armies of Nero, who compiled first meteria medica, 6 volumes described about 600 plants. Drugs were discussed from the standpoint of name, source, identification; test for adulteration, preparation of the dosage form, what it would do, and for what condition it would be used. This contribution was important because it established the framework for later pharmacopoeias.

Works of Galen (131-201); dealing physiology & meteria medica and were used widely for the next 1400 years.

With decline of Rome Empire scholarship transferred to Byzantium where during the 5th century, Publius Vegetius complied a veterinary treatise that included prescription for farm animals.

Following the fall of Rome, Europe entered into dark ages. Custodians of knowledge and developers of medical thought during this period were found in Muslim culture. They developed the practice of pharmacy to a high level and were the first to distil wines and beers to obtain ethanol for preparing tinctures. Also they were the first to regulate the practice of pharmacy to standardize the preparation of prescriptions.

Geber Ibn Hazar (702-765): An influential Persian writer, classified drugs and poisons of his time, recognized that the difference between drugs & poisons was a matter of dosage. Any drug is poison if given large enough amounts.

Europe: During renaissance, the first pharmacopoeia was compiled by the German Valrius Cordus (1514-1544), carefully described techniques to be employed in preparation of drugs in marked contrast to the secrecy prevailing prior to his time. Opium (laudanum) introduced in clinical use by Paracelsus.

17th&18th centuries were the era of nationalism and flowering individual genius. Drugs trade flourished and medical experiment begun. Drugs such as Cinchona (quinine), coffee, tea, cocoa, curare, digitalis and variety of alkaloids were discovered.

John Hunter: conducted controlled clinical experimentation.

William Withering: an account of Foxglove and some of its medical uses. His observations on the use of digitalis in the treatment of dropsy are still pertinent.

Edward Jennor: Principles of prophylactic Immunization against smallpox described Anaphylaxis and set the stage for later development of preventive medicine, immunology therapy.

William Harvey: circulation of blood.

Christopher Wren (1623-1723): first I/V injection of drugs into dog

Alexander Wood (1853): hypodermic needle & syringe. This has major influence on later pharmacological experimentation.

During this period scientific societies developed as scientific information was disseminated. Pharmacopoeias well developed and principal sources of information concerning drugs.

19th century:
Friedrich Serturner: German pharmacist isolated the specific narcotic substance from opium and named it Morphine after morpheus Roman god of sleep. This was followed rapid isolation of many alkaloids.

Francosis Magendie: and his pupil Claude Bernard & James Black established the foundations for modern pharmacology and outlined its unique scientific problems: MOA, dose response relationship, site of action etc. Rud Olph Bucheim at the university of Dorpat in Estonia established first labaratory for pharmacolgy.

Oswald Schmiedeberg: led in establishing pharmacology as an independent scientific discipline based upon experimental methodology.

John.J.Abel: regarded as father of pharmacology in U.S.A., founded journal of Biological Chemistry and journal of pharmacology & Experimental Therapeutics and was instrumental in the formation of American society of Pharmacology & Experimental Therapeutics (Abel, 1926).

L.Meyer: Jones was instrumental in shifting emphasis in the veterinary curriculum from material medica to the science of veterinary pharmacology. The decisive event in this transition was publication of the first edition of the textbook by Jones in 1954. That is veterinary pharmacology & therapeutics.

Scope of pharmacology:

Pharmacology: Pharmacology is an experimental science dealing with the properties of drugs and their effects on living systems. It has induced study of sources of drugs (pharmacognosy), action and fate in the body (pharmacodynamics), use in the treatment of disease (therapeutics), and poisonous effects (toxicology).

Drug: term derived from French word Drogue, meant herb. Articles intended to be used in the diagnosis mitigation, treatment, or prevention of disease in humans or other animals; and articles other than food intended to affect the structure or function of the body.

Pharmacodynamics: refers to study of the response of an organism to action of drugs in absence of disease.

Therapeutics: term described treatment of disease in general and includes use of drugs, surgery, radiation behavioral modification and other modalities.

Rational Pharmacotherapeutics: When we can seek out the reasons of drug action, eg. Adrenaline in Bronchial Asthma.

Empirical: In rare cases, we still fail to elicit pharmacological reasons of drug action, yet that particular drug is used successfully to cure. Eg. Colchicum for gout.

Pharmacokinetics: Defined as the mathematical description of temporal changes in concentration of drugs with in the body. Such studies provide the experimental basis for drug dosage regimens in various animals.

Veterinary Clinical Pharmacology: Study of drugs in animal patients. This functions at the interface between pharmacology and medicine to integrate pharmacological principles with knowledge of veterinary internal medicine. Controlled evaluation of the efficacy and safety of drug therapy in animal patients is a major concern of veterinary clinical pharmacology.

Chemotherapy: is a branch of pharmacology dealing with drugs that selectively inhibit or destroy specific agents of disease such as bacteria, viruses, fungi and other parasites. Use of this term has been extended to the use of drugs in treatment of neo plastic diseases. Drugs that are useful as chemotherapeutic agents affect the pathogen or abnormal cell more adversely than normal cells of host.

Toxicology: Recently defined as science that defines limits of safety of chemical agents to human and animal populations.

Posology: is a study of medicine dosage, which varies with the species of animals, the intended effects of drugs and individual tolerance or susceptibility.

Dose: quantity of medication to be administered at one time.

Dosage: determination and regulation of doses.

Metrology: study of weights and measures as applied to preparation and administration of drugs.

Pharmacy: is a separate and complementary health-care, profession, concerned with collection, preparation, standardization and dispensing of drugs.

Pharmaceutics: large-scale manufacture of drugs.
Pharmacist: The pharmacist is well equipped to advice the veterinary practitioner on matters relevant to drug dosage forms, incompatibilities, drug interactions and medicinal chemistry as well as to fulfill traditional role of compounding and dispensing appropriate dosage forms of drugs.

Materia Medica: is an absolute didactic subject that was concerned with pharmacy, posology, pharmacognacy and indications for therapeutic use of drugs. Latin word- medical materials, deals its source compositions, physical, chemical properties, incompatibilities, preparations, doses and indications for therapeutic.

This subject was purely descriptive in nature and has been replaced in the modern veterinary medical curriculum by the science of comparative pharmacology.

Pharmacopoeias: Drug compendia, reference resources, consisting of officially recognized drugs, gives information on source, properties, purity and its potency of recognized drugs & tests for their identity.

Official publication of drug standards:

United States pharmacopoeia (USP): legally recognized drug compendium for the USA. It is continuously revised by the US pharmacopoeia convention from 1940 onwards. It is now being revised for every 5 years.

National Formulary (NF): Published by the American pharmaceutical Association. It is served the need of pharmacists for standardization of certain pure drugs that were not used widely enough to be in the USP.
During 1975-80 revision period, the two publications were combined, USP and NF. USP and NF are derived their official status from the food and cosmetic Act of 1906 and was continued in the new Act of 1938.

The United States Dispensatory: is an encyclopedia work that includes general information 0n both old and new drugs found thought the world. It is non-official publication, drugs not included in pharmacopoeia.

I.P. : International Pharmacopoeia or Indian Pharmacopoeia.
B.P. : The British Pharmacopoeia
B.P.C. : British Pharmaceutical Codex.
B.N.F. : The British National Formulary.
N.N.D. : New And Non official Drugs.
ADR : Accepted Dental Remedies.
B.Vet. C.: The British Veterinary Codex.

The abbreviation of the Pharmacopoeia is written after the name of the drug (Tr. Iodine I.P.), i.e., Tri Iodine corresponding to the standard tincture iodine included under the Indian pharmacopoeia.

Other Sources of Drug Information:
Physicians Desk Reference (PDR)
American Medical Association Drug Evaluation.