GENERAL PHARMACOLOGY

Jyotiranjan Roul
(Whatsapp: 9028329566, 7020129690)
OBJECTIVES
At the end of this chapter the students will be able to:
• Define various terminologies used in Pharmacology.
• Know about nature and sources of drugs.
• Know routes of drug administration
• Understand pharmacodynamics like mechanism of drug action,
dose relation ship and pharmacokinetics like absorption,
distribution, metabolism and excretion (ADME) of drugs.
• Understand theoritical pharmacokinetics like half-life, order of
kinetics, steady state plasma concentration.
• Understand drug safety and effectiveness like factors affecting drug
action and adverse drug reactions.
WHAT IS PHARMACOLOGY?
• Pharmacology is a branch in science which deals with the effects of
drugs on living organisms/ living systems (pharmacodynamics) and the
effects of living organisms with drugs (pharmacokinetics).
• The term pharmacology is derived from the Greek word ‘Pharmakon’
means ‘Drug’ and ‘logus’ means ‘science’.
• Pharmacology can be defined as science which deals with Mechanism
of action, therapeutic uses, adverse effects of drugs and their fate in
body.
• Pharmacology includes drug composition and their properties, drug
interactions (drug-drug interactions, drug-food interactions),
toxicology, therapy, and clinical uses.
• Pharmacology is subdivided into two categories:
• Pharmacodynamics
• Pharmacokinetics
• PHARMACODYNAMICS:
Pharmacodynamics means what the drug does to the body.
Examples: Drug Actions, Therapeutic Effects, Adverse drug
effects.
• PHARMACOKINETICS:
Pharmacokinetics means what the body does to the drug.
Examples: Absorption, Distribution, Metabolism, Excretion.
• SOME IMPORTANT HONOURS IN FIELD OF PHARMACOLOGY.

• Father of Pharmacology: Oswald Schmiedberg

• Father of Indian Pharmacology: Col. Ramnath Chopra
• Father of Modern Pharmacology: Sir James Black
• Father of chemotherapy: Paul Ehrlich
• Father of Material Medica: Dioscorides
• Discovery of insulin ( in 1921): Banting and Best
• Discovery of penicillin: Alexander Fleming
• Discovery of streptomycin: Selman Abbraham Waksman
• WHAT IS THE NEED TO STUDY PHARMACOLOGY IN MEDICAL
FIELD?

• To screen the drug for getting desired active drug

• To find out the mode of action/ mechanism of action of drugs
• For quantification of drug activities
• To provide preclinical data which is essential for human study
• To determine potency (bioassay) of drugs
• For research and development of new molecules as well as old
drugs
• DEFINE DRUG. MENTION ITS USES.
• According to WHO, Drug is any substance or product that is used or intended to
be used to modify or explore physiological systems or pathological states for the
benefit of the recipient.
• They are used for prevention, diagnosis and treatments of diseases.
• Prevention:
• BCG vaccine is used for prevention of TB
• Propranolol is used for migraine prophylaxis
• Diagnosis:
• Barium meal examination is used for Peptic ulcer diagnosis.
(A Barium Meal is an x-ray examination of the upper gastrointestinal tract. It involves swallowing a liquid contrast called
barium which coats the lining of the oesophagus (gullet), stomach and small intestine so that it can be seen on x-rays.)
• Edrophonium is primarily used as a diagnostic tool for myasthenia gravis.
• Treatment:
• Antibiotics are used for microbial infections
• Anti-tb drugs are used for treatment of TB
• Analgesics are used to relieve pain
• Antipyretics are used to relieve fever
• MENTION BRANCHES OF PHARMACOLOGY AND WRITE THEIR APPLICATIONS.
• Pharmacodynamics
• Pharmacodynamics means what the drug does to the body.
• It deals with interactions of drugs with receptors present in the body.
• It includes the study of drug actions, therapeutic effects, and adverse drug
effects.
• Example: Acetylcholine binds with muscarinic receptor (M2) present in heart and
decreases heart rate and force of cardiac contraction.
• Pharmacokinetics
• It is the branch of pharmacology concerned with the movement of drugs within
the body.
• Pharmacokinetics deals with the four stages of drugs/chemicals passing through
the body: absorption, distribution, metabolism and excretion.
• Absorption: The process of movement of drug from its site of administration
to the systemic circulation is called as absorption.
• Distribution: Drug distribution refers to the movement of a drug to and from
the blood and various tissues of the body (for example, fat, muscle, and brain
tissue). In other words, distribution means the pattern of scattering of drugs
to different body tissues. Drugs are generally distributed through various
body fluid compartments such as (a) plasma (b) interstitial fluid compartment
(c) transcellular compartment.
• Metabolism/ Biotransformation: Metabolism of drug means chemical
alterations/changes of drugs in the body by enzymes. Major site of drug
metabolism is liver. Other sites are: kidney, git etc.
• Excretion: Drug excretion means the removal of unaltered/altered form of
drug out of the body. The major routes are renal, hepatobiliary and
pulmonary. The minor routes of excretion are saliva, sweat, tears, breast milk,
vaginal fluid, nails and hair. The rate of drug excretion affects its duration of
action. The drug that is excreted slowly has longer duration of action.
• Toxicology
• It is the study of poisonous effect of drugs and other chemicals. It
includes detection, prevention and treatment of poisonings.
• Drug toxicity occurs if drug is administered above the therapeutic
doses or drug is used for prolonged period.
• It also can occur if kidneys are unable to excrete the drug. Drug toxicity
may be reversible or irreversible, depending upon the organs affected.
• Example of reversible toxicity includes liver toxicity due to paracetamol
overdose/prolonged use, whereas example of irreversible toxicity
includes permanent hearing loss (due to 8th cranial nerve damage)
because of excessive use of streptomycin.
• Pharmacovigilance
Pharmacovigilance is the pharmacological science relating to
the
• Detection
• Assessment
• Understanding and
• Prevention
of adverse effects, particularly long term and short term side effects of medicines.
Generally speaking, Pharmacovigilance is the science of
• Collecting
• Monitoring
• Researching
• Assessing and
• Evaluating
information from healthcare providers and patients on the
adverse effects of medications, biological products, herbalism
and traditional medicines with a view to
• Identifying new information about hazards associated with
medicines
• Preventing harm to patients
• Chemotherapy
• Chemotherapy is the treatment of cancer) with specific drugs/chemical
agents which have selective toxicity for the cancer cell with no/minimal
effects on the host cells. Examples: Methotrexate, Cyclophosphamide,
Carmustine, Lomustine.
Clinical Pharmacology
• Clinical Pharmacology is the scientific study of drugs (both old and new)
in man. It includes pharmacodynamics and pharmacokinetics studies in
healthy volunteers and in patients.
• Clinical Pharmacology is the scientific discipline that involves all aspects
of the relationship between drugs and humans.
• Its breadth includes the discovery and development of new drugs, the
application of drugs as therapeutic agents, the use of drugs, the
beneficial and harmful effects of drugs in individuals and society, and the
• Clinical Trials
• Clinical trial is systematic study of pharmaceutical products on
human subjects (whether patients or non-patient volunteers) in
order to discover or verify the clinical, pharmacological
(pharmacodynamics / pharmacokinetics), and / or adverse
effects, with the object of determining their safety and / or
efficacy.
• Before a new drug comes to the market, it is largely tested in
animals and in vitro studies (in laboratory) for safety and efficacy.
If the drug is found to be promising in these studies, an
application called IND (Investigational New Drug) is filed with the
United States Food and Drug Administration. If the permission is
granted, then drug is tested in humans. This testing is called
• Therapeutics
• It is the branch of pharmacology that deals with the art and
science of treatment of disease.
• It is the application of pharmacological information together
with the knowledge of disease, for the prevention and cure of
the disease.
• Pharmacy
• Pharmacy is the branch of Pharmacology and is the art and
science of compounding by dispensing drugs, preparing
suitable dosage form for administration to man and animals.
The health profession blends health science with chemical
science and effective use of drugs.
• Pharmacogenetics

• It is the branch of pharmacology dealing with the genetic variations

that cause difference in drug response among individuals or
population.
• Example includes succinyl choline which is a skeletal muscle relaxant
used in general anasthesia.
• It is metabolized by pseudocholine esterase and has short duration of
action. The presence of enzyme is determined by the gene and lack of
this is recessively inherited. This may lead to respiratory paralysis,
apnea and death.
• Pharamcogenomics
• Pharmacogenomics is the broader application of genomic
technologies to new drug discovery and further
characterization of older drugs.
• Recombinant DNA technology involves the artificial joining of
DNA of one specie to another.
• E. coli is mostly used. In this way we can get huge amounts
of drug in purified form which is less antigenic. Examples
include GH, interferon and vaccines.
DIFFERENT NOMENCLATURES OF DRUGS
• There are generally 4 categories of drug names.
• Chemical name/ scientific name of drugs: It describes the exact chemical
makeup of the drug and placing of atoms and molecular structures of drug.
Example: N-(4-hydroxyphenyl) acetamide
• Non-proprietary name/ Generic name of drugs: It is the name accepted by a
competent scientific body/authority. It is the name provided to a drug before it
becomes official. Example: Diazepam
• Official name of drugs: It is the name that listed in USP-NF. It is similar to generic
name. Example: Diazepam
• Proprietary (Brand/ trade) name of drugs: It is the name assigned by the
manufacturer and is his property or trade mark. One drug may have multiple
proprietary/brand/trade names depending on the number of manufacturers.
Example: Crocin
• DIFFERENT SOURCES OF DRUGS
• PLANT SOURCE:
• Plant source is the oldest source of drugs. Most of the drugs in ancient times
were derived from plants. Almost all parts of the plants are used i.e. leaves,
stem, bark, fruits and roots.
• Leaves:
• Atropine is derived from atropa belladonna.
• The leaves of digitalis Purpurea are the source of digitoxin and digoxin,
which are cardiac glycosides used for the treatment of congestive cardiac
failure.
• The leaves of eucalyptus give eucalyptus oil, which is used in cough syrup.
• The leaves of tobacco provide nicotine.
• Flowers:
• Poppy seeds (papaver somniferum) provides morphine which is an opoid.
• Vinca rosea gives some natural anticancer drugs like vincristine and vinblastine.
• Fruits:
• Calabar beans give physostigmine, which is cholinomimetic agent.
• Senna pod gives anthracine, which is a purgative (used in
constipation).
• Seeds:
• Castor oil seeds give castor oil.
• Calabar beans give Physostigmine, which is a cholinomimetic drug.
• Seeds of Nux Vomica give strychnine, which is a CNS stimulant.
• Roots:
• Ipecacuanha root gives Emetine, used to induce vomiting as in
accidental poisoning. It also has amoebicidal properties.
• Rauwolfia serpentina gives reserpine, a hypotensive agent.
• Bark:
• Cinchona bark gives quinine and quinidine, which are
antimalarial drugs. Quinidine also has antiarrythmic properties.
• Atropa belladonna gives atropine, which is anticholinergic.
• Hyoscyamus Niger gives Hyosine, which is also anticholinergic.
• Stem:
• Chondrodendron tomentosum gives tuboqurarine, which is skeletal
muscle relaxant used in general anesthesia.
• ANIMAL SOURCES:
• Insulin, used in treatment of Diabetes mellitus is secreted from pancreas.
• Human chorionic gonadotropin (hCG) used for the treatment of infertility, is
derived from urine of pregnant women.
• Sheep thyroid is a source of thyroxin.
• Cod liver oil is used as a source of vitamin A and D.
• Anterior pituitary is a source of pituitary gonadotropins, used in treatment of
infertility.
• Blood of animals is used in preparation of vaccines.
• Stomach tissue contains pepsin and trypsin, which are digestive juices used in
treatment of peptic diseases in the past.
• MINERAL SOURCES:
• Metallic and Non metallic sources:
• Iron is used in treatment of iron deficiency anemia.
• Mercurial salts are used in Syphilis.
• Zinc is used as zinc supplement. Zinc oxide paste is used in wounds and in
eczema.
• Iodine is antiseptic. Iodine supplements are also used.
• Gold salts are used in the treatment of rheumatoid arthritis.
• Miscellaneous Sources:
• Fluorine has antiseptic properties.
• Borax has antiseptic properties as well.
• Selenium as selenium sulphide is used in anti dandruff shampoos.
• Petroleum is used in preparation of liquid paraffin.
• SYNTHETIC/ SEMI SYNTHETIC SOURCES:
• Synthetic Sources:
• When the nucleus of the drug from natural source as well as its chemical
structure is altered, we call it synthetic. Examples include Aspirin, diazepam.
• Semi Synthetic Source:
• When the nucleus of drug obtained from natural source is retained but the
chemical structure is altered, we call it semi-synthetic. Examples include
Apomorphine, Diacetyl morphine, Ethinyl Estradiol, Homatropine, Ampicillin and
Methyl testosterone.
• MICROBIOLOGICAL SOURCES:
• Penicillium notatum is a fungus which gives penicillin.
• Actinobacteria give Streptomycin.
• Aminoglycosides such as gentamicin and tobramycin are obtained from
streptomycis and micromonosporas.
• RECOMBINANT DNA TECHNOLOGY:
• Recombinant DNA technology involves cleavage of DNA by enzyme restriction
endonucleases.
• The desired gene is coupled to rapidly replicating DNA (viral, bacterial or
plasmid).
• The new genetic combination is inserted into the bacterial cultures which allow
production of vast amount of genetic material.
• Advantages:
• Huge amounts of drugs can be produced.
• Drug can be obtained in pure form.
• It is less antigenic.
• Disadvantages:
• Well equipped lab is required.
• Highly trained staff is required.
• WRITE SHORT NOTE ON ESSENTIAL MEDICINES.
•
• Essential medicines are those medicines, which satisfy the priority health care needs of the population.
• These are drugs which are intended to be available within the context of functioning health systems at
all times in adequate amounts, in the appropriate dosage forms, with assured quality and adequate
information, and at a price the individual and the community can afford.
• They are selected with due regard to public health relevance, evidence on efficacy and safety, and
comparative cost-effectiveness.
• The concept of essential medicines is forward-looking. It incorporates the need to regularly update
medicines selections to reflect new therapeutic options and changing therapeutic needs; the need to
ensure drug quality; and the need for continued development of better medicines, medicines for
emerging diseases, and medicines to meet changing resistance patterns.
• List of some essential medicines include:
• Isoflurane
• Nitrous oxide
• Oxygen
• Lidocaine
• Acetylsalicylic acid
• Ibuprofen
• Paracetamol
• WRITE SHORT NOTE ON ORPHAN DRUGS.

• Orphan drugs are used for diagnosis, prevention or treatment of life-threatening or very serious
diseases or very rare disorders/diseases. These are named “orphan” because pharmaceutical
industry has little/no interest in developing and marketing these drugs, which are meant for only a
small number of patients. For these companies, high cost of bringing these products to market
would not be recovered by the sales of the products.
• These are not developed by the pharmaceutical industry for economic reasons but which respond
to public health need.
• Examples of some rare diseases include:
• Acromegaly
• Acquired hemophilia A
• Alpha-thalassemia
• Amyotrophic lateral sclerosis
• Anaplastic thyroid cancer
• Aplastic anemia
• Anthrax
• Kaposi sarcoma
• Examples of some orphan drugs include:
• Octreotide: (Brand name: Sandostatin LAR) - Manufactured by Novartis used in
treatment of acromegaly.
• AbobotulinumtoxinA (Brand name: Dysport) - Manufactured by Ipsen Limited
used in treatment of cerebral palsy
• Clofazimine (Brand name: Lamprene®) - Manufactured by Novartis
Pharmaceutical Corporation. FDA-approved for treatment of lepromatous
leprosy.
• Thalidomide (Brand name: Thalomid) - Manufactured by Celgene Corporation.
FDA-approved for acute treatment of the cutaneous manifestations of moderate
to severe erythema nodosum leprosum.
• Cladribine (Brand name: Leustatin (injection)) - Manufactured by Ortho Biotech.
FDA-approved for the treatment of hairy cell leukemia.
• Moxetumomab pasudotox (Brand name: Lumoxiti) - Manufactured by
AstraZeneca Pharmaceuticals LP. FDA-approved for the treatment of adult
patients with relapsed or refractory hairy cell leukemia (HCL).
• Pentostatin for injection (Brand name: Nipent®) - Manufactured by SuperGen,
Inc. FDA-approved for treatment of alpha-interferon-refractory hairy cell
leukemia.
• Capsaicin (Brand name: Qutenza) - Manufactured by NeurogesX, Inc.
FDA-approved for management of neuropathic pain associated with postherpetic
neuralgia.
• Paclitaxel (Brand name: Taxol) - Manufactured by Bristol-Myers Squibb Co.
FDA-approved for the second line treatment of AIDS-related Kaposi's sarcoma.
• Brentuximab vedotin (Brand name: Adcetris) - Manufactured by Seattle
Genetics, Inc. FDA-approved for the treatment of adult patients with previously
untreated Stage III or IV classical Hodgkin lymphoma (cHL), in combination with
chemotherapy.
• Nivolumab (Brand name: Opdivo) - Manufactured by Bristol-Myers Squibb Co.
FDA-approved for the treatment of adult patients with Classical Hodgkin
lymphoma.
• Halofantrine (Brand name: Halfan™) - Manufactured by GlaxoSmithKline.
FDA-approved for the treatment of adults who can tolerate oral medication and
who have mild to moderate malaria caused by Plasmodium falciparum or
Plasmodium vivax.
• Tafenoquine (Brand name: Krintafel) - Manufactured by GlaxoSmithKline
FDA-approved for the radical cure (prevention of relapse) of Plasmodium vivax
malaria in patients aged 16 years and older who are receiving appropriate
antimalarial therapy for acute P. vivax infection.
• Mefloquine HCl (Brand name: Lariam) - Manufactured by Hoffmann-La Roche, Inc.
FDA-approved for the treatment of acute malaria due to Plasmodium falciparum
and Plasmodium vivax.
• Eculizumab (Brand name: Soliris) - Manufactured by Alexion Pharmaceuticals, Inc.
FDA-approved for the treatment of adult patients with generalized Myasthenia
Gravis (gMG) who are anti-acetylcholine receptor (AchR) antibody positive.
• DESCRIBE PRODRUG IN DETAIL.
•
• The term prodrug is usually applied to compounds/ drugs those are inactive in
their parent form(s) but which, after administration, are chemically transformed
to the active derivative.
• They are chemically modified inert compound which upon administration
releases the active parent drug to elicit its pharmacological response within the
body.
• In most cases, prodrugs contain a promoiety (linker) that is removed by
enzymatic or chemical reactions, while other prodrugs release their active drugs
after molecular modification, such as an oxidation or reduction reactions.
• Prodrugs are often designed to improve bioavailability when a drug itself is
poorly absorbed from the gastrointestinal tract.
• Several pharmacokinetic reasons exist for developing prodrugs:
• To achieve more complete or predictable absorption of the drug.
• To reduce incomplete and variable systemic bioavailability by preventing extensive
presystemic metabolism.
• To improve access to the site of action, e.g. penetration of the blood-brain barrier.
• To activate selectively a drug in the intended target tissue, thus avoiding undesirable
systemic effects.
• To optimise either the rate of onset or duration of action of a drug by improving
absorption, distribution or elimination characteristics.
• Applications of prodrugs:
• Improvement of bioavailability by alteration of drug's solubility.
• Prodrugs for site selective drug delivery.
• Prolongation of action.
• Minimizing toxicity.
• Protection from presystemic metabolism.
• Examples of prodrugs include:
• Carbimazole(inactive) ---- Methimazole (active)
• Chloramphenicol palmitate (inactive)---- Chloramphenicol (active)
• Cortisone(inactive) ---- Hydrocortisone(active)
• Dipivefrine(inactive) ---- Epinephrine(active)
• Enalapril (inactive)---- Enalaprilat(active)
• Estradiol sulfamate (inactive)---- Estradiol (active)
• Fosphenytoin (inactive)---- Phenytoin (active)
• Levodopa (inactive)---- Dopamine (active)
• Mercaptopurine(inactive)----Methylmercaptopurine(active)
• Minoxidil(inactive) ---- Minoxidil sulphate (active)
• Prednisone(inactive)---- Prednisolone (active)
• Pivampicillin(inactive)---- Ampicillin(active)
• Prontosil (inactive)---- Sulfanilamide (active)
• Vanciclovir (inactive)---- Aciclovir (active)