WELCOME TO DEPARTMENT OF PHARMACOLOGY, NEIGRIHMS

Dr. D. K. Brahma MD (Pharma)

Asstt. Professor and in-charge

Department of Pharmacology

NEIGRIHMS

PHARMACOLOGY

AN INTRODUCTION

History

Pioneers of Medicine and Pharmacology:

• Hippocrates (450 B.C.)• Francois Magendie (1783 - 1855)• Claude Bernerd (1813 - 1878)• Rudolf Buchheim (1820 to 1879)

What is Pharmacology ?

• From the Greek Pharmacon (drug), logos (a discourse or treatise)

• Broadly defined as how chemical agents affect living processes:• Hormones• Neurotransmitters• Growth factors• Drugs (pharmaceuticals)• Toxic agents in the environment

…contd.

• The medicinal/organic chemists may create the candidate compound (sometimes referred to as a new chemical entity, NCE), it is the pharmacologist who is responsible for testing it for pharmacological activity.

• Ultimately will lead to the discovery of novel drugs for therapeutic intervention

What is a Drug?

• French: Drogue – a dry herb• A single active chemical entity present

in a medicine that is used for diagnosis, prevention and treatment of diseases

• WHO – in 1966 – “ Drug is any substance or product which is used or intended to be used to modify or explore physiological systems or pathological states for the benefit of the recipient.”

• Therapeutic or diagnostic benefits

…contd.

• Pharmacology studies the effects of drugs and how they exert their effects:• Paracetamol can reduce body

temperature in case of fever by inhibiting an enzyme known as cyclooxygenase in CNS, which is responsible for the synthesis of a number of inflammatory mediators.

• Penicillin cures certain bacterial infections by disrupting the synthesis of bacterial cell walls by inhibiting a key enzyme.

Physiology Biochemistry

Chemistry Medicine

Pharmacology

Pharmacology is the unique combination of several Biomedical Sciences!

Recommended Text Books

Text Book Author Edition

The Pharmacological Basis of Therapeutics

Goodman Gillman

11th Edition

Basic and Clinical Pharmacology

Bertram G Katzung

7th Edition

Essentials of Medical Pharmacology

K. D. Tripathi 6th edition,2008

Pharmacology and Pharmacotherapeutics

Satoskar and Bhandarkar

20th Edition

Branches of

Pharmacology• TWO MAIN BRANCHES - Pharmacokinetics &

PharmacodynamicsPharmacokinetics:(What Body does to Drugs?)

• Study the FATE of drugs once ingested and the variability of drug response in varying patient population

• Includes absorption, distribution, metabolism and excretion of Drugs

Pharmacodynamics:(What Drugs do to the Body?)

• Study the mechanisms by which Drugs act?• Also study endogenous agents

Relationship – Dynamics and Kinetics

Dosage Regimen

Concentration in Plasma

Concentration at the site of action

AbsorptionDistributionMetabolismExcretion

Pharmacokinetics

Pharmacodynamics

Effect

Branches of Pharmacology

Pharmacotherapeutics:

Use of Drugs for prevention and cure of diseases – clinical management of diseases

Pharmacy and Clinical Pharmacy

Definitions• It is the art and science of compounding and

dispensing drugs or preparing suitable dosage forms for administration of drugs in man and animals. It also includes identification, selection, collection, purification, isolation, standardization and quality control of medicinal substances.

• Clinical pharmacy is a health science discipline in which pharmacists provide patient care that optimizes medication therapy and promotes health, wellness, and disease prevention

Some Other Definitions

• Pharmacoepidemiology: Study of effect of Drugs on populations

• Pharmacoeconomics: Study of cost effectiveness of drug treatment; the cost of medications is of worldwide concern, particularly among certain groups such as elderly and AIDS patients

Definitions – contd.

• Chemotherapy: It is the branch of therapeutics which is concerned with the effects of drugs upon microorganisms and parasites, living or multiplying in a living organism. It also includes the drugs used in malignancy

• Pharmacognosy: is the science of identification of drugs

• Toxicology: is the science of poisons which includes detection and measurement of poisons as well as treatment of poisoning. Poisons are the substances causing harmful, dangerous or fatal symptoms in man and animals.

Definitions – contd.

• Pharmacopoeia:Pharmacopoeia: It is an official code containing a selected list of the established drugs and medicinal preparations with descriptions of their physical properties and tests for their identity, purity and potency. Define the standards of preparations. Examples- BP, USP, IP an EP

Definitions – contd.

• National Formulary:National Formulary: It is the book published as product information on drugs available to prescribers in respective countries

Examples – National formulary – BNF by BMA and PSGB

National Formulary of India is published by Govt. of India.

Definitions – contd.

• Martindale The Extra Pharmacopoeia: It is a voluminous database published periodically by The Pharmaceutical Press for Council of Royal Pharmaceutical Society of Great Britain• It contains concise reports on action and

uses of drugs available in most of the world.

Essential Medicines

• WHO defines – “Essential Medicines are those that satisfy the priority healthcare needs of the population. Essential medicines are intended to be available within the context of functioning health systems at all times and in adequate amounts, in appropriate dosage forms, with assured quality and adequate information, and at a price the individual and the community can afford.”

• 1977 – 1996 - 2003

Orphan Drugs

• These are the drugs or biological products for diagnosis, prevention and treatment of a rare disease or a more common disease (endemic only in poor countries) for which there is no reasonable expectation that the cost of developing and marketing will be recovered from the sale of these medicines.

• Examples: Rifabutin, Succimer, Fomepizole and liposomal amphotericin B etc.

Drug Nomenclature

1. Chemical Name – Chemical name and code name

• Describe substances chemically• For example - para-

acetylaminophenol2. Non-proprietary Name – USAN, BAN,

rINN, generic name.3. Proprietary Name (Brand Name) -

Manufacturer

Drug Nomenclature – contd.1. Chemical Name –

• Describe substances chemically• For example - para-acetylaminophenol

2. Non-proprietary Name – (USAN and BAN)

• PARACETAMOL

3. Proprietary Name – • Crocin, Calpol and ……..

(Similarly for aspirin …..)

Drug Nomenclature – contd.• Chemical Name – “N-(4-Nitro-2-

phenoxyphenyl) methanesulfonamide” [International union of Pure and Applied chemistry (IUPAC)]

• Non-proprietary Name – Nimesulide

• Proprietary Name – Nise, Nimulid …. etc.

Drug Nomenclature – New drug being developed1. Chemical Name or Code name –

RO 15-172882. Non-proprietary Name: Flumazenil(BAN, USAN and rINN) – approved

name/official name3. Proprietary name: Anexate,

Lanexat, Mazicon, Romazicon

Sources of Drugs

• Plant sources – Morphine, digoxin, quinine, atropine, reserpine , vinca alkaloids and paclitaxel.

• Animal sources – Insulin, Thyroid extract, heparin, gonadotrophins and antitoxic sera.

• Minerals – Liquid paraffin, magnesium sulfate, magnesium trisilicate, ferrous sulfate and kaolin.

• Micro – organisms – Bacteria and fungi – Penicillin, Streptomycin

• Synthetic – Analgesics, hypnotics, anticancer drugs and antimicrobials

• Genetic Engineering – Human insulin, growth hormone genes

• Hybridoma technique – monoclonal antibodies• origin

Plant Sources

• Alkaloids: Water soluble salts of water insoluble nitrogenous compounds

• Glycosides: Ether-like combination of sugar with other organic acids. Acid hydrolysis separates sugar from non-sugr moiety

• Oils: Glycerides of oleic, palmitic or stearic acids• Fixed oils: Peanut oil, coconut oil and castor oil• Volatile oils: Peppermint oil, ginger, eucalyptus oil

etc.• Resins: Oxidized or polymerized volatile oils• Oleoresins: Mixture of volatile oils and resins• Gums: Secretory products of plants

Opium Alkaloid Extraction

Routes of Drug Administration

Choices of Routes of Drugs

• Drugs may be acidic, basic, or neutral and come in a variety of chemical forms such as small organic molecules, large polymers such as proteins, carbohydrates and other compounds with complex chemistries• Physical and chemical properties of drug –

solid/gas/liquid or solubility, pH etc.• Site of desired action – localized or generalized• Effect of digestive juices and first pass metabolism of

drug• Accuracy of dosage required• Condition of the patient – unconscious, vomiting etc

Local Routes

1. Topical – External application of the drug to the surface for localized action, e.g. lotion, ointment, cream, powder, paints, and spray etc.

2. Deeper tissues – Certain deep areas can be approached by syringe and needle, e.g. intra-articular, intra-medullarly, intra-lesional injection, intrathecal and infiltration

3. Arterial supply – Closed intra arterial injection, e.g. angiography and anticancer drugs.

Routes - Enemata

• Application of medicaments into rectum• Two types:

• Evacuant enema: Mainly liquid form for local action e.g., soap water enema• Quantity of fluid 600 ml

• Retention enema: Mainly solid form meant for systemic action e.g., prednisolone enema

Systemic Routes – 1.Oral (enteral)ADVANTAGES:• Self medication possible

– no assistance required• Vast area of absorption• Simplicity of procedure – no

extra cost• Slow in action and hence

safe with some risky drugs• Both solid and liquid dosage

forms can be given

DISADVANTAGES:• Onset of action is tardy• Irritant and unpalatable

drugs cannot be administered

• Absorption is irregular with some drugs e.g. aminoglycosdes

• May induce nausea and vomiting

• Not useful in presence of vomiting and diarrhoea

• Can be destroyed by gastric juice – penicillin G, insulin

• Cannot be used in unconscious and uncooperative patient.

Oral Route – contd.

• Enteric coated: with acetate-pthalate, glutean and anionic polymers of methacrylic acid and its esters. • To prevent gastric irritation and alteration of

drug in stomach.• To achieve desired concentration of drug in

small intestine• To retard the absorption of drug

• Controlled release (CR): Timsules/Spansules• To provide uniform medication for

prolonged period

2. Sublingual

• Kept under the tongue or crushed and spread over the buccal mucosa

• Advantages: • rapid absorption – action in 1 minute• liver is bypassed – directly in systemic circulation • can spit out the drug• Unconscious patients

• Disadvantages:• Only lipid soluble drugs• Uncooperative patients• Irritation of mucosa

Drugs: GTN (Glyceryl trinitrate), Buprenorphine (Nifedepine)

3. Rectal

• Irritant and unpleasant drugs as suppositories or retention enema

• Can be used in presence of vomiting and unconsciousness

• Absorbed by external hemorrhoid veins – bypasses liver

Drugs – Diazepam, Indomethacin and Aminophylline etc.

4. Inhalation

• Very rapid absorption due to vast surface area of lungs• General anesthetics – gases and liquids• Pressurized metered dose aerosols - MDI• Dry powder inhalation - Rotahalers

5. Nasal

• Absorbed by mucous membrane of the nose

• Hepatic first pass metabolism and gastric juices are bypassed

(GnRH agonists like Leuprolide, dDAVP and calcitonin)

6. Parenteral (Par – beyond, enteral – intestine)

Advantages:• Unconscious and

uncooperative patient• In presence of vomiting

and diarrhea• Irritant drugs • By pass alimentary juice

and 1st pass metabolism• Rapid action and

accuracy of dose

Disadvantages:• Costly and painful• Self medication is

difficult• Less safe and chance of

infection• Injury to nerves and

arteries• Risky

Parenteral Route – contd.

• Intradermal• Subcutaneous• Intramuscular• Intravenous• Intrathecal• Intraperitoneal

Intradermal and Subcutaneous

Intradermal: BCG and sensitivity TestsSubcutaneous:• Non-irritant substances• Small amount as less vascular• Self injection is possible• Avoid in shock• Repository depot preparations – aqueous suspensions Best example – InsulinHypodermoclysis

Intramuscular

• Soluble substances, mild irritants, suspensions and colloids

• Sites of Injection – buttock, deltoid muscle

• No IM injection to child before walking

Intravenous route

Advantages• Quick action – ideal for

emergency• Desired concentration can

be obtained • No hepatic first pass

metabolism• Can be used in

unconscious and uncooperative patients

Disadvantages• Costly – special apparatus

required• Thrombophlebitis and local

irritation• Self medication not

possible• Action cannot be halted• Extravasation may cause

severe irritation• Aseptic and antiseptic

measures to be maintained

Transcutaneous Routes

• Innunction: Nitroglycerin in angina pectoris• Iontophoresis: Galvanic current is for penetration of

drugs to deeper tissues – anode and cathode iontophoresis e.g., salicylates

• Jet injection: Painless injection – high velocity jet produced through a microfine orifice

• Transdermal therapeutic system (Novel drug delivery): Examples – GTN, Nicotine and Estrdiol • Scopolamine patch

• Implants: Biodegradable and non-biodegradable. Example - Norplants

Transcutaneous images

Transdermal

Inunction

Dermojet

Special Drug Delivery System• Ocusert: Pilocarpine, progestsert• Prodrug: Examples

• levodopa to dopamine• Chloramphenicol palmitate

• Targeted delivery: Monoclonal antibodies

• Liposomes: daunorubicin, doxorubicin nd amphotericin B etc

Remember

• Drug Nomenclature• Sources of Drugs with examples of each• Active pharmacological components of

plants• Routes of administration of Drugs with

examples• Advantages and Disadvantages of

different routes• Special drug delivery systems

Thank You

Montoux test