PHARMACY ACT In the earlier part of this century any one could prepare any drug in anyway and

give it to anyone and anything could happen to him without anybody being held responsible for it. The pharmacy Act sought to correct this state of affaire and was passed with the dual objectives of formalizing education and training of would be pharmaceutical professionals and exercise control over their professional work. The Act extends to the whole of India (except Jammu & Kashmir state) and has been amended twice in 1959, 1976 & 1982 to cater to changed social needs. OBJECTIVES OF THE ACT: 1. To frame a Programme of education and practical training for persons desirous of entering the professions of Rx to ensure that such persons have a fund of knowledge and skills suitable for the practice of the profession in the modern age. 2. To restrict the practice of profession to such qualified and trained professionals only and to monitor their professional work. The above objectives are envisaged to be achieves by entrusting responsible of education to a Central Council know as Rx Council of India and by providing for constitution of Pharmacy Council in each state for registration and monitoring of pharmacists in that state. Narcotic and psychotropic substances Act and rules: Coca, Opium & hemp though excellent drugs are habit forming substances and as such their unrestricted use are a danger from the social point of view. In a view of the degenerative effect of these drugs on the individuals, Government of different countries thought it fit to restrict their use to bonafied medicinal purposes only. The cultivation of poppy was brought under control in India in 1857, when opium Act was enacted to regulate the production of opium. After the word war II and the formation of league of 27th September 1924 & 19th February 1925 (known as Geneva convention) Nations a meeting of some nations was held at Geneva on to consider ways and means of suppressing the contraband traffic in and abuse of the dangerous drugs. Based on the consideration of Geneva Convention. The dangerous drugs Act 1930 was passed by the Indian legislature. But in spite of this laws use of addictive drugs has been increased through out the world. So that the existing laws emerged into narcotic & psychotropic drugs Act with stringent penalty for committing offenses. Medicinal preparation and toilet preparations act and rules: Alcohol has always been a fascinating friend of mankind. From time immemorial it has been used as a euphoric drink in some form or the other and though still it is mainly used for drinking purposes, it has found excellent uses in some fields. Such as manufacture of medicines and toilet preparations. Drinking alcohol for pleasures sake is an abuse, while using it for toilet preparations may be classed as luxury. But use of alcohol for preparing medicine is a necessity. For this reason alcohol which is used either

for drinking or for manufacture of toilet goods such as perfumes, is subject to a much higher rate of excise duty than that whi9ch is used for the manufacture of such medicinal preparations which cannot be used as ordinary alcoholic beverages. In order that the alcohol obtained at lower rate of duty, there would be a possibility of abuse of such medicinal formulations. This act regulate the procurement of alcohol for the manufacture of alcoholic medicinal formulation and specify the penalties for committing offences. Drugs and cosmetics act: Drugs and cosmetics act control the import, manufacture, and sale of the several classes of the scheduled drugs and it provides for the establishment of following agencies Agency 1. Advisory a. Drug technical advisory board b. Drug consultative committee functions To advise central and state government on technical matters arising out of the operation of the act. To advise government and drug technical advisory board on issues related to uniform operations of the act through out the country. To analyze and report on samples of drugs/ cosmetics sent by custom collectors/ courts. To analyze and report on samples of drugs/cosmetics sent by drug inspectors can analyze the samples of private agencies on prescribed payment. Incharge of drug control. Issues of license and implementation of act. To inspect licensed establishments and assists licensing authorities in implement of the act. Implementation of the act to certain extent with respect to imported drugs and cosmetics.

2.

Analytical a. Central drug laboratory b. State drug control lab

3.

Executives a. Licensing authority b. Drug inspectors c. Customs collectors

Drugs and Magic Remedies (Objectionable advertisements) Acts and Rules: The art of advertisement is essentially a means through which one introduces his products and services to users. There is a fundamental difference between advertisement of ordinary consumer goods and that of drugs. The former are made directly to the consumer. The later are addressed to the medical pharmaceutical and nursing professions and not directly to the public. This is so because the drugs and medicines due to their therapeutic potencies and toxicities require a lot discretion and judgment in their use, which the lay public cannot duly exercise. This means that if the drugs are directly

advertised to the public, it may lead to self medication with disastrous effects. This makes the control over the advertisements, relating to the drugs and medicines.

Drug Development
Introduction A drug is defined as any substance (other than a food or device) intended for use in the diagnosis, cure, relief, treatment, or prevention of disease or intended to affect the structure or function of the body. (Oral contraceptives are an example of drugs that affect the function of the body rather than a disease.) Drugs can be divided into two categories: prescription drugs and nonprescription drugs. Prescription drugsthose considered safe for use only under medical supervisionmay be dispensed only with a prescription from a licensed professional with governmental privileges to prescribe (for example, a physician, dentist, podiatrist, nurse practitioner, physician's assistant, or veterinarian). Nonprescription drugsthose considered safe for use without medical supervision (such as aspirin)are sold overthe-counter. In the United States, the Food and Drug Administration (FDA) is the government agency that decides which drugs require a prescription and which may be sold over-the-counter. Some knowledge of drug names can help in understanding drug product labels. Every drug has at least three namesa chemical name, a generic (nonproprietary or official) name, and a trade (proprietary or brand) name. The chemical name describes the atomic or molecular structure of the drug. This name is usually too complex and cumbersome for general use. So usually, an official body assigns a generic name to a drug. The generic names for drugs of a particular type (class) usually have the same ending. For example, the names of all beta-blockers, which are used to treat such disorders as high blood pressure, end in "olol." The trade name is chosen by the pharmaceutical company that manufactures or distributes the drug. Patented drugs are usually sold under a trade name. Generic versions of trade-name drugsmanufactured after expiration of the patentmay be sold under the generic name (for example, ibuprofen) or under their own trade name (for example, Advil). Understanding what group a drug belongs to is also useful. Broadly, drugs are classified by therapeutic groupthat is, by what disorder or symptom they are used to treat. For example, drugs used to treat high blood pressure are called antihypertensives, and drugs used to treat nausea are called antiemetic drugs (emesis is the technical term for vomiting).

Within each therapeutic group, drugs are categorized by classes. Some classes are based on how the drugs work in the body to produce their effect. For example, calcium channel blockers, one class of antihypertensives, lower blood pressure by preventing calcium from entering certain cells. Calcium is necessary for the contraction of muscles, including those in the walls of arteries. So calcium channel blockers hinder the contraction of muscles in artery walls and thus cause arteries to widen, so that blood can flow through them more easily. Calcium channel blockers affect the contraction of heart muscle less, and they do not interfere with the contraction of muscles under conscious control (skeletal muscle). Many of the drugs in current use were discovered by experiments conducted in animals and humans. However, many drugs are now being designed with the specific disorder in view: Abnormal biochemical and cellular changes caused by disease are identified; then compounds that may specifically prevent or correct these abnormalities (by interacting with specific sites in the body) can be designed. When a new compound shows promise, its structure is usually modified many times to optimize its ability to target the intended site (selectivity) and remain attached to the site (affinity) and to optimize its strength (potency), effectiveness (efficacy), and safety. Other factors, such as whether the compound is absorbed through the intestinal wall and whether it is stable in body tissues and fluids, are also considered. These factors involve what the body does to the drug (drug kinetics) and what the drug does to the body (drug dynamics) Ideally, a drug is highly selective for its target site, so that it has little or no effect on other body systems; that is, it has minimal or no side. The drug should also be very potent and effective, so that low doses can be used, even for disorders that are difficult to treat. The drug should be effective when taken by mouth (for convenient administration), absorbed well from the digestive tract, and reasonably stable in body tissues and fluids so that, ideally, one dose a day is adequate. During drug development, standard or average doses are determined. However, people respond to drugs differently. Many factors, including age, weight, genetic makeup, and the presence of other disorders, affect drug response. These factors must be considered when doctors determine the dose for a particular patient. How are new drugs discovered? New drugs begin in the laboratory with chemists, scientists and pharmacologists who identify cellular and genetic factors that play a role in specific diseases. They search for chemical and biological substances that target these biological markers and are likely to have drug-like effects. Out of every 5,000 new compounds identified during the discovery process, only five are considered safe for testing in human volunteers after preclinical evaluations. After three to six years of further clinical testing in patients, only one of these compounds is ultimately approved as a marketed drug for treatment.

The following sequence of research activities begins the process that results in development of new medicines: Target identification. Drugs usually act on either cellular or genetic chemicals in the body, known as targets, which are believed to be associated with disease. Scientists use a variety of techniques to identify and isolate a target and learn more about its functions and how these influence disease. Compounds are then identified that have various interactions with drug targets helpful in treatment of a specific disease. Target prioritization/validation. To select targets most likely to be useful in the development of new treatments for disease, researchers analyze and compare each drug target to others based on their association with a specific disease and their ability to regulate biological and chemical compounds in the body. Tests are conducted to confirm that interactions with the drug target are associated with a desired change in the behavior of diseased cells. Research scientists can then identify compounds that have an effect on the target selected. Lead identification. A lead compound or substance is one that is believed to have potential to treat disease. Laboratory scientists can compare known substances with new compounds to determine their likelihood of success. Leads are sometimes developed as collections, or libraries, of individual molecules that possess properties needed in a new drug. Testing is then done on each of these molecules to confirm its effect on the drug target. Lead optimization. Lead optimization compares the properties of various lead compounds and provides information to help pharmaceutical and biotechnology companies select the compound or compounds with the greatest potential to be developed into safe and effective medicines. Often during this same stage of development, lead prioritization studies are conducted in living organisms (in vivo) and in cells in the test tube (in vitro) to compare various lead compounds and how they are metabolized and affect the body.

Drug Discovery and Drug Design

The discovery of new drugs and their development into commercial products takes place across the broad scope of the pharmaceutical industry. The basic underpinning for this effort is the cumulative body of scientific and biomedical information generated worldwide in institutes, academic centers, and industry. The combined efforts of chemists, biologists, molecular biologists, pharmacologists, toxicologists, statisticians, physicians, pharmacists, pharmaceutical scientists, engineers and many others participate in drug discovery and development. Some pharmaceutical firms focus their research and development (R&D) activities on new prescription drugs for human use, other firms concentrate on the development of OTC medications, generic drugs, biotechnology products, animal

health care drugs, diagnostic products, and/or medical devices. Many of the large pharmaceutical companies develop and manufacture products of various types, with some firms having subsidiary companies for specialized functions and products Sources of New Drugs New drugs may be discovered from a variety of natural sources or synthesized in the laboratory. They may be discovered by accident or as the result of many years of tireless pursuit. Throughout history, plant materials have served as a reservoir of potential new drugs. Yet only a small portion of the approximately 270,000 known plants thus far have been investigated for medicinal activity. Certain major contributions to modem drug therapy may be attributed to the successful conversion of botanic folklore remedies into modem wonder drugs. The chemical reserpine, a tranquilizer and hypotensive agent, is an example of a medicinal chemical isolated by design from the folklore remedy Rauwolfia serpentina. Another plant drug, periwinkle, or Vinca rosea, was first scientifically investigated as a result of its reputation in folklore as an agent useful in the treatment of diabetes mellitus. Plant extracts from Vinca rosea yield two potent drugs, which when screened for pharmacologic activity, surprisingly exhibited antitumor capabilities. These two materials, vinblastine and vincristine, since have been used successfully in the treatment of certain types of cancer, including acute leukemia, Hodgkin's disease, lymphocytic lymphoma, and other malignancies. Another example, paclitaxel (Taxol), prepared from an extract of the Pacific yew tree, is used in the treatment of ovarian cancer. After the isolation and structural identification of active plant constituents, organic chemists may recreate them by total synthesis in the laboratory or more important, use the natural chemical as the starting material in the creation of slightly different chemical structures through molecular manipulation. The new structures, termed semi synthetic drugs, may have a slightly or vastly different pharmacologic activity from that of the starting substance, depending on the nature and extent of chemical alteration. Other plant constituents that in themselves may be inactive or rather unimportant therapeutically may be chemically modified to yield important drugs with profound pharmacologic activity. For example, the various species of Dioscorea, popularly known as Mexican yams, are rich in the chemical steroid structure from which cortisone and estrogens are semisynthetically produced. Animals have served humans in their search for drugs in a number of ways. They not only have yielded to drug testing and biologic assay but also have provided drugs that are mannered from their tissues or through their biologic processes. Hormonal substances, such thyroid extract, insulin, and pituitary hormone obtained from the endocrine glands of cattle, sheep, and swine, are lifesaving drugs us daily as replacement therapy in the human body. The urine of pregnant mares is a rich source of estrogens. Knowledge of the structural architecture of the individual hormonal

substances has produced a variety of synthetic and semisynthetic compounds with hormone like activity. The synthetic chemicals used oral contraceptives are notable examples. The use of animals in the production of various biologic products, including serums, an toxins, and vaccines, has had lifesaving significance ever since the pioneering work Edward Jenner on the smallpox vaccine England in 1796. Today the poliomyelitis vaccine is prepared in cultures of renal monk tissue, the mumps and influenza vaccines in fluids of chick embryo, the rubella (Germ measles) vaccine in duck embryo, and the smallpox vaccine from the skin of bovine calves inoculated with vaccinia virus. New vaccines for diseases as AIDS and cancer are being developed through the use of cell and tissue cultures. Today we are witnessing a new era in the development of pharmaceutical products as a result of the advent of genetic engineering, the submicroscopic manipulation of the double helix, the spiral DNA chain of life. Through this process will come more abundant and vastly purer antibiotics, vaccines, and yet u known chemical and biologic products to combat human disease. The two basic technologies that drive the generic field of drug development are recombinant DNA and monoclonal antibody production. Common to each technique is the ability to manipulate and produce proteins, the building blocks of living matter. Proteins are an almost infinite source of drugs. Made up of long of amino acids, their sequence and spatial configuration offer a staggering number of possibilities. Both recombinant rDNA and monoclonal antibody production techniques influence cells' ability to produce proteins. The more fundamental of the two techniques is recombinant DNA. It has the potential to produce almost any protein. Genetic material can be transplanted from higher species, such as humans, into a lowly bacterium. This so called gene splicing can induce the lower organism to make proteins it would not otherwise have made. Such drug products as human insulin, human growth hormone, hepatitis B vaccine, epoetinalpha, and interferon are being produced in this manner. ..........Whereas recombinant DNA techniques involve the manipulation of proteins within the cells of lower animals, monoclonal antibody production is conducted entirely within the cells of higher animals, including the patient. The technique exploits the ability of cells with the potential to produce a desired antibody and and stimulating an unending stream of pure antibody production. These antibodies have the capacity to combat the specific target. Monoclonal antibodies have an enormous potential to change the face of medicine and pharmacy in the next decade, and applications for their use are already in progress. Diagnostically, for example, monoclonal antibodies are used in home pregnancy testing products. Their use ensures that a woman can perform the test easily in a short period with high reproducibility and in an inexpensive manner. In these tests, the monoclonal

antibody is highly sensitive to binding on one site on the human chorionic gonadotropin (HCG) molecule, a specific marker to pregnancy because in healthy women, HCG is synthesized exclusively by the placenta. In medicine, monoclonal antibodies are being used to stage and to localize malignant cells of cancer, and it is anticipated that they will be used in the future to combat disease such as lupus erythematosus, juvenile-onset diabetes, and myasthenia gravis. Human gene therapy, used to prevent, treat, cure, diagnose, or mitigate human disease caused by genetic disorders, is another promising new technology. The human body contains up to 100,000 genes. Genes that are aligned on a double strand of DNA in the nucleus of every cell control all of the body's functions. Base pairs of adenine and thymine (A and T, respectively) and cytosine and guanine (C and G, respectively) constitute the instructions on a gene. Only genes necessary for a specific cell's function are active or expressed. When a gene is expressed, a specific type of protein is produced. In genetic diseases, gene expression may be altered and/or gene sequences may be mismatched, partly missing, or repeated too many times, causing cellular malfunction and disease. NONSTEROIDAL ANTIINFLAMATORY DRUGS AND ANTIPYRETIC ANALGESICS (NSAID). Classification: A. 1. 2. 3. 4. 5. 6. 7. 8. Nonselective COX inhibitors (conventional NSAIDs) Salicylates: Aspirin, Diflunisal. Pyrazolone derivatives: Phenylbutazone, Oxyphenbutazone. Indole derivatives: Indomethacin, Sulindac. Propionic acid derivatives: Ibuprofen, Naproxen, Ketoprofen, Flurbiprofen. Anthranilic acid derivative: Mephenamic acid. Aryl-acetic acid derivatives: Diclofenac. Oxicam derivatives: Piroxicam, Tenoxicam. Pyrrolo-pyrrole derivative: Ketorolac.

B. Preferential COX-2 inhibitors Nimesulide, Meloxicam, Nabumetone C. Selective COX-2 inhibitors Celecoxib, Rofecoxib, Valdecoxib D. Analgesic- antipyretics with poor antiinflammatory action 1. Paraaminophenol derivative: Paracetamol (Acetaminophen). 2. Pyrazolone derivatives: Metamizol (Dipyrone), Propiphenazone. 3. Benzoxazocine derivative: Nefopam. Therapeutic Uses: A. Salicylates 1. Analgesic

2. 3. 4. 5. 6. B.

antipyretic Acute Rheumatic fever Rheumatic arthritis Osteoarthritis Postmyocardial infarction and Poststroke patients

Pyrazolons 1. Rheumatic arthritis 2. Ankylosing spondylitis 3. Acute gout C. Indole derivatives 1. Rheumatic arthritis 2. Ankylosing spondylitis 3. Psoriatic arthritis 4. Acute gout D. Propionic acid derivatives 1. Analgesic and antipyretic 2. Rheumatic arthritis, Osteoarthritis and other musculoskeletal disorders 3. analgesic in case of soft tissue injury E. Anthranilic acid derivative 1. Analgesic in muscle 2. dysmenorrhoea 3. Rheumatic arthritis, and Osteoarthritis F. Aryl-acetic acid derivatives 1. Rheumatic arthritis, and Osteoarthritis 2. Ankylosing spondylitis 3. dysmenorrhoea 4. Post traumatic and post operative inflammatory conditions G. Oxicam derivatives 1. Short term analgesic 2. long term anti-inflammatory drug 3. Rheumatic arthritis, and Osteoarthritis 4. Ankylosing spondylitis 5. Acute gout 6. Musculoskeletal injuries 7. dysmenorrhoea Preferential COX-2 inhibitors 1. Analgesic, antipyretic and anti-inflammatory 2. Rheumatic arthritis, and Osteoarthritis Selective COX-2 inhibitors 1. Rheumatic arthritis, and Osteoarthritis Paraaminophenol derivative 1. Analgesic for headache, musculoskeletal pain, dysmenorrhoea,etc. Benzoxazocine derivative

1. 2.

Used topically as analgesic for painful muscle or joints. Osteoarthritis, sprains, sports injuries, tenosinovitis, backache, spondylitis and other soft tissue rheumatism.

CHOLINERGIC DRUGS (Cholinomimetic, Parasympathomimetic)

CHOLINERGIC AGONISTS Choline esters 1. 2. 3. 4. Uses: Choline esters are seldom used because of Methacholine was occasionally used to terminate Tachycardia. Bethanechol has been used in postoperative urinary retention, neurogenic bladder atony, congenital reflux. Pilocarpine is used as miotic. ANTICHOLINERASES Reversible Cabamates 1. Physostigmine 2. Neostigmine 3. Pyridostigmine 4. Edrophonium 5. Rivastigmine, Donepezil Acridine Tacrine Uses: 1. * Insecticides Nerve gases for Chemical Warfare As miotic a). In glaucoma Irreversible Organophosphates 1. Dyflos (DFP) 2. Echothiophate 3. Parathion*, Malathion* 4. Diazinon* 5. Tabun, Sarin, Soman Carbamates 1. Carbaryl* (SEVIN) 2. Propoxur* (BAYGON) its prominent side effects. Paroxysmal Supraventricular and postpartum nonobstructive megacolon and gastrophageal Acetylcholine Methacholine Carbachol Bethanechol Alkaloids 1. 2. 3. Muscarine Pilocarpine Arecoline

2. 3. 4. 5. 6. 7.

b). To counteract the effect of mydriatics after refraction testing. c). To prevent the formation of adhesions between iris and lens or iris and cornea. Neostigmine is used in the treatment of Myasthenia gravis. Post paralytic ileus/ urinary retention. Postoperative decurarization. Cobra bite. Belladona poisoning Alzheimers disease.

ANTICHOLINERGIC DRUGS
1. 2. NATURAL ALKALOIDS Atropine Hyosine (Scopolamine) SEMISYNTHETIC DERIVATIVES Homatropine Atropine Methonitrate Hyosine butyl bromide Ipratropoium bromide Tiotropium bromide SYNTHETIC COMPOUNDS (a) Mydriatics Cyclo pentolate Tropicamide (b) Antisecretory Antispasmodics: (i) Quarternary compounds Propanthaline Oxyphenonium Clidinium Pipenzolate Methylbromide Isopropamide Glycopyrolate (ii) Tertiary amines Dicyclomine Oxybutinin Flevoxate Pirenzepine Telenzepine (c) Antiparkinsonian: Trihexyphenidyl Procyclidine Biperiden Benztropine Cycrimine

3.

Ethopropazine

ADRENERGIC SYSTEM AND DRUGS

1. DIRECT SYMPATHOMIMETIC Adrenaline Noradrenaline Isoprenaline Phenylephrine Methoxamine Xylametazoline Salbutamol 2. INDIRECT SYMPATHOMIMETIC Tyramine 3. MIXED ACTION SYMPATHOMIMETIC Ephedrine Amphetamine Mephentermine

THERAPEUTIC CLASSIFICATION OF ADRENERGIC DRUGS

1. Pressor agents Noradrenaline Ephedrine Dopamine 2. Cardiac Stimulants Adrenaline Isoprenaline 3. Bronchodilators Adrenaline Isoprenaline Salbutamol 4. Nasal Decongestants Phenylephrine Xylometazoline Oxymetazoline 5. CNS Stimulants Amphetamine Dexamphetamine 6. Anorectics Fenfluramine Dexfenfluramine 7. Uterine relaxant and vasodilators Phenylephrine Methoxamine Mephentermine Dobutamine Terbutaline Salmeterol Formeterol Naphazoline Pseudoephedrine Phenyl propanolamine Methamphetamine Sibutramine

Ritodrine Isoxsuprine

Salbutamol Terbutaline

THERAPEUTIC USES 1. Used in Hypotensive state 2. Used in the treatment of i. Cardiac arrest ii. Stokes adams syndromes iii. Partial or complete A V block iv. Congestive heart failure 3. Bronchial asthma 4. Allergic disorders 5. mydratic 6. CNS uses i. Narcolepsy ii. Epilepsy iii. Parkinsonism iv. Hyperkinetic children v. Obesity 7. Nocturnal enuresis in children and urinary incontinence 8. uterine relaxants 9. Insulin Hypoglycemia.

ANTI ADRENERGIC DRUGS

ADRENERGIC BLOCKING AGENTS I. Nonequilibrium type (i) - Haloalkylamine Phenoxybenzamine II. Equilibrium type(competitive) A. Nonselective (i) Ergot alkaloids Ergotamine, Ergotoxine (ii) Hydrogenated ergot alkaloids Dihydroergotamine (DHE), Dihydroergotoxine (iii) Imidazolines - Tolazoline, Phentalamine (iv) Miscellaneous - Chlorpromazine, Ketenserin B. 1 selective Prazosin, Terazosin, Doxazosin, Tamsulosin C. 2 selective Yohimbine Therapeutic Uses: 1. Pheochromocytoma (tumour of adrenal medullary cells)

2. 3. 4. 5. 6. 7.

Hypertension Secondary Shock Peripheral vascular diseases Congestive heart failure (CHF) Benign hypertrophy of prostate (BHP) Migraine

ADRENERGIC BLOCKING AGENTS Nonselective (1 and 2) a. Without intrinsic sympathomimetic activity Propranolol, Sotolol, Timolol b. With intrinsic sympathomimetic activity Pindolol c. With additional blocking property Lebetolol, Carvedilol Cardioselective (1) Metoprolol, Atenolol,Acebutolol, Bisoprolol, Esmolol, Betaxolol, Celiprolol Selective (2) Butoxamine, ICI 1185551 Therapeutic Uses: 1. Hypertension 2. Angina Pectoris 3. Cardiac arrhythmias 4. Myocardial infarction(MI) 5. Congestive heart failure (CHF) 6. Pheochromocytoma 7. Dissecting aortic aneurysm 8. Thyrotoxicosis 9. Migraine 10. Anxiety 11. Essential tremor 12. Glaucoma 13. Hypertrophic cardiomyopathy