) Siricily As Per Syllabus Prescribed for B. Pharmacy, Semester-IV by Pharmacy Council of India, New Dethi Bose ‘M. Pharm. HOD & Associate Professor Assistant Professor Department of Pharmacology ‘Smt. S. S. Patil College of Pharmacy, ‘Smt. S. S. Patil College of Pharmacy, ‘Chopda, Maharashtra, India ‘Chopda, Maharashtra, India 1M. Pharm, Ph.D, FAPP, FICPHS, FSRHCP, FRSH, FSPER M. Pharm, Associate Professor Associate Professor ‘Smt. S. S. Patil College of Pharmacy, Kota College of Pharmacy, ‘Chopda, Maharashtra & Kota (Rajasthan), Join Secretaries ‘SPER Central Branch & Present NUE IPAVAPPIRSHISRH exiCE ONY ‘Maharashtra State Branch REF EREPharmacology is the science of drugs. The word, Pharmacology derived from fwo Greek words. means “The drugs” & means “The science”, It is the study of substances that interact with living systems through chemical processes, especially through binding to regulatory molecules and activating or inhibiting normal body processes. OR Pharmacology deals with interaction of exogenously administered chemical molecules with living systems, or any single chemical substance which can produce a biological response is a ‘drug’ It is the study of Influence of drug on living system, ability of drug to induce response such as pharmacological, physiological, biological and physicochemical. Primary concern of Pharmacology is not the studying the. biological effects that result from the administration of chemical substances but rather the dual aims of: Providing an understanding of normal and abnormal human physiology and biochemistry through the application of drugs as experimental tools. Applying to oF the information gained from fundamental investigation and observation. Drug is any substance is intended for mitigation, treatment, prevention, cure and diagnosis of any disease or disorder and maintain the good quality of health is known has Drug. Any substance is important to impart or give the therapeutic activity for diagnosis, mitigation, prevention and treatment or cure of disease is called drug. (What body does to the drug)2 This refers to movement of the drug in and alteration of the drug by the body. It deals with the rate of absorption, distribution, binding or localization or storage, biotransformation and excretion of the drug. (What drug does to the body) This includes physiological and biochemical effects of drugs and their mechanism of action at organ system /subcellular/macromolecular levels. This branch of pharmacology deals with the study of drugs on human beings. This branch of pharmacology deals with the study of adverse effects of drugs. It also deals with the study of toxic reactions to chemicals, environmental or industrial toxins. Detection and treatment of toxicity due to drugs or poisons are dealt in toxicology. Toxicology forms an important part of pharmacology. It is general term describing the use of drugs in the treatment of disease. It comprises of: Rational & Empirical Pharmacotherapeutics. This area of pharmacology examines the relation of genetic factors with variations in response to drugs. Such variations are known as idiosyncratic reactions, because of in born error of drug metabolism It is the study of dosage & dose schedules. Dose for various age groups, like geriatrics & pediatrics or different weight groups are calculated using posology. It is the branch of pharmacology, dealing with the identification (screening) and comparative evaluation (quantitative or qualitative) of drugs. It is the treatment of systemic infection/malignancy with specific drugs that have selective toxicity for the infecting organism/ malignant cell with no/minimal effects on the host cells. Itis the art and science of compounding and dispensing drugs or preparing suitable dosage forms for administration of drugs to man or animals. It includes collection, identification, purification, isolation, synthesis, standardization and quality control of ‘medicinal Substances. The large scale manufacture of drugs is called Pharmaceutics. It is primarily a technological science. Use of genetic information to guide drug therapy.The study of drug effects at population level, it is concerned with variability of drugs effects between individuals in population and between populations. Eg: Responders and non-responders to LT antagonist therapy in case of asthma Branch of pharmacology dealing with cost and benefits of drugs used therapeutically. ee = ‘Study of preparation/dose Pharmacology formulation of drug__ Pharmacy = Study of drugs Pharmacology Exogenous substance Use of drug in related that has an treatment of diseases Definitions. effect on body 7_ Therapeutics Toxicology Study of poison Use of crude plant extracts for medicinal use, Herbal medicine P Pharmacognosy Study of medicine derived from natural Phytotherapy sources (plants & animals) Fig. 1.1: Various Branches related to pharmacology Pharmacology is one of the cornerstones of the drug discovery process. The medicinal chemist may create the candidate compound, but the pharmacologist is the one who tests it for physiologic activity. A promising compound is investigated by many other scientists’ toxicologists, microbiologists, clinicians but only after the pharmacologist has documented a potential therapeutic effect. This article briefly presents the historical development of pharmacology and some of the basic methods used.4 Pharmacology studies the effects of drugs and how they exert their effects. There is a distinction between what a drug does and how it acts. Thus, amoxicillin cures a strep throat, and cimetidine promotes the healing of duodenal ulcers. Pharmacology asks “How”? Amoxicillin inhibits the synthesis of cell wall mucopeptide by the bacteria that cause the infection, and cimetidine inhibits gastric acid secretion by its antagonist action on histamine H2 receptors. The main tasks of pharmacologists in the search for and development of new medicines are: Screening for desired activity. Determining mode of action. Quantifying drug activity when chemical methods are not available. Synthetic organic chemistry was born in 1828, when Friedrich Wohler synthesized urea from inorganic substances and thus demolished the vital force theory: The birth date of pharmacology is not as clear-cut. In the early 19thcentury, physiologists performed many pharmacologic studies. Thus, Francois Magendie studied the action of nux vomica (a strychnine-containing plant drug) on dogs, and showed that the spinal cord was the site of its convulsant action. His work was presented to the Paris Academy in 1809. In 1842, Claude Bernard discovered that the arrow poison curare acts at the neuromuscular junction to interrupt the stimulation of muscle by nerve impulses. Approximate dates > 2000 BC Magical potions Herbal remedies = 16000 sss ‘apothecaries = 1800 Natural products" Pathology Pharmaceutical Teron tt, Ps oe wie en T Spabetc Biochemistry = iee comsty ——_, Ja Synthetic Se Moloeiar =1970 i 4 boa _sropharmaceutcals 2000 Pharmacology €———— Fig. 1.2: History of Pharmacology(460B.C.-377B.0), was the first to attempt to separate the practice of medicine from religion and superstition, developed his pledge of proper conduct for doctors. “will use treatment to help the sick according to my ability and judgment, but never with the view to injury and wrong doing...Into whatsoever houses I enter, Iwill enter to help the sick” An early Indian medical practitioner and one of regarded as the He perfected many herbal based cures and natural remedies and was credited with the discovery of the antiseptic properties of turmeric and the preservative properties of salt which he incorporated in his cures. Ancient Hindu Medical Text Describes 760 herbs. describes more than 650 drugs of animal, plant and mineral origins are used Pioneered the use of chemicals and minerals (zinc) in medicine. Vigorously opposed polypharmacy , or the prescription of multiple ingredients in a single medicine. Extract of foxglove plant, used to treat dropsy (congestive heart failure) in 1785. Contains digitoxin and digoxin; today called digitalis. Discovered Synthetic organic chemistry was born in 1828, when Friedrich Wohler synthesized urea from inorganic substances and thus demolished the vital force theory. A Greek Physician, he personally researched each plant and its uses. About 65 AD, he wrote "Regarding Medical Matters" on the "preparation, properties, and testing of drugs. Five volume book on the uses of over 1,000 plants and minerals. For nearly 1500 yeats, De Materia Medica was the supreme authority on medicine and pharmacology in western civilization. A French Phggiologist In 1842, Claude Bernard discovered that the arrow poison acts at the to interrupt the stimulation of muscle by nerve impulses. Claude Bernard also called Father of “Modern Experimental Medicine”, Bernard's ‘eqperiments changed medicine.The discovery of role of The discovery of a new function of the liver is the "Internal secretion” of glucose into the blood (1848). The production of sugar by washed excised liver (1855) and the isolation of glycogen (1857). The demonstration that curare specifically blocks motor nerve endings (1856). He also established the existence of Vasomotor system and observed & Generally recognized as the Schmiedeberg obtained his medical doctorate in 1866 with a thesis on the measurement of chloroform in blood. In 1872, he became professor of pharmacology at the University of Strassburg In 1878, he published a classic text, In 1885, he introduced urethane as hypnotic in his 46 years at Strasburg; Schmiedeberg trained most of the men who became professors at other German universities and in several foreign countries. He was largely responsible for the preeminence of the German pharmaceutical industry up to World War II. In the United States, the first chair in pharmacology was established at the University of Michigan in 1890 under John Jacob Abel, an American who had trained under Schmiedeberg. Ss ‘An American Pharmacologist, ph.D from the university of Michigan and trained under Schmiedeberg. In the United States, the first chair in pharmacology was established at the University of Michigan in 1890 under John Jacob Abel. In 1893, Abel went to Johns Hopkins University in Baltimore, where he had a long and brilliant career. Also called: 1857- 1938, Gave the name: as a subject before this call “Materia Medica”. He was second to isolate (1897-1898) from adrenal gland extracts (first was ‘Napoleon Cybulski in 1895). Isolated, (914). Isolation of histamine from pituitary extracts (1919). Preparation of, (1926). His student) in adrenal extracts in 1906.The German pharmacist, who isolated the administered a very large dose (100 mg) to himself and three friends. All experienced the symptoms of severe opium poisoning for several days. The alkaloid was named for ‘A German Pharmacologist, brilliantly obtained his doctor's degree with a thesis about techniques of isolations of frog's heart. In 1902 at London, in Starling's laboratory, he met for the first time who becomealifelong friend. Later on in 1909, he was appointed to the Chair of Pharmacology in Graz and thereafter in 1921, he proved the & in 1936 He received the He designed his most famous experiment, which provided the first evidence for the ‘existence of chemical transmission in a synapse. ‘The legend tells that he had the idea of the experiment in a dream and that he ran to the lab in the middle of the night. The experiment was very simple and became a prototype for all investigations of chemical factors in the nervous system. An Received his M.D. from Cambridge in 1909. Worked under John Langle & Paul Ehrlich, also a Fast friend of Otto Loewi. Dale became the Director of the Deptt of Biochemistry and Pharmacology at the National Institute for Medical Research, London in 1914. Also served as President of the Royal Society from 1940 to 1945. First identified acetylcholine in 1914 as a possible neurotransmitter, Loewi showed its importance in the nervous system. (Shared the 1936 This principle states that each neuron releases only one type of neurotransmitter. Only fall in BP occurs when an alpha blocker is given before injecting adrenaline He demonstrated this in cat & used Ergot alkaloids as alpha blocker.Also called Father of Obtained MD degree from Cambridge University in 1908 and in 1921: Appointed as the first professor of pharmacology in newly established and parallel headed the Department of pharmacology at the Calcutta medical college: From 1941 to 1957: he was Director of the Drug Research Lab at Srinaga. He Ist introduced and done systematic study of Had a major contribution in establishing the Lucknow (presently known as Central Drug Research Institute, (CDR0. He pioneered research on herbal drugs in India. Indian Posts & Telegraphidepartment has issued a commemorative stamp in his honor. German scientist in the fields of hematology, immunology, and chemotherapy: He is noted for curing syphilis and for his research in autoimmunity. He coined the term and popularized the concept of a ‘Also coined the term (earlier called as receptive substance by ). Ehrlich skillfully transformed diphtheria antitoxin along with Emil Adolf von Behring, into an effective preparation, his first world renowned achievement. However, von Behring cheated Ehrlich out of both recognition and financial reward. Only von Behring received Scottish biologist and pharmacologist. His best-known discoveries are the: Discovery of the Antibiotic from the mold in 1928 which was a discovery by chance. On Fleming returned to his lab. After vacation. Before leaving, he, had stacked all his cultures of.staphylococci on a bench in a corner of his laboratory. On returning, Fleming noticed that one culture was contaminated with a fungus, and that the colonies of staphylococci that had immediately surrounded it had been destroyed, whereas other colonies farther away were normal. He shared the in Physiology or Medicine in 1945 with and who purified penicillin. Sir Frederick Grant Banting, (1891-1941) was a Canadian medical scientist & doctor. Charles Best February (1899-1978) was his assistant. Known for the one of the most significant advances in medicine, enabling an effective treatment for diabetes. iIn 1921, Banting traveled to Toronto to visit JJ.R. Macleod at University of Toronto, where he used his lab for this discovery. A German pathologist and bacteriologist. Done extensive work on infections & antibiotics. Credited with the discovery of Sulfonamidochrysoidine (KI-730) - the first commercially available antibiotic (marketed under the brand name Prontosil). He found the sulfonamide Prontosil to be effective against streptococcus, and treated his own daughter with it, saving her the amputation of an arm. In 1939, Domagk received the Nobel Prize in Physiology or Medicine for this discovery, the first drug effective against bacterial infections. Famous American Clinical Pharmacologist. Medical degree from Columbia University in 1947. i Lasagna joined the faculty of Johns Hopkins University in 1954, where he established the first ever clinical Pharmacology department. 3 In 1964, Lasagna revised the Hippocratic Oath ; Conceptualize controlled clinical trials and the placebo effect. 4 Lasagna’s work led to the improvement of controlled clinical trials to test drug effectiveness, and improved the regulation of drugs for effectiveness and safety. The incidence of patient availability sharply decreases when a clinical trial begins and returns to its original level as soon as the trial is completed. A Scottish Pharmacologist. Studied Medicine at Univ. of St. Andrew. In 1950, he joined the University of Glasgow. He was interested in the effect of adrenaline on the human heart. Joined ICI Pharmaceuticals in’ 1958. In 1964 he joined Smith, Kline and French for whom he worked for nine years until 1973. He was awarded the Nobel Prize for Medicine in 1988 for his work. He established the Physiology Department at Univ. of Glasgow. He developed Propranolol while working for ICI, which later became the world’s best- selling drug. Black was developing a similar method of treatment for stomach ulcers, but ICI did not wish to pursue the idea so Black resigned in 1964 and joined Smith, Kline and French. While there, Black developed his second major drug, cimetidine (brand name Tagamet) in 1975 and soon out sold to become the world's Ist billion dollar drug.10Fry Father of Modern Medicine. Father of Modern Experimental Pharmacology. Father of Modern Pharmacology. Father of Modern Chemotherapy. Father of American Pharmacology. Father of Indian Pharmacology. Father of Clinical Pharmacology Nobel Laureates in Pharmacology. First antimicrobial drugs (magic bullet). Isolation and discovery of insulin and its application in the treatment of diabetes. ; Chemical transmission of nerve impulses. Discovery of penicillin and its curative effect in various infectious diseases. Hormones of the adrenal cortex, their structure and biological effects. Antagonists that block biologically active amines, including the first antihistaminic. Transmitters in the nerve terminals and the mech. For storage, release, and inactivation. Mechanisms of the action of hormones with regard to inhibition and stimulation of cyclic AMP. Discovery of prostaglandins ‘and the mechanism of action of aspirin which inhibits prostaglandin synthesis. : Development of the first beta-blocker, propranolol, and anticancer agents that block nucleic acid synthesis. Discovery of G proteins and the role of these proteins in signal transduction in cells. by He failed to disinfect cultures of bacteria when leaving for his vacations, only to find them contaminated with molds, which killed the bacteria. therapeutic action on actinic keratosis, was initially investigated for its anti-cancer actions.12 action on baldness; originally it was an oral agent for treating hypertension. Ttwas observed that bald patients treated with it grew hair too. 4 an anti-impotence drug. It was initially studied for use in hypertension and angina pectoris. Phase I clinical trials under the direction of Ian Osterloh suggested that the drug had little effect on angina, but that it could induce marked penile erections. The libido-enhancing effect of The first anti-psychotic drug, was discovered by French pharmacologist He wanted to add an antihistaminic to prevent surgical shock and noticed that patients treated with it were unusually calm before the operation. The first antidepressants, and were Ist used in schizophrenics (imipramine) é in the t/t of TB (iproniazid). Mustine ~ a derivative of mustard gas (a chemical weapon). In 1943, physicians noted that the white cell counts of US soldiers, accidentally exposed mustard gas shells were decreased, and mustard gas was investigated as a therapy for Hodgkin's lymphoma. The anesthetic Its properties were discovered when British chemist, tested the gas on himself and some of his friends, and soén realised that nitrous oxide considerably dulled the sensation of pain, even if the inhaler was still semi-conscious. Thanks to the work of Schmiedeberg, Abel, and others like them, the field of pharmacology grew rapidly in the 20th and 21st centuries. Many drugs, from lifesaving antibiotics, to important hormonal compounds like insulin (to treat diabetes) “were developed. Pharmacologists not only studied what effects a drug would have on an animal or a human, they also studied the drug itself. Meaning, they would study the structure of the compound and relate tiny changes within the compound itself to the effects those changes would have upon the way a drug would act. Oswald Schmiedeberg (1838-1921) is generally recognized as the founder of modern pharmacology. The son of a Latvian forester, Schmiedeberg obtained his medical doctorate in 1866 with a thesis on the measurement of chloroform in blood. He worked at Dorpat under Buchheim, succeeding him in 1869. In 1872, he became professor of pharmacology at the University of Strassburg, receiving generous government support in the form of a magnificent institute of pharmacology. He studied the pharmacology of chloroform and chloralhydrate. In 1869, Schmiedeberg showed that muscarine evoked the same effect on the heart as electrical stimulation of the vagus nerve. In 1878, he published a classic text, Outline of Pharmacology, and in 1885, he introduced urethane as a hypnotic.13 In his 46 years at Strassburg, Schmiedeberg trained most of the men who became professors at other German universities and in several foreign countries. He was largely responsible for the preeminence of the German pharmaceutical industry up to World War IL In the United States, the first chair in pharmacology was established at the University of Michigan in 1890 under John Jacob Abel, an American who had trained under Schmiedeberg. In 1893, Abel went to Johns Hopkins University in Baltimore, where he had a ong and brilliant career. His major accomplishments include the isolation of epinephrine from adrenal gland extracts (1897-1898), isolation of histamine from pituitary extract (1919), and preparation of pure crystalline insulin (1926). His student Reid Hunt discovered acetylcholine in adrenal extracts in 1906. Today, there is a pharmacology department in every college of medicine or pharmacy. Pharmacology depends largely on experiments conducted in laboratory animals, but even the human animal may be used asa test subject. Friedrich Serturner, the German pharmacist who isolated the first alkaloid from opium in 1805, administered a whopping dose (100 mg) to himself and three friends. All experienced the symptoms of severe opium poisoning for several days. The alkaloid was named morphine, for Morpheus, the Greek god of sleep. ‘An interesting example of the use of humans for testing occurred in the 1940s. Although digitalis had been a standard medication for heart disease for more than a century; there were still no reliable methods for evaluating its potency. Biological assays (bioassays) were performed on frogs, pigeons, and cats, but none were totally satisfactory. In 1942, a group of cardiologists published “a method for bioassay of digitalis in humans”. The assay was based on quantitative changes in the electrocardiogram (ECG) of patients in the cardiac clinics of two New York City hospitals. It was hard to find patients whose ECGs could be standardized of 97 patients in whom calibration of the ECG was tried, only 18 proved: to be satisfactory assay subjects. Fortunately, chemical research on the active glycosides of digitalis, and development of analytical methods, soon rendered all digitalis bioassays obsolete. Although humans are no longer used as ad hoc laboratory animals, they are essential in clinical pharmacology. When a new drug compound has gone through sufficient preclinical testing to show potential therapeutic action and reasonable safety on short-term administration, and the data have been reviewed by the FDA, the compound is administered to a small number of human volunteers under closely controlled and monitored conditions. These Phase I clinical trials provide information about dosage and the most common side effects to be expected. The animals most frequently used in pharmacologic studies are mammals. Mice are preferred because of their small size, ease of breeding, and short generation time. Rats,cu Suinea pigs, rabbits, and dogs are also used; each has special characteristics that make it ‘optimal for certain types of tests. Experimental pharmacology uses animals in various ways. Intact animals are essential for the acute, subacute, and chronic toxicity tests that a new drug substance must undergo, and for important special tests such as teratology and carcinogenicity. Pharmacology per se tends to use excised (isolated) organs or tissues and animals that are surgically prepared in various ways to aid in the detection and study of target activities. Early in the development of pharmacologic techniques, it was found that an isolated organ or tissue remained functional for several hours in a bath containing a physiologic solution of salts through which oxygen was bubbled. Henrick Magnus (1802-1870) first applied this method to a strip of small intestine, Jean-Francois Heymans (1904) worked with the mammalian heart, and Claude Bernard experimented with isolated nerve-muscle Preparations. The organ or tissue is so suspended that the contraction or relaxation of the muscle is mechanically transmitted to a stylet. The stylet writes on a drum covered with smoked paper rotated by clockwork at a constant speed. This device, called a kymograph, graphically records motion or pressure. The effects of drug substances added to the bath can thus be visualized. The kymograph is a relatively crude device. In’ modern laboratories, organ and tissue movements are transmitted by force transducers to polygraph machines, which produce similar tracings. Or the polygraph is replaced by computerized equipment that issues a digital record. The surgical preparation of animals is illustrated by the following examples. As early as 1849, the German anatomist Amold Berthold transplanted testicular tissue into a capon (@ castrated rooster) and showed that this induced growth of the comb. This basic method was used in the 20th century to isolate and study the male sex hormones. Similarly, in 1924, Americans Edgar Allen and Edward Doisy used ovariectomized rats to test the action of estrogenic hormones. To study anti-inflammatory agents, rats can be made arthritic by injection of an oily suspension of killed bacteria (Freund’s adjuvant), Drugs affecting gastric secretion may be studied in animals by forming a Heidenhain pouch—a small sac of the stomach, vagally denervated and closed off from the main cavity, but with an opening through the abdominal wall. The scope of pharmacology has expanded greatly over the last decade to incorporate many new approaches such as: i. Computer assisted drug design ii. Genetic screens iii, Protein engineering15 iv. Novel drug deiivery Vehicles Our society needs pharmacologists who understand the basis of modern therapeutics for careers within, academic, pharmaceutical and governmental laboratories to study and develop tomorrow's drugs. The effect of the body on the drug. To produce its characteristic effects, a drug must be present in appropriate concentrations at its sites of action. Thus, it is important to know the interrelationship of the absorption, distribution, binding, biotransformation, and excretion of a drug and its concentration at its locus of action. (oral or parenteral): A drug must be absorbed and achieve adequate concentration at its site of action in order to produce its biological effects. Thus, when a drug is applied to a body surface (eg., G.L tract, skin, etc), its rate of absorption will determine the time for its maximal concentration in plasma and at the receptor to produce its peak effect. The blood, total body water, extracellular, lymphatic and cerebrospinal fluids are involved in drug movement throughout the body. Depending upon its chemical and physical properties, the drug may be bound to plasma proteins or dissolved in body fat, delaying its progress to its sites of action or excretory mechanism. This is how certain drugs are handled by the body in preparation for their elimination and includes the fate of drugs-biotransformation (eg. hydrolysis, conjugation, oxidation-reduction). ‘The kidney is the most important organ for drug excretion but the liver, lung and skin are also involved in drug elimination. Drugs excreted in feces are mostly derived from unabsorbed, orally ingested drugs or from metabolites excreted in the bile and not reabsorbed by the intestine. The physical and chemical properties, especially the degree of ionization of the drug, are important in the rate of excretion. Normal variations occur in population pharmacokinetic constants (absorption rates, elimination rates). Other factors include age, weight, obesity, edema, concurrent diseases, other drugs (various interactions including effects on protein binding or metabolic rate), diet, dose interval and route of administration, genetic variations in elimination rate Drugs activity over the body The effect of the drug on the body. Pharmaco-dynamics is the study of the relationship of drug concentration and the biologic effect (physiological or biochemical). For most drugs it is necessary to know the site of action and mechanism of action at the lei of the organ, functional system, or tissue.16 For example, the drug effect may be localized to the brain, the neuromuscular junction, the hheart, the kidney, etc. Often the mechanism of action can be described in biochemical or molecular terms. ‘Most drugs exert effects on several organs or tissues, and have unwanted as well as therapeutic effects. There is a dose-response relationship for wanted and unwanted (toxic) effects. Chemical structures of drugs can provide information about mechanism of action, pharmacokinetics, stability, and metabolic fate. ‘A modification of the chemical structure of a drug may accentuate or diminish its pharmacological effects, often providing clues as to the mechanism of action. A picture of the biological reactive site (the receptor) can be developed in such studies. Also, drugs are metabolized by body systems, which may convert the parent drug to a more active or a less active form. The drug structure can be modified to enhance or diminish the rate of metabolic conversion. ‘The organ or cellular target of drug action. Macromolecules in cells or cell membranes with which drugs interact to exert their effects. Usually the interacting forces are reversible ionic and Van der Waals bonds of relatively low energy, but sometimes covalent bonds are formed (eg. organophosphate insecticides). Emphasis is placed on the therapeutic use of drugs for the treatment of disease in clinical pharmacology, internal medicine and therapeutics. There are specific clinic disorders or disease entities for which a given drug may be prescribed and the physician must weigh the potential benefit of drug use against the risks of adverse effects. Where detoxification of the drug by the liver is important. It is important to know that the presence of disease or organ pathology may influence the actions of a drug. Conditions such as age, pregnancy, concomitant administration of other drugs and disease may alter the patient's response to a given drug. It is an archaic term describing dosage regimens. Consideration of dosage schedules is a part of pharmacokinetics. The fraction of drug administered which is actually absorbed and reaches the systemic circulation following oral dosing. Preparations of the same drug by different manufacturers may have a different bioavailability. It is important that the physician write clear, error-free directions for the drug provider (pharmacist) and for the patient. Physicians must guard against ibing too many drugs, or preparations of little value.7 Drugs of unproven clinical value should be avoided, as well as potentially toxic agents if drugs equally effective but less dangerous are available. Risk-benefit and cost-benefit should be considered. Drugs may be prescribed by generic name, since often a less expensive drug product can be obtained in this way. A particular manufacturer may be specified if the physician has reason to believe a better or more reliable preparation is available from that manufacturer. In addition to its formal chemical name, a new drug is usually assigned a code name by the pharmaceutical manufacturer. If the drug appears promising and the manufacturer wishes to place it on the market, a United States Adopted Name (USAN) is selected by the USAN Council which is sponsored by: i, The American Medical Association. ii, The American Pharmaceutical Association. iii. The United States Pharmacopoeial Convention The aspect of Toxicology deals with the adverse effects of chemical agents. Toxicology is concerned not only with drugs used in therapy but also with the other chemicals that may be responsible for household, environmental or industrial intoxication. Addresses medicological aspects of the use of chemicals that are harmful to animals or man. Analytical chemistry and fundamental toxicological principles are hybridized to underlie this aspect of toxicology. Nonetheless accidental poisoning with drugs is a health problem of major significance. More than 1/4 of the fatalities and about 1/2 of all poisonings occur in children under 5 years of age. All common household articles that are poisonous should be made unavailable to children, and poisonous rodenticides and insecticides should not be placed in the home Focuses on toxic events that are caused by or are uniquely associated with drugs or other chemicals The study of drug effects at population level, it is concerned with variability of drugs effects between individuals in population and between populations. Eg: Responders and non-responders to LT antagonist therapy in case of asthma. It is the treatment of systemic infection/malignancy with specific drugs that have selective toxicity for the infecting organism/ malignant cell with no/minimal effects on the host cells.LINICAL MEDICINE VETERINARY UNIGALMEDICINE VETERINAEY puarwiacy BIOTECHNOLOGY PATHOLOGY CHEMISTY | | \ | \ Pharmaceutics! Medicinal arpacsites! ciophemacouicss —Toxisony —Semy PsvcHotocy ¢ Phamacoknata/| | Biochemical ‘dug metanolin fmm pharmecolony Wowcular | mother eal Ea ‘ystems pharmacology New Caciovascilar — Gasvortesinal pharmacology pharmacology Pharmacology mune: Restiatory pharmacology pharmecc}ogy [Pharvecogensice Pharmacogenomics -«~Pharnacbeplemiiogy——_Phamacooconomics I I t 1 GENETICS Genomics: CLINICALEPIDEMIOLOGY —_-HEALTHECONOMICS Fig. 13: Scope of Pharmacology in various fields Drug is any substance is intended is used as mitigation, treatment, prevention, cure and Diagnosis of disease and disorder and maintain the good quality of health is known has Drug. Any substance is important to impart or give the therapeutic activity is known has drug and it can be taken up by various route. Thereare four Sources of Drug: Drug is a substance which is used for the following purposes: Diagnosis of the disease Prevention of the disease. ‘Treatment of disease. Prevention of pregnancy (ie. contraception). ‘Maintenance of optimal health. Relieve disease symptoms. Aspirin, Tylenol.To avoid getting a disease. Hepatitis B vaccine, Flu vaccine. Help determine disease presence. Radioactive dyes. Eliminate the disease. Antibiotics. Help keep the body functioning normally. Insulin. Sources of ‘Synthetic 19 Preventative Plant Animal s s Eg. Atropine Insulin Papaverine Thyroid Digitalis ete. Mineral Liquid Paraffin Mag. Sulphate ete. Synthetic Micro- organism Aspirin, Penicillin Sulphonamide Other ete. ete. Fig 1.4: Different sources of drug with example ‘The Drugs in natural source are obtained from the following natural sources: A. Plants B. Animal Sources Genetic- Eng. Insulin Hormones Antibiotics20 C. Mineral D. Microorganisms Following categories of drugs are derived from roots, leaves or barks of plants: These are nitrogenous heterocyclic bases, which are pharmacologically active principles of plants. They are composed of carbon, hydrogen, nitrogen and oxygen. They are bitter in taste and are often poisonous. These are, therefore, used in small doses. ‘© They are insoluble in water. However, they form salts with acids which are soluble in water. 1. | Atropine ‘Atropa Belladdona Leaf Antocholinergic 2. | Quinine Chinchona’ Bark ‘Antimalerial 3. | Morphine Opium’ Driedlatex | Analgesic, Antitussive 4. | Reserpine Rauwolfia serpentina | Root ‘Tranquilizer 5 | Strychnine | Nux-Vomica Seeds ‘Anticancer They are ether-like combination of sugar moiety with non-sugar moiety. They are called glycosides, if the sugar moiety is glucose. Sugar moiety is not essential for the pharmacological activity but it governs thepharmacokinetic properties of the glycoside. In the body it may be removed to liberate aglycone. 4 Glucose ——O—— Non Sugar Glycoside Pharmacological activity resides in the non-sugar moiety that is called aglycone (orgenin). Some examples are digitoxin, digoxin and ouabain.2 They are liquids which are insoluble in water. They are of three types and are used for various medicinal purposes. Essential oils are obtained from leaves or flower petals bysteam distillation, and have an aroma. They have no caloric or food value. They do not form soaps with alkalis. They do not leave greasy stain after evaporation. On prolonged stay, they do not become rancid (foul smell). They are frequently used as carminatives and astringents in mouth-washes. Some of these oils are solid at room temperature and sublime on heating e.g. menthol and camphor. Other examples are clove oil, peppermint oil, eucalyptus oil and ginger oil. These are glycerides of stearic, oleic and palmitic acid. They are obtained from the seeds that are present within the cells as crystals or droplets. They are non-volatile and leave greasy stains on evaporation They have caloric or food value. They form soaps with alkalies. On prolonged stay, they become rancid. They do not have marked pharmacological activity and have little pharmacological useexcept castor oil (purgative) or arachis oil (demulcent). They may be of vegetable origin e.g. olive oil, castor oil, croton oil and peanut oil or of animal origin e.g. cod liver oil, shark liver oil and lard. ‘These are mostly petroleum products and extracted by fractional distillation. ‘These are mixtures of hydrocarbons of the methane and related aliphatic series. ‘These are extracted in various consistencies - hard paraffin, soft paraffin and liquid paraffin. Hard and soft paraffins are used as yehicles for preparation of ointments while liquid paraffin is employed as a purgative. These are colloidal exudates from plants which are polysaccharides chemically and yield simple sugars on hydrolysis. Upon addition of water, some of them swell or dissolve or form adhesive mucilage orremain unchanged. In gut agar and psyllium seeds act as hydrophilic colloids and function as bulk purgatives.Gum acacia and gum tragacanth are used as suspending agents in making emulsions and mixtures. These are ill-defined solid substances found in plants, and are polymers of volatile oil. ‘They are produced by oxidation and polymerization of volatile oils. ‘They are insoluble in water but soluble in alcohol, chloroform and ether. Examples: oleoresins (aspidium); gum resins (asafoetida); oleogum resin (myrrh); balsams (benzoin, tolu, peru); benzoin shellac, podophyllum. Benzoin is used as inhalation in common cold. Tincture benzoin is applied as antiseptic protective sealing over bruises. Colophony (an oleoresin) is used as an ingredient in various plasters. Shellac (from Lucifer lacca) is used for enteric coating of tablets. Balsams are used in the treatment of cough and bronchitis for their antiseptic andprotective properties. Podophyllum is used as an irritant purgative. These are non-nitrogenous phenolic plant constituents which have an astringent action. Pyrogallol tannins are glycosides of glucose that occur in oak galls. Pyrocatechol tannins are sugar-free derivatives of catechol that are present in catechu andeucalyptus. Tannic acid is tannin that is obtained from oak galls and is used for treating burns anddiarrhoea. Some animal sources continue to be used to procure some modern drugs because of cumbersome and expensive procedures for the synthesis of such chemicals. For example: extracted from pork and beef pancreas, is used for the treatment of diabetes mellitus. i Thyroid powder for treating hypothyroidism. Heparin is used as an anticoagulant. Hormones and vitamins are used as replacement therapy. Vaccines (cholera, T.B. smallpox, polio and antirabic) and sera (antidiptheria andantitetanus) are used for prophylaxis /treatment. Many life-saving drugs are obtained from fungi, moulds and bacteria.nd 23 Sr.No. Drug alga care. yeounen ane (Bacteria fungi eto) 1 Penicillin Penicillium notatum | 2 | Chloramphenicol ——_| Streptomyces Venezuela : Grisofulvin Penicillium griseoputoum [4 | Neomycin Streptomyces fradiae [ streptomycin Streptomyces griseus Minerals or their salts are useful pharmacotherapeutic agents For example: Ferrous sulfate is used in iron deficiency anaemia, Magnesium sulfate is employed as purgative. Magnesium trisilicate, aluminium hydroxide and sodium bicarbonate are used as antacidsfor hyperacidity and peptic ulcer. Kaolin (aluminium silicate) is used as adsorbett in antidiarrheal mixtures. Radioactive isotopes of iodine, phosphorus, gold are employed for the diagnosis/ treatment of diseases particularly malignant conditions. Sometimes semi-synthetic processes are used to prepare drugs when the synthesis of drugs(complex molecules) may be difficult, expensive and uneconomical or when the natural source may yield impure compounds. In these situation this methods plays an important role. Some examples are semi synthetic and! derivatives. Prepared by chemically modifying substances that are available from natural source improve to its potency, efficacy and also reduce side effects For Example: Heroine from Morphine Bromoscopolamine from scopolamine Homoatropine from atropine Animal insulin changed to be like: Human insulin. 6-aminopenicillanic acid derivatives.‘At present majority of drugs used in clinical practice are prepared synthetically, such as aspirinoral antidiabetics, antihistamines, amphetamine, chloroquine, chlorpromazine, general and local ‘anaesthetics, paracetamol, phenytoin, synthetic _ corticosteroids, sulphonamides and thiazide diuretics. ‘Most of the synthetic drugs are prepared synthetically ie. by chemical process ( reaction) withthe help of the knowledge of phytochemical investigation. Alterations are made on the naturally found structure of the drug to improve its effect andto improve the finances of pharmaceutical companies. They are chemically pure. ‘The process of preparing them is easier and cheaper. Control on the quality of the drug is excellent. Since the pharmacological activity of a drug depends on its chemical structure andphysical properties, more effective and safer drugs can be prepared by modifying thechemical structure of the prototype drug. ‘This is relatively a new field which is being developed by mixing discoveries from molecular biology, recombinant DNA technology, DNA alteration, gene splicing, immunology and immunopharmacology. Some of the recent developments are genetically engineered novel vaccines recombinant DNA engineered insulins for diabetes and and for hairy cell leukaemia. For instance: genetically engineered formation. According to “Those drugs that satisfy the priority of healthcare needs of the population” They should there be available in adequate amounts & in an appropriate dosage form. List must be updated time to time. Direct responsibility of each country to evaluate & adopt a list of essential drugs according to its own policy in the field of health.25 ‘of the concept is that a Limited number of drugs lead to: A better supply of drugs. More rational prescribing. Procurement of good quality at lower Costs. Easier storage, distribution and Dispensing. Focused training and drug information. More experience with fewer drugs, Better recognition of adverse drug Reactions (adr). rational drug use & Essential medicine list, by who, in india, Bangaldesh, iran, norway. is particularly relevant for developing Countries, where a large % of population is below poverty line & therefore is exposed to a greater risk of morbidity & mortality due to infections & infestations. Also can’t afford expensive new drugs. Don’t have access to large tertiary care Hospitals. Based on jpattern — incidence & prevalence of diseases in the country. Adequate data on safety & efficacy about the drug. Availability in a dosage form of suitable Strength, for which adequate quality In terms of ~ bioavailability can be assured Stability under climate conditions. Pharmaceutical form ~ on the basis of cost, p/k, bioavailability, stability, local preference. Compare 2 drugs in respect of — Preferably as a single active ingredient. Fixed dose combination — only when proven advantage over single.26 National lst of ‘essential medicines Allthe drugs in the world Registered medicines ‘Supplementary specialist medicines Referral hospital Private sector Fig. 1.3: National or Institutional list of essential medicines 1977 First Model list published + 200 active substances. List is revised every two years by WHO Expert Committee. April 2003 revised Model list contains 315 active substances, 2007, a separate list for children up to 12 years was included. Latest, The 18th edition for adults and the 4 edition for children were released in April 2013. Ensures availability of most required drugs at all times, in sufficient amounts and in appropriate dosage forms. , Keeps a check on the prices of generically listed drugs. : Substantial savings (50-60 %) including foreign exchange is possible without compromising the quality of health-care. Curtailing the no. of drugs imroves drug dispensing é& patient compliance. Procurement & distribution can be uniform & systemic. Model product: list of essential drugs with information. minimum drug needs for a basic health care system, listing the most cost-effective drugs for priority conditions (selected on the basis of burden of disease and potential for safe and cost-effective treatment).27 essential drugs for priority diseases which are cost-effective but not necessarily affordable or for which specialized health care facilities may be needed and essential drugs for less frequent diseases Identification of public-health need for a medicine. Development of the medicine; phase I - II - II trials. Regulatory approval in a number of countries. Effective and safe medicine on the market More experience under different field circumstances; post-marketing surveillance. Price indication for public sector use. Review by WHO disease programme; define comparative effectiveness and safety in real- life situations, comparative cost effectiveness and public health relevance. Medicine included in WHO treatment guideline Submission to WHO Expert Committee on Essential Drugs. Medicine included in WHO Model List. He process by which medicines are selected is critical. An essential medicines list which is imposed from above will not reflect the needs of the users or be accepted by them. It is therefore very important that the process be consultative and transparent, that the selection criteria be explicit, that the selection of the medicines be linked to evidence-based standard clinical guidelines, that the clinical guidelines and the list be divided into levels of care, and that both are regularly reviewed and updated. A review of the clinical guidelines and the list should be carried out at least every second year, and their use and the impact should be monitored. A standing committee should be appointed to give technical advice. This committee may include people from different fields, such as medicine, nursing, pharmacology, pharmacy, public health, consumer affairs and health workers at grass-roots level. Formal and informal consultations may be organized with interested parties, including representatives of professional bodies, pharmaceutical manufacturers, consumer organizations and the government budget and finance group. However, the final medicines selection by the committee members should be carried out independently.List of common diseases and complaints | es Treatment choice Pore Training and Supervision Serie arines a | Fig, 14: Common diseases and complaints ceeds to be accepted by the committee is that not all evidence is the result of a systematic review of clinical trials carries more’ ational study without controls, and much more than ‘An important principle that né ‘equally strong. For example, weight than the result of an observ personal experience of individual experts. ‘The strength of the evidence defines the strength of the recommendation. Routes of drug administration refer tothe right path or the required route through which @ drug has to be administered into the body to obtain maximum benefit. {A drug administered into the body undergoes several chemical and metabolic changes, ‘These changes reduce the availability of the drug at its final site of action in the body. For: example, some drugs may not be effective when administered orally, but may be effective when administered through injection. Right Patient Right Drug Right Dose Right Route29 Right Time Right Documentation Choosing the correct route of drug administration reduces or bypasses these changes, thereby helping to obtain the drug’s maximum therapeutic effect. In addition, some drugs are maximally absorbed when they are administered through a particular route as compared to another route. An intravenous route of administration of the drug results in 100% bioavailability. According to the Oxford Concise Medical Dictionary. Bioavailability is “the proportion of a drug that is delivered to its site of action in the body. This is usually the amount entering the circulation and may be low when the drugs are given by mouth”, There are several reasons which determine the preferred route of administration of a particular drug. These include: solid, liquid, and gas. For example, drugs in gas form are given by inhalation. solubility, pH, and irritant properties. For example, a skin lesion can be treated with local creams so that maximal effect can be obtained and side effects on the other parts of the body can be avoided. For example, oral or injection antibiotics will be required for infections affecting the internal organs of the body. Drugs used in emergencies are usually given intravenously for quick effect.Local ‘Skin Topical a all venue Enteral Parentral Inhalation Oral Intravenous Transdermal Subic Intramucular Intrathecal Rectal Intradermal Intraarticular ‘Subcutaneous Classification of Route of drug administration For example, since nitroglycerine is digested to a large extent when taken orally, it is given by alternate routes. Rapidity of the desired response in case of emergency or in routine treatment. Cases of emergency usually require intravenous injections so that the medication can reach its site of action quickly. Requirement of accurate dose (of the dose in case of intravenous or inhalational routes can be adjusted accurately during the treatment depending on the patient's response).31 3, Patient condition and compliance (pediatric or geriatric patients, or unconscious patients, or any disease conditions). For example, unconscious patients cannot take drugs orally. Compliance refers to whether the patient follows medical advice correctly or not. This is the most common and easiest route of administration where drugs are given by mouth. Dosage forms administered orally includes: Tablets Capsule Syrup Suspension Emulsion, Solution Elixer The oral route is considered as the first choice of route of drug administration as it is most convenient, cheap and usually a safe method of drug administration. The orally administered medicines are mostly absorbed in the small intestine, and to some extent in the stomach. Some orally administered drugs are specially designed with an enteric coating to withstand the stomach’s digestive juices and to disintegrate in the small intestine. First pass metabolism is a major problem that is encountered with orally administered drugs. The drugs absorbed from the small intestine first reach the liver through the portal circulation “The first pass effect or the first pass metabolism is the process of drug metabolism by which the drug concentration is reduced to some extent by the liver before it enters the bloodstream”. Hence, the oral dose is usually higher when compared with the dose administered through other routes because of the first pass effect by the liver. The bioavailability of the orally administered drug may increase when the'liver suffers from a disease such as cirrhosis. Two or more drugs taken together can also alter a drug's bioavailability and therefore dosage adjustment may be needed. Drugs undergo first pass metabolism to a variable extent. Commonly used drugs that undergo extensive first pass metabolism are: Cimetidine, lidocaine, Propranolol, Nitroglycerin, Diazepam, Midazolam, Morphine, Pethidine, Imipramine, and Buprenorphine. Some drugs like insulin are destroyed by the gast orally. secretions and therefore cannot be givenMetabolism Metabolism Hepatic + Pigestive_, portal ——eLiver —— oem system Rest of the body Fig. 1.6: First Pass metabolism by liver Drugs such as aspirin or (NSAIDs) may irritate the gastrointestinal tract by harming the gastric lining and aggravate existing stomach ulcers. Some drugs are poorly absorbed orally or undergo extensive first pass metabolism, which may reduce the effectiveness of the drug. ‘The oral route of drug administration is not preferred in: Unconscious patients. Patients with restrictions to oral intake. Patients who are vomiting. Emergency situations where a rapid response is necessary. in Latin term means Drugs administered through this route diffuse into the bloodstream through the Hssues under the tongue. The mucous membrane under the tongue is supplied with a bed of rich capillaries. ‘Therefore, the sublingual route has a faster absorption rate when compared with the oral route, The sublingual route of drug administration has an advantage of bypassing the liver first pass effect. As a result, a lower dose of the drug is required when compared with the oral route. Excess drug can be spat out. The dosage forms used sublingually include the sublingual tablets, strips, drops, and sprays.Drugs used sublingually include and The buccal route is the route of administration where the medicine is placed between the gums and the inner lining of the cheek. This route of administration has the same advantages as of sublingual route but the difference is the site of application, Fentanyl buccal patches, Nicotine tablets as smoking cessation aid and Prochlorperazine in treating nausea and vomiting May irritate the already existing open sores in the mouth. Extended-release formulations and large doses cannot be used. Inconvenience in placing on the exact site. The medicine effect will be reduced if accidentally swallowed. Nausea and vomiting may occur if the medicine is associated with unpleasant taste. oer cg guns) {Butea RESON Pan nat [BUCCAL REGION {SUBUNGUAL REGION Sakae Inner tp [BUCCAL REGION] (BUSLINGUAC REGION ‘ge guns) (Butea RESO. ry Alte Sours . Alter 10 nours Fig. 1.7: Location of Sublingual and Buccal Routeand low cost route of administration when compared to ‘The rectal route offers a faster, safer, several other alternative routes. “The medicines given by rectal route are absorbed by the rectum’s blood vessels and enter the bloodstream. ‘A drug administered rectally has a faster less nausea when compared with the oral route. ‘The rectal route of administration undergoes less first pass effect and the drug concentration is also reduced only to a slighter extent from actual drug concentration. ‘The disadvantage of a rectal route is an erratic or irregular absorption, unacceptability of the route by some patients, onset of action, high bioavailability, and produces, and the of administration for children and elderly patients. terile precautions. iculties, bowel obstruction, and decreased Best route Does not require hospital care setting and special st Useful for patients suffering from swallowing diffi propulsive movements in the gastrointestinal tract. Helps patients with terminal stage of illness. It can be administered to unconscious patients. Larger quantities of drugs can be used. Ultrasound probe. Fig. 1.8: Location of Rectal routeto he es on he ed 35 Parenteral route of drug administration means administering the drug through routes that bypass the digestive tract, through injections. The administration requires skilled medical personnel who administer the medication with the help of a syringe and needle or a catheter using aseptic precautions. The cost is higher than that of oral dosage forms and involves the pain of the prick of the needle, which may be scary for some. The most commonly used parenteral routes of administration are subcutaneous, intravenous, intramuscular, and intradermal injections. Rapid absorption and faster onset of action of the drug.The medication bypasses the liver first pass effect. No risk of degradation of the drug by digestive juices. Suitable for uncons ious patients, Low concentration of drug required. Intradermal route of drug administration involves injecting the medication into the dermis, a layer just below the epidermis of the skin. The amount of drug administered through this route is usually less than 0.5ml. This route has the longest absorption time among parenteral medications and is often used for diagnostic purposes for tests such as penicillin sensitivity, diphtheria test and Dick test for scarlet fever. The for tuberculosis is also administered intradermally. The body's reaction to intradermal medicines is more easily visible as the site of administration is closer to the surface. Injection sites: Inner surface of the forearm, upper back under the scapula / shoulder blade A subcutaneous injection is administered under the skin into the fat layer just below the dermis of the skin. The absorption from the subcutaneous route is slow and sustained action as the tissue sites have fewer blood vessels. It has a slower action compared to intravenous but faster than an intradermal route. Drugs used: Measles vaccine, insulin, morphine, and goserelin (a drug used to suppress sex hormones), Injection sites: Outer area of the upper arm, abdomen, upper thigh, upper back, and upper area of the buttock.njecting the medicine directly into ‘The intramuscular route of drug administration involves i the absorption rate is faster than the muscle. As muscles are rich in large blood vessels, subcutaneous and intradermal routes. “The disadvantage of this route is it may lead to nerve or vein damage. Drugs used: Penicillin, haloperidol, diazepam, vitamin B12, methotrexate, platelet-rich plasma injections, vaccines such as tetanus and Injection sites: Muscle area of the upper arm, buttocks or thigh. ‘The route by which the medicines are directly introduced into the bloodstream through a. vein is known as intravenous route of administration. ‘The intravenous route is considered to be the fastest route of drug administration. ‘The injections and the infusions are administered by this route have 100% bioavailability. ch as lactated Ringer’s solutions, parenteral nutrition. Electrolyte fluids, buffer solutions su blood and blood-related infusions. medicines such as amino acids and vitamins, al catheter, midline catheter, Peripheral lines, central lines, peripherally inserted centr tunneled lines and implantable ports. Inflammation of blood vessels could occur. Not suitable for oily and insoluble preparations. Permeation of fluid may occur to the surrounding tissues. Special apparatus such as infusion pumps, drip chamber, peripheral cannula and pressure bags are required. Intermuscular Subcutaneous - ew 4 Intravenous { , a rade CM ete Dorms Subcutaneous issue Deas ie Muscle Fig. 19: Vaarious Route of Parentral drug Administration37 The word in Greek means The topical route of administration refers to the application of the medicines to body surfaces such as skin and mucous membranes and includes transdermal patches, instillation applied to the eye, drops placed into the ear or medications applied to the surface of the tooth. These are painless in contrast to the parenteral route. A few drugs like are administered nasally. A transdermal patch is a medicated adhesive patch which is placed over the skin to deliver specific or controlled dose into the bloodstream for a period of time. The drug enters the blood stream by a process of diffusion at a controlled rate. It is convenient to use. The disadvantages of this route are that it can be used only for the drugs with small molecules which can penetrate the skin. Nicotine patches, contraceptive patches, Opioid patches, Nitroglycerin patches, Clonidine patches and estrogen patches. Apply to the clean, dry, or unbroken skin. Make sure the adhesive patch sticks firmly. Wash your hands after applying a patch. Use only one patch at a time. Patches are to be removed while undergoing x-ray or MRI scan. If any skin irritation develops, the application site should be changed. Rotation of application sites is encouraged. The removed patches should be disposed of safely by folding the sticky sides together to avoid contact with children. If the patch falls off completely do not reapply but use the fresh one as per the dosing schedule. Upper chest, upper outer arm, hip, lower abdomen. Instillations include liquids or semisolid preparations introdi~ conjunctival sac (eye), ear, nose and open wounds.This is used for washing the urinary bladder, vagina, uterus, and urethra; it is mainly used for antiseptic purposes. The enepidermic routes involve the application of creams, ointments, lotions, and poultices that are applied to the surface of the skin. The epidermic routes include the oily preparations that are rubbed onto the skin such as rubefacients to provide counter irritation. The rubefacient dilates the capillaries under the skin and increases the blood circulation used in treating the pain in various musculoskeletal disorders. The medicines are applied to the throat to treat the throat infections with, the help of a thin brush. Glycerin is the commonly used base to stick to the mucous membrane for a long period of time. Examples are Iodine throat paints, Tannic acid throat paints. The inhalational route of administration is an easy method of administration where the medicines directly pass into lungs. This route has quick action with minimal side effects and requires a lesser dose. Volatile drugs and gases such as salbutamol aerosols and nebulization or steam inhalations of tincture benzoin. The airway must be accessible. Special apparatus and supervision or assistance is required. Irritation of the airways may occur. | Sy abo or toustion ely reenact ~ioteietpas, ap Sublingual Irvathecal csr Sustained ofect Teanscermal Fig. 1.10:Summary Digram of Various Route of Drug Administration ~