Badyal - Practical Manual of Pharmacology

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Badyal - Practical Manual of Pharmacology

  1. 1. Practical Manual of Pharmacology
  2. 2. JAYPEE BROTHERS MEDICAL PUBLISHERS (P) LTD New Delhi • Ahmedabad • Bengaluru • Chennai • Hyderabad • Kochi Kolkata • Lucknow • Mumbai • Nagpur Dinesh Badyal MBBS, MD (PGI) Associate Professor DepartmentofPharmacology ChristianMedicalCollege Ludhiana,Punjab India PracticalManualofPharmacology ®
  3. 3. Published by Jitendar P Vij Jaypee Brothers Medical Publishers (P) Ltd Corporate Office 4838/24 Ansari Road, Daryaganj, New Delhi - 110002, India, Phone: +91-11-43574357 Registered Office B-3 EMCA House, 23/23B Ansari Road, Daryaganj, New Delhi - 110 002, India Phones: +91-11-23272143, +91-11-23272703, +91-11-23282021 +91-11-23245672, Rel: +91-11-32558559, Fax: +91-11-23276490, +91-11-23245683 e-mail: jaypee@jaypeebrothers.com, Visit our website: www.jaypeebrothers.com Branches  2/B, Akruti Society, Jodhpur Gam Road Satellite Ahmedabad 380 015, Phones: +91-79-26926233, Rel: +91-79-32988717 Fax: +91-79-26927094, e-mail: ahmedabad@jaypeebrothers.com  202 Batavia Chambers, 8 Kumara Krupa Road, Kumara Park East Bengaluru 560 001, Phones: +91-80-22285971, +91-80-22382956 91-80-22372664, Rel: +91-80-32714073, Fax: +91-80-22281761 e-mail: bangalore@jaypeebrothers.com  282 IIIrd Floor, Khaleel Shirazi Estate, Fountain Plaza, Pantheon Road Chennai 600 008, Phones: +91-44-28193265, +91-44-28194897 Rel: +91-44-32972089, Fax: +91-44-28193231, e-mail: chennai@jaypeebrothers.com  4-2-1067/1-3, 1st Floor, Balaji Building, Ramkote Cross Road, Hyderabad 500 095, Phones: +91-40-66610020, +91-40-24758498 Rel:+91-40-32940929Fax:+91-40-24758499 e-mail: hyderabad@jaypeebrothers.com  No. 41/3098, B & B1, Kuruvi Building, St. Vincent Road Kochi 682 018, Kerala, Phones: +91-484-4036109, +91-484-2395739 +91-484-2395740 e-mail: kochi@jaypeebrothers.com  1-A Indian Mirror Street, Wellington Square Kolkata 700 013, Phones: +91-33-22651926, +91-33-22276404 +91-33-22276415, Rel: +91-33-32901926, Fax: +91-33-22656075 e-mail: kolkata@jaypeebrothers.com  Lekhraj Market III, B-2, Sector-4, Faizabad Road, Indira Nagar Lucknow 226 016 Phones: +91-522-3040553, +91-522-3040554 e-mail: lucknow@jaypeebrothers.com  106 Amit Industrial Estate, 61 Dr SS Rao Road, Near MGM Hospital, Parel Mumbai 400 012, Phones: +91-22-24124863, +91-22-24104532, Rel: +91-22-32926896, Fax: +91-22-24160828 e-mail: mumbai@jaypeebrothers.com  “KAMALPUSHPA” 38, Reshimbag, Opp. Mohota Science College, Umred Road Nagpur 440 009 (MS), Phone: Rel: +91-712-3245220, Fax: +91-712-2704275 e-mail: nagpur@jaypeebrothers.com Practical Manual of Pharmacology © 2008, Jaypee Brothers Medical Publishers All rights reserved. No part of this publication should be reproduced, stored in a retrieval system, or transmitted in any form or by any means: electronic, mechanical, photocopying, recording, or otherwise, without the prior written permission of the author and the publisher. This book has been published in good faith that the material provided by author is original. Every effort is made to ensure accuracy of material, but the publisher, printer and author will not be held responsible for any inadvertent error(s). In case of any dispute, all legal matters are to be settled under Delhi jurisdiction only. First Edition: 2008 ISBN 978-81-8448-362-8 Typeset at JPBMP typesetting unit Printed at Ajanta Offset & Packagins Ltd., New Delhi
  4. 4. To My beloved students (who have been my teachers too) and My daughter Anvi
  5. 5. Preface We are what we repeatedly do, excellence then is not an act, but becomes a habit. —Aristotle To impart skills to budding doctors practical pharmacology is an essential area of teaching. This practical manual describes what you do with your own hands which will help you throughout the life. This manual has been written keeping in view the desired shift in the pharmacology practical teaching from pharmacy based redundant experiments to more meaningful, clinically relevant problem based exercises. The topics covered in the manual have been carefully selected based on the most recent (2007) improvised problem based curriculum design for pharmacology (Appendix I). The book covers all essential components to impart the necessary required skills to students in the subject of pharmacology as per prevailing regulations in the country. The manual highlights the important skills to be imbibed by budding doctors which will aid in rational therapeutics. The manual covers all feasible exercises in pharmacology. The manual is flexible enough to suggest various modifications for various medical colleges as per availability of material for practicals. A time schedule is also included (Appendix II), which can be modified as per requirements. The exercises vary from simple demonstrations to computer simulation models. Special care is taken to keep the cost of material needed for practicals as low as possible. There are sufficient examples for students to apply the concepts learned in practicals. There are also new topics like ethics, which has become very important now after implementation of consumer protection Act to doctors. I am thankful to all my students for sharing their concern about existing pharmacology practicals and for their views on modifications in pharmacology practical training. That in a way, encouraged me to write this manual. I am thankful to Mr Tarun Duneja of M/s Jaypee Brothers Medical Publishers (P) Ltd, New Delhi for expediting the publication. I hope that students and teachers would benefit from this manual. Suggestions for improvements from teachers and students are most welcome. Dinesh Badyal dineshbadyal@rediffmail.com
  6. 6. Contents Section1: ClinicalPharmacy 1. Introduction to Clinical Pharmacy ........................................................................3 2. Weights, Measures and Abbreviations ...............................................................7 3. Labeling of Drugs ....................................................................................................13 4. Pharmacy Preparations ..........................................................................................21 5. Common Dosage Forms and Routes of Administration-I .............................30 6. Common Dosage Forms and Routes of Administration-II............................39 7. Common Dosage Forms and Routes of Administration-III ..........................54 Section2: ExperimentalPharmacology 8. Introduction to Experimental Pharmacology ....................................................73 9. Effects of Drugs on Rabbit Eye ............................................................................75 10. Effect of Drugs on Frog Heart ...............................................................................80 11. Effect of Drugs on Rabbit Intestine ....................................................................86 12. Effect of Drugs on Dog Blood Pressure .............................................................90 13. Short Experiments for Efficacy and Safety .......................................................94 14. Ethics and Animals .................................................................................................98 Section3: ClinicalPharmacology 15. Introduction to Clinical Pharmacology ........................................................... 103 16. Pharmacokinetic Parameters and Calculations ............................................ 104
  7. 7. x  Practical Manual of Pharmacology 17. Prescription Writing Through Problem Based Learning (Rational Prescribing).......................................................................................... 112 18. Critical Evaluation of Prescription (Audit of Prescriptions) ..................... 157 19. Problem Based Drug Interactions .................................................................... 162 20. Adverse Drug Reaction (ADR) Monitoring ................................................... 178 21. Therapeutic Drug Monitoring (TDM) ............................................................. 187 22. Drug Use in Special Population/Diseases/Physiological Conditions...... 194 23. Critical Appraisal of Drug Promotional Literature ..................................... 207 24. Therapeutic Follow-up Cases/Problems ......................................................... 215 25. New Drug Development ..................................................................................... 219 26. Calculation of Drug Doses and Dilutions ...................................................... 223 27. Evaluation of Drug Formulations ..................................................................... 232 28. Ethics and Humans .............................................................................................. 238 29. Management of Some Common Poisonings .................................................. 243 30. Objective Structured Practical Examination (OSPE) ................................... 253 Appendix I ............................................................................................................... 257 Appendix II ............................................................................................................. 259 Appendix III ............................................................................................................ 261 Appendix IV ............................................................................................................ 262 Terminologies Used in Pharmacology ............................................................... 283 Index ......................................................................................................................... 287
  8. 8. Section 1 Clinical Pharmacy
  9. 9. C H A P T E R Introduction to Clinical Pharmacy1 Earlier, pharmacy used to be typically related to preparing and dispensing of drugs only. In those days, a doctor would himself prepare or formulate the drug in his dispensary and dispense it to his patients. This practice is now almost obsolete. These days doctor gets all the drugs in ready-made form. The pharmaceutical industry (Ranbaxy, Cipla, etc.) are now manufacturing these drugs on mass scale. The doctor’s job is to rationally prescribe and use these drugs. With this, there is now shift in pharmacy practicals. The redundant practicals comprising of preparing and dispensing can be replaced by more clinically relevant clinical pharmacy practicals. That’s why this chapter focusses on clinical pharmacy and not just pharmacy. I feel that a budding doctor needs to be trained better in recognizing various dosage forms available to be used for patients, correct way of administration of these drugs and interpretation of information on drug labels. A number of medical colleges have reduced/ deleted pharmacy preparation practicals from the course. The MCI also insists on replacing unnecessary pharmacy practicals with more relevant clinical pharmacy practicals. Some people are still continuing with pharmacy preparation practicals as they find no alternative available. However, we can generate alternatives with the available resources in the department. These alternatives can be easily arranged with no cost involved. To achieve this, total number of pharmacy practicals can be divided into 12 practical sessions assuming that there is one practical session per week, so this comes out to be initial three months of pharmacology practical course (Appendix 2). Conventional pharmacy is art of preparation, compounding and dispensing of drugs. It also includes interpretation and evaluation of prescriptions. Some hospitals have their own pharmacies. Usually it is managed by a qualified pharmacist. There can be main pharmacy and satellite pharmacies throughout the hospital. These hospitals usually follow a computerised coded system for drugs. The common source to get drugs is usually chemist shops which can be labeled as retail pharmacies. There is a difference between functioning of pharmacies in hospitals and chemist shops. The pharmacies in hospitals, these days do not manufacture/ prepare a large number of drugs. Only few preparations related with dermatological sciences are prepared. In chemist shops only ready-made drugs are available. The common functions of both is to advise proper use of drugs and other precautions to patients. At some places they also provide information to doctors, nurses and other health care providers.
  10. 10. 4  Practical Manual of Pharmacology Instruments which are used in pharmacy are: DISPENSING BALANCE It is meant for weighing of more than 100 mg of a substance, i.e. sensitivity is 100 mg. Left pan is made up of metal (for putting weights). Right pan is made up of glass/metal for putting substances to be weighed. Advantages of glass pan is that it is inert, non-reactive, can be easily washed and anything sticking to it can be seen. A butter paper can be used to weigh salts, salts do not stick to butter paper. This balance is sensitive for most of pharmacy work for common preparations (Fig. 1.1). It can be dismantled and packed in a small wooden box. These days electronic balances (Fig. 1.2) are available which can be conveniently used to measure even a very small quantity of drugs. The information about balance will help a doctor in clinics when you need to give a small dose to a child or when you want to divide one dose into multiple doses. Usually pharmacist/pharmacologist is approached by pediatric department to divide the dose into small multiple fractions. WEIGHTS Students are provided with a box containing weights ranging from 1 to 100 gm. There is one additional small box containing very small weights ranging from 1 to 500 mg. MEASURING CYLINDERS AND FLASK (FIG. 1.3) The capacity can vary from 5 to 1000 ml. They are used for measuring liquid or solution, but they are less accurate as compared to pipettes. They are safer as compared to pipettes. With pipettes there are chances of contact of liquid with oral cavity, hence manual pipettes are not recommended. MORTAR AND PESTLE It is made up of porcelain. It is used to grind the drug to powder form and also used to mix ingredients of powders, liquid or semiliquid, ointments, mixtures, suspensions, etc. These days glass mortar and pestle are available (Fig. 1.4). An advantage is that less drug sticks to glass and they are easy to clean. Fig. 1.1: Dispensing balance and weights
  11. 11. Introduction to Clinical Pharmacy  5 CONTAINERS (FIG. 1.5) Prescription bottle is used for liquids of low viscosity like mixtures, suspensions and solutions. It is made up of glass or plastic. Wide mouth bottle is used for solutions of high viscosity like ointment, etc. Amber coloured bottle prevents degradation of solution inside by absorption of UV rays, e.g. calamine lotion. SPATULAS They are used to mix various chemicals, e.g. powders or ointments. They are formed of plastic or metal (Fig. 1.6). PILL TILE It is used to mix the powders or ointments. WASH BOTTLE It contains tap or demineralised water. Fig. 1.2: Electronic Balance Fig. 1.3: Measuring cylinder and flask Fig. 1.4: Mortar and Pestle Fig. 1.5: Dispensing bottle Fig. 1.6: Spatula
  12. 12. 6  Practical Manual of Pharmacology PHARMACEUTICAL CONTAINERS The basic requirement for a container is that it should not interact with the formulation. Glass, plastics are commonly used components of containers. Glass containers have some disadvantages, e.g. leaching of alkali and insoluble flakes into the formulation. These can be offset by the choice of an appropriate glass material, e.g. phenytoin has the ability to (in dilute solution) to react with glass. When added to glass infusion bottles much of the drug remains stuck to the glass and does not reach the patient. Plastic containers are convenient to handle but the major disadvantage is the two-way permeation or ‘breathing’ through the container walls. Volatile oils, perfumes and flavouring agents can permeate through plastics to some extent. Components of emulsions and creams have been reported to migrate through the walls of some plastics causing either a deleterious change in the formulation or collapse of the container. Loss of moisture from a formulation is also common, e.g. paraldehyde (a hypnotic) is one example. This liquid dissolves plastic so it must be injected parenterally using glass syringe. Closure must form an effective seal for the container. It must not react chemically or physically with the formulation. Rubber is a common component of stoppers, cap liners, and parts of dropper assemblies. Absorption of the active ingredients, preservatives into the rubber and the extraction of one or more components of rubber into the formulation is a common problem. The application of an epoxy lining to the rubber closure reduces the amount of leached extractives but has no effect on the absorption of the preservative from the solution. Teflon- coated rubber stoppers may prevent most of the leaching and absorption. OBJECTIVES At the end of this session a student shall be able to: 1. Identify various instruments used in pharmacy. 2. Describe uses of instruments used in pharmacy.
  13. 13. These are important to know dose and other details about administration of drugs. The drugs and solutions can be measured by using various units. Metric or decimal system of measure is usually used to measure due to two advantages: i. Its tables are simple as they are based on decimal system of notation ii. Its tables of length, volume and weight are conveniently correlated. METRIC SYSTEM In metric system: • Base for weight is kilogram (kg) • Base for volume is litre (l) Measures of weight (mass) in metric system 1 kilogram (kg) = 1000 grams (G or g) 1 gram = 1000 milligrams (mg) 1 milligram (10-3 g) = 1000 micrograms (μg or mcg) 1 microgram (10-6 g) = 1000 nanograms (ng) 1 nanogram (10-9 g) = 1000 picograms (pg) 1 picogram (10-12 g) = 1000 femtograms (fg) Measures of capacity (volume) in metric system 1 liter (L) = 1000 milliliters (ml) 1 ml = 1000 μl Another less commonly used system is imperial system. It can be: a. Avoirdupois system Standard for weight = pounds (lb) 1 lb = 7000 grains 1 lb = 16 ounce (oz) C H A P T E R Weights, Measures and Abbreviations 2
  14. 14. 8  Practical Manual of Pharmacology b. Apothecary system (UK)/Troy system Standard for weight is grains 1 oz = 480 grains 1 lb = 12 oz Measure for volume in both these system is Gallon 1 gallon (C. or gal.) = 4 quarts = 8 pints 1 quart (qt.) = 2 pints = 32 fluid ounces 1 pint (pt.) = 16 fluid ounces (fl. oz. or ) CONVERSION BETWEEN SYSTEMS Weight 2.2 pounds = 1 kilogram (kg.) 1 grain (gr.) = 60 milligrams (mg.) Fluid Measure 1 fluid ounce (fl. oz.) = 30 milliliters 1 pint = 473 milliliters There are also domestic measures to measure: Domestic weights and measures Domestic measures Metric equivalent 1 drop = 1/20 ml, 1 ml = 20 drops (approx.) 1 teaspoonful = 5 ml 1 dessertspoonful = 10 ml 1 tablespoonful = 15 ml 1 glassful = 150 ml 1 tumblerful = 240 ml PHARMACEUTICAL CALCULATIONS 1. Percent Calculation The word percentage can have different meanings under different circumstances. In solution, we are dealing with solids that are weighed and liquids that can be weighed or measured. There are three different percentage solutions. a. Percentage weight in weight (w/w)—expresses the number of grams of solute in 100 ml of solution. b. Percentage weight in volume (w/v)—expresses the number of grams of solute in 100 ml of solution, regardless of whether water or another liquid is used as the solvent. c. Percentage volume in volume (v/v)—expresses the number of milliliters of solute in 100 ml of solution. a. Percent weight in volume (%w/v) It is a solution of solid in liquid and represents number of solutes per 100 ml of solution.
  15. 15. Weights, Measures and Abbreviations  9 1% w/v is 1 g of solute in a total of 100 ml of solution. 1% w/v means 1 part by weight, whereas the solvent is added upto 100 parts. 1% = 10 mg/ml e.g. To calculate the quantity of CaCl2 required for 200 ml preparation of 1% solution in distilled water 1% means 1 g/100 ml for 100 ml volume, CaCl2 = 1 g For 200 ml CaCl2 = 1/100 × 200 = 2 g b. Percent by weight (%w/w) It represents number of grams of solute per 100 gm of solution. 1% w/w is 1 g of solute in 100 g solution. Add solid 1 part by wt and then add upto 100 parts, ensuring uniform mixing (Highly viscous substances like glycerin are considered solids and are measured in grams) e.g. To prepare 25 g of 10% of a drug 10% means 10 g/100 g of the preparation if 100 g has drug = 10 g 25 g of preparation will have drug = 10/100 × 25 = 2.5 g c. Percent by volume (%v/v) It is a preparation of a liquid in liquid and represents number of millilitres of solute per 100 ml of solution. 1% v/v is 1 ml of a liquid constituent in 100 ml of solution, e.g. To make 2% v/v, to 2 part of volume of the constituent add upto 100 parts by volume. 2. Proportion Calculation Involves mixing of 2 similar preparations of different strength to produce a preparation of intermediate strength. Proportions are equations containing ratios of equal value. For example 3:4 = 6:8. This may also be written as fractions, 3/4 = 6/8. (see chapter 27 for more). 3. Others i. Units Potency of certain drugs like heparin, insulin either cannot be determined by chemical or physical methods or these methods are very costly. The measurement of these drugs is expressed in units. The unit is based on the effect/ amount of effect produced by a particular amount of drug in biological systems, i.e. isolated tissues of animals or whole animals, e.g. 40 units of insulin. ii. Molality: It is the number of moles of solute in 1000 grams of solvent. iii. Normality: It is the number of gram equivalents of solute dissolved in 1000 ml of solution.
  16. 16. 10  Practical Manual of Pharmacology ABBREVIATIONS USED IN PRESCRIPTIONS A prescription should be written in simple and/or in regional language without using abbreviations, however, certain abbreviations are still in use as under: A. Time of Drug Administration Phrase Abbreviation Meaning ante cibum ac before meals post cibum pc after meals hora somni hs at bedtime opus in die od once a day bis bis twice bis in die bid twice daily ter in die tid three times a day ter die sumendum tds three times a day quarter in die qid four times a day quaque q every 6 hour quarta quake qqh every 4 hour omni mane om every morning omni nocte on every night si opus sit sos when required statim stat immediately ad libitum Ad lib freely, use as much as one desires omni die od every day repetatur Rep let it be repeated B. Formulations Phrase Abbreviation Meaning capsula cap capsule tabella tab tablet liquor liq solution mistula mist mixture injectio inj an injection ampoule amp an ampoule syrupus syr syrup gutta gtt drops nebula nebul spray
  17. 17. Weights, Measures and Abbreviations  11 C. Routes of Drug Administration Phrase Abbreviation Meaning intramuscular IM by Intramuscular injection intravenous IV by Intravenous injection subcutaneous sc by subcutaneous injection per os po by mouth per vaginam PV by vaginal route bolus bol as a large single dose (usually IV) D. Others Phrase Abbreviation Meaning Ad Ad to, up to aqua aq water receipe R (you) take signa sig you write aurio dextra ad right ear aurio laeve al left ear auris utrae au both ears oculus dexter od right eye oculus sinister os left eye oculus uterque ou both eyes ex modo prescripto emp as directed misce M mix dispensa Disp. Dispense signa sig you write tablespoon tbsp tablespoon teaspoon tsp teaspoon OBJECTIVES At the end of this session a student shall be able to: 1. Understand meaning of all abbreviations used in Pharmacology. 2. Convert various measurements given. 3. Understand percent and proportion calculations.
  18. 18. 12  Practical Manual of Pharmacology Exercise in examination based on these practical can be: 1. Expand the following: a. Cap. Rifampicin 600 mg od ac b. Tab. diazepam 5 mg hs c. Syr. Amoxycillin 5 ml tid po d. Tab. FeSO4 200 mg 2 bd pc e. Tab. PCM 500 mg sos f. Inj. Ampicillin 0.5 g IM qid 2. What do you understand by: a. 1% NaCl solution b. 15% tannic acid glycerin c. 5% lignocaine ointment
  19. 19. C H A P T E R Labeling of Drugs3 If you pick up a strip of any medicine, you will find a lot of information on it, regarding drug name, manufacturer, expiry date, etc. as shown below in Figure 3.1. Fig. 3.1: Labels on premanufactured medicines Let us discuss in detail what various components of these labels are. COMMERCIAL PREPARATIONS Label of the given dosage form consists of Name and quantity of the drug Pharmacopeias used for preparation
  20. 20. 14  Practical Manual of Pharmacology Batch No Manufacturing and expiry date Manufacturing license number Maximum retail price (MRP) Schedule of the drugs, i.e. H, L, P, X, etc. Instructions about use of drugs Address of the pharmaceutical company To explain these terms let us discuss some general points: A. DRUGS ARE CLASSIFIED INTO VARIOUS CATEGORIES 1. Prescription-only Drugs: These drugs are dispensed by pharmacist only when you have a prescription from a registered medical practitioner (RMP), e.g. diazepam, morphine and antimicrobials. Prescription is a written order from physician for pharmacist. Registered medical practitioner is a doctor registered with regional or central medical council. An allopathic RMP can not prescribe drugs from homeopathic stream and vice versa, e.g. an allopathic doctor can not prescribe Liv 52. These drugs are covered under Schedule 'H' in India (Fig. 3.2). These drugs are considered to be unsafe for general use, except under medical supervision. They are dispensed only on physician's prescriptions. 2. Over-the counter (OTC) drugs: These are non prescription drugs, i.e. these can be purchased from pharmacies or chemist shops without a prescription. These drugs are considered safe and medical supervision is not required; e.g. Paracetamol. The drugs which are mainly used as OTC drugs are: • H2 -antihistamines • NSAIDs • Oral contraceptives • Hydrocortisone cream • Nicotine-cessation of smoking OTC drugs may lead to adverse drug reactions (ADRs) because of: • Incorrect self-diagnosis and choice of incorrect therapy • Incorrect route of administration • Excessively prolonged use • Risk of dependence and abuse • Food and drug interactions • Storage in incorrect conditions Fig. 3.2: Schedule H warning
  21. 21. Labeling of Drugs  15 • Failure to recognise o Contraindications o Interactions o Warnings o Precautions So to avoid these, whenever you use an over-the-counter (OTC) medicine, reading the drug label is important for taking care of yourself and your family. This is especially true because you probably take OTC medicines without first seeing a doctor. The label tells you what a medicine is supposed to do, who should or shouldn't take it, and how to use it. The OTC medicine labels have always contained usage and safety information for consumers, but now the information will be more uniform and easier to read and understand (Fig. 3.3). All nonprescription, over-the-counter (OTC) medicine labels have detailed usage and warning information so consumers can properly choose and use the products. You'll find this information: • Active Ingredient: Therapeutic substance in product; amount of active ingredient per unit. • Uses: Symptoms or diseases the product will treat or prevent. • Warnings: When not to use the product; conditions that may require advice from a doctor before taking the product; possible interactions or side effects; when to stop taking the product and when to contact a doctor; if you are pregnant or breastfeeding, seek guidance from a health care professional; keep product out of children's reach. • Inactive Ingredients: Substances such as colors or flavors. • Purpose: Product action or category such as antihistamine, antacid, or cough suppressant. Fig. 3.3: Labeling of OTC medicine
  22. 22. 16  Practical Manual of Pharmacology • Directions: Specific age categories, how to take, how much, how often, and how long. • Other Information. How to store the product properly, and required information about certain ingredients such as the amount of calcium, potassium, or sodium the product contains. • The expiry date, when applicable (date after which you should not use the product). • Lot or batch code (manufacturer information to help identify the product). • Name and address of manufacturer, packer or distributor. • Net quantity of contents (how much of the product is in each package). • What to do if an overdose occurs. B. DRUG NOMENCLATURE You will frequently find existence of multiple names for a single drug. These names are: 1. Chemical name: It indicates full name according to chemical constituents. It is lengthy, complicated and not commonly used, e.g. 4-[2-Hydroxy-3-[(1-methyl ethyl) amino] propoxy] benzene acetamide for atenolol. 2. Non proprietary name/Generic name/Approved name: Name in official books which is accepted worldwide, e.g. aspirin. It allows identification of different products with the same ingredient to be identified, although there are few exceptions, e.g. adrenaline in India is known and epinephrine in United States of America. Drugs if prescribed by generic name are cheaper as promotional expenditure is avoided, but quality control is difficult for generic drugs. 3. Proprietary name/Trade name/Brand name: Names given by innovative manufacturing company, e.g. Crocin for paracetamol. Patent protection enables innovative pharmaceuticals to market the drug exclusively till the patent expires. After that the same drug is available under various brand names, e.g. paracetamol brand names are crocin, acemol, bepamol, calpol and dolopar. Brand names are popular names of the drug and are easy to remember, but so many brand names for a single drug can create confusion in prescribing. Brand names are expensive also as advertisement cost is added. The drugs can have strikingly similar names leading to prescription errors or medication errors. To overcome these WHO has initiated a programme on selection of International non-proprietary names (INN) for assigning a unique, globally accepted and recognized name. C. PHARMACOPOEIA Name is usually followed by the reference according to which drug was prepared, e.g. IP means Indian pharmacopoeia. Pharmacopoeia is a class of DRUG COMPENDIA (official books of summarized information sources). The term pharmacopoeia is derived from two Greek words—Pharmakon (means drug) and poiein (means make). Pharmacopoeia contains formula or other standards required for preparation and testing of drugs to ensure uniform purity and potency. The description of preparation given in pharmacopoeia is known as
  23. 23. Labeling of Drugs  17 monograph. These monographs describes drug, characteristics for identification, standards of purity and strength limits of impurities, assay method of drugs, storage and instructions. Drug and the information mentioned in pharmacopoeia are official. It also includes official range of dosage for drugs, system of weights, measures and the formulations and the methods used for sterilization of pharmaceutical products. Most of the countries have their own pharmacopoeia. Other source for this type of information is National Formulary. These are the books of standards for drugs and devises. These are compilations of those drugs, which have been recognized as legal standards of purity, quality and strength by government agency of that country. Official reference books of India: Indian Pharmacopoeia (IP) National Formulary of India (NFI) Chemical and Medical Formulary of India Drug Bulletins International official books: British Pharmacopoeia (BP) British Pharmaceutical Codex (BPC) United States Pharmacopoeia (USP) International Pharmacopoeia (By WHO for those countries who do not have their own pharmacopoeia) Others: British National Formulary Martin Dale's Extra Pharmacopoeia Physician's Desk Reference D. THESE DAYS YOU MAY FIND A DRUG NAME CARRYING A POST SUFFIX. These are: D-dispersible, e.g. Doxycycline-D CR-controlled release, e.g. Indomethacin-CR SR-sustained release, e.g. Diclofenac-SR E. DRUGS SCHEDULES AND ACTS Sometimes you will find drug names followed by a boxed warning, e.g. Schedule H drug. These are based on drugs schedules and acts. There are various drug schedules and acts in India. The important ones are as per Drugs and Cosmetics Act (1940) as amended in 2001 are:
  24. 24. 18  Practical Manual of Pharmacology DRUG SCHEDULES Schedule A: gives specimen of prescribed form. Schedule B: gives fees for test and analysis of drugs. Schedule C: gives details with biological and other special products. Schedule D: is concerned with exemption regarding drug import. Schedule FF: gives details of standard ophthalmic solutions. Schedule G: deals with details of drugs to be labeled 'CAUTION-it is dangerous to take this medicine except under medical supervision'. Schedule H: deals with drugs and medicine to be sold on prescription-only. Schedule I: lists all ailments for which no cure can be claimed, e.g. AIDS. Schedule Q: deals with cosmetics. Schedule R: deals with standards for contraceptives. Schedule W: gives details of drugs which should be marketed under generic name only. Schedule X: deals with psychotropic drugs which require special license for manufacturing and sale. Schedule Y (new addition): specifies the requirements and guidelines on conduct of clinical trials, import and manufacturing of new drugs. FDA (USA) SCHEDULES ARE: Schedule I (C-I) • High abuse potential • No accepted medical use in the United States • Examples: heroin, marijuana, LSD (lysergic acid diethylamide), peyote Schedule II (C-II) • Potential for high abuse with severe physical or psychological • dependence • Examples: narcotics such as meperidine, methadone, morphine, oxycodone, amphetamines and barbiturates Schedule III (C-III) • Less abuse potential than schedule II drugs • Potential for moderate physical or psychological dependence • Examples: nonbarbiturate sedatives, nonamphetamine stimulants, limited amounts of certain narcotics Schedule IV (C-IV) • Less abuse potential than schedule III drugs • Limited dependence potential • Examples: some sedatives and anxiety agents, nonnarcotic analgesics
  25. 25. Labeling of Drugs  19 Schedule V (C-V)* • Limited abuse potential Examples: small amounts Drugs which are prepared and dispensed by pharmacist usually have different label than the ones prepared by pharmaceutical industry. The label is divided into two: 1. Primary Label 2. Secondary Label PRIMARY LABEL It is the main label used on pharmacy preparations. It should be proportional to the size of container and it usually should occupy middle 1/3rd of the container. It should cover less. This label should have following information: Title of preparation, e.g. The Powder Name : Age/Sex : Reg. No. : Directions : Date/Signature Registration no. Directions/instructions to patients for proper use of drug. Name of the pharmacy laboratory from which the drugs have been dispensed. SECONDARY LABEL As obvious from the name, it is the other label than the primary label. It is smaller in size and is usually put above the primary label with a small gap in between. This label usually contains some important precautions about the use of drug in capital letters, for example: Shake Bottle Well Before Use The number of secondary labels may be more than one. OBJECTIVES At the end of this session a student shall be able to: 1. Understand all information written on label of drugs. 2. Understand primary and secondary labels. 3. Knows drug nomenclature.
  26. 26. 20  Practical Manual of Pharmacology Exercise in examination bases on these practical can be: 1. Enumerate all the information written on the label of drugs: A strip of tablets A container of liquid An ampoule A vial 2. What do you understand by the following terms? Mention the clinical importance of each of them. a. Manufacturing Date b. Expiry Date c. Batch Number d. MRP e. Schedule H
  27. 27. C H A P T E R PharmacyPreparations4 To give an idea to students about how drugs are prepared in pharmacy, a few pharmacy preparations practicals can be demonstrated in two session. Exercise 1: To prepare and dispense 50 ml of Calamine lotion Formula: For 100 ml Calamine 15 gm Zinc oxide 5 gm Bentonite 63 gm Liquefied phenol 0.5 ml Sodium citrate 5 gm Glycerine 5 ml Purified water ad 100 ml PROCEDURE • Weigh out the calculated quantities of calamine, zinc oxide and bentonite. Mix them thoroughly in a mortar. • Take 20 ml of purified water in graduated flask and add the required quantity of sodium citrate. • Pour a little of water from flask into mortar containing calamine, bentonite and zinc oxide. Triturate to make homogenous paste. Add required amount of glycerin and phenol to this mortar and triturate. • Transfer the mixture to the flask. Rinse the mortar with a little quantity of purified water and transfer this rinsing into the flask. Add sufficient quantity of water to make up the final volume 50 ml. Transfer it to an amber coloured bottle, label and dispense. HOW TO APPLY • Wash and completely dry the affected area before applying the lotion. Shake lotion well before use.
  28. 28. 22  Practical Manual of Pharmacology Secondary Labels Primary Label ← ← • Apply this medication to the affected area of skin, generally three to four times daily or as directed by your physician. • Do not dilute or mix with other lotions. LABELING FOR EXTERNAL USE ONLY SHAKE WELL BEFORE USE Name Rajesh Singh Age/Sex 35 M Address 145, BRS Nagar, Ludhiana Directions: Apply on the affected part with cotton swab. Do not rub. Sign and Regd No. of 24-05-2007 Pharmacist Pharmacy, ABC Delhi PHARMACOLOGICAL ACTIONS Calamine: Calamine is a mixture of zinc oxide (ZnO) with about 0.5% iron (III) oxide (Fe2 O3 ). It is the main ingredient in calamine lotion and is used as an antipruritic to treat sunburn, eczema, rashes, poison ivy, chickenpox, insect bites and stings. It is used as a mild antiseptic to prevent infections that can be caused by scratching the affected area. It is also used to dry weeping or oozing blisters and acne abscesses. It is also used as colouring agent in various cosmetics. Zinc oxide: It is insoluble in water, used as dusting powder, ointment, lotion and paste. It has soothing and protective action in eczema. It is also used as mild astringent for skin. Bentonite: It is colloidal aluminum silicate insoluble in water but swells into a homogenous mass. It is used as suspending agent because it increases the viscosity of the vehicle. It is also used as a bulk laxative. It should be sterilised before using on open wounds. Sodium citrate: It helps in the dispersion of solids in this preparation and reduces the viscosity of this preparation. Liquefied phenol: It has an antiseptic and mild local anesthetic effect. However, in the amount used, it acts as a preservative in this preparation. It is particularly required as glycerin promotes the growth of microorganisms. Glycerine: When applied locally it acts as an emollient and helps in penetration of ingredients by making the skin moist and soft. Due to its viscous nature, the lotion stays for a longer time at the site of application. It is hygroscopic in nature, so prevents drying up and cracking of skin and the lesions.
  29. 29. Pharmacy Preparations  23 Secondary Label Primary Label ← ← THERAPEUTIC USES 1. In pruritis: used as soothing and protective lotion. 2. To allay pain and swelling of sun burns. 3. For prickly heat 4. Any other irritating skin condition 5. It is also used in herpes zoster and chickenpox. PRECAUTIONS • Avoid contact with the eyes, on the inside of your nose, mouth or genital area • Contraindicated if known sensitivity or allergy to any ingredient • Ask a doctor before using calamine lotion on children younger than 6 months of age. Exercise 2: To prepare and dispense 25 ml of Mandle's throat paint Formula for 100 ml: For 100 ml Iodine 1.24 gm Potassium iodide 2.48 gm Mentha oil 0.40 ml Water 2.48 ml Alcohol 90% 3.76 ml Glycerine upto 100 ml PROCEDURE • Weigh out the required amount of iodine and potassium iodide and transfer to a glass jar. 10 drops of water and 5 ml of glycerin. Stir the contents. When contents are completely dissolved, add required amount of Mentha oil and dissolve it. • Transfer the contents into a measuring cylinder and add glycerin to make volume upto 25 ml. Transfer contents into amber colored bottle, label and dispense. LABELING FOR EXTERNAL USE ONLY Name Rajesh Singh Age/Sex 35 M Address 145, BRS Nagar, Ludhiana Directions: Apply on the affected part with cotton swab. 3 times a day. Sign and Regd No. of 24-05-2008 Pharmacist Pharmacy, ABC Delhi
  30. 30. 24  Practical Manual of Pharmacology PHARMACOLOGICAL ACTIONS Iodine: It is nonmetallic component. It acts locally and has antiseptic properties. It is an oxidising agent and acts as bactericidal. Potassium iodide: It is used to dissolve iodine as iodine is highly soluble in aqueous solution. Water acts as solvent for potassium iodide. Mentha oil acts as flavouring agent and is volatile. Alcohol is used to dissolve mentha oil and glycerin. It also acts as preservative, antiseptic and astringent. Glycerine helps iodine to stick to affected area for longer period. It also has antiseptic action and reduces edema. THERAPEUTIC USES 1. Tonsillitis 2. Pharyngitis PRECAUTIONS Do not take food/water half an hour before and after the application of the paint. Exercise 3: To prepare and dispense 1:5000 solution of Potassium Permanganate with directions to dilute it to 1:15000 before use. Calculations Prepare 1% stock solution 1% stock solution is 1 gm in 100 ml or 1000 mg in 100 ml or 100 mg in 10 ml or 100 mg in 1 ml For 1:5000 solution of KMnO4 we need: 1g in 5000 thousand ml or 1000 mg in 5000 ml or 10 mg in 50 ml Procedure 1. Measure accurately 100 mg of KMnO4 crystals. Dissolve it in 10 ml of distilled water (1% stock solution). Stir with a glass rod to mix potassium permanganate solution. 2. Take 1 ml of solution and add 49 ml of water to make volume 50 ml. This is 1:5000 solution. 3. Label and dispense it in an amber coloured bottle to privet oxidation.
  31. 31. Pharmacy Preparations  25 Secondary Label Primary Label ← ← LABELING FOR EXTERNAL USE ONLY Name Rajesh Singh Age/Sex 35 M Address 145, BRS Nagar, Ludhiana Directions: Dilute the solution before use by mixing 1 part of solution with 2 parts of water. Use it for gargles and mouth washes 3-4 times in a day. Sign and Regd No. of 24-05-2009 Pharmacist Pharmacy, ABC Delhi STORAGE CONDITIONS It should be stored in a tightly corked container in a cool dark place away from the sunlight. PHARMACOLOGICAL ACTIONS Potassium permanganate has bactericidal and fungicidal activity. Potassium permanganate, on contact with organic matter, liberates nascent oxygen that oxidizes enzymes essential for living microorganisms and their metabolism, thus producing antiseptic effects. It also acts as astringent. It is readily soluble in water. THERAPEUTIC USES The major uses of this preparation are: 1. As disinfectant for water and utensils-1 in 100 solution. 2. As a cleansing application to ulcers and abscesses-1 in 1,000 solution. 3. As mouthwash (in gingivitis and steatites), gargles (Condyl's gargles), for washing wounds and for vaginal irrigation-1 in 4,000 solution. 4. Sitz's baths given in hemorrhoids, piles and fissures. 5. As gastric lavage in the treatment of morphine, opium, strychnine, aconitine and other alkaloid poisonings (but not for cocaine and atropine because they are not easily oxidised by potassium permanganate)-1 in 5,000 solution is employed as applications for weeping skin lesions and for urethral irrigation-1 in 5,000 and 1 in 10,000 solutions. 6. Treatment of snake bite (effective only if the venom is on the skin). It oxidize venom (within 1-2 minutes of bite).
  32. 32. 26  Practical Manual of Pharmacology ADVERSE EFFECTS • The crystals and concentrated solutions of KMnO4 are caustic and can cause corrosive burns. • Higher concentration can cause skin irritation, edema and mucous membrane turns brown. • There can be staining of clothes • Do not disinfect surgical instruments, rusting can happen. Exercise 4: To prepare and dispense one dose of oral rehydration powder for 1000 ml of oral rehydration solution (ORS) ORS is a simple, cheap and effective treatment for diarrhea-related dehydration, e.g. cholera or rotavirus. It consists of a solution of salts and other substances such as glucose, sucrose, citrates or molasses, which is administered orally. It is used around the world, but is most important in the Third World, where it saves millions of children from diarrhea, still their leading cause of death. WHO FORMULA (FOR 1 LITRE ORS) Sodium chloride 3.5 gm Sodium citrate 2.9 gm Potassium chloride 1.5 gm Glucose anhydrous 20.0 gm OBJECTIVE OF ORS • To prevent dehydration • To reduce mortality. PROCEDURE • Weigh the required quantities of sodium chloride, sodium citrate, potassium chloride and glucose. • Mix them on a paper placed over pill tile by using powder spatula. • Put the powder in a packet (Fig. 4.1). • Label the packet and dispense. Fig. 4.1: Folding of packet for powder
  33. 33. Pharmacy Preparations  27 Name Akash Age/Sex 20 M Address 132, BRS Nagar, Ludhiana Directions: Dissolve the contents of powder in 1000 ml of freshy boiled and cooled water and take frequent sips. Sign and Regd No. of 24-05-2007 Pharmacist Pharmacy, ABC Ludhiana The frequency of sips will depend on level of dehydration. PHARMACOLOGICAL ACTIONS In diarrhea loss of water and electrolytes leads to dehydration. Hence, both water and electrolytes are given for treatment of dehydration. If water alone is given it will dilute the salts present in body and aggravates the condition. WHO ORS (for 1 litre) provides following salts as mEq/L: Na+ 90.0 K+ 20.0 – 3HCO 30.0 Glucose 111.0 Cl- 80.0 Osmolarity of 311 mOsm/l 215 calories PHARMACOLOGICAL ACTION OF SALTS Sodium chloride As you know, sodium is the main ion involved in various processes in the body, e.g. action potential generation. It helps to maintain muscle tone. Symptoms associated with hyponatremia are fatigue, muscle weakness, abdominal cramps, confusion, hypotension, weak pulse, cyanosis, oliguria, tachycardia, loss of skin elasticity and dryness of mucous membranes. Glucose Glucose is the source of energy. Apart from that it helps in absorption of sodium. Molar ratio of glucose is more than sodium in ORS. Sodium is absorbed through facilitated diffusion or cotransport with the help of glucose. Other contents provide sufficient amount of potassium, chloride and bicarbonate lost in diarrhea. Sodium citrate is the source of HCO3 – and also provides stability to the solution. Potassium chloride influences the muscle action and ameliorates the cramps. Chloride helps to maintain the fluid balance and production of gastric acid.
  34. 34. 28  Practical Manual of Pharmacology THERAPEUTIC USES 1. Diarrhoea Oral rehydration therapy is widely considered to be the best method for combating the dehydration caused by diarrhea and/or vomiting. Rehydration does not stop diarrhea, but keeps the body hydrated and healthy until the diarrhea passes. ORS is recommended in mild to moderate cases of diarrhea. Intravenous fluids are required in severe cases of dehydration. The amount of rehydration that is needed depends on the size of the individual and the degree of dehydration. Rehydration is generally adequate when the person no longer feels thirsty and has a normal urine output. A rough guide to the amount of ORS solution needed in the first 4-6 hours of treatment for a mildly dehydrated person is: • Up to 5 kg (11 lb): 200-400 ml • 5-10 kg (11-22 lb): 400-600 ml • 10-15 kg (22-33 lb): 600-800 ml • 15-20 kg (33-44 lb): 800-1000 ml • 20-30 kg (44-66 lb): 1000-1500 ml • 30-40 kg (66-88 lb): 1500-2000 ml • 40 plus kg (88 lb): 2000-4000 ml The degree of dehydration can be assessed by following parameters: — Pulse in dehydration has low volume and is thready. — No tears, dry mouth in case of moderate to severe dehydration. — Urine output is decreased in dehydration. 2. Heat stroke. 3. In patients of burns/surgery to maintain hydration. 4. Change from parenetral to enteral therapy. 5. High grade fever. HOME MADE ORS In a glassful of water, add I teaspoonful of sugar and a pinch of salt. You can also add half a lemon. Rice water and dal water can also be used. or An inexpensive home-made solution consists of 8 level teaspoons of sugar and 1 level teaspoon of table salt mixed in 1 liter of water. A half cup of orange juice or half of a mashed banana can be added to each liter both to add potassium and to improve taste. SUPER-ORS In this amino acids are added, e.g. alanine and glycine.
  35. 35. Pharmacy Preparations  29 NEW WHO ORS Because of the improved effectiveness of reduced osmolarity ORS solution, especially for children with acute, non-cholera diarrhoea, WHO and UNICEF now recommend that countries use and manufacture the following formulation in place of the previously recommended ORS solution. REDUCED OSMOLARITY ORS Ingredient (grams/litre) ion (mmol/litre) Sodium chloride (2.6) Sodium (75) Glucose, anhydrous (13.5) Glucose, anhydrous (75) Potassium chloride (1.5) Chloride (65)/Potassium (20) Trisodium citrate, dihydrate (2.9) Citrate (10) Total Osmolarity = 245. In the human body, the plasma osmolality is about 285 mOsm/l. PRECAUTIONS • Hot water should not be used as it may lead to breakdown of bicarbonate and alteration in flavor • Do not use if the solution is coloured. • Always use freshly prepared solution. • The solution made should not be used 24 hours after its preparation. • Use clean utensils to make solution. Today, the total production is around 500 million ORS sachets per year, with the children's rights agency UNICEF distributing them to children in around 60 developing countries. ORS represents a cheap and effective way of reducing the millions of deaths caused each year by diarrhea. OBJECTIVES At the end of this session a student shall be able to: 1. Understand how preparations are made in hospital pharmacy. 2. Various parts of a label on hospital pharmacy preparations.
  36. 36. Various dosage forms of drugs are used in therapy. Before discussing dosage forms let's see what are the various sources of drugs. SOURCES OF DRUGS Plants: One third of allopathic drugs are still derived from plants. Problem associated with a plant drug are: identification of plant, conditions of storage, standardization of active principle, purity and maintenance of supply line, e.g. morphine, codeine Animals: Some drugs are still obtained from animals due to expensive and cumbersome synthesis, e.g. gonadotropins, heparin Microorganisms: Antimicrobials are obtained, e.g. penicillin, erythromycin Minerals: Some minerals are important for body and given prophylactically or for treatment of deficiency, e.g. Zinc Synthetic: Most of the drugs in use today are synthetic in origin. These drugs are chemically pour and it is easy to maintain their supply, e.g. oral antidiabetics Semisynthetic: Changes are made after synthesis, e.g. insulin Biosynthetic: Recombinant technology is used to produce drugs, e.g. recombinant insulin Drugs need to be presented in a form that can be administered to an organism. Formulation is a recipe by which a drug is prepared. Drug formulation can allow specific tissue sites to be selectively targeted or systemic absorption of the drug to be avoided. Formulation is not only about a small amount of a drug that needs to be encapsulated or bottled for easy delivery but it is also about how to present a drug for administration so that it is guaranteed to reach the target area. The administration of drugs is one of the most important and exacting duties performed in caring for sick and injured patients. The appropriate drug given in the correct dosage will very often hasten a patient's recovery. On the other hand, an inappropriate drug or dosage may worsen a patient's condition or even result in his death. C H A P T E R Common Dosage Forms and RoutesofAdministration-I 5
  37. 37. Common Dosage Forms and Routes of Administration-I  31 To discuss formulation we will discuss route of administration of drugs, dosage forms used and their advantages and disadvantages. Various routes of drug administration are: A. For systemic effects 1. Enterable-oral, sublingual, etc. 2. Parenteral (which bypasses GIT)-i.v, i.m. etc. B. For local effects 3. Local, e.g. topical application C. Special preparations, e.g. controlled release Remember that there are six "rights" in the administration of drugs: 1. Right patient 2. Right drug 3. Right dose 4. Right route 5. Right time 6. Right documentation ORAL The drug is given through mouth. It is the commonest and most acceptable method of drug administration. ADVANTAGES 1. Most convenient and cheapest 2. Non-invasive, painless and no assistance is required. 3. Aseptic precautions are not required. 4. Both, solid and liquid dosage forms can be given • Solid preparations are: tablets, capsules, moulded tablets, powders, spansules, etc. • Liquid preparations are: syrups, mixtures, elixirs, emulsions, etc. ORAL-TABLETS A tablet is a disc, containing one or more medications, prepared by compressing a granulated powder (Fig. 5.1). As most drugs are presented in small quantities (sometimes less than a milligram), other materials (excipients) must be added to make them easy to handle, to be seen and to compress. Tablets must have property to disintegrate in the gastrointestinal tract. Fig. 5.1: Tablets
  38. 38. 32  Practical Manual of Pharmacology Capsules and tablets should be swallowed with a glass of water with the patient in upright posture either sitting or standing, as this enhances the passage into the stomach and permits rapid dissolution. Giving drugs orally to a recumbent patient should be avoided if possible, especially in the case of drugs which can damage the esophageal mucosa, e.g. doxycyline, iron salts, etc. Oesophagitis induced by these drugs is very difficult to treat. Tablets may be scored i.e. a line demarcation is there to divide tablet into two equal parts (Fig. 5.2). DISADVANTAGES 1. Action is slow so it is not suitable for emergency 2. Unpalatable drugs (e.g. paraldehyde) are difficult to administer 3. It may cause gastrointestinal adverse effects e.g. nausea and vomiting (e.g. emetine) 4. It can not be used for non cooperative/unconscious/vomiting patients 5. Certain drugs are not absorbed if given by this route (e.g. streptomycin) 6. Certain drugs are destroyed by gastric juices (penicillin G, insulin) or extensively metabolized during first pass in the liver or GIT (e.g. nitroglycerine, testosterone, lidocaine). ORAL-CAPSULES They can be of two types: 1. Hard gelatin type: It contains the drug as solid. It can be opened. Capsules can come in many colors for easy identification. Hard capsule consists of 2 cylinders which fit into one another (Fig. 5.3), e.g. amoxycillin capsules. 2. Soft gelatine type: It contains the drug in liquid or semi-liquid form. They are completely sealed (Fig. 5.4). They are useful for liquid drugs and for drugs which are water insoluble, e.g. nifedipine Gelatin is heterogenous mixture of water soluble proteins of high molecular weight. Pearls are transparent or translucent capsules that contain liquid or semisolid drugs, e.g. vitamin A capsules. Fig. 5.3: CapsulesFig. 5.2: Tablets Fig. 5.4: Soft Capsules
  39. 39. Common Dosage Forms and Routes of Administration-I  33 ADVANTAGES 1. Masks the bad smell and taste of drugs. 2. Avoids destruction by gastric juice and avoids gastric irritation. DISADVANTAGE More expensive than tablets. ORAL-Pills means round or ovoid body, usual coated with sugar or even silver or gold paint, e.g. oral contraceptives. Tablets, capsules and pills are packed in the plastic coated paper or aluminum strips or in blister packing (Fig. 5.5). ORAL-powder: Powder is a solid form of drugs, which is finely divided and intimately mixed (Fig. 5.6). They are mainly of three types. (i) Simple powders: contain one ingredient only, e.g. glucose powder. (ii) Compound powders: contain more than one ingredients, e.g. ORS powder. Simple powder - ORS and (iii) Effervescent powder, e.g. Antacid effervescent powder, Seidlitz. Powders are packed in sachets. ADVANTAGES 1. They are flexible in compounding. 2. Powders have a good chemical stability. DISADVANTAGES 1. Needs proper instruction for preparing. 2. Time consuming to prepare. 3. It is not suitable for dispensing bitter drugs. For effective use of this dosage form, required amount of powder to be dissolved in required amount of water prior to administration and then to be taken orally. Fig. 5.6: PowderFig. 5.5: Packed tablets, capsules
  40. 40. 34  Practical Manual of Pharmacology ORAL-LIQUIDS Liquid oral formulations include syrups, mixtures, solutions, reconstituted oral solutions, elixirs and gels (Fig. 5.7). These two preparations (suspension and emulsion) have tendency to separate and requires a thorough mixing before administration. Liquids for oral use are usually dispensed in plastic or glass bottles. ADVANTAGES OF LIQUID PREPARATIONS 1. They are more quickly acting than pills or tablets, which require previous disintegration before absorption. 2. Certain substances can only be given in the liquid form, e.g. liquid paraffin. 3. Certain chemical substances, e.g. potassium chloride can cause gastric irritation if taken in the form of powder or tablet. 4. Patients are sometimes prone to doubt the efficacy of the treatment they are receiving unless it includes something in the bottle (e.g. placebo effect). 5. Usefulness of some substances are largely dependent upon administration of diffusible form, e.g. magnesium sulphate in the form of suspension. Syrups: They are liquid oral preparations in which the vehicle is concentrated aqueous solution of sucrose or other sugar. ADVANTAGES 1. They are sweet in taste so masking the bad taste of drugs, especially suitable for children. 2. Quicker effect than tablets which require previous disintegration. DISADVANTAGES 1. Maintenance not easy. 2. They are costlier than tablets. PRECAUTION Close the bottle properly after use. Elixir: Some drugs are insoluble in water, they are dissolved in alcohol. These preparations are termed elixirs. They are clear liquid oral preparations containing hydroalcoholic vehicle, e.g. bromhexine, promethazine. ADVANTAGE Potent or nauseous drugs are pleasantly flavored and usually attractively coloured so patient compliance is better. Fig. 5.7: Syrup
  41. 41. Common Dosage Forms and Routes of Administration-I  35 DISADVANTAGES 1. Maintenance not easy. 2. They are costlier than tablets. PRECAUTION Close the bottle properly after use. Suspension: A liquid preparation that is made from a drug in solid form but not dissolved in alcohol is refers to as a suspension. It is a liquid medicament containing insoluble (diffusible or indiffusible) solid substances which are homogeneously distributed throughout the vehicle with or without the help of a suspending agent (Fig. 5.8). ADVANTAGES 1. They are chemically more stable than the syrup. 2. Mask the unpleasant taste and odor of the drugs. 3. Insoluble solids can be given in liquid form. DISADVANTAGES 1. A suitable preservative is required to avoid microbial contamination. 2. For effective use of this dosage form, shake the bottle well before use. Emulsions: They are liquid medicaments containing two immiscible liquids, one of which is broken into minute globules, each globule being surrounded by a thin film of emulsifying agent and then dispersed throughout the other liquid, e.g. liquid paraffin emulsion. ADVANTAGES 1. Oily drugs can be given in this form 2. Oil in finely dispersed state is quickly absorbed. 3. Emulsifying agents mask the unpleasant taste and smell of the drugs. DISADVANTAGES 1. A suitable preservative is required to avoid microbial contamination. 2. For effective use of this dosage form, shake the bottle well before use. Factors affecting oral route of administration: 1. Drug characteristics 2. Luminal pH along the GI tract 3. Destruction in GIT 4. Surface area per luminal volume 5. Blood perfusion 6. The presence of bile and mucus Fig. 5.8: Suspension
  42. 42. 36  Practical Manual of Pharmacology 7. The nature of epithelial membranes 8. Presence of food 9. Gut motility 10. First pass metabolism DRUG CHARACTERISTICS 1. Unionised drugs are lipid soluble, hence absorption is better. 2. Most of the drugs are absorbed from small intestine due to large surface area, longer contact time and rich vascular supply. 3. Presence of food usually delays absorption. 4. Some drugs are destroyed by gastric juices e.g. insulin, so these can not be given by oral route. 5. First pass metabolism decreases bioavailability of drugs by oral route e.g. propranolol. 6. Gut motility and gastric emptying time also affect absorption of orally administered drugs. ORAL- SPECIAL PREPARATIONS Coated preparations Sometimes a drug needs to be disintegrated not in the stomach but in the intestine. The tablets are coated with material which does not disintegrate in the acidic conditions of the stomach but only in the alkaline conditions of the intestine, e.g. enteric coated aspirin to avoid local toxicity in stomach. • Coated tablets: Tablets may be sugar-coated or film-coated to disguise bad-tasting drugs, e.g. Chloroquine tablet. • Dispersible tablets: Tablets may be dispersible to avoid loss of disintegration in stomach or to avoid local toxicity in oesophagus, e.g. doxycyline. These dispersible tablets are to be dissolved in water prior to administration • Chewable tablets: When chewed it disintegrates due to its creamy base, e.g. antacid tablets, antihelminthic tablets and vitamin C tablets. It is useful to children who have difficulty in swallowing and to the adults who dislike swallowing, but tablet is expensive. • Effervescent tablets: Prepared by compressing granular effervescent salts. It disintegrates fast when added to water and acts by releasing carbon dioxide (Fig. 5.9). Effervescence masks the bad taste of drug. It may give psychological effect to patient, e.g. alkaline tablet, antacid tablet, aspirin tablet. The tablet is very sensitive to moisture and expensive also. The tablet to be dissolved in a glass of water and the same to be taken orally while effervescence is present. Take in upright posture either standing or sitting. Fig. 5.9: Effervescent tablets
  43. 43. Common Dosage Forms and Routes of Administration-I  37 • Lozenges: These are disc shaped solid dosage forms, e.g. menthol, dextromethorphan. They have local action in oral cavity. There is slow and continuous effect of the drug on the mucous membrane of the throat. SUSTAINED RELEASE (SR) PREPARATIONS Drug is enclosed within device in such a way that the rate of drug release is controlled by its permeation through a membrane wall (Fig. 5.10). These preparations release drug slowly providing longer duration of action, e.g. diclofenac sodium SR. These are also known as retard or controlled release preparations, e.g. pilocarpine-releasing ocular insert for 4-day continuous glaucoma treatment. ADVANTAGES 1. It modifies the rate of release of drug into the gastrointestinal tract. 2. It prolongs the effect of drug and also reduces the frequency of administration. 3. Patient compliance is better. DISADVANTAGES 1. It is expensive as compared to uncoated tablets. 2. Dose dumping at one site producing local toxicity/systemic and loss of control release mechanism. Sustained release preparations can be formed by various techniques as follows: 1. Membrane system—drug enclosed in polymers from where it is released slowly. 2. Matrix system—drug is incorporated in a porous matrix. 3. Coated granules—drug molecules are coated, which release drug at different rates (Fig. 5.11). RECTAL Drugs in the form of suppositories are inserted into the anal canal, e.g. diazepam in children suffering from status epilepticus. Rectum has rich vascular supply, so absorption is quick. ADVANTAGES 1. Unconscious, vomiting patient 2. Swallowing problems 3. In case of a difficulty to find the vein for intravenous injection 4. Uncooperative children 5. Unpleasant drugs Fig. 5.10: SR
  44. 44. 38  Practical Manual of Pharmacology DISADVANTAGES 1. Anal or rectal irritation. 2. Inconvenient, aesthetic considerations. 3. Absorption slow, irregular and unpredictable. 4. They are made to melt at body temperature, so needs to be kept refrigerated. They can even melt on the hand before insertion. The patients need to be educated about the best position for insertion and also to remove the plastic cover. OBJECTIVES At the end of this session a student shall be able to: • Write down the name dosage form of the drug displayed at the various stations. • Give instructions to patients on the proper usage of each dosage form. • Write two important advantages of the dosage form. • Write two important disadvantages of the dosage form. Exercises for this session can be arranged in stations. Each station has various dosage forms. The stations can have the above mentioned dosage forms like: Tablets–dispersible, sustained release, controlled release, enteric coated, sublingual tablets, pills Capsules–soft/hard gelatine capsules, pearls, spansules Liquid oral formulations (mixtures)–syrups, mixtures, solutions, reconstituted oral solutions, elixirs, suspensions, etc. Fig. 5.11: Delivery systems and drug release
  45. 45. Any method of drug administration that avoids the gastrointestinal tract is termed parenteral administration. Parenteral is derived from combination of 2 words: Par = beyond Enteral = intestinal Transdermal, intranasal, rectal are, therefore, parenteral methods. However, the usual term parenteral is reserved for drug injections. ADVANTAGES 1. They can be employed in an unconscious or an uncooperative patient. 2. They can be employed in cases of vomiting and diarrhoea and in the patients unable to swallow. 3. Drugs which might irritate the stomach or which are not absorbed orally can be administered, e.g. aminoglycosides. 4. They avoid drug modification by the alimentary juices and liver enzymes e.g. Insulin, nitroglycerine. 5. Rapid action and accuracy of dose are ensured. DISADVANTAGES 1. Less safe, once given the action of given drug will become irreversible 2. More expensive 3. Inconvenient for use, self-medication being difficult 4. Liable to cause infection if proper care is not exercised 5. Likely to injure important structures such as nerves and arteries if not given properly. Strict aseptic precaution should be taken while giving injection in order to prevent infections due to HIV and Hepatitis B virus. Disposable syringe and needle should be used and should be purchased from an authentic source. Needle should be broken down and syringe should be discarded after use. Injections: An injection is a method of putting liquid into the body with a hollow needle and a syringe which is pierced through the skin long enough for the material to be forced into the body. Preparations meant for parenteral administration must be sterile. Depending C H A P T E R Common Dosage Forms and RoutesofAdministration-II 6
  46. 46. 40  Practical Manual of Pharmacology upon the volume, they are supplied in sealed glass ampoules, e.g. streptomycin or rubber capped multi-dose vials, e.g. multivitamins or large infusion bottles, e.g. 5% dextrose or in polypropylene pouches, e.g. metronidazole. DOSAGE FORMS FOR INJECTIONS i. Aqueous or clear solution for subcutaneous/intramuscular/intravenous use. ii. Suspension for intramuscular/intravenous use. iii. Emulsion for intravenous use. Oily solution for intramuscular use long-acting forms of subcutaneous/intramuscular injections are available for various drugs; these are called depot injections. iv. Powder to be reconstituted for intramuscular/intravenous use. Powder has to be dissolved or suspended in colloidal form before injecting by adding an adequate quantity of a suitable solvent (e.g. streptomycin) because reconstitution of drug reduces the shelf life and stability. PARENTERAL Intravenous injections (IV) An intravenous infusion is a liquid administered directly into the bloodstream via a vein. Drug is given in one of the superficial veins. Drug is either given as: 1. Bolus IV injection, e.g. adenosine in PSVT (immediate action is required), furosemide in acute pulmonary edema. 2. Slow IV injections over 5-10 minutes, e.g. calcium gluconate in arrhythmias (to avoid toxicity of calcium on heart). 3. Slow IV infusion, e.g. oxytocin in induction of labour (slow and sustained action is required) (Fig. 6.1). This is done by dissolving drug in 50-100 ml of isotonic glucose or saline. 4. Rapid IV infusion is sometimes used, e.g. fluids in shock. Drug is usually in aqueous form (Fig. 6.2). It should be nonirritant to vascular endothelium. Fig. 6.2: IV fluidFig. 6.2: IV infusion
  47. 47. Common Dosage Forms and Routes of Administration-II  41 ADVANTAGES 1. 100% bioavailability 2. Immediate onset of action, so it can be used in emergencies 3. Titration of dose can be done 4. First pass metabolism bypassed 5. GIT adverse effects not present 6. Can be used in unconscious, uncooperative and vomiting patients. DISADVANTAGES 1. Aseptic precautions are mandatory 2. Vital organs are exposed to high concentration of drug 3. Thrombophlebitis 4. Expensive 5. Invasive 6. Painful 7. Trained person is required 8. If the drug extravasates there may be necrosis and sloughing, e.g. with pentothal sodium, quinine. Before learning technique of IV injection it is important to learn to fill the syringe with drug. Drug can be available as liquid or powder form. It can be present in single dose ampoule or multidose vial. Exercise: How to aspirate drug from ampoule into syringe? REQUIREMENTS Syringe of appropriate size, ampoule with required drug or solution, needle of right size, disinfectant, gauze (Fig. 6.3). TECHNIQUE 1. Wash your hands properly with soap and water. 2. Take out syringe and needle from disposable pack taking care not to touch naked end of syringe. 3. Put the needle on the syringe. 4. Remove the liquid from the neck of the ampoule by flicking or tapping it or swinging it fast in a downward spiralling movement. 5. File around the neck of the ampoule. 6. Carefully break off the top of the ampoule. Protect your fingers with gauze if ampoule is made of glass. 7. For a plastic ampoule twist the top. 8. Remove cover from needle.
  48. 48. 42  Practical Manual of Pharmacology 9. Aspirate the fluid from the ampoule. 10. Remove any air from the syringe. 11. Clean up, dispose of working needle safely and wash your hands. Exercise: How to aspirate drug from vial into syringe? REQUIREMENTS Vial, syringe of the appropriate size, needle of right size, disinfectant, gauze. TECHNIQUE 1. Wash your hands properly with soap and water. 2. Take out syringe and needle from disposable pack taking care not to touch naked end of syringe. Use a syringe with a volume of twice the required amount of drug or solution. 3. Put the needle on the syringe. 4. Remove protective covering from vial cap. Disinfect the top of the vial with a cotton swab soaked in disinfectant (Fig. 6.3). 5. Remove cover from needle. 6. Suck up as much air as the amount of solution needed to aspirate. 7. Insert needle into vial through rubber cap and push down and then mix. 8. Pump air into vial (creating pressure). 9. Aspirate the required amount of solution and 0.1 ml extra. Make sure the tip of the needle is below the fluid surface (Fig. 6.4). 10. Pull the needle out of the vial. 11. Remove the air from the syringe. 12. Clean up, dispose of waste safely and wash your hands. Fig. 6.3:Ampoule Fig. 6.4:Aspiration
  49. 49. Common Dosage Forms and Routes of Administration-II  43 Exercise: How to dissolve dry medicine in vial and aspirate drug solution into syringe? Antibiotic drugs such as penicillins, streptomycin and the tetracyclines often are manufactured and supplied to you in the form of a sterile powder in a vial which must be reconstituted with sterile water for injection, normal saline solution, or other suitable diluent (solvent) REQUIREMENTS Vial with dry medicine to be dissolved, syringe of the appropriate size, needle of right size, disinfectant, gauze. TECHNIQUE 1. Wash your hands properly with soap and water. 2. Take out syringe and needle from disposable pack taking care not to touch naked end of syringe. 3. Put the needle on the syringe. 4. Aspirate solvent into syringe from the ampoule. 5. Remove protective covering from cap of vial. Disinfect the rubber cap (top) of the vial containing the dry/powdered medicine. 6. Insert the needle into the vial, hold the whole unit upright. 7. Suck up as much air as the amount of solvent already in the syringe. 8. Inject only the fluid into the vial, not the air. 9. Shake well. 10. Turn the vial upside-down. 11. Inject the air into the vial (creating the pressure). 12. Aspirate the total amount of solution. 13. Remove any air from the syringe. 14. Clean up, dispose of waste safely and wash hands. It is recommended that all antibiotics that are reconstituted and are to be used later, should be labeled in the following way (see example): 1. Hour and date reconstituted. 2. Strength of reconstituted antibiotic. 3. Initials of the preparer. Exercise: How to inject by Intravenous route? REQUIREMENTS Syringe, drug, needle 20G, liquid disinfectant, cotton wool, adhesive tape and tourniquet. PROCEDURE 1. Wash your hands properly with soap and water 2. Reassure the patient and explain the procedure 3. Uncover arm completely 1400 hrs 9 Mar 07 50,000 units/ml
  50. 50. 44  Practical Manual of Pharmacology 4. Have the patient relax and support his arm below the vein to be used 5. Apply tourniquet, tell patient to clinch fist and look for a suitable vein 6. Wait for the vein to swell. Disinfect skin 7. Stabilize the vein by pulling the skin taut in the longitudinal direction of the vein. Do this with the hand you are not going to use for inserting the needle. 8. Insert the needle at an angle of around 35° (Fig. 6.5) 9. Puncture the skin and move the needle slightly into the vein (3-5 mm) 10. Hold the syringe and needle steady 11. If blood appears hold the syringe steady, you are in the vein. If it does not come, try again 12. Loosen tourniquet. Withdraw needle swiftly. Check for pain, hematoma 13. Press sterile cotton wool onto the opening. Secure with adhesive tape 14. Check the patient's reactions and give additional reassurance, if necessary 15. Clean up, dispose of waste safely and wash your hands. Exercise: Model for IV injections for students in laboratory REQUIREMENTS A simple model for IV administration can be used to teach the students about the process of IV injection. Model of hand with vein (made of latex glove stuffed with mattress foam and a rubber tube filled with red ink placed under the latex glove on top of the cotton), IV infusion sets, butterfly needles, IV fluid bottles. Follow same procedure as described forIV injection. GENERAL PRINCIPLES Apart from the specific technique of injecting, there are a few general rules that you should be kept in mind. 1. Expiry dates: Check the expiry dates of each item including the drug. If you make housecalls and keep stock of injections, check the drugs in your medical bag regularly to make sure that they have not passed the expiry date. 2. Drug: Make sure that the vial or ampoule contains the right drug in the right strength. 3. Sterility: During the whole preparation procedure, material should be kept sterile. Wash your hands before starting to prepare the injection. Disinfect the skin over the injection site. 4. Prudence: Once the protective cover of the needle is removed extra care is needed. Do not touch anything with the unprotected needle. Once the injection has been given take care not to prick yourself or somebody else. 6. Waste: Make sure that contaminated waste is disposed of safely. Fig. 6.5: IV injection
  51. 51. Common Dosage Forms and Routes of Administration-II  45 7. Do not use plastic tubing for glyceryl trinitrate, paraldehyde. 8. Protect nitroprusside from light by covering infusion set with brown paper. PARENTERAL-IM Intramuscular injections Drug is injected in one of the large skeletal muscles of the body, i.e. deltoid, gluteus and in infants in anterolateral region of the thigh in middle third region. Skeletal muscle is highly vascular and its capillaries contain small pores which enable substances of small molecular weight to pass through into the bloodstream. Several muscles of the body have considerable mass and can be injected with quantities of up to several millilitres of fluid without inducing discomfort to the patient. Generally, intramuscular injections are not self-administered, but rather by a trained medical professional, e.g. many vaccines, antibiotics, and long-term psychoactive agents. Aqueous solutions better absorbed than oily solutions. Depot preparations in oil can be given to prolong duration of action. The degree of tissue perfusion and condition of the injection site will influence the rate of drug absorption. ADVANTAGES 1. Rate of absorption is reasonably uniform. 2. Less painful. 3. Onset of action-fairly rapid. 4. Depot preparations can be given. 5. In addition to soluble substances, mild irritants, suspensions and colloids can be injected by this route. DISADVANTAGES 1. Aseptic precautions are mandatory. 2. Danger of injecting into blood stream. 3. Intramuscular absorption is not always faster than oral absorption. 4. The volume of injection should not be more than 10 ml. 5. Pain at the site of injection, irritation, abscess formation or tissue and nerve damage may occur. Rapid absorption may cause even death. PRECAUTIONS 1. Do not inject in gluteal region in a child until child starts walking. Inject into lateral part of thigh. 2. Heparin should not be given IM (hematoma). 3. Injury to nerves leading to paresis of muscles can occur. Never give IM injection to child with suspected poliomyelitis. Fig. 6.6: Sites for IM injection in adults
  52. 52. 46  Practical Manual of Pharmacology 4. A healthy well developed person can tolerate 3.0 ml in large muscles, this does NOT include the deltoid. For elderly, thin clients or children the total amount should not exceed 2.0 ml. No more than 1.0 ml should be given to young children and older infants. Exercise: How to inject drug by intramuscular route? REQUIREMENTS Syringe filled with the drug to be administered (without air), needle 22G, liquid disinfectant, cotton wool, adhesive tape. PROCEDURE 1. Wash your hands properly with soap and water 2. Reassure the patient and explain the procedure 3. Uncover the area to be injected (lateral upper quadrant major muscle lateral side of upper leg, deltoid muscle Fig. 6.6) 4. Disinfect the skin and tell the patient to relax the muscle 5. Insert needle swiftly at the angle of 90° (watch depth) 6. Aspirate briefly, if blood appears withdraw needle. Replace it. 7. Inject slowly (less painful) 8. Withdraw needle swiftly 9. Press sterile cotton wool onto the opening. Fix with adhesive tape Check the patient's reaction and give additional reassurance, if necessary 10. Clean up, dispose of waste safely and wash your hands. Exercise: How to inject drug by intramuscular route in an orange model? REQUIREMENTS Syringe filled with the drug to be administered (without air), needle 22G, liquid disinfectant, cotton wool, adhesive tape, Orange. Orange peel gives resistance and feeling of injecting through skin. When needle enters inside orange it gives feeling of injecting in muscle. PROCEDURE Same as above. PARENTERAL-SC A subcutaneous injection is administered into the subcutis, the layer of skin directly below the dermis and epidermis, collectively referred to as the cutis. Subcutaneous injections are highly effective in administering such medications as insulin, morphine, diacetylmorphine or goserelin (Fig. 6.7). Drug is injected into loose subcutaneous tissue. Hyaluronidase can increase absorption, which breaks down intracellular matrix. A person Fig. 6.7: SC injection
  53. 53. Common Dosage Forms and Routes of Administration-II  47 with type I diabetes mellitus typically injects insulin subcutaneously. Places on the body where people can inject insulin most easily are: • The outer area of the upper arm • Just above and below the waist, except the area right around the navel (a 2-inch circle) • The upper area of the buttock, just behind the hip bone • The front of the thigh, midway to the outer side, 4 inches below the top of the thigh to 4 inches above the knee. Subcutaneous—the volume to be administer is 1.0 ml or less. ADVANTAGES 1. Self-administration possible. 2. Drugs in oil or implants can be given. 3. Action of the drug is sustained and uniform (Fig. 6.8). Fig. 6.8: ROA and concentration time curve DISADVANTAGES 1. Painful 2. Onset of action-slower 3. Only non-irritant substances can be injected by this route. Subcutaneous drug implants can act as depot therapy, e.g. Medroxyprogesterone. Exercise: How to inject drugs subcutaneously?
  54. 54. 48  Practical Manual of Pharmacology REQUIREMENTS Syringe with the drug to be administered (without air), needle 25G, liquid disinfectant, cotton wool, adhesive tape. PROCEDURE 1. Wash hands with soap and water. 2. Reassure the patient and explain the procedure. 3. Uncover the area to be injected (upper arm, upper thigh, abdomen). 4. Disinfect skin, "Pinch" fold of the skin. 5. Insert needle in the base of the skin-fold at an angle of 20 to 30°. 6. Release skin. 7. Aspirate briefly, if blood appears: withdraw needle, replace it with a new one, if possible, and start again from point 4. 8. Inject slowly (0.5-2 minutes). 9. Withdraw needle quickly. 10. Press sterile cotton wool onto the opening. Fix with adhesive tape. 11. Check the patient's reaction and give additional reassurance, if necessary. 12. Clean up, dispose of waste safely and wash hands. Insulin is administered only using an insulin syringe. Most insulin vials contain 100 units/ ml. Insulin may be administered subcutaneously, intramuscularly (rarely used) and intravenously. Regular insulin is the only type that may be given IV since it does not contain any additives to prolong the action. Regular insulin is clear. If the vial is cloudy, it has been contaminated and should be discarded. Longer acting insulin is cloudy and may have a precipitate on the bottom of the vial. Be sure to mix the vial well by rotating it between the hands. PARENTERAL-INTRADERMAL INJECTION Drug or substance is injected into the dermis using a fine needle. The absorption is very slow and only small quantities of the drug can be given by this route. This route is used for specific purpose only. Intradermal—the volume to be administered is 0.1 ml or less, e.g. BCG vaccine. Other less commonly used injectable routes are: Intra-thecal injectons are made into the cerebrospinal fluid. This drug are given to get drugs directly into the central nervous system by avoiding the blood brain barrier commonly used for spinal anesthesia and chemotherapy. Epidural injections is just like intrathecal but the drug is deposited above the dura and not in the cerebrospinal fluid. Local anesthetics are often given this way during surgical procedures, specially for procedures involving the pelvic and inferior regions, to block. Intra-arterial injections: To deliver high concentration of anticancer drugs in malignancy, e.g. vasodilator drugs in the treatment of vasospasm and thrombolytic drugs for treatment of embolism.
  55. 55. Common Dosage Forms and Routes of Administration-II  49 Intra-articular injections: are used to inject drugs directly into joint. But strict aseptic precautions are a must (Fig. 6.9). PARENTERAL- SUBLINGUAL Highly lipid soluble drugs can be absorbed from sublingual and buccal mucosa, e.g. Nitroglycerin, a potent vasodilator, used in angina. ADVANTAGES • This form of administration avoids the mixing of drug with food and/or gastric juices which may impede absorption. • Immediate action, can be used in emergency. • Action can be terminated by spitting the remaining drug. • Bypasses hepatic first pass metabolism (Fig. 6.10). Fig. 6.9: Intraarticular injection Fig. 6.10: Circulation DISADVANTAGES 1. Drug taste must be pleasant. 2. Irritant drugs cannot be given. Can produce ulcers in mouth. PARENTERAL-TRANSDERMAL The skin is relatively more impermeable to drugs than other stratified epithelia. The skin is useful to administer drugs which are very lipophilic and active in very small amounts. Drug is present in patches (Fig. 6.11) which release drug at constant and predictable rate. No peaks or troughs of drug concentration are seen. Site used are-chest, abdomen, upper arm, buttocks. Transdermal drug delivery avoids problems such as gastrointestinal irritation, Fig. 6.11: Patch
  56. 56. 50  Practical Manual of Pharmacology metabolism, variations in delivery rates and interference due to the presence of food. It is also suitable for unconscious patients. The technique is generally non-invasive and aesthetically acceptable and can be used to provide local delivery over several days. Examples are: • Nicotine patches-help stop smoking. • Oestradiol-prevent menopausal symptoms. • Fentanyl cytrate-prevent severe pain. • Nitrate patches-for angina. Transdermal delivery system (patches) can be of various types (Fig. 6.12) as follows: 1. Membrane controlled The drug in solution or bound to polymer is held in a reservoir between an occlusive backing film and a rate controlling micropore membrane. The drug is absorbed into systemic circulation by diffusion. 2. Matrix controlled The drug is homogeneously mixed with rate controlling polymer and rate of release is controlled by its diffusion through polymer matrix. 3. Sandwich type Combination of membrane and matrix type. Matrix is coated with a rate controlling polymer membrane. Rate of absorption depends on: Fig. 6.12: Transdermal delivery
  57. 57. Common Dosage Forms and Routes of Administration-II  51 • Degree of hydration. • Keratinisation. • Rate of blood flow through skin. ADVANTAGES 1. Bypasses first pass metabolism. 2. Maintains constant plasma levels for a longer period. 3. Less side effects. 4. Easy to discontinue if toxicity appears. 5. No GIT side effects. 6. Convenient to use, compliance improves. DISADVANTAGES 1. Local irritation, erythema. 2. Onset of action-slower. 3. Can not achieve high concentration in plasma. 4. Can not deliver drugs in a pulsatile manner. 5. Development of tolerance. 6. Expensive. Methods to increase permeation • Physical, e.g. iontophoresis. • Chemical, e.g. sorption promoters. • Biological, e.g. skin metabolism inhibitors. Instructions for correct use of this dosage form: 1. Do not apply over bruised or damaged skin. 2. Do not wear over skin folds or under tight clothing and change spots regularly. 3. Apply with clean, dry hands. 4. Clean and dry the area of application completely. 5. Remove patch from package, do not touch 'drug' side. 6. Place on skin and press firmly. Rub the edges to seal. 7. Remove and replace according to instructions. OBJECTIVES At the end of this session a student shall be able to: • Write down the dosage form of the drug displayed at the various stations. • Administer the drug properly by required method.
  58. 58. 52  Practical Manual of Pharmacology • Understand and describe precautions required during use of each dosage form. • Write two important advantages of the given dosage form. • Write two important disadvantages of the given dosage form. Exercises for this session can be arranged in stations. Each station has various dosage forms. The stations can have the above mentioned dosage forms like: Ampoules, vials, IV set, syringes, needles, patches. DEMONSTRATE 1. How you will aspirate drug from an ampoule/vial? 2. How you will make solution of dry drug for injection? 3. How you will inject drug through IV route/ IM route? Exercise 1: Inject 0.1 ml of saline intravenously into the model provided. Check-list 1. Wipes area with spirit from centre to periphery. 2. Waits for the spirit to dry. 3. Positions needle with bevel facing upwards. 4. Holds syringe in correct manner (without touching needle). 5. Inserts needle into skin first. 6. Withdraws to check whether in vein. 7. Pushes plunger smoothly and completely. 8. Withdraws and wipes area with cotton. 9. Disposes needle (without recapping) and syringe correctly. 10. Completes procedure smoothly without disruption. Exercise 2: Give clear instructions on the proper use of a transdermal nitroglycerine patch to this patient. Check-list 1. Greets the patient. 2. Offers a seat. 3. Opens pack. 4. Right side has to be on skin. 5. Over the lateral chest wall. 6. Change every day. 7. Do not place on exactly same site. 8. If irritation or redness - come to doctor.
  59. 59. Common Dosage Forms and Routes of Administration-II  53 9. Not more than two patches in a day. 10. Check whether it is there after bath. Exercise 3: You have decided to put this 24 years female going to get married, on oral contraceptives after having taken a history and done a physical examination. Give instructions on the use of this packet of contraceptive pills which contain low dose combination pills. Check-list 1. Explains that she will be on a contraceptive. 2. To start on fifth day of menstrual cycle. 3. To start a new packet at end of this without gap. 4. If pill is missed to take it next day. 5. If more than 2 pills are missed additional contraceptive cover. 6. Additional methods for first cycle. 7. Explains withdrawal bleeding. 8. Explains breakthrough bleeding. 9. To take at same time each night. 10. When to return - next visit.
  60. 60. LOCAL This refers to the application of a drug to an area of the body for direct treatment. Usually there is inefficient absorption (1-15%). High local tissue levels nevertheless achievable, often higher than by systemic route. Toxicity usually not a problem. DROPS Eye and nose drops are made isotonic to avoid pain or discomfort. Ear drops are formulated as oily solutions to coat and adhere to the aural cavity. EYE DROPS They are aqueous or oily solutions for instilling into conjunctival sac (Fig. 7.1). They are used as anesthetics, anti infective or anti inflammatory agents, miotics, mydriatics and artificial tears. For example atropine sulphate (mydriatic), pilocarpine nitrate (miotic), timolol maleate. ADVANTAGES 1. Local effect at required place. 2. Easy to apply. 3. Drug interactions can be avoided. DISADVANTAGES 1. It requires repeated application. 2. Systemic effects can occur following absorption. 3. May cause irritation. 4. Once seal is broken, should be used within 1 month. PROCEDURE 1. Wash your hands. 2. Do not touch the dropper opening. 3. Look upward. Fig. 7.1: Eye drops C H A P T E R Common Dosage Forms and RoutesofAdministration-III 7
  61. 61. Common Dosage Forms and Routes of Administration-III  55 4. Pull the lower eyelid down to make a 'gutter' or pouch. 5. Bring the dropper as close to the 'gutter' as possible without touching it or the eye. 6. Instill the prescribed number of drops (usually 1 or 2) in the 'gutter'. 7. Close the eye for about two minutes. Do not shut the eye too tight. 8. Excess fluid can be removed with a tissue. Do not rub. 9. If more than one kind of eye drop is used wait at least five minutes before instilling the next drops. Eye-drops may cause a burning feeling but this should not last for more than a few minutes. If it does last longer, consult a doctor or pharmacist. EYE OINTMENT They are semisolid preparations with a greasy base, to be applied in the eye, e.g. neomycin eye ointment, chloramphenicol eye ointment, tetracycline eye ointment. ADVANTAGE They have longer duration of action. DISADVANTAGE Due to greasy base eyes may become sticky. PROCEDURE 1. Wash your hands. 2. Do not touch anything with the tip of the tube. 3. Tilt the head backwards a little. 4. Take the tube in one hand and pull down the lower eyelid with the other hand, to make a 'gutter'. 5. Bring the tip of the tube as close to the "gutter" as possible. 6. Apply the amount (usually 1 cm length) of ointment. 7. Close the eye for two minutes. 8. Remove excess ointment with a tissue. 9. Clean the tip of the tube with other tissue. EAR DROPS They are aqueous or oily solutions instilled in the ear, e.g. wax softeners, sodium bicarbonate. ADVANTAGE Avoid systemic side effect due to its local action. DISADVANTAGE Local irritation can occur.
  62. 62. 56  Practical Manual of Pharmacology PROCEDURE 1. Lie on one side with the ear upward. 2. Gently pull the lobe to expose the ear canal. 3. Instill the amount (usually 4-5) of drops. 4. Wait for five minutes before turning to the other ear. 5. Use cotton wool to close the ear canal after applying the drops only if the manufacturer explicitly recommends this. 6. Ear drops should not burn or sting longer than a few minutes (Fig. 7.2). NASAL DROPS They are aqueous solutions of drugs instilled into the nose with a dropper, e.g. Xylometazoline, ephedrine, etc. ADVANTAGE Local and quick action. DISADVANTAGES 1. Absorption can occur producing systemic effect. 2. May cause local irritation. PROCEDURE 1. Blow the nose. 2. Sit down and tilt head backward strongly or lie down with a pillow under the shoulders; keep head straight. 3. Insert the dropper one centimeter into the nostril. 4. Instill the number of drops prescribed (usually 3-4 drops). 5. Sit up after a few seconds, the drops will then drip into the pharynx. 6. Repeat the producer for the other nostril, if necessary. 7. Rinse the dropper with boiled water. NASAL SPRAYS These are drugs or combinations of drugs (Fig. 7.3) which by virtue of their high vapor pressure, can be carried by an air current into nasal passage and exert their effect, e.g. Beclomethasone, calcitonin, vasopressin, etc. ADVANTAGES 1. Easy to use. 2. It covers large surface area so quick absorption. DISADVANTAGE Explosion may occur in hot environment as the contents are under pressure.
  63. 63. Common Dosage Forms and Routes of Administration-III  57 PROCEDURE 1. Blow the nose. 2. Sit with the head slightly tilted forward. 3. Shake the spray. Insert the tip in one nostril. 4. Close the other nostril and mouth. 5. Spray by squeezing the vial (flask, container) and sniff slowly. 6. Remove the tip form the nose and bend the head forward strongly (head between the knees). 7. Sit up after a few seconds; the spray will drip down the pharynx. 8. Breath through the mouth. 9. Repeat the procedure for the other nostril, if necessary. 10. Rinse the tip with boiled water. SUPPOSITORIES A suppository (Fig. 7.4) is a drug delivery system that is inserted either into the rectum (rectal suppository), vagina (vaginal suppository) or urethra (urethral suppository) where it dissolves. They are used to deliver both systemically acting and locally acting medications. They are solid, uniformly medicated masses of medicaments, e.g. glycerin, bisacodyl. ADVANTAGES 1. Local application for systemic as well as local effect 2. Especially helpful for unconscious or in a patient who can not take orally. DISADVANTAGES 1. Inconvenient and some times irritant 2. Aesthetic concerns 3. Local irritation. Fig. 7.3: Nasal spray Fig. 7.4: SuppositoryFig. 7.2: Ear drops
  64. 64. 58  Practical Manual of Pharmacology PROCEDURE 1. Wash your hands. 2. Remove the covering (unless too soft). 3. If the suppository is too soft let it harden first by cooling it (fridge or hold under cold running water, still packed) then remove covering. 4. Remove possible sharp rims by warming in the hand. 5. Moisten the suppository with cold water. 6. Lie on your side and pull up your knees. 7. Hold the suppository by the non pointed end and insert the tip into the anal opening. 8. Now just gradually push, keep pushing (it may be further than you imagine) and at some point the suppository will be pulled into the rectum by the anal sphincter. Remain lying down for several minutes. 9. Try not to have a bowel movement during the first hour. VAGINAL PESSARIES It is the term applied to suppository shaped medications for vaginal administration. This is a topical treatment and it is important that the drug coats all the vagina mucosa. Vaginal medications whether in pessaries or cream come with applicators which are designed to reach the upper parts of the vaginal canal. Vaginal preparations which are left in situ are best used at night because the vagina has no means of retention like sphincters and the medication can run out. Vaginal tablet (Pessary) with applicator They are vaginal suppositories intended for introduction into vagina, e.g. nystatin, metronidazole. ADVANTAGES 1. Local application 2. Avoid systemic effect. DISADVANTAGES It may cause staining and irritation. PROCEDURE 1. Wash your hands. 2. Remove the wrapper from the tablet. 3. Place the tablet into the open end of the applicator. 4. Lie on your back, draw your knees up a little and spread them apart. 5. Gently insert the applicator with the tablet in front into the vagina as far as possible, do not use force.
  65. 65. Common Dosage Forms and Routes of Administration-III  59 6. Depress the plunger so that the tablet is released. 7. Withdraw the applicator. 8. Discard the applicator (if disposable). 9. Clean both parts of the applicator thoroughly with soap and boiled lukewarm water (if not disposable). Without applicator 1. Wash your hands. 2. Remove the wrapper from the tablet. 3. Dip the tablet in lukewarm water just to moisten it. 4. Lie on your back, draw your knees up and spread them apart. 5. Gently insert the tablet into the vagina as high as possible, do not use force. OINTMENTS These are lipid-based. They have a greasy appearance and feel. The drug is trapped under the dressing and, the layer of the skin is soften from sweating, enabling the drug to penetrate deeply into the tissues. Eye ointments are formulated to melt quickly so that vision is not impaired. PASTES They have a very high powder content. They are useful in protecting areas of skin from moisture, being water repellent. GEL AND LOTIONS They are used on the hairy areas of the body. Alcoholic gels or lotion are less messy than ointments or creams, but the evaporation of carrier is rapid, therefore, there is little penetration of the drug (Fig. 7.5). JELLIES For urethral application. DUSTING POWDER They are free flowing very fine powders having particle size < 150 µm for external use. They are used to treat superficial skin conditions. They are sterilized by dry heat and supplied in airtight glass or plastic jars with reclosable perforated lid or sprinkler holes at top. Commonly used dusting powders are purified talc, magnesium sulphide powder, neomycin powder, sulphacetamide sodium, sulphadiazine powder. Fig. 7.5: Gel

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