McKenna's Pharmacology, 2e

McKenna’s Pharmacology for Nursing and Health Professions - Second Edition -

S ample C ontents

Chapter One Introduction to Nursing Pharmacology

Chapter Two Drugs and the body

Chapter Three Toxic effects of drugs

Chapter Four Clinical decision making in drug therapy

Chapter Five Mathematics and dosage calculations

McKenna’s Pharmacology for Nursing and Health Professionals - Second Edition - Lisa McKenna PhD, MEdSt, RM, RN Anecita Gigi Lim RN, PhD

1

PA R T

Introduction to nursing pharmacology

 1 Introduction to drugs 2  2 Drugs and the body 15  3 Toxic effects of drugs 31

 4 Clinical decision making in drug therapy 42  5 Mathematics and dosage calculations 53  6 Challenges to effective drug therapy 60

1

Learning objectives Upon completion of this chapter, you should be able to: 1. Define the word pharmacology. 2. Outline the steps involved in developing and approving a new drug in Australia and New Zealand. 3. Describe the legislative controls on drugs that have abuse potential. 4. Differentiate between generic and brand-name drugs, over-the-counter and prescription drugs. 5. Explain the benefits and risks associated with the use of over-the-counter drugs. Introduction to drugs

Test your current knowledge of drugs with a PrepU Practice Quiz!

Glossary of key terms adverse effects: drug effects that are not the desired therapeutic effects; may be unpleasant or even dangerous brand name: name given to a drug by the pharmaceutical company that developed it; also called a trade name chemical name: name that reflects the chemical structure of a drug

drugs: chemicals that are introduced into the body to bring about some sort of change generic drugs: drugs sold by their chemical name; not brand (or trade) name products generic name: the original designation that a drug is given when the drug company that developed it applies for the approval process genetic engineering: process of altering DNA, usually of bacteria, to produce a chemical to be used as a drug New Zealand Medicines and Medical Devices Safety Authority (MEDSAFE): a business unit of the Ministry of Health and the authority responsible for the regulation of therapeutic products in New Zealand orphan drugs: drugs that have been discovered but would not be profitable for a drug company to develop; usually drugs that would treat only a small number of people; these orphans can be adopted by drug companies to develop over-the-counter (OTC) drugs: drugs that are available without a prescription for self-treatment of a variety of complaints; deemed to be safe when used as directed pharmacology: the study of the biological effects of chemicals pharmacotherapeutics: clinical pharmacology—the branch of pharmacology that deals with drugs; chemicals that are used in medicine for the treatment, prevention and diagnosis of disease in humans phase I study: a pilot study of a potential drug conducted with a small number of selected, healthy human volunteers phase II study: a clinical study of a proposed drug by selected doctors using actual people who have the disorder the drug is designed to treat; the subjects must provide informed consent phase III study: use of a proposed drug on a wide scale in the clinical setting with people who have the disease the drug is designed to treat phase IV study: continual evaluation of a drug after it has been released for marketing post-marketing surveillance: monitoring the safety of medicines and medical devices in use preclinical trials: initial trial of a chemical thought to have therapeutic potential; uses laboratory animals, not human subjects teratogenic: having adverse effects on the fetus Therapeutic Goods Administration (TGA): Australian commonwealth government agency responsible for the regulation and enforcement of drug evaluation and distribution policies

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C H A P T E R 1  Introduction to drugs

T he human body works through a complicated series of chemical reactions and processes. Pharmacology is the study of the biological effects of chemicals. Drugs are chemicals that are introduced into the body to cause some sort of change. When drugs are administered, the body begins a sequence of processes designed to handle the new chemicals. These processes, which involve breaking down and eliminating the drugs, in turn affect the body’s complex series of chemical reactions. In clinical practice, healthcare providers focus on how chemicals act on living organisms. Nurses and midwives deal with pharmacothera­ peutics , or clinical pharmacology, the branch of pharmacology that uses drugs to treat, prevent and diagnose disease. Clinical pharmacology addresses two key concerns: the drug’s effects on the body and the body’s response to the drug. For many reasons, understanding how drugs act on the body to cause changes and applying that knowledge in the clinical setting are important aspects of practice. For instance, people today often follow complicated drug regimens and receive potentially toxic drugs. Many also manage their care at home. A drug can have many effects, and the nurse or midwife must know which ones may occur when a particular drug is administered. Some drug effects are therapeutic, or helpful, but others are undesirable or potentially dangerous. These negative effects are called adverse effects . (See Chapter 3 for a detailed discussion of adverse effects.) The nurse and midwife are in a unique position regarding drug therapy because care responsibilities • Intervening to make the drug regimen more tolerable • Providing individual and family teaching about drugs and the drug regimen • Monitoring the overall care plan to prevent medication errors Knowing how drugs work makes these tasks easier to handle, thus enhancing the effectiveness of drug therapy. This text is designed to provide the pharmacological basis for understanding drug therapy. The physiology of a body system and the related actions of many drugs on that system are presented in a way that allows clear understanding of how drugs work and what to antici- pate when giving a particular type of drug. Thousands of drugs are available for use, and it is impossible to memorise all of the individual differences among drugs in a class. This text addresses general drug information. It is useful to refer to McKenna’s Drug Handbook for Nursing and Midwifery or to another drug guide to obtain specific details required for safe and effective drug administration. Drug details are include the following: • Administering drugs • Assessing drug effects

changing constantly. Practising nurses and midwives must be knowledgeable about these changes and rely on an up-to-date and comprehensive drug guide in the clinical setting. A section related to care considerations for indi- viduals receiving particular drugs can be found in each chapter of this book. This includes assessment points, implementation or particular interventions that should be considered, and evaluation points will provide a guide for using clinical decision making to effectively incorporate drug therapy into care. This information can be used to develop an individual care plan for each individual. The monographs in McKenna’s Drug Handbook for Nursing and Midwifery can be used to provide the specific information that you need to plan care for each particular drug you might be giving. The various sections of each drug monograph (Figure 1.1) can provide information to help in the development of appropriate teaching guides and drug cards for reference in the clinical setting. SOURCES OF DRUGS Drugs are available from varied sources, both natural and synthetic. Natural sources include plants, animals and inorganic compounds. Natural sources Chemicals that might prove useful as drugs can come from many natural sources, such as plants, animals or inorganic compounds. To become a drug, a chemical must have a demonstrated therapeutic value or efficacy without severe toxicity or damaging properties. Plants Plants and plant parts have been used as medicines since prehistoric times. Even today, plants are an important source of chemicals that are developed into drugs. For example, digitalis products used to treat cardiac dis- orders and various opiates used for sedation are still derived from plants. Table 1.1 provides examples of drugs derived from plant sources. Drugs also may be processed using a synthetic version of the active chemical found in a plant. An example of this type of drug is dronabinol, which contains the active ingredient delta-9-tetrahydro­ cannabinol found in marijuana. This drug helps to prevent nausea and vomiting in people with cancer but does not have all of the adverse effects that occur when the marijuana leaf is smoked. Marijuana leaf is a controlled substance with high abuse potential and has no legal or accepted medical use. The synthetic version of the active ingredient allows for an accepted form to achieve the desired therapeutic effect in cancer

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P A R T 1  Introduction to nursing pharmacology

692 Hormonal drugs

Sulfonylurea: Increased risk of hypoglycae- mia. CONTRAINDICATIONS Contraindicated in individuals hypersensi- tive to the drug or any of the ingredients. CARE CONSIDERATIONS • Monitor blood glucose levels closely. • Monitor white cell counts regularly. • Whenused in conjunctionwith a sulfonyl- urea, dosage of the sulfonylurea may need reducing to avoid hypoglycaemia. PATIENT TEACHING • Advise person that drug may be taken with or without food. • Advise person to continue taking the medication even if feeling well. • Advise individual to report persistent, severe abdominal pain to doctor immedi- ately. vildagliptin Galvus Pregnancy risk category B3 Use in sport: Permitted AVAILABLE FORMS Tablets: 50 mg INDICATIONS & DOSAGES ➤ Management of type 2 diabetesmellitus in dual combination— Adults: In dual combination with metfor- min, 50 mg PO in the morning or 50 mg PO b.i.d. In dual combination with a sulfonylurea, 50 mg PO once daily in the morning. Adjust-a-dose: Avoid if creatinine clear- ance is below 50 mL/minute. Avoid in per- son with hepatic impairment. ACTION Enhances glycaemic control in type 2 dia- betes by improving beta-cell receptiveness to glucose, stimulating insulin synthesis and

sitagliptin Januvia

Pregnancy risk category B3 Use in sport: Permitted AVAILABLE FORMS Tablets: 25 mg, 50 mg, 100 mg INDICATIONS & DOSAGES

➤ Management of diabetesmellitus type 2— Adults over 18 years: 100 mg PO once daily. Adjust-a-dose: Adults with moderate

PO once daily.

ACTION Enhances glycaemic control in type 2 dia- betes by improving beta-cell receptiveness to glucose, stimulating insulin synthesis and release and lowering glucagon secretion leading to reduced production of glucose in the liver.

Route

Onset

Peak

Duration

PO

Unknown

1–4 hrs

24 hrs

ADVERSE REACTIONS CNS: headache. ENT: nasopharyngitis. GI: abdominal pain, diarrhoea, nausea, vomiting, pancreatitis. Haematological: neutrophilia. Musculoskeletal: rhabdomyolysis. Skin: generalised exfoliative dermatitis, rash, urticaria, Stevens-Johnson syndrome. Other: hypersensitivity reactions such as anaphylaxis,angio-oedema, rash, urticaria and other skin conditions. INTERACTIONS Drug-drug. Digoxin: May slightly increase plasma digoxin levels. Metabolic: hypoglycaemia. Renal: acute renal failure.

Reactions may be common , uncommon, life-threatening , or COMMONAN

REATENING.

FIGURE 1.1  Example of a drug monograph from McKenna’s Drug Handbook for Nursing and Midwifery (7th edn).

sufferers. It is only available in Australia through the Australian Government’s Special Access Scheme. Ingestion of a plant-derived food can sometimes lead to a drug effect. For instance, the body converts natural liquorice to a false aldosterone—a hormone found in the body—resulting in fluid retention and hypokalaemia or low serum potassium levels if large amounts of liquorice are eaten. However, people seldom think of liquorice as a drug. DH_7E_Ch_53.indd 692

Finally, plants have become the main component of the growing alternative therapy movement. Chapter 6 discusses the alternative therapy movement and its impact on today’s drug regimens. Animal products Animal products are used to replace human chemicals that fail to be produced because of disease or genetic problems. Until recently, insulin for treating diabetes was obtained exclusively from the pancreas of cows and 30/01/14 2:40 PM

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C H A P T E R 1  Introduction to drugs

■■ TABLE 1.1 Drugs derived from plants Plant Product

each of which has slightly different properties, making a particular drug more desirable in a specific situa- tion. Throughout this book, the icon will be used to designate those drugs of a class that are considered the prototype of the class, the original drug in the class or the drug that has emerged as the most effective. For example, the cephalosporins are a large group of antibiotics derived from the same chemical structure. Alterations in the chemical rings or attachments to that structure make it possible for some of these drugs to be absorbed orally, whereas others must be given par- enterally. Some of these drugs cause severe toxic effects (e.g. renal toxicity), but others do not. ■■ TABLE 1.2 Elements used for their therapeutic effects Element Therapeutic use Aluminium Antacid to decrease gastric acidity Management of hyperphosphataemia Prevention of the formation of phosphate urinary stones Fluorine (as fluoride) Prevention of dental cavities Prevention of osteoporosis Gold Treatment of rheumatoid arthritis Iron Treatment of iron deficiency anaemia ■■ Clinical pharmacology is the study of drugs used to treat, diagnose or prevent a disease. ■■ Drugs are chemicals that are introduced into the body and affect the body’s chemical processes. ■■ Drugs can come from plants, foods, animals, salts of inorganic compounds or synthetic sources. DRUG EVALUATION After a chemical that might have therapeutic value is identified, it must undergo a series of scientific tests to evaluate its actual therapeutic and toxic effects. This process is tightly controlled by the Therapeutic Goods Administration (TGA) , an agency of the Australian Department of Health and Ageing that regulates the development and sale of drugs. TGA-regulated tests are designed to ensure the safety and reliability of any drug approved in this country. For every 100,000 chemicals that are identified as being potential drugs, only about five end up being marketed. Before receiving final TGA KEY POINTS KEY POINTS

Ricinus communis

Seed Oil Castor oil (Neolid)

Digitalis purpurea (foxglove plant)

Leaves Dried leaves Digitalis leaf

Papaver somniferum (poppy plant)

Unripe capsule Juice Opium Morphine (MS Contin, Ordine) Codeine Papaverine

pigs. Now genetic engineering —the process of altering DNA—permits scientists to produce human insulin by altering Escherichia coli bacteria, making insulin a better product without some of the impurities that come with animal products. Thyroid drugs and growth hormone preparations also may be obtained from animal thyroid and hypo- thalamic tissues. Many of these preparations are now created synthetically, however, and the synthetic preparations are considered to be purer and safer than preparations derived from animals. Inorganic compounds Salts of various chemical elements can have therapeu- tic effects in the human body. Aluminium, fluoride, iron and even gold are used to treat various conditions. The effects of these elements were usually discovered acci- dentally when a cause–effect relationship was observed. Table 1.2 shows examples of some elements used for their therapeutic effects. Synthetic sources Today, many drugs are developed synthetically after chemicals in plants, animals or the environment have been tested and found to have therapeutic activity. Scien- tists use genetic engineering to alter bacteria to produce chemicals that are therapeutic and effective. Other tech- nical advances allow scientists to alter a chemical with proven therapeutic effectiveness to make it better. Some- times, a small change in a chemical’s structure can make that chemical more useful as a drug—more potent, more stable, less toxic. These technological advances have led to the development of groups of similar drugs, all of which are derived from an original prototype, but

■■ TABLE 1.3 Comparison of generic, chemical, and brand names of drugs thyroxine sodium ← generic name →

poractant alfa

← ←

→ →

chemical name brand names

l -thyroxine,T 4

dipalmitoylphosphatidylcholine

Eutroxsig, Oroxine

Curosurf

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P A R T 1  Introduction to nursing pharmacology

approval to be marketed to the public, drugs must pass through several stages of development. These include preclinical trials and phase I, II and III studies. The drugs listed in this book have been through rigorous testing and are approved for sale to the public, either with or without a prescription from a healthcare provider. In New Zealand, the New Zealand Medicines and Medical Devices Safety Authority (MEDSAFE) is responsible for administering the Medicines Act 1981 and Regulations 1984. MEDSAFE is responsible for applying a framework of controls designed to ensure that the therapeutic products available in New Zealand are those that can be expected to have greater benefits than risks if used appropriately. This is achieved through the pre-marketing and the post-marketing surveillance processes that are set-up by the Ministry of Health. The pre-market approval system for medicines is managed by MEDSAFE. The subsidisation of medi- cines is managed by PHARMAC (the Pharmaceutical Management Agency). PHARMAC is a Crown Entity whose primary objective is to secure, for eligible people in need of pharmaceuticals, the best health outcomes that are reasonably achievable from pharma- ceutical treatment from within the funding provided. MEDSAFE and PHARMAC work independently, and MEDSAFE is not involved in funding issues. Post- marketing surveillance monitors the safety of medicines and medical devices in use. Products shown to be unsafe are removed from use, and prescribers are advised about new safety information for products. Preclinical trials In preclinical trials , chemicals that may have thera- peutic value are tested on laboratory animals for two main purposes: (1) to determine whether they have the presumed effects in living tissue, and (2) to evaluate any adverse effects. Animal testing is important because unique biological differences can cause very differ- ent reactions to the chemical. These differences can be found only in living organisms, so computer-generated models alone are often inadequate. At the end of the preclinical trials, some chemicals are discarded for the following reasons: • The chemical lacks therapeutic activity when used with living animals. • The chemical is too toxic to living animals to be worth the risk of developing into a drug. • The chemical is highly teratogenic (causing adverse effects to the fetus). • The safety margins are so small that the chemical would not be useful in the clinical setting. Some chemicals, however, are found to have therapeu- tic effects and reasonable safety margins. This means that the chemicals are therapeutic at doses that are

reasonably different from doses that cause toxic effects. Such chemicals will pass the preclinical trials and advance to phase I studies. Phase I studies A phase I study uses human volunteers to test the drugs. These studies are more tightly controlled than preclini- cal trials and are performed by specially trained clinical investigators. The volunteers are fully informed of possible risks and may be paid for their participation. Usually, the volunteers are healthy, young men. Women are not good candidates for phase I studies because the chemicals may exert unknown and harmful effects on a woman’s ova, and too much risk is involved in taking a drug that might destroy or alter the ova. Women do not make new ova after birth. Men produce sperm daily, so there is less potential for complete destruction or altera- tion of the sperm. Some chemicals are therapeutic in other animals but have no effects in humans. Investigators in phase I studies scrutinise the drugs being tested for effects in humans. They also look for adverse effects and toxicity. At the end of phase I studies, many chemicals are dropped from the process for the following reasons: Some chemicals move to the next stage of testing despite undesirable effects. For example, the antihyper- tensive drug minoxidil ( Loniten ) was found to effectively treat malignant hypertension, but it caused unusual hair growth on the palms and other body areas. However, because it was so much more effective for treating malignant hypertension at the time of its development than any other antihypertensive drug, it proceeded to phase II studies. (Now, its hair-growing effect has been channelled for therapeutic use into various hair-growth preparations such as Rogaine. ) Phase II studies A phase II study allows clinical investigators to try out the drug on individuals who have the disease that the drug is designed to treat. People are told about the possible benefits of the drug and are invited to partici- pate in the study. Those who consent to participate are fully informed about possible risks and are monitored very closely, often at no charge to them, to evaluate the drug’s effects. Usually, phase II studies are performed at various sites across the country—in hospitals, clinics and doctors’ offices—and are monitored by representa- tives of the pharmaceutical company studying the drug. At the end of phase II studies, a drug may be removed from further investigation for the following reasons: • They lack therapeutic effect in humans. • They cause unacceptable adverse effects. • They are highly teratogenic. • They are too toxic.

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C H A P T E R 1  Introduction to drugs

Therapeutic Goods Administration approval Drugs that finish phase III studies are evaluated by the TGA, which relies on committees of experts familiar with the specialty area in which the drugs will be used. Only those drugs that receive TGA committee approval may be marketed. Figure 1.2 recaps the various phases of drug development discussed. An approved drug is given a brand name (trade name) by the pharmaceutical company that developed it. The generic name of a drug is the original designa- tion that the drug was given when the drug company applied for the approval process. Chemical names are names that reflect the chemical structure of a drug. Some drugs are known by all three names. It can be con- fusing to study drugs when so many different names are used for the same compound. In this text, the generic and chemical names always appear in straight print, and the brand name is always italicised (e.g. minoxidil [ Rogaine ]). Table 1.3 compares examples of drug names. The entire drug development and approval process can take 5 to 6 years, resulting in a so-called drug lag in Australia and New Zealand. In some instances, a drug that is available in another country may not become available here for years. The TGA regards public safety as primary in drug approval, so the process remains strict; however, it can be accelerated in certain instances involving the treatment of deadly diseases. For example, some drugs (e.g. delavirdine [ Rescriptor ] and efavirenz [ Stocrin ]) that were thought to offer a benefit to individ- uals with acquired immune deficiency syndrome (AIDS), a potentially fatal immune disorder, were pushed through because of the progressive nature of AIDS and

• It is less effective than anticipated. • It is too toxic when used with people. • It produces unacceptable adverse effects.

• It has a low benefit-to-risk ratio, meaning that the therapeutic benefit it provides does not outweigh the risk of potential adverse effects that it causes. • It is no more effective than other drugs already on the market, making the cost of continued research and production less attractive to the drug company. A drug that continues to show promise as a thera­ peutic agent receives additional scrutiny in phase III studies. Phase III studies A phase III study involves use of the drug in a vast clinical market. Prescribers are informed of all the known reactions to the drug and precautions required for its safe use. Prescribers observe individuals very closely, monitoring them for any adverse effects. Some- times, prescribers ask people to keep journals and record any symptoms they experience. Prescribers then evaluate the reported effects to determine whether they are caused by the disease or by the drug. This informa- tion is collected by the drug company that is developing the drug and is shared with the TGA. When a drug is used widely, totally unexpected responses may occur. A drug that produces unacceptable adverse effects or unforeseen reactions is usually removed from further study by the drug company. In some cases, the TGA may have to request that a drug be removed from the market.

Phase IV continued evaluation

Orphan drugs

All chemicals that theoretically may have therapeutic activity

Preclinical trials of efficacy and toxicity

Drugs cleared for human testing

Drugs cleared for

Drugs cleared for large scale

Drugs approved for marketing by TGA and MEDSAFE

Phase I studies

Phase II studies

Phase III studies

limited clinical studies

clinical studies

Drugs that 1. Lack therapeutic activity 2. Are too toxic; teratogenic 3. Have a small safety margin

Drugs that 1. Lack therapeutic activity in humans 2. Are too toxic 3. Produce unacceptable side effects

Drugs that 1. Are less effective than expected 2. Are too toxic 3. Produce unacceptable side effects 4. Have a low benefit-to- risk ratio 5. Are not as effective as available drugs

Drugs that 1. Produce unacceptable side effects 2. Produce unexpected responses

Drugs dropped from study

FIGURE 1.2  Phases of drug development.

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P A R T 1  Introduction to nursing pharmacology

the lack of a cure. All literature associated with these drugs indicates that long-term effects and other infor- mation about the drug may not yet be known. In addition to the drug lag issue, there also are concerns about the high cost of drug approval. In 2011, Morgan et al. published a systematic review on the costs of drug development. These authors found that the estimated cost of taking a chemical from discovery to marketing as a drug could be as high as $US 1.8 billion. Because of this kind of financial investment, pharmaceu- tical companies are unwilling to risk approval of a drug that might cause serious problems and prompt lawsuits. Phase IV studies After a drug is approved for marketing, it enters a phase of continual evaluation, or phase IV study . Prescribers are obligated to report to the TGA any untoward or unexpected adverse effects associated with drugs they are using, and the TGA continually evaluates this infor- mation. Some drugs cause unexpected effects that are not seen until wide distribution occurs. Sometimes, those effects are therapeutic. For example, individuals taking the antiparkinsonism drug amantadine ( Symmetrel ) were found to have fewer cases of influenza than other people, leading to the discovery that amantadine is an effective antiviral agent. In other instances, the unexpected effects are danger- ous. In 1997, the diet drug dexfenfluramine ( Ponderax ) was removed from the market only months after its release because people taking it developed serious heart problems. In 2004, the drug company Merck withdrew its cyclooxygenase-2 (Cox-2) specific non-steroidal anti-inflammatory drug rofecoxib ( Vioxx ) from the market when post-marketing studies seemed to show a significant increase in cardiovascular mortality in indi- viduals who were taking the drug. These problems were not seen in any of the premarketing studies of the drug. The effects were only seen with a much wider use of the drug after it had been marketed. ■■ The TGA carefully regulates the testing and approval of all drugs in Australia. ■■ To be approved for marketing, a drug must pass through animal testing, testing on healthy humans, selective testing on people with the disease being treated and then broad testing on people with the disease being treated. LEGAL REGULATION OF DRUGS The Therapeutic Goods Administration (TGA), a division of the Commonwealth Department of Health KEY POINTS KEY POINTS

and Ageing, is responsible for administering the provi- sions of the Therapeutic Goods Act 1989 in Australia that regulates the manufacture, availability and supply of drugs. Each state and territory also has Acts and Regulations that deal with control and administration of drugs. In most cases, the strictest law is the one that prevails. Nurses and midwives should become familiar with the rules and regulations in the area in which they practise. They have a professional responsibility to be informed of the legislation underpinning administration and supply of drugs. MEDSAFE is New Zealand’s Medicines and Medical Devices Safety Authority. MEDSAFE is a business unit of the Ministry of Health (Acts and Regu­ lations; Medicine Management) and is the authority responsible for the regulation of therapeutic products in New Zealand. This includes medicines, related products, herbal medicines, medical devices, controlled drugs used as medicines, etc. through the Medicines Act 1981 and Regulations 1984, and parts of the Misuse of Drugs Act 1975 and Regulations 1977. The overall objective of these Acts is to ensure the quality, safety and efficacy of therapeutic goods, including medicines and medical devices, available to the Australian and New Zealand public. The Australian and New Zealand Governments are currently working to harmonise the regulatory arrange- ments for therapeutic products between both countries. Both governments signed a Treaty in Wellington in December 2003 to establish a single, bi-national agency to regulate therapeutic products, including medical devices and prescription medicines, and over-the- counter, complementary and alternative medicines. Transition to the new agency, Australia New Zealand Therapeutic Products Agency (ANZTPA) is underway. This agency will eventually replace the Australian TGA and the New Zealand MEDSAFE, will be accounta- ble to both Australian and New Zealand Governments and will have a fully functional office in both countries. Under the joint Australia–New Zealand therapeutic products agency (the joint agency), products represented as being for therapeutic use are to be regulated as thera- peutic products. This includes complementary medicines such as herbal, vitamin and mineral supplements, other nutritional supplements, traditional medicines and aromatherapy oils. Table 1.4 provides a summary of Aus- tralian and New Zealand legislation around medications. Safety during pregnancy As part of the standards for testing and safety, the TGA requires that each new drug be assigned to a pregnancy category (Box 1.1). The categories indicate a drug’s potential or actual teratogenic effects, thus offering guidelines for use of that particular drug in pregnancy. Research into the development of the human fetus,

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C H A P T E R 1  Introduction to drugs

■■ TABLE 1.4 Australian and New Zealand

■■ BOX 1.1  Australian Drug Evaluation Committee (ADEC) – Classification of drugs in pregnancy

legislation affecting the clinical use of drugs

Commonwealth of Australia

Therapeutic Goods Act 1989 Therapeutic Goods Regulation

Category Description A

National Health Act 1953 Narcotic Drugs Act 1967

These drugs have been taken by a large number of pregnant women without identified risk to the fetus. These drugs have been taken by limited numbers of women without evidence of increased fetal malformation. Animal studies have not indicated a higher than normal incidence of fetal impairment. These drugs have been taken by limited numbers of women without evidence of increased fetal malformation or other harmful effect. Animal studies are inadequate. There are no data to suggest increased risk. These drugs have been taken by limited numbers of women without evidence of increased fetal malformation or other harmful effect. Animal studies have shown increased incidence of fetal effects. These drugs have caused or been suspected to cause fetal or neonatal effects, but the effects are often reversible and not congenital malformations. These drugs have caused, or have been suspected as causing, fetal malformation or irreversible damage. These drugs are not recommended for use in pregnancy due to a high risk of causing permanent damage to the fetus.

Australian Capital Territory

Drugs of Dependence Act 1989 Drugs of Dependence Regulations Poisons and Drugs Act 1978 Poisons Act 1933 Poisons Regulations Poisons andTherapeutic Goods Act 1966 Poisons andTherapeutic Goods Regulation 2002 Poisons and Dangerous Drugs Act 2007 Poisons and Dangerous Drugs Regulations Health Act 1937 Health (Drugs and Poisons) Regulation 1996

B1

New South Wales

B2

Northern Territory

Queensland

B3

South Australia Controlled Substances Act 1984 Controlled Substances (Poisons) Regulations 1996 Tasmania Poisons Act 1971 Poisons Regulations Victoria Drugs, Poisons and Controlled Substances Act 1981

C

D

Drugs, Poisons and Controlled Substances Regulations 2006

Western Poisons Act 1964 Poisons Regulations New Zealand Medicines Act 1981 Australia

X

Medicines Act Amended 2005 Medicine Regulations 1984 Misuse of Drugs Act 1975 Misuse of Drugs Regulation

Taken from Dempsey et al. p.749

Each prescriber has a prescriber number, which allows for monitoring of prescription patterns and possible abuse. Nurses and midwives should be familiar with not only the guidelines for controlled substances, but also the local policies and procedures within their state, territory or even their workplace, which might be even more rigorous. Generic drugs When a drug receives approval for marketing from the TGA, the drug formula is given a time-limited patent, in much the same way as an invention is patented. The length of time for which the patent is extant depends on the type of chemical involved. When the patent runs out on a brand-name drug, the drug can be produced by other manufacturers. Generic drugs are chemicals that are produced by companies involved solely in the manufacturing of drugs. Because they do not have the research, the advertising or, sometimes, the quality control departments that pharmaceutical companies

especially the nervous system, has led many healthcare providers to recommend that no drug should be used during pregnancy because of potential effects on the developing fetus. In cases in which a drug is needed, it is recommended that the drug of choice be one for which the benefit outweighs the potential risk. Drugs and poisons schedules In 2003, the Australian Health Minister’s Advisory Council established categories for ranking the abuse potential of various drugs and management of poisons in the Uniform Scheduling of Drugs and Poisons. There are nine schedules under which drugs are classified. Box 1.2 contains descriptions of each category or schedule. Those of specific relevance to nurses and midwives are sched- ules 2, 3, 4, 8 and occasionally 9. It is important that all health professionals involved in dispensing, prescribing and administering medicines are aware of their responsi- bilities in regard to each of the relevant schedules.

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P A R T 1  Introduction to nursing pharmacology

Orphan drugs Orphan drugs are drugs that have been discovered but are not financially viable and therefore have not been “adopted” by any drug company. Orphan drugs may be useful in treating a rare disease or they may have poten- tially dangerous adverse effects. Orphan drugs are often abandoned after preclinical trials or phase I studies. Some drugs in this book have orphan drug uses listed. More information about orphan drugs, and current listings, can be found at www.tga.gov.au/industry/ pm-orphan-drugs.htm. Over-the-counter drugs Over-the-counter (OTC) drugs are products that are available without prescription for self-treatment of a variety of complaints. Some of these agents were approved as prescription drugs but later were found to be very safe and useful for individuals without the need of a prescription. Some were not rigorously screened and tested by the current drug evaluation protocols because they were developed and marketed before the current laws were put into effect. Many of these drugs were “grandfathered” into use because they had been used for so long. The TGA is currently testing the effectiveness of many of these products and, in time, will evaluate all of them. Although OTC drugs have been found to be safe when taken as directed, nurses and midwives should consider several problems related to OTC drug use: • Taking these drugs could mask signs and symptoms of underlying disease, making diagnosis difficult. • Taking these drugs with prescription medications could result in drug interactions and interfere with drug therapy. • Not taking these drugs as directed could result in serious overdoses. Many people do not consider OTC drugs to be medi- cations and therefore do not report their use. Nurses and midwives must always include specific questions about OTC drug use when taking a drug history and should provide information in all drug-teaching protocols about avoiding OTC drug use while taking prescription drugs. ■■ Generic drugs are drugs no longer protected by patent and can be produced by companies other than the one that developed them. ■■ OTC drugs are available without a prescription and are deemed safe when used as directed. ■■ Orphan drugs are drugs that have been discovered but are not financially viable because they have a limited market or a narrow margin of safety. These drugs may have then been adopted for development by a drug company in exchange for tax incentives. KEY POINTS KEY POINTS

■■ BOX 1.2  Uniform scheduling of drugs and poisons in Australia

Schedule

Description

1

This schedule is left blank Substances available from

2 Pharmacy

Medicine

pharmacies, or from people licensed to sell these drugs Substances that require professional

3 Pharmacist

Only Medicine advice but are available from a pharmacist 4 Prescription Substances that are prescribed by a Only Medicine person permitted under state or

territory legislation to prescribe, and available from a pharmacy by prescription Hazardous substances that are available to the public but require care with handling Substances that are readily available to the public but are more hazardous, requiring strong warnings Substances that are highly harmful and require special manufacture, handling and use precautions Substances with potential for Substances that are prohibited due to the potential for abuse; use is limited to approved medical or scientific research purposes dependence

5 Caution

6 Poison

7 Dangerous

Poison

8 Controlled

Drug

9 Prohibited

Substance

Taken from Dempsey et al. p.748

have, they can produce the generic drugs more cheaply. In the past, some quality-control problems were found with generic products. For example, the binders used in a generic drug might not be the same as those used in the brand-name product. As a result, the way the body breaks down and uses the generic drug may differ from that of the brand-name product. In that case, the bioavailability of the drug is different from that of the brand name product. It is often recommended that a drug be dispensed in the generic form if one is available. This requirement helps to keep down the cost of drugs and healthcare. Some prescribers, however, specify that a drug prescrip- tion be “dispensed as written” (DAW), that is, that the brand-name product be used. By doing so, the prescriber ensures the quality control and the action and effect expected with that drug. These elements may be most important in drugs that have narrow safety margins, such as digoxin ( Lanoxin ), a heart drug, and warfarin ( Coumadin ), an anticoagulant. The initial cost may be higher, but some prescribers believe that, in the long run, the cost to the individual will be less.

11

C H A P T E R 1  Introduction to drugs

SOURCES OF DRUG INFORMATION The fields of pharmacology and drug therapy change so quickly that it is important to have access to sources of information about drug doses, therapeutic and adverse effects and nursing-related implications. Textbooks provide valuable background and basic information to help in the understanding of pharmacology, but in clinical practice it is important to have access to up-to-the-minute information. Several sources of drug information are readily available. Nurses and midwives often need to consult more than one source. Drug labels Drug labels have specific information that identifies a specific drug. For example, a drug label identifies the brand and generic names for the drug, the drug dosage, the expiration date and special drug warnings. Some labels also indicate the route and dose for admini­ stration. Figure 1.3 illustrates an example of a drug label.

Understanding how to read a drug label is essential. Nurses and midwives need to become familiar with each aspect of the label. Package inserts All drugs come with a package insert prepared by the manufacturer according to strict TGA regulations. The package insert contains all of the chemical and study information that led to the drug’s approval. Package inserts sometimes are difficult to understand and are almost always in very small print, making them difficult to read. The TGA (www.tga.gov.au), MEDSAFE (www. medsafe.govt.nz) and New Zealand Formulary websites are good resources for finding the prescribing informa- tion or package insert for most drugs. Reference books A wide variety of reference books are available for drug information. The MIMS is a compilation of package insert information from drugs used in Australia. As the content can be quite technical, the book may be difficult to use.

Prescription status Indicates drug is prescription only

Drug dose Dose available in this product

Quantity Amount of the drug in this package

Lot number Specific drug batch from which this drug was produced; important for recall information

Brand name Name given to the drug by the manufacturer

Generic name Chemical name of the drug listed by the TGA

Expiration date Indicates date after which the drug should not be used

Australian Register of Therapeutic Goods (ARTG) number Number used to identify a specific drug Storage information

Drug manufacturer Pharmaceutical company

FIGURE 1.3  A sample drug label. (Used with permission from AstraZeneca Pty Ltd.)

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P A R T 1  Introduction to nursing pharmacology

Therapeutic Guidelines provides a wide range of drug information in a series of systematic guides, such as antibiotics and gastrointestinal pharmacology. These guidelines draw upon a range of evaluated literature and research. McKenna’s Drug Handbook for Nursing and Mid- wifery has drug monographs organised alphabetically and includes care implications and important teaching points specifically relevant to nursing and midwifery practice. Numerous other drug handbooks are also on the market and readily available for nurses and midwives to use. Journals Various journals can be used to obtain drug informa- tion. For example, the Medical Letter is a monthly review of new drugs, drug classes and specific treat- ment protocols. Many clinical nursing and midwifery journals offer information on new drugs, drug errors and care implications. Australian Prescriber is a useful source of easily interpreted pharmacology information and is freely available online. Internet information Many individuals now use the Internet as a source of medical information and advice. Nurses and midwives need to become familiar with what is available on the Internet and what people may be referencing, and have skills in critiquing the credibility of these sources. ■■ Drugs are chemicals that are introduced into the body to bring about some sort of change. ■■ Drugs can come from many sources: plants, animals, inorganic elements and synthetic preparations. ■■ The TGA regulates the development and marketing of drugs to ensure safety and efficacy in Australia. ■■ Preclinical trials involve testing of potential drugs on laboratory animals to determine their therapeutic and adverse effects. ■■ Phase I studies test potential drugs on healthy human subjects. ■■ Phase II studies test potential drugs on individuals who have the disease the drugs are designed to treat. ■■ Phase III studies test drugs in the clinical setting to determine any unanticipated effects or lack of effectiveness. ■■ TGA pregnancy categories indicate the potential or actual teratogenic effects of a drug. ■■ Generic drugs are sold under their chemical names, not brand names; they may be cheaper but are not necessarily as safe as brand-name drugs. CHAPTER SUMMARY

■■ Orphan drugs are chemicals that have been discovered to have some therapeutic effect but that are not financially advantageous to develop into drugs. ■■ OTC drugs are available without prescription for the self-treatment of various complaints. ■■ Information about drugs can be obtained from a variety of sources, including the drug label, reference books, journals and Internet sites. Knowing your strengths and weaknesses helps you to study more effectively. Take a PrepU Practice Quiz to find out how you measure up!

ONLINE RESOURCES

An extensive range of additional resources to enhance teaching and learning and to facilitate understanding of this chapter may be found online at the text’s accompanying website, located on thePoint at http://thepoint.lww.com. These include Watch and Learn videos, Concepts in Action animations, journal articles, review questions, case studies, discussion topics and quizzes.

WEB LINKS

Healthcare providers and students may want to consult the following Internet sources: www.anztpa.org Home page of the Australia New Zealand Therapeutic Product Agency (ANZTPA). www.australianprescriber.com Australian Prescriber home page. www.medsafe.govt.nz Home page of MEDSAFE New Zealand. www.nps.org.au Home page of MedicineWise, National Prescribing Service. www.tga.gov.au Home page of the Therapeutic Goods Administration. Barton, J. H. & Emanuel, E. J. (2005). The patient-based pharmaceutical development process: rationale, problems and potential reforms. JAMA, 294, 2075–2082. Cardinale, V. (1998). Consumers looking for more answers, clearer directions. Drug Topics Supplement, 142 (11), 23a. Davies, C. A. (2004). Keeping advertisers honest—An overview of the regulation of the advertising of medicines and medical devices in Australia. Australian Prescriber, 27 , 124–127. Dempsey, J., Hillege, S. & Hill, R. (2014). Fundamentals of Nursing and Midwifery: A Person-centred Approach to Care (2nd Australian and New Zealand edn). Sydney: Lippincott Williams & Wilkins. BIBLIOGRAPHY

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C H A P T E R 1  Introduction to drugs

Drug Enforcement Agency. (2000). Guidelines for prescription of narcotics for physicians . Washington, DC: U.S. Government Printing Office. Gilman, A., Hardman, J. G. & Limbird, L. E. (Eds). (2006). Goodman and Gilman’s the Pharmacological Basis of Therapeutics (11th edn). New York: McGraw-Hill. Koo, M. M., Krass, I. & Aslani, P. (2003). Factors influencing consumer use of written drug information. Annals of Pharmacotherapy, 37 (2), 259–267. Kuo, G. M. (2003). Pharmacodynamic basis of herbal medications. Annals of Pharmacotherapy, 37 (2), 308. McKenna, L. (2012). Pharmacology Made Incredibly Easy (1st Australian and New Zealand edn). Sydney: Lippincott Williams & Wilkins.

McKenna, L. & Mirkov, S. (2014). McKenna’s Drug Handbook for Nursing and Midwifery (7th edn). Sydney: Lippincott Williams & Wilkins. Morgan, S., Grootendorst, P., Lexchin, J., Cunningham, C. & Greyson, D. (2011). The cost of drug development: A systematic review. Health Policy, 100 (1), 4–17. Sun, S. X., Lee, K. Y., Bertram, C. T. & Goldstein, J. L. (2007). Withdrawal of COX-2 selective inhibitors rofecoxib and valdecoxib: Impact on NSAID and gastroprotective drug prescribing and utilization. Current Medical Research and Opinion, 23 (8), 1859–1866.

C H E C K Y O U R U N D E R S T A N D I N G

5. The ADEC pregnancy categories: a. indicate a drug’s potential or actual teratogenic effects. b. are used for research purposes only. c. list drugs that are more likely to have addicting properties. d. are tightly regulated by the TGA. 6. Healthy young women are not usually involved in phase I studies of drugs because: a. male bodies are more predictable and responsive to chemicals. b. females are more apt to suffer problems with ova, which are formed only before birth. c. males can tolerate the unknown adverse effects of many drugs better than females. d. there are no standards to use to evaluate the female response. 7. A person has been taking fluoxetine ( Prozac ) for several years, but when picking up the prescription this month, found that the tablets looked different and became concerned. The health professional, checking with the pharmacist, found that fluoxetine had just become available in the generic form and the prescription had been filled with the generic product. The nurse should tell the person: a. that the new tablet may not work at all and the person should carefully monitor response. b. that generic drugs are available without a prescription and they are just as safe as the brand-name medication. c. that the law requires that prescriptions be filled with the generic form if available to cut down the cost of medications. d. that the pharmacist filled the prescription with the wrong drug and it should be returned to the pharmacy for a refund.

Answers to the questions in this chapter can be found in Appendix A at the back of this book.

MULTIPLE CHOICE Select the best answer to the following. 1. Clinical pharmacology is the study of: a. the biological effects of chemicals.

b. drugs used to treat, prevent or diagnose disease. c. plant components that can be used as medicines. d. binders and other vehicles for delivering medication. 2. Phase I drug studies involve: a. the use of laboratory animals to test chemicals. b. people with the disease the drug is designed to treat. c. mass marketing surveys of drug effects in large numbers of people. d. healthy human volunteers who are often paid for their participation. 3. The generic name of a drug is: a. the name assigned to the drug by the pharmaceutical company developing it. b. the chemical name of the drug based on its chemical structure. c. the original name assigned to the drug at the beginning of the evaluation process. d. the name that is often used in advertising campaigns. 4. An orphan drug is a drug that: a. has failed to go through the approval process. b. is available in a foreign country but not in this country. c. has been tested but is not considered to be financially viable. d. is available without a prescription.