McKenna's Pharmacology, 2e

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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.