involving biochemical processes in the responding cell and organ systems in the body with which it interacts. Before administering treatment, the prescriber must be aware of any individual characteristics that might influence the drug’s effects. The most important of these are the age and health of the patient, as well as the degree or severity of the individual’s physical impairment by disease or condition. To avoid toxicity, drugs are typically administered in the lowest dosage that brings about the desired benefit and in conjunction with other drugs that limit the toxicity of the first drug. In addition, specific drug actions may be increased by adjusting the concentration of drug available to receptors in different parts of the body by administering the drug by a different route—as an inhalant, for example, instead of a pill. These factors are typically incorporated into client assessment when prescribing specific drugs: ● Age : Very young and elderly individuals have a limited ability to metabolize and excrete drugs. In neonatal cases, hepatic enzyme systems are not fully functioning, so drug metabolism is reduced and there is increased risk of toxicity. In the elderly, there is a longer period of metabolism by the liver and a decline in renal function, which may produce a situation of delayed excretion by the kidneys and a prolonged drug action. ● Body weight : Body size affects the amount of drug distributed and available. This is the reason many drugs are prescribed according to body weight, especially for long-term treatment. ● Nutritional level : Malnourishment alters drug distribution and metabolism. Poor diets may slow enzyme activity, which delays the drug’s metabolism. Reduction in plasma protein (i.e., a low-protein diet), may alter drug availability. ● Food/drug interactions : Food may enhance or inhibit drug absorption. ● Diseases : Diseases like Crohn’s disease, renal disease, or liver disease (hepatitis, cirrhosis, liver failure) may affect absorption. Circulatory diseases, including heart failure and peripheral vascular disease, reduce distribution and transportation of drugs throughout the body. ● Genetic/ethnic factors : Good or poor enzymatic function can be inherited. ● Pregnancy and lactation : Both may affect drug absorption and distribution. (Bailey, 1983) Stages of drug development and review ● Investigational new drug application (IND) : The pharmaceutical industry sometimes provides advice to the FDA prior to submission of an IND. Sponsors— companies, research institutions, and other organizations that take responsibility for developing a drug—must show the FDA results of preclinical testing they’ve done in laboratory animals and what they propose to do for human testing. At this stage, the FDA decides whether it is reasonably safe for the company to move forward with testing the drug in humans. ● Clinical trials : Drug studies in humans can begin only after an IND is reviewed by the FDA and a local institutional review board (IRB). The board is a panel of scientists and nonscientists in hospitals and research institutions that oversees clinical research. The local IRBs approve the clinical trial protocols, which describe the type of people who may participate in the clinical trial, the schedule of tests and procedures, the medications and dosages to be studied, the length of the study, the study’s objectives, and other details. The review boards
treatment. Usually, if the individual’s response changes over the course of administration, it is a decrease in effect, called a tolerance , to the drug. When responsiveness decreases rapidly after administration of the drug, the response is referred to as tachyphylaxis . When administering a drug for the first time, the prescriber must consider a number of factors, including the potential of a particular drug to produce tolerance or tachyphylaxis, as well as the individual’s age, gender, body size, health, genetic factors, and other drugs the individual is taking. Four main properties are associated with variation in drug responsiveness among different individuals or within a particular individual at different points in time: 1. Changes in the concentration of a drug that reaches a receptor: Pharmacokinetic differences, including differences in absorption rate of a drug, how the drug is distributed through different compartments of the body, and/or differences in eliminating the drug from the blood. Changes in the concentration will alter what receptors it reaches, changing the drug’s effects. While many differences can be anticipated according to characteristics like age, weight, health, and function of the liver and kidneys, for example, specials tests must be administered to confirm the presence of different drug- metabolizing enzymes or other genetic differences. 2. Variation in the concentration of an endogenous receptor ligand is associated specifically with variability in responses to drug antagonists. Partial agonists may exhibit even more extreme responses. 3. Changes in the number or function of receptors: Studies show that changes in drug responsiveness may be caused by increases or decreases in the number of receptor sites or by changes in the efficiency in the coupling of receptors. In some cases, the change in the number of receptors involved is brought about by hormones; in other cases, the agonist ligand itself causes a decrease in the number of receptor sites involved or the coupling efficiency (desensitization) of its receptors. These properties may contribute to tachyphylaxis, or tolerance to the drug, and can occur with either agonists or antagonists. Genetic factors can also play a role in changing the number or function of specific receptors. 4. The largest and most important set of mechanisms that causes variation in responsiveness to a drug is associated with changes in post receptor processes, that is, events that occur after the drug binds to receptors,
The FDA's drug review process: Ensuring drugs are safe and effective Over the last 150 years, the FDA has evolved from a small division of the U.S. Patent Office to one of the largest consumer protection agencies in the world. Its mission includes ensuring that new medical treatments reach the public as quickly as possible while simultaneously ensuring that new treatments are both safe and effective (Van Norman, 2016). Often, a drug is developed to treat a specific disease. An important use of a drug may also be discovered by accident.
For example, Retrovir (zidovudine, also known as AZT ) was first studied as an anticancer drug in the 1960s with disappointing results. It wasn’t until the 1980s that researchers discovered the drug could treat AIDS. The FDA approved the drug, manufactured by GlaxoSmithKline, for that purpose in 1987. Most drugs that undergo preclinical (animal) testing never even make it to human testing and FDA review. The drugs that do must undergo the agency’s rigorous evaluation process, which scrutinizes everything about the drug—from the design of clinical trials to the severity of side effects to the conditions under which the drug is manufactured.
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Book Code: MLA1225
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