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INTRODUCTION

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This chapter will be most useful after having a basic understanding of the material in Chapter 24, Drug Addiction in Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 12th Edition. The specific pharmacology (including the mechanisms of action) of drugs mentioned in Chapter 14 is discussed in previous or subsequent chapters. The drugs presented in Chapter 14 are discussed in relation to their ability to produce tolerance, physical dependence, and addiction. No Mechanisms of Action Table nor Clinical Summary Table are included as a part of Chapter 14 because new drugs are not introduced. The few drugs that are used therapeutically to treat specific drug addictions are discussed in the narratives of the clinical cases. In addition to the material presented here, the 12th Edition includes:

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  • Table 24-2 Dependence among Users 1990 to 1992

  • Figure 24-2 Cocaine-induced changes in CNS dopamine release

  • Figure 24-3 Nicotine concentrations in blood resulting from five different nicotine delivery systems

  • A detailed discussion of the variables affecting the onset and continuation of drug abuse and addiction

  • A detailed discussion of the different types of tolerance

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LEARNING OBJECTIVES

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  • Understand the pharmacological principles of tolerance, physical dependence, and withdrawal.

  • Describe the characteristic withdrawal syndromes for the commonly abused drugs.

  • Know the patterns of abuse behavior and the toxicity of the commonly abused drugs.

  • Know the available pharmacological interventions for the acute treatment and long-term management of the commonly abused drugs.

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CASE 14-1

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A 56-year-old obese woman is being treated with immediate-release oxycodone for chronic back pain. She is also taking a muscle relaxant, cyclobenzaprine, and a short-acting benzodiazepine for sleep.

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  1. What concerns are there with the use of an opiate-like immediate-release oxycodone for the treatment of chronic pain?

    Rapid-onset, short-duration opioids are excellent for acute short-term use, such as during the postoperative period. As tolerance and physical dependence develop, however, the patient may experience the early symptoms of withdrawal between doses, and during withdrawal, the threshold for pain decreases. The diversion of prescription opioids such as oxycodone and hydrocodone to illegal markets has become an important source of opiate abuse in the United States (see answer to Case 14-1c below).

    The risk for addiction is highest in patients complaining of pain with no clear physical explanation or in patients with evidence of a chronic, non-life-threatening disorder. Examples are chronic headaches, backaches, abdominal pain, or peripheral neuropathy. Even in these cases, an opioid may be considered as a brief emergency treatment, but long-term treatment with opioids should be used only after other alternatives have been exhausted.

  2. Over the past year this patient has doubled her dose of oxycodone. Why has she increased the dose of oxycodone?

    While abuse and addiction are complex conditions combining many variables (see Table 14-1), there are a number of relevant pharmacological phenomena that occur independent of social and psychological dimensions. First are the ...

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