A 37 Year Old Woman Visited Her Dentist For Removal Of Her Wisdom Teeth

Case Study Why am I not getting pain relief?

A37-year-old woman visited her dentist for removal of her wisdom teeth. The teeth were found to be impacted, and removal necessitated extensive surgery. Following completion of the procedure on one side of the mouth, the patient was given a prescription for acetaminophen 300 mg with codeine 30 mg (combination product) for the relief of pain. The patient took the prescription as prescribed for approximately 2 days, but little pain relief was achieved. She called the dentist to get a prescription for another analgesic. What is a possible explanation for this lack of efficacy?

Answer: Codeine itself is a very weak analgesic but is metabolized to morphine, which produces most of the analgesic effect following codeine administration. The metabolism of codeine to morphine is carried out by cytochrome P450 2D6, an enzyme that exhibits genetic polymorphism. The patient may be deficient in CYP2D6 and thus unable to convert codeine into its active metabolite, morphine; hence analgesic efficacy is lacking.

Pharmacokinetics is the description of the time course of a drug in the body, encompassing absorption, distribution, metabolism, and excretion. In simplest terms, it can be described as what the body does to the drug. Pharmacokinetic concepts are used during drug development to determine the optimal formulation of a drug, dose (along with effect data), and dosing frequency. For drugs with a wide therapeutic index (difference between the minimum effective dose and the minimum toxic dose), knowledge of the drug's pharmacokinetic properties in that individual patient may not be particularly important. For example, nonsteroidal antiinflam-matory drugs, such as ibuprofen, have a wide therapeutic index, and thus knowledge of the pharmacokinetic parameters in a given individual is relatively unimportant, since normal doses can vary from 400 to 3200 mg per day with no substantial difference in acute toxicity or effect. However, for drugs with a narrow therapeutic index, knowledge of that drug's pharmacokinetic profile in an individual patient has paramount importance.

If there is little difference between the minimum effective dose and the toxic dose, slight changes in a drug's pharmacokinetic profile, or even simply interindividual differences, may require dosage adjustments to minimize toxicity or maximize efficacy. For example, the blood concentrations of the antiasthmatic drug theophylline must usually be maintained within the range of 10-20 ^g/mL. At concentrations below this, patients may not obtain relief of symptoms, while concentrations above 20 ^g/mL can result in serious toxicities, such as seizures, arrhythmias, and even death. Thus, a drug's pharmacokinetic profile may have important clinical significance beyond its use in drug development.

Coping with Asthma

Coping with Asthma

If you suffer with asthma, you will no doubt be familiar with the uncomfortable sensations as your bronchial tubes begin to narrow and your muscles around them start to tighten. A sticky mucus known as phlegm begins to produce and increase within your bronchial tubes and you begin to wheeze, cough and struggle to breathe.

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