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Variable Factors Influencing Drug Action

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Factors that have been identified as contributors to a variable response to drugs.

Patients often state, "The medication really knocked me out!" or "That medication didn't the touch pain!" The effects of drugs are unexpectedly potent in some patients, whereas other patients show patient little response at the same dosage. In addition, some patients react differently to the same dosage of a drug administered at different times. Because  of individual patient variation, exact responses to drug therapy are difficult to predict. The following factors have been identified as contributors to a variable response to drugs.

Age

Infants and the very elderly tend to be the most sensitive to the effects of drugs. There are important differences in the absorption, distribution, metabolism, and excretion of drugs in premature neonates, full-term newborns, and children. The aging process brings about changes in body composition and organ function that can affect the elderly patient's response to drug therapy.

Body Weight

Considerably overweight patient may require an increase in dosage to attain the same therapeutic response as the general population. Conversely, patient who are underweight (compared with the general population) tend to required lower dosages for the same therapeutic response. It is extremely important to obtain accurate heights and weights to patients because the dosage of medicine may be calculated using these parameters. Most pediatric dosages are calculated by milligrams of drug per kilogram (mg/kg) of body wight to adjust for growth rate. The dosages of other medicines, particularly the chemotherapeutic agents, are ordered based on body surface area (BSA). To ensure accurate measurements, weight should be taken at the same time, with similar clothing at admission, and at intervals ordered by the physician throughout  the provision of care.

Metabolic Rate

Patients with a higher than average metabolic rate tend to metabolize drugs more rapidly, thus requiring either larger doses or more frequent administration. The converse is true for those with lower than average metabolic rates. Chronic smoking enhances the metabolism of some drugs (e.g., theophylline), thus requiring larger doses to be administered more frequently for a therapeutic effect.

Illness

Pathologic conditions may alter the rate of absorption, distribution, metabolism, and excretion. For example, patient in shock have reduced peripheral vascular circulation and will absorb intramuscularly or subcutaneously injected drugs slowly. Patients who are vomiting may not be abe to retain a medication in the stomach long enough for dissolution and absorption. Patients with disease such as nephrotic syndrome or malnutrition may have reduced amounts of serum proteins in the blood necessary for adequate distribution of drugs. Patients with kidney failure must have significant reductions in the dosages of medications that are excreted by the kidneys.

Psychological Aspects

Attitudes and expectations play a major role in a patient's response to therapy and the willingness to take the medication as prescribed. Patients with diseases that have relatively rapid consequences if therapy is ignored, such as type 1 (insulin dependent) diabetes, usually have a good rate of compliance. Patients with "silent" illnesses, such as hypertension, tend to be much less compliant with the treatment regimen.

Another psychological consideration is the "placebo effect" and the "nocebo effect". It is well documented that a patient's positive expectations about treatment and the care received can positively affect the outcome of therapy, a phenomenon known as the placebo effect (Latin, I will please). Although more difficult to prove because of ethical considerations, it is also felt that negative expectations about the therapy and the care received can have a nocebo effect (Latin, I will harm), resulting in less than optimal outcomes of therapy. It is thought that the nocebo effect plays a major role in psychogenic illness, especially in stress-related problems, by worrying about it. Caregivers can help diminish the nocebo effect by having a positive mental attitude and emphasizing the positive aspects of therapy.

A placebo is a drug dosage form, such as s tablet or capsule, that has no pharmacologic activity because the dosage form has no active ingredients. When taken, the patient may report a therapeutic response. This response can be beneficial in patients being treated for such illness as anxiety, because the patient tends to take fewer potentially habit-forming drugs. Placebos are frequently used in studies of new medicine compared with the inert placebo. The American Pain Society and the Agency for Health Care Policy and Research recommend the avoidance of deceitful use of placebos in pain management violates a patient's rights to the highest quality of care possible.

Tolerance

Tolerance occurs when a person begins to require a higher dosage to produce the same effects that a lower dosage once provided. An example is the person who is addicted to heroin. After a few weeks of use, larger doses are required to provide the same "high". Tolerance can be caused by psychological dependence, or the body may metabolize a particular drug more rapidly than before, causing the effects of the drugs to diminish more rapidly.

Dependence

Drug dependence, also known as addiction or habituation, occurs when a person is unable to control the ingestion of drugs. The dependence may be physical, in which the person develops withdrawal symptoms if the drug is withdrawn for certain period, or psychological, in which the patient is emotionally attached to the drug. Drug dependence occurs most commonly with the use of the schedule, or controlled, medications such as opiates and benzodiazepines. Many people, especially elderly, worry about becoming addicted to pain medication and therefore may not take pain medication even when it is needed. The nurse needs to assure them that studies have shown the less than 1% of patients using oploids for pain relief become addicted, and that it is important for their overall well-being to be as pain-free as possible.

Cumulative Effect

A drug may accumulate in the body if the next dosage is administered before the previously administered dose has been metabolized or excreted. Excessive drug accumulation may result in drug toxicity. An example of drug accumulation is the excessive ingestion of alcoholic beverages. A person becomes "drunk" or "inebriated" when the rate of consumption exceeds the rate of metabolism and excretion of the alcohol.

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