Week 2 Chapter 4 Pharmacokinetics Flashcards
adverse effect
A side effect is generally considered a predictable pharmacologic action on body systems other than the action intended. Side effects can be either “good” or “bad,” depending on the situation. Any unwanted effect is an adverse effect. For example, hydroxyzine is a strong antihistamine medication that can be used to prevent itching. Two side effects of this drug are antiemetic activity and anxiety relief, both of which may be considered good but not the primary drug function. Meperidine (Demerol) causes frequent nausea and vomiting, which are adverse effects. The good side effects of hydroxyzine will lessen the adverse effects of meperidine while simultaneously relieving anxiety often associated with pain. However, another side effect of hydroxyzine is constipation, which could lead to impaction and a severely adverse outcome. Thus, all adverse effects need to be considered, and an acceptable ratio between the good and adverse effects should be sought for all drug therapy.
affinity
Receptors are specific biologic sites located on a cell surface or within a cell (Fig. 4-1). Receptors can be thought of as “keyholes” into which specific keys (drugs) may fit. Drugs have specific affinity (attraction) for their specific receptors. Strong affinity for a receptor allows a drug to elicit an agonist, antagonist, or mixed agonist/antagonist interaction. The organ on or in which the desired effect occurs is generally called the target organ. The target organ can represent any organ or system in the body.
agonist
An agonist is a drug or natural substance with an affinity for specific receptor sites that produces a physiologic response, usually predictable. A drug agonist simply stimulates or enhances the body’s natural response to stimulation. An example of such activity is seen with the use of epinephrine in a patient suffering acute bronchospasm secondary to anaphylaxis. Epinephrine will stimulate a beta-2 β2 receptor in the lungs to cause bronchodilation. The β2 receptor is normally stimulated by endogenous epinephrine, known as adrenaline, but the patient may not have enough of his or her own epinephrine to prevent severe respiratory distress when suffering acute anaphylaxis. Administration of epinephrine, a β2-receptor agonist, can enhance the normal physiologic function of the β2receptor to stimulate bronchodilation. No new function was developed; a normal physiologic/biologic function was simply enhanced. Using the lock-and-key analogy, the endogenous epinephrine “key” plugs into the receptor site “lock” to open the door for bronchodilation to occur. The problem in acute anaphalaxis is that not enough keys are available to unlock enough doors to allow bronchodilation to stop the crisis. The epinephrine given to the patient is like pouring many new keys into the bloodstream to unlock many more doors.
allergic reaction
An allergic reaction results from an immune-mediated response by the body against the drug and is not necessarily related to dose. Both toxic and allergic effects are adverse.
Absolutely no drugs are completely safe. All have potential to cause side, adverse, toxic, and allergic effects in the human body. In some cases the effects are immediately noticed; other cases require weeks to manifest the effects. Patients should never be given a medication without proper, systematic, and critical thought. Even water has killed those who have overdosed on it!
antagonist
Drugs with antagonist activity will block receptors for which they have affinity. The normal physiologic/biologic function carried out by the receptor cannot ensue; the door cannot be opened because the keyhole is blocked. In the previous example, a patient with severe anaphylaxis may have worsening respiratory distress if given the drug propranolol, a β2-receptor blocker. Propranolol acts as an antagonist to the normal function of the β2receptor in the lungs.
Breaking the words “agonist” and “antagonist” into their parts helps to keep the two from being confused. The agonist enhances a response. The word antagonist is agonist with the prefix “ant” added, which means against. So antagonists diminish the response either of endogenous agonists or other drugs. Box 4-1 provides a more complete list of definitions.
enzyme
Enzymes occur throughout body systems and are generally considered catalysts responsible for initiating biochemical reactions. Many enzymes begin working after becoming attached to a particular substrate; this is analogous to a drug attaching to a receptor. A drug-enzyme interaction occurs when a drug resembles the substrate to which an enzyme usually attaches. Stimulation or blockade of the enzyme will then occur as a result of the drug, thus producing a pharmacodynamic reaction.
An example of this type of pharmacodynamic reaction is seen with nerve gas (as used in chemical warfare). Some nerve gases act to “tie up” (or block) acetylcholinesterase enzyme. Acetylcholinesterase enzyme metabolizes acetylcholine, a neurotransmitter responsible for nerve stimulation. Inhibition of acetylcholinesterase enzyme allows acetylcholine to accumulate, reaching toxic levels in the nervous system. After reaching toxic levels, acetylcholine will produce marked nausea and vomiting, massive diarrhea, profuse sweating, pulmonary edema, and seizures. This will progress until the drug effects on acetlycholinesterase are stopped.
Another example, seen more frequently in medicine, is the cytochrome P450 enzyme interactions with various medications. Cytochrome P450 enzyme is responsible for metabolism of many medications. Any interference with this enzyme can lead to decreased metabolism with concomitant drug accumulation. Cimetidine, an antiulcer medication, is one drug that antagonizes cytochrome P450 very strongly. Theophylline, an antiasthma medication, is one drug that requires the enzyme for metabolism. Combining cimetidine and theophylline can and does lead to theophylline poisoning, if not closely monitored. Since theophylline poisoning can rapidly become fatal, it should be apparent why it is important to understand drug-enzyme interactions.
drug-drug interaction
A drug-drug interaction occurs when two or more drugs act in unison to produce additive agonist, synergistic, or antagonist responses. Many drugs will alter the metabolism of other drugs, thus leading to accumulation and possible toxicity. Some drugs, such as the sedative-hypnotics, will synergize with others in their class. Synergism means that two drugs act together to give a pharmacologic response that is greater than the additive response expected. Alcohol plus diazepam (Valium) is a good example of a synergistic combination. The sedative properties of either drug alone may not make a person comatose at small doses. When alcohol is taken with diazepam, however, the patient may experience severe central nervous system depression with a comatose state.
Another type of drug-drug interaction is chemical incompatibility. When two drugs with different chemical composition are placed together, they may precipitate to an insoluble complex or may chemically destroy their activity.
duration of action
Period from onset of drug action to the time when response is no longer perceptible.
onset of action
Interval between the time a drug is administered and the first sign of its effect.
mechanism of action
The method by which a drug elicits effects is known as the mechanism of action. Drugs produce effects through drug-receptor interactions (stimulation or blockade), drug-enzyme interactions, or nonspecific drug interactions.
half-life of elimination
The time required for the current serum drug concentration to decline by 50% is termed the biologic half-life, or half-life of elimination. The half-life of elimination generally remains stable for each particular drug, unless metabolism and excretion are altered (as in septic shock). The drug dosage does not generally alter the half-life of elimination. However, a few drugs, such as phenytoin, aspirin, and alcohol, may have alterations in their respective half-lives of elimination when dosages overwhelm the biologic capacity for metabolism. Fig. 4-3 uses theophylline, an antiasthma drug, to illustrate the concept of half-life of elimination.
minimum effective concentration
Lowest plasma concentration that produces the desired drug effect.
peak serum concentration
Highest plasma concentration attained from a dose.
pharmacodynamics
After absorption and distribution, a drug reaches its site of action to produce an effect. Pharmaco refers to drugs, and dynamics refers to what happens when two things meet and interact—that is, the drugs and your body. In essence, pharmacodynamics is the study of how the effects of a drug are manifested. Various terms are used in pharmacodynamics, including mechanism of action, onset of action, therapeutic effect, adverse effect, toxicity, termination of action, side effect, and allergic reaction.
receptor
Receptors are specific biologic sites located on a cell surface or within a cell (Fig. 4-1). Receptors can be thought of as “keyholes” into which specific keys (drugs) may fit. Drugs have specific affinity (attraction) for their specific receptors. Strong affinity for a receptor allows a drug to elicit an agonist, antagonist, or mixed agonist/antagonist interaction. The organ on or in which the desired effect occurs is generally called the target organ. The target organ can represent any organ or system in the body.
target organ
Receptors are specific biologic sites located on a cell surface or within a cell (Fig. 4-1). Receptors can be thought of as “keyholes” into which specific keys (drugs) may fit. Drugs have specific affinity (attraction) for their specific receptors. Strong affinity for a receptor allows a drug to elicit an agonist, antagonist, or mixed agonist/antagonist interaction. The organ on or in which the desired effect occurs is generally called the target organ. The target organ can represent any organ or system in the body.
serum concentration-time profile
After drug administration, the amount that reaches and remains in the systemic circulation depends on the rates and extent of absorption, distribution, metabolism, and elimination. Fig. 4-2 is a graphic representation of response once drugs are administered; it shows what happens over time, as indicated by the serum concentrations of a drug: the serum concentration-time profile (Box 4-2).
therapeutic effect
The closer the calculation is to 1, the more dangerous the drug. If it takes a lethal dose to obtain a therapeutic effect, you may kill your patient at the same time you are trying to cure him.
