Which aspect of drug therapy indicates to the nurse whether a drug is having a beneficial effect

Unless therapeutic drug monitoring is being used to forecast a dose or there are concerns about toxicity, samples should be taken at steady state (4-5 half-lives after starting therapy1-3

At steady state, plasma concentration is usually proportional to receptor concentration. Some drugs, such as perhexiline, which has a very long half-life in patients who are 'poor metabolisers', should be monitored before steady state is achieved to prevent toxicity developing after the first few doses. Another example where early monitoring may be useful is after phenytoin loading, where measurement of the plasma concentration can give a preliminary indication of adequate dosing.

The timing of the collection of the sample is important as the drug concentration changes during the dosing interval. The least variable point in the dosing interval is just before the next dose is due. This pre-dose or trough concentration is what is usually measured. For drugs with long half-lives such as phenobarbitone and amiodarone, samples can be collected at any point in the dosage interval.1-3

Correct sample timing should also take into account absorption and distribution. For example, digoxin monitoring should not be performed within six hours of a dose, because it will still be undergoing distribution and so plasma concentrations will be erroneously high.1-3

Occasionally, sampling at the time of specific symptoms may detect toxicity related to peak concentrations of, for example, carbamazepine and lithium.

For once-daily dosing of aminoglycosides, the timing of the blood sample is determined by the method of monitoring. For example, it is collected 6-14 hours post-dose when a nomogram is used, or twice within the dosing interval to calculate the area under the concentration-time curve.4-5 When aminoglycosides are prescribed in multiple daily doses to treat, for example, enterococcal endocarditis, then trough samples are measured to minimise toxicity and assess whether concentrations are adequate for efficacy.

Regardless of the absorption site, the drug must cross the cell membrane to reach the systemic circulation. This can occur primarily in one of two ways, either through passive (simple) diffusion or carrier-mediated membrane transporters. 

The most common mechanism of absorption for drugs is passive diffusion. This process can be explained through the Fick law of diffusion, in which the drug molecule moves according to the concentration gradient from a higher drug concentration to a lower concentration until equilibrium is reached. Passive diffusion can occur in an aqueous or lipid environment. Aqueous diffusion occurs in the aqueous compartment of the body, such as interstitial space or through aqueous pores in the endothelium of blood vessels. Drugs that are bound to albumin or other large plasma proteins cannot permeate most aqueous pores. On the other hand, lipid diffusion occurs through the lipid compartment of the body. Therefore it is considered the most important factor for drug permeability due to the greater number of lipid barriers that separate the compartments of the body. The lipid-aqueous partition coefficient of the drug can be used to determine how rapidly the drug moves between lipid and aqueous mediums. 

Another mechanism of absorption is via carrier-mediated membrane transporters. Numerous specialized carrier-mediated membrane transport systems are present in the body to transport ions and nutrients, particularly in the intestine. Such systems include active and facilitated diffusion. Active diffusion is an energy-consuming system essential for GI absorption; and renal and biliary excretion of many drugs. This process facilitates the absorption of some lipid insoluble drugs, which mimics natural physiological metabolites such as 5-fluorouracil from the GI tract. In contrast to passive diffusion, active diffusion enables the movement of drugs from regions with low drug concentrations to regions with higher drug concentrations.

With active diffusion, the carrier binds to form a complex with the drug. This complex facilitates the transportation of the drug across the membrane and then disassociates on the other side. The carrier molecule may be highly specific to the drug molecule. Drugs sharing similar structures can compete with each other for the carrier in absorption sites. Since there are only a small number of carrier molecules available, the binding sites on the carrier may become saturated if the drug concentration is very high, after which the dose increases do not affect the concentration of the drug. While some transporters facilitate absorption, other transporters such as P-glycoprotein (P-gp) can effectively impede drug absorption. P-gp (also known as MDR1) is an energy-dependent efflux transporter that facilitates the secretion of molecules back into the intestinal lumen, thereby restricting overall absorption. Facilitated diffusion is another transporter system that appears to play a minor role in terms of drug absorption. It is similar to the active diffusion system in that both are saturable and exhibit drug selectivity and competition kinetics. However, the main differences are that facilitated diffusion does not require energy, and unlike active transport, does not enable the movement against a concentration gradient. An example of a facilitated diffusion system is the organic cation transporter 1 (OCT1), which facilitates the movement of some drugs such as metformin, an antidiabetic agent.[4]

Drug-specific factors that affect drug absorption include the physicochemical and pharmaceutical variables of drugs. One example of the physicochemical variables is the drug solubility and the effect of pH and pKa, where most drugs act as weak acids or bases in solutions in both ionized and non-ionized forms. The ionized drugs are hydrophilic and cannot cross the membrane of the cell. Whereas the non-ionized drugs appear to be lipophilic and can penetrate the cell membrane easily by simple diffusion. The distribution of weak electrolytes across membranes would result from the pH gradient across the membrane and the drug's pKa. Weakly acidic drugs are easily absorbed in a low pH medium such as in the stomach. Whereas weakly basic drugs are not absorbed until they reach the higher pH medium in the small intestine.[5][6] 

Other physicochemical variables such as particle size and surface area, dissolution rate, amorphism, polymorphism characteristics, and nature of the dosage form will also affect systemic drug absorption. The rate of dissolution is the amount of the solid substance that turns into a solution per time at standard conditions of pH, solvent composition, and temperature, with a constant surface area. For example, cisapride, a gastroprokinetic agent, has a low aqueous solubility. However, it has good oral bioavailability due to its rapid rate of dissolution in GI fluids. The particle size is inversely related to the dissolution rate. Thus, reducing particle size increases surface area and, consequently, a higher dissolution rate. Micronizing the drug particles increases the dissolution rate and solubility. For example, digoxin is found to have 100% bioavailability in the micronized tablet. Furthermore, the internal structure of the drug can be either in a crystalline or amorphous form.

Polymorph is a term in which the solid substance has more than one crystalline form. The polymorphs can vary in their physical properties, such as solubility, hardness, and melting point. For example, chloramphenicol palmitate has three polymorphic forms A, B, & C. Among all these, form B is found to have the highest absorption and bioavailability. Pharmaceutical variables include the presence of different excipients (inactive ingredients), which may increase or decrease the absorption rate depending on the added ingredient. There are several dosage forms in which the drug can be administered. Each dosage form has a different absorption rate depending on many factors, including the nature of the dosage form and the site of administration. Generally, for orally administered dosage forms, solutions have a higher rate of absorption. Other pharmaceutical variables include drug expiration and storage condition.[5]

Patient-specific factors affecting the drug absorption (physiological variables) include age, gastric emptying time, intestinal transit time, disease status, blood flow at the absorption site, pre-systemic metabolism, and GI content.  With increased age, many physiological changes occur, which may lead to decreased drug absorption. Critically ill patients may have reduced blood flow to the GI tract, which will result in reduced drug absorption. Generally, intestinal absorption is more critical for most drugs than any other site in the GI tract due to the increased surface area of the intestinal mucosa. The duodenal mucosa has the quickest drug absorption because of such anatomical characteristics as villi and microvilli, which provide a large surface area. However, these villi are much less abundant in other parts of the GI tract. Drugs may be absorbed from the GI tract at a different rate. Before orally administered drugs reach the circulation, they can be metabolized within the gut wall or the liver. This is known as first-pass metabolism, which will result in a decreased amount of active drug absorbed. Food content appears to affect the absorption rate of many orally administered drugs. For example, the absorption rate of levodopa, an antiparkinsonian drug, is decreased when administered with protein-containing food. While the absorption of albendazole, an antiprotozoal agent, is enhanced with lipid-containing food.[7]

What are the nursing responsibilities of the nurse in drug therapy?

What is the nursing process in drug therapy?

Which of the following is the goal of drug therapy?

What is the term for when one drug increases the action or the effect of another drug?