Drug Stability

Stability refers to the length of time that a drug retains its original properties and characteristics. Factors that affect stability include pH, number of additives in the solution (e.g., parenteral nutrition solutions contain many additives), dilution, time (e.g., some drugs, once mixed, are stable only for a few hours), light exposure, temperature, order in which additives are put into the solutions, and type of container (e.g., insulin adsorption in polyvinyl chloride [PVC] containers). Drug pH is an important factor because most drugs are stable in a very narrow pH range.

Drug Incompatibility

Incompatibility is an undesirable reaction that occurs between the drug and the solution, the container, or another drug. Incompatibilities are influenced by a number of factors such as temperature, pH, concentration, time together in solution, and the specific order of mixing (Gahart et al., 2021). There are three types of drug incompatibility: physical, chemical, and therapeutic.

Physical Incompatibility

A physical incompatibility refers to a visible reaction that occurs, such as changes in color, haziness, turbidity, precipitate formation, and gas formation. The most common type of physical incompatibility is precipitate formation.

Some precipitation may be microcrystalline (i.e., smaller than 50 microns) and not apparent to the eye. Use of a 0.22-micron inline filter reduces the amount of microcrystalline precipitates. The presence of calcium in a drug or solution increases the risk for precipitation if it is mixed with another drug (Ayers et al., 2020). Ringer's solution preparations contain calcium, so check carefully for compatibility before adding any drug to this solution. Other physical incompatibilities caused by insolubility include the increased degradation of drugs added to sodium bicarbonate and the formation of an insoluble precipitate when sodium bicarbonate is combined with other medications in emergency situations.

The following are important recommendations regarding physical drug incompatibilities:

• Do not mix drugs prepared in special diluents with other drugs.
• When administering a series of medications, each drug should be prepared in a separate syringe/infusion container. This will lessen the possibility of precipitation. Insolubility may also result from the use of an incorrect solution to reconstitute a drug.
• Follow the manufacturer's directions for reconstituting drugs and remember that pharmacy-prepared medications are preferred to reduce the risk of contamination and instability.

NURSING FAST FACT!

To prevent physical IV drug incompatibility during administration, best practice is to always flush the infusion device with 0.9% sodium chloride before and after each medication infusion. However, some drugs (e.g., amphotericin B) are not compatible with sodium chloride. In such cases, use 5% dextrose in water for flushing before and after administration. The dextrose should always be flushed from the catheter with 0.9% sodium chloride because the dextrose can provide nutrients supporting microbial growth if allowed to dwell in the catheter lumen (Gorski et al., 2021, p. S113).

Chemical Incompatibility

A chemical incompatibility involves the degradation of the drug, which may occur for a variety of reasons, for example, drug decomposition. It is differentiated from physical incompatibility in that the reaction may not be visible. The most common cause of chemical incompatibility is the reaction between acidic and alkaline drugs or solutions, which results in a pH level that is unstable for one of the drugs. A specific pH or a narrow range of pH values is required for the solubility of a drug and the maintenance of its stability after it has been mixed.

Therapeutic Incompatibility

A therapeutic incompatibility is an undesirable effect that occurs in the patient as a result of two or more drugs being given concurrently. An increased therapeutic or a decreased therapeutic response is produced. This incompatibility may occur when therapy dictates the use of two antibiotics. For example, the effects of penicillin may be antagonized by bacteriostatic antibiotics such as chloramphenicol, sulfonamides, tetracyclines, and erythromycin (Gahart et al., 2021).

Therapeutic incompatibility may go unnoticed until the patient fails to show the expected clinical response to the drug or until peak and trough levels of the drug show a lack of therapeutic levels. If an incompatibility is not suspected, the patient may be given increasingly higher doses of the drug in an attempt to obtain the therapeutic effect. When more than one antibiotic is prescribed for intermittent infusion, it is generally best to stagger the time schedule so that each antibiotic can be infused individually.

Adsorption

Adsorption is the attachment of a liquid or gas to a solid surface. In infusion therapy, some infusion drugs and solutions adsorb to glass or plastic. With adsorption, the patient receives a smaller amount of the drug than was intended. The amount of adsorption is difficult to predict and is affected by the drug concentration, solution of the drug, amount of surface contacted by the drug, and temperature changes.

An example of adsorption is the binding of insulin to plastic and glass containers. The insulin rapidly adsorbs to IV containers and tubing until all potential adsorption sites are saturated. The potency of insulin may be reduced by at least 20% and possibly up to 80% before it reaches the vein (Gahart et al., 2021). Methods for reducing adsorption include use of additives such as albumin, electrolytes, vitamins, or other medications or use of a syringe pump that has less surface area for adsorption (Gahart et al., 2021). Another example of a medication that is readily adsorbed into PVC bags or administration sets is nitroglycerin. Non-PVC tubing and non-PVC or glass bottles are recommended.

As discussed in Chapter 5, di(2-ethylhexyl) phthalate (DEHP), a known toxin, is a plasticizer used in making PVC bags soft and pliable. DEHP is lipophilic and can leach into lipid-based solutions. In the package inserts, many drug manufacturers recommend nonphthalate delivery systems. The INS Standards (Gorski et al., 2021, p. S124) recommend DEHP-free administration sets for administration of lipid-based infusates. Many companies are manufacturing nonphthalate IV bags and tubing to prevent this problem.

Cultural and Ethnic Considerations: Drug Administration

Genetic predispositions to different rates of metabolism cause some patients to be prone to overdose reactions to the “normal dose” of medication, whereas other patients are likely to experience a greatly reduced benefit from the standard dose of the medication.

Some ethnic and cultural groups, including Chinese Americans, have a high incidence of glucose-6-phosphate dehydrogenase (G6PD) deficiency. Since G6PD deficiency causes fragility of the red blood cells, administration of some drugs (e.g., analgesics, some antimicrobials) may result in anemia in these individuals. Caffeine, a component of many drugs, is excreted more slowly by Asian Americans. Chinese Americans may also require smaller doses of certain drugs even after body weight and surface are taken into consideration (Chang, 2017).

NURSING FAST FACT!

Be knowledgeable of the pharmacological implications relative to patient clinical status and diagnosis. Verify that all solution containers are free of cracks, leaks, and punctures.