Adverse Drug Reactions

CHAPTER 1 Adverse Drug Reactions

Any pharmacologic agent has the potential to cause an adverse reaction in a patient. In some instances, a reaction is inherent, dose-dependent, and predictable. In others, it is considered idiosyncratic and may occur even when the drug is administered at recommended doses. To prevent or treat any adverse drug reaction, it is important to use drugs properly as well as to diagnose and treat problems promptly and appropriately.


Adverse drug reactions can manifest in various ways. Therefore, they are often difficult to diagnose. The different presentations of ADRs are described below.


The determination of causality in cases of potential ADRs can be difficult. Definitive diagnosis often involves consideration of the timing of drug administration, the mechanism of the drug’s known toxicity, and the effects of drug withdrawal and reintroduction of drug administration. The effect of reintroduction of the drug is not always possible to determine, particularly in the clinical setting, and depends on the severity of the reaction. Similarly, withdrawing the drug may not be possible, particularly if it is an essential drug and there is no suitable substitute drug available from a different class. In these instances, a reduction in drug dosage may be the only possible route. Therefore, most instances of clinical ADRs are diagnosed on the basis of temporal relationship and the likelihood of the drug causing that effect.

If this approach is used, one must take into account the background frequency of the event and other confounding factors, such as the actual disease process being treated and the effects of concurrently administered drugs. For instance, a horse that develops signs of colic while receiving misoprostol may be developing colic secondary to misoprostol’s effects on smooth muscle contractility, or the colic may be a result of an unrelated gastrointestinal disturbance, such as an impaction, or the primary disease process being treated, such as gastric ulceration or right dorsal colitis. Because colic is such a frequent occurrence in horses, attributing this sign to a drug would require large numbers of horses to develop similar signs during a similar period during or after administration of the given drug. Ventricular arrhythmias, on the other hand, are infrequent in horses, and if arrhythmia develops after initiation of treatment with digoxin, it is most likely related to administration of the drug.

Therapeutic Drug Monitoring

Therapeutic drug monitoring (TDM) can be an extremely useful tool for diagnosing dose-related ADRs. The purpose of TDM is to relate plasma concentrations in the patient with the known therapeutic or toxic concentrations of the drug. The most common methods used in TDM are high-pressure liquid chromatography, fluorescence polarization immunoassay, and radioimmunoassay. High-pressure liquid chromatography can be used to detect the largest number of drugs and can accurately and specifically quantitate a drug and its metabolites in plasma or other media. It is also expensive and time consuming. The fluorescence polarization immunoassay method is very easy to perform and has been used for TDM in veterinary practice. Drugs commonly monitored via this method include aminoglycosides, cyclosporin, digoxin, phenobarbital, procainamide, quinidine, and theophylline. One drawback to this analytic method is that these assays have been developed and validated for human plasma, and their sensitivity and specificity in veterinary species may vary, particularly with the production of drug metabolites, such as cyclosporine, that cross-react with the immunoassay. Radioimmunoassay kits have been used for TDM, particularly with opiate drugs and corticosteroids, which are therapeutic at very low plasma concentrations that may be difficult to detect with other methods. TDM is most effective if the therapeutic and toxic plasma concentrations are known, but this information is scarce in veterinary medicine. Available data are summarized (Table 1-1).

Table 1-1 Therapeutic and Toxic Plasma Drug Concentrations Used for Therapeutic Drug Monitoring in Veterinary Medicine

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May 28, 2016 | Posted by in EQUINE MEDICINE | Comments Off on Adverse Drug Reactions

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Drug Therapeutic Concentrations Toxic Concentrations
Amikacin 40 μg/mL (peak) ≥3 μg/mL (trough)
Bromide 100-200 mg/dL (monotherapy) N/A
200-300 mg/dL (combination therapy)
Cyclosporine 300-600 ng/mL (trough) N/A
Digoxin 0.5-2 ng/mL (6-8 h after dose) ≥2.5 ng/mL
Gentamicin 20-40 μg/mL (peak) ≥2 μg/mL (trough)
Lidocaine 1-3 μg/mL (for prokinetic effects) 2-4 μg/mL
Phenobarbital 15-40 μg/mL (peak) ≥40 μg/mL