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Chapter 4: Drugs

Diana Nicoll; Chuanyi Mark Lu

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    AMA Citation
    Nicoll D, Lu C. Nicoll D, Lu C Nicoll, Diana, and Chuanyi Mark Lu.Drugs. In: Nicoll D, Mark Lu C, McPhee SJ. Nicoll D, Mark Lu C, McPhee S.J. Eds. Diana Nicoll, et al.eds. Guide to Diagnostic Tests, 7e New York, NY: McGraw-Hill; . http://accesspharmacy.mhmedical.com/content.aspx?bookid=2032&sectionid=152255431. Accessed April 26, 2019.
    MLA Citation
    Nicoll D, Lu C. Nicoll D, Lu C Nicoll, Diana, and Chuanyi Mark Lu.. "Drugs." Guide to Diagnostic Tests, 7e Nicoll D, Mark Lu C, McPhee SJ. Nicoll D, Mark Lu C, McPhee S.J. Eds. Diana Nicoll, et al. New York, NY: McGraw-Hill, , http://accesspharmacy.mhmedical.com/content.aspx?bookid=2032&sectionid=152255431.

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UNDERLYING ASSUMPTIONS

The basic assumptions underlying therapeutic drug monitoring (see Table 4–1) are that drug metabolism varies from patient to patient and that the plasma level of a drug is more closely related to the drug’s therapeutic effect or toxicity than is the dosage. For certain drugs that are intended for long-term use (see Table 4–2), close monitoring with appropriate routine hematology and chemistry tests may be necessary to avoid or minimize drug-associated adverse events.

TABLE 4–1.THERAPEUTIC DRUG MONITORING.1
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TABLE 4–1. THERAPEUTIC DRUG MONITORING.1
Drug Effective Concentrations Half-Life (hours) Dosage Adjustments Comments
Amikacin

Conventional dosing:

Peak: 20–30 mg/L; trough: <10 mg/L

High dose once daily:

Peak: 60 mg/L; trough: <5 mg/L

 2–3; ↑ in uremia ↓ in renal dysfunction Concomitant kanamycin or tobramycin therapy may give falsely elevated amikacin results by immunoassay.
Amitriptyline 95–250 ng/mL 9–25 Drug is highly protein-bound. Patient-specific decrease in protein binding may invalidate quoted therapeutic reference interval for effective concentration.
Carbamazepine 4–12 mg/L 10–15 ↓ in severe renal or hepatic disease

Induces its own metabolism.

Metabolite 10,11-epoxide exhibits 13% cross-reactivity by immunoassay and is pharmacologically active. Adverse reactions: skin reactions, myelosuppression.
Cyclosporine 100–300 mcg/L (ng/mL) whole blood 6–12 ↓ in renal dysfunction, liver disease Cyclosporine is lipid-soluble (20% bound to leukocytes; 40% to erythrocytes; 40% in plasma, highly bound to lipoproteins); the binding is temperature-dependent in vitro and concentration-dependent in vivo. HPLC and LC-tandem mass spectrometry methods are highly specific for parent drug and considered the gold standard assays. Monoclonal fluorescence polarization immunoassay (FPIA) and monoclonal chemiluminescence immunoassay also measure cyclosporine reliably; polyclonal immunoassays are less specific owing to cross-reaction with drug metabolites. Anticonvulsants and rifampin increase metabolism. Erythromycin, ketoconazole, and calcium channel blockers decrease metabolism. The main adverse reaction is concentration-related nephrotoxicity.
Desipramine 100–250 ng/mL 13–23 Drug is highly protein-bound. Patient-specific decrease in protein binding may invalidate quoted therapeutic reference interval for effective concentration.
Digoxin

HF: 0.5–0.9 ng/mL

Atrial fibrillation: 0.5–2 ng/mL

 36–42; ↑ in uremia, HF ↓ in renal dysfunction, HF, hypothyroidism; ↑ in hyperthyroidism

Bioavailability of digoxin tablets is 50–90%.

Specimen must not be drawn within 4 hours of an intravenous dose or 6 hours of an oral dose.

Dialysis does not remove a significant amount.

Hypokalemia potentiates toxicity.

Digitalis toxicity is a clinical and not a laboratory diagnosis.

Digibind (digoxin-specific antibody) therapy of digoxin overdose can interfere with measurement of digoxin levels depending on the digoxin assay.

Elimination reduced by amiodarone, quinidine, and verapamil.
Ethosuximide 40–100 mg/L

Child: 30–40

Adult: 50–60

 Levels used primarily to assess clinical response and compliance. Toxicity is rare and does not correlate well with plasma concentrations.
Gentamicin

Conventional dosing: Peak: 4–8 mg/L; trough: <2 mg/L

High dose once daily: Peak: 20 mg/L; trough: undetectable

 2–3; ↑ in uremia (7.3 during dialysis) ↓ in renal dysfunction

Draw peak specimen (conventional dosing) 30 minutes after end of 30- to 60-min infusion.

Draw trough just before next dose.

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