Duane Bates

Ototoxicity Induced by Gentamicin and Furosemide

OBJECTIVE: To present a case of ototoxicity induced by furosemide and once-daily gentamicin therapy. CASE SUMMARY: A 60-year-old white woman presented to the hospital with community-acquired pneumonia and urinary tract infection. The antibiotic regimen included gentamicin and, after 5 doses, the patient reported profound bilateral hearing loss. A Pure Tone Audiogram suggested moderate to moderately severe sensorineural hearing loss bilaterally. The only risk factors present included her age, elevated temperature, and the use of furosemide. DISCUSSION: Several risk factors may predispose a patient to developing aminoglycoside ototoxicity: the 1555 chromosomal mutation, preexisting disorders of hearing and balance, hypovolemia, bacteremia, liver and renal dysfunction, and the simultaneous administration of other ototoxic medications. The cumulative dose and duration of aminoglycoside therapy are more important than serum concentrations. Administration of an aminoglycoside followed by furosemide may increase the risk of ototoxicity. The aminoglycoside interacts with the cell membranes in the inner ear, increasing their permeability. This theoretically allows the loop diuretic to penetrate into the cells in higher concentrations, causing more severe damage. CONCLUSIONS: Auditory toxicity occurred after only 5 days of gentamicin therapy and 1 dose of furosemide. An aminoglycoside followed by furosemide may increase the risk for ototoxicity. Clinicians need to be aware of the synergistic potential of ototoxic medications.

Carbamazepine Toxicity Induced by Lopinavir/Ritonavir and Nelfinavir

Objective: To present a case of carbamazepine toxicity induced by lopinavir/ritonavir and nelfinavir. Case Summary: A 50-year-old HIV-positive male developed excessive drowsiness secondary to carbamazepine when an antiretroviral regimen containing lopinavir/ritonavir was introduced. The carbamazepine serum concentration increased 46%. Subsequently, the patient developed a possible adverse skin reaction to his antiretrovirals and was hospitalized. The protease inhibitor was changed to nelfinavir. Within 3 days, the patient again developed excessive drowsiness and became unsteady on his feet. This time, the carbamazepine serum concentration had increased by 53%. In both instances, the carbamazepine dosage was decreased by 33%, which resulted in resolution of symptoms. Discussion: Carbamazepine undergoes extensive hepatic metabolism. The major metabolic pathway involves oxidation of carbamazepine via CYP3A4 to an active metabolite, carbamazepine-10,11-epoxide. Protease inhibitors are well-known CYP3A4 inhibitors. Other cases of carbamazepine toxicity secondary to protease inhibitors are reviewed. A MEDLINE search (1966–May 2006) revealed 4 cases of carbamazepine toxicity secondary to antiretrovirals. Carbamazepine serum concentrations increased two- to threefold from baseline. Vertigo, drowsiness, disorientation, ataxia, and vomiting occurred within 12 hours to 2 months, which resolved with reduction of the carbamazepine dosage. Conclusions: An objective causality assessment suggests that our patient became drowsy and unsteady on his feet secondary to a carbamazepine–protease inhibitor interaction. Lopinavir/ritonavir and nelfinavir may decrease carbamazepine metabolism, causing an elevation in carbamazepine serum concentrations. Carbamazepine toxicity may be prevented by reducing the carbamazepine dosage by 25–50% when protease inhibitors are introduced. A carbamazepine serum concentration should be repeated 3–5 days after the protease inhibitors are started.

Possible Celecoxib-Induced Gastroduodenal Ulceration:

TO THE EDITOR:Nonsteroidal antiinflammatory drugs (NSAIDs) are among the most commonly prescribed drugs in North America. At least 10–20% of patients experience dyspepsia while taking NSAIDs; 13 of every 1000 patients with rheumatoid arthritis who take NSAIDs for one year develop a serious gastrointestinal (GI) complication. 1 It has been estimated that 16 500 NSAID -related deaths occur in patients with rheumatoid arthritis or osteoarthritis every year in the US. This has led to the development of cyclooxygenase (COX)-2 inhibitors such as celecoxib and rofecoxib. This newer class of drugs is intended to have a better GI adverse effect profile than nonspecific COX inhibitors. 2-4 It has been suggested 4 that for every 100 patients treated with a COX-2 inhibitor instead of a nonspecific COX inhibitor, one symptomatic ulcer may be prevented during the first year of exposure. We report a case of possible celecoxib-induced gastric and duodenal ulcers. Case Report.A 57-year-old African-American man reported abdominal pain, bloating, and dizziness and was transported to the hospital by emergency medical services. He described four melena stools and two watery stools with frank blood, and one episode of hematemesis within the preceding 24 hours. His past medical history included coronary artery disease with angioplasty five years previously, hypertension, cardiomyopathy with left ventricular dysfunction (ejection fraction 25%), gastroesophageal reflux disease, dyslipidemia, and chronic left shoulder pain. The medications on admission included losartan 25 mg/d; carvedilol 12.5 mg twice daily; digoxin 0.25 mg/d; furosemide 40 mg/d; enteric-coated aspirin 325 mg/d, which he had been taking for three years; nitroglycerin patch 0.4 mg/h for 12 hours per day; atorvastatin 20 mg/d; and celecoxib 200 mg twice daily. His family physician had prescribed celecoxib 200 mg twice daily four months prior to this event for shoulder pain. Physical examination revealed a 5’7” obese man (91 kg). On admission, his BP was 80/60 mm Hg, HR 100 beats/min, RR 20 breaths/min, and an oxygen saturation of 93% on 4 L/min of oxygen. He received a 200-mL bolus of NaCl 0.9%, which increased his BP to 102/68 mm Hg. His cardiopulmonary examination revealed a grade I–II/VI pansystolic murmur and good breath sounds with fine crackles to both bases. A musculoskeletal examination showed decreased strength bilaterally in the upper extremities. His abdominal and central nervous system examinations were unremarkable. Laboratory parameters on admission included chloride 107 mEq/L (normal 98–111), carbon dioxide 28 mEq/L (21–31), potassium 4.1 mEq/L (3.5–5), sodium 142 mEq/L (135–145), creatinine 1.1 mg/dL (0.6–1.2), and BUN 33.1 mg/dL (8–18). Complete blood cell count revealed hemoglobin 12 g/dL (14–18), white blood cells 7.8 × 103/mm3 (3.8–11), and platelets 170 × 103/mm3 (150–400). The international normalized ratio was 1.0 (0.9–1.1). Liver function tests showed a bilirubin of 0.7 mg/dL (0.1–1), alkaline phosphatase 40 U/L (39–117), and alanine aminotransferase 40 U/L (1–60). Creatine kinase (CK) was elevated (303 IU/L, normal 40–200), with three normal CK-MB fractions. An electrocardiogram showed sinus bradycardia, left ventricular hypertrophy with QRS widening, and T-wave inversion consistent with ischemia. The patient did not complain of chest pain. A serum digoxin concentration was 1.3 ng/mL (0.9–2.2). The patient was cross-matched for four units of blood, but did not receive a transfusion. Endoscopy revealed a 1.5-cm duodenal ulcer and multiple small gastric ulcers. The duodenal ulcer was injected with 9 mL of epinephrine 1:10 000 and cauterized. The patient received an intravenous bolus of pantoprazole 40 mg, followed by a continuous infusion of 8 mg/h for 48 hours. Helicobacter pyloristatus was not tested; he was empirically started on eradication therapy with amoxicillin 1 g twice daily and clarithromycin 500 mg twice daily for seven days. Pantoprazole was discontinued and oral omeprazole 40 mg twice daily was started after 48 hours. The omeprazole dose was to be decreased to 20 mg/d after seven days. The patient had one melena stool 24 hours after admission, and a small amount of frank blood in his stool on day 2. He was discharged after three days with a hemoglobin of 11 g/dL and was instructed not to restart atorvastatin until after the completion of clarithromycin therapy due to the risk of rhabdomyolysis. 5 The family physician was made aware that clarithromycin may increase digoxin concentrations. 6

Thiamine prescribing practices within university-affiliated hospitals: A multicenter retrospective review

BACKGROUND Patients with suspected thiamine deficiency should receive treatment with parenteral thiamine to achieve the high serum thiamine levels necessary to reverse the effects of deficiency and to circumvent problems with absorption common in the medically ill. OBJECTIVE To quantify rates of parenteral administration of thiamine across university-affiliated hospitals and to identify factors associated with higher rates of parenteral prescribing. DESIGN Multicenter, retrospective observational study of thiamine prescriptions. METHODS Prescriptions for thiamine were captured from computerized pharmacy information systems across participating centers, providing information concerning dose, route, frequency, and duration of thiamine prescribed from January 2010 to December 2011. SETTING Fourteen university-affiliated tertiary care hospitals geographically distributed across Canada, including 48,806 prescriptions for thiamine provided to 32,213 hospitalized patients. RESULTS Parenteral thiamine accounted for a statistically significant majority of thiamine prescriptions (57.6%, P < 0.001); however, oral thiamine constituted a significant majority of the total doses prescribed (68.4%, z = 168.9; P < 0.001). Protocols prioritizing parenteral administration were associated with higher rates of parenteral prescribing (61.3% with protocol, 45.8% without protocol; P < 0.001). Patients admitted under psychiatry services were significantly more likely to be prescribed oral thiamine (P < 0.001). CONCLUSIONS Although parenteral thiamine accounted for a statistically significant majority of prescriptions, oral thiamine was commonly prescribed within academic hospitals. Additional strategies are needed to promote parenteral thiamine prescribing to patients with suspected thiamine deficiency.

Phytonadione therapy in a multiple-drug overdose involving warfarin.

We cared for a patient who ingested an unknown amount of acetaminophen with zopiclone and warfarin. The only liver function test that was abnormal was an increased international normalized ratio (INR), which remained elevated despite treatment with subcutaneous phytonadione and a prolonged infusion of N‐acetylcysteine. An interaction between acetaminophen and warfarin may have decreased the hepatic metabolism of warfarin. The patient received numerous antibiotics that may have contributed to the increased INR. The prolonged elevation of INR also may have been due to infrequent administration of phytonadione.

An evaluation of verbal and written methods in counselling cancer patients.

INTRODUCTION Despite increased public awareness of health care related issues, studies have shown that many patients do not know how, when, or with what to take their medications and are not aware of potential side effects. • Other studies have shown that inadequate communication about medication is one of the principal reasons why 30 to 50 percent of patients deviate from their medical regimen. · Providing the patient with written information leaflets about prescription drugs has been shown to help reinforce the verbal counselling a patient receives.• In an effort to assess our prescription counselling service, an evaluation was conducted by the Pharmacy Department at the Tom Baker Cancer Centre (TBCC), an outpatient treatment facility. The purpose was to assess patient recall of his/her therapeutic regimen, as well as to obtain feedback about the written information leaflet provided. The objective of the evaluation was also to assess the patients subjective impressions of the counselling session and to determine if patients could recall the proper procedure forrefilling their medication.