Adverse Drug Reaction Probability Scale Research Articles

The importance of monitoring adverse drug reactions in pediatric patients: the results of a national surveillance program in Italy

Objective: To gain information on safety of drugs used in pediatrics through a 4-year post-marketing active pharmacovigilance program. The program sampled the Italian population and was termed ‘Monitoring of the Adverse Effects in Pediatric population’ (MEAP).Research design and methods: Adverse drug reactions (ADRs) were collected for individuals aged 0 – 17 years treated in hospitals and territorial health services in Lombardy, Tuscany, Apulia and Campania; located to gain an appropriate sampling of the population. ADRs were evaluated using the Adverse Drug Reaction Probability Scale (Naranjo) and analyzed with respect to time, age, sex, category of ADR, seriousness, suspected medicines, type of reporter and off-label use.Results: We collected and analyzed reports from 3539 ADRs. Vaccines, antineoplastic and psychotropic drugs were the most frequently pharmacotherapeutic subgroups involved. Seventeen percent of reported ADRs were serious; of them fever, vomiting and angioedema were the most frequently reported. Eight percent of ADRs were associated with off-label use, and 10% were unknown ADRs. Analysis of these revealed possible strategies of therapy optimization.Conclusions: The MEAP project demonstrated that active post-marketing pharmacovigilance programs are a valid strategy to increase awareness on pediatric pharmacology, reduce underreporting and provide information on drug actions in pediatrics. This information enhances drug therapy optimization in the pediatric patients.

Energy Drink–Induced Acute Kidney Injury

To report a case of acute renal failure possibly induced by Red Bull. A 40-year-old man presented with various complaints, including a recent hypoglycemic episode. Assessment revealed that serum creatinine was elevated at 5.5 mg/dL, from a baseline of 0.9 mg/dL. An interview revealed a 2- to 3-week history of daily ingestion of 100 to 120 oz of Red Bull energy drink. Resolution of renal dysfunction occurred within 2 days of discontinuation of Red Bull and persisted through 10 months of follow-up. Rechallenge was not attempted. Energy-drink-induced renal failure has been reported infrequently. We identified 2 case reports via a search of MEDLINE, one of which occurred in combination with alcohol and the other of which was not available in English. According to the Food and Drug Administration's (FDA's) Center for Food Safety and Applied Nutrition Adverse Event Reporting System, between 2004 and 2012, the FDA has received 166 reports of adverse events associated with energy drink consumption. Only 3 of the 166 (0.18%) described renal failure, and none were reported with Red Bull specifically. A defined mechanism for injury is unknown. Assessment of the Naranjo adverse drug reaction probability scale indicates a probable relationship between the development of acute renal failure and Red Bull ingestion in our patient. Acute kidney injury has rarely been reported with energy drink consumption. Our report describes the first English language report of acute renal failure occurring in the context of ingestion of large quantities of energy drink without concomitant alcohol.

Probable Association of an Attack of Bilateral Acute Angle-Closure Glaucoma With Duloxetine

To report a patient who had an attack of bilateral acute angle-closure glaucoma (ACG) probably associated with the use of duloxetine. The case reported here involves an 81-year-old Caucasian woman whose past ocular history was unremarkable except for high hyperopia and cataract. The patient developed ocular symptoms 2 days after starting duloxetine, a serotonin norepinephrine reuptake inhibitor (SNRI) and was diagnosed with acute ACG. The elevated intraocular pressure (IOP) was successfully lowered with medical treatment, and the patient was advised to discontinue duloxetine. She subsequently underwent laser iridotomy in both eyes, and her IOP remained adequately controlled. A score of 6 was obtained using the Naranjo adverse drug reaction probability scale, suggesting duloxetine as the probable cause of the attack of ACG in this patient. There are a few previous reports of acute ACG associated with venlafaxine, another member of the class of SNRIs. In addition, there are several reports of ACG associated with members of the related class of selective serotonin reuptake inhibitors (SSRIs)-namely, fluoxetine, paroxetine, fluvoxamine, sertraline, citalopram, and escitalopram. The mechanism responsible for the precipitation of ACG by members of these 2 classes of drugs is likely a result of mydriasis caused by their adrenergic effects, weak anticholinergic activities, or the increased levels of serotonin. Because the SNRIs, including duloxetine, and SSRIs are commonly used in the management of depression or chronic pain, caution is warranted with the use of these drugs in patients with risk factors for ACG.

Propylene Glycol–Related Delirium After Esmolol Infusion

Excipients used in oral or intravenous preparations may cause serious adverse events. We present the case of a 15-year-old boy with hypertrophic cardiomyopathy. In the pediatric intensive care unit, he received high doses of continuous intravenous esmolol (range = 20-400 µg/kg/min) for cardiac rhythm control. After a few days he developed a delirium not responding to high doses of antipsychotics or discontinuation of benzodiazepines. We eventually realized that the IV esmolol formulation contained high doses of propylene glycol and ethanol, which may accumulate after prolonged infusion and cause intoxication. Intoxication with propylene glycolcan cause neuropsychiatric symptoms. The boy's propylene glycol plasma concentration was approximately 4 g/L, whereas clinical symptoms arise at concentrations above 1 to 1.44 g/L. Application of the Naranjo adverse drug reaction probability scale suggested a probable relationship (score 6) between the propylene glycol infusion and the delirium. After discontinuation of esmolol, the delirium disappeared spontaneously. This is the first case describing excipient toxicity of esmolol, with an objective causality assessment revealing a probable relationship for the adverse event-namely, delirium-and esmolol. Although excipient toxicity is a well-known adverse drug reaction, this case stresses the importance for easily available information for and education of physicians.

A Case of Thyroid Storm Induced by Iodine-Containing Dietary Supplements and Homeopathic Remedies.

Objective: We report the case of a patient who presented to the hospital in thyroid storm following the use of several iodine-containing dietary supplements (DS) and homeopathic remedies (HR). Case Summary: The patient was a 76-year-old woman with no personal or family history of thyroid or autoimmune disease. On laboratory assessment, a thyroid panel showed that her total T3 and T4 were elevated at 334 ng/dL and 14.6 µg/dL, respectively; thyroid stimulating hormone was undetectable; and thyroid stimulating immunoglobulin was positive at 7.4. The patient had been consuming 170 µg of iodine daily for the past 2 months via her DS and HR. An objective causality assessment using the Naranjo adverse drug reaction probability scale revealed that an adverse effect was probable. The patient likely suffered from iodine-induced thyrotoxicosis secondary to the consumption of numerous DS and HR. Discussion: Dietary supplements and homeopathic remedies can pose significant health risks. The safety of these products is not assured as they are incompletely monitored by the Food and Drug Administration. Individuals who take these compounds do so at their own risk and should pay close attention to product contents. Conclusions: The labeling of DS and HR products may be misleading. Pharmacists and clinicians are advised to inquire about the use of DS and HR products. When use is identified, the products should be subject to a thorough review.

Arterial Hypertension and Posterior Reversible Cerebral Edema Syndrome Induced by Risperidone

Posterior reversible cerebral edema syndrome is a generally reversible neurologic condition that is diagnosed based on distinctive clinical and radiologic findings. The condition, which is mostly associated with severe arterial hypertension, has also been reported to be induced by several medications. We made the diagnosis of hypertension with posterior reversible cerebral edema syndrome in a lean 12-year-old girl treated with the second-generation antipsychotic risperidone. We applied the Naranjo Adverse Drug Reaction Probability Scale and the World Health Organization-Uppsala Monitoring Centre system for causality assessment to the present case. Both scales indicated that a relationship to risperidone was likely. Second-generation antipsychotic agents may occasionally induce an increase in blood pressure even in the absence of overweight. Given this possibility, we recommend routine monitoring of blood pressure during therapy with these agents.

Carfilzomib‐Associated Tumor Lysis Syndrome

Multiple myeloma is the second most common type of hematologic malignancy. It is a B-cell malignancy that affects the bone marrow and often results in thrombocytopenia as well as renal dysfunction. Treatment options range from oral and intravenous chemotherapy to bone marrow transplantation and supportive care. Carfilzomib was approved by the U.S. Food and Drug Administration in 2012 as a treatment option for patients with refractory multiple myeloma who have received at least two previous therapies and have demonstrated recent disease progression. According to the product labeling, the frequency of tumor lysis syndrome (TLS) is less than 1% in patients treated with carfilzomib. To our knowledge, no postmarketing events of TLS have been reported or published. We describe a 55-year-old man with relapsed multiple myeloma who developed a case of TLS that occurred after he received his first two doses of carfilzomib therapy on days 1 and 2; he also had chronic kidney disease secondary to his neoplastic disease. Beginning on day 4, his uric acid levels spiked to critical levels, prompting the use of rasburicase, which returned the levels to within normal limits. His phosphorus and creatinine levels increased during days 5 and 6. On day 8, the patient died, likely due to a combination of disease progression and the adverse effects of treatment. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 6) between the patient's development of TLS and carfilzomib therapy. The Hill criteria were used as a secondary measure to ensure causality, which also suggested a link between the patient's development of TLS and the administration of carfilzomib. This case report shows that even the most unlikely of adverse events may occur with medications, especially in the case of a new or recently approved medication. Caution must be taken when deciding to treat and when choosing hydration and premedications with regard to biologic and chemotherapeutic medications. In this case, additional hydration may have been considered. Although given the extent of the adverse reaction combined with the patient's underlying renal dysfunction, extra fluid may or may not have proven beneficial. The use of prophylactic rasburicase or allopurinol could have been considered, but these measures are not typically used with multiple myeloma due to the low incidence of TLS. All things considered, this unlikely adverse reaction may occur in certain patients. If other cases such as this occur, it may be advisable to use TLS prophylaxis in the future in certain patient populations, including those with renal dysfunction or worsening disease states.

EPA-0761 – The application of naranjo's adverse drug reaction (ADR) probability scale to elicit the direct correlation between NRG3 consumption and the onset of psychotic symptoms

Background NGR3 substance is usually in the form of a white powder that is consumed by humans to create a legal high; feelings of euphoria and reduce tiredness. It is a GHB analogue and when consumed turns into GHB in the body. A 40year old male patient who ingested NRG3 was admitted thrice with symptoms of hearing voices, hyperactivity, agression and the inability to sleep. Aim and objective To determine the probability of onset of psychotic symptoms as an effect of ingestion of NRG3. Methodology To apply Naranjo's ADR probability scale and on the basis of the weighted questions of the scale, which examine factors such as temporal association of drug administration and event occurrence, alternative causes for the event, drug levels, dose-response relationships and previous patient experience with the substance NRG3. Results Using the scale, the score indicated that there was a definite adverse drug reaction with NRG3. Conclusions A definite adverse drug reaction of psychotic symptoms did occur with the ingestion of NRG3.

Acute dyskinesia: A rare adverse effect of oxcarbazepine in epilepsy with neurobehavioral symptoms

We are reporting an 11-year-old female child of febrile partial seizure since age of 3 months and transient neurobehavioral changes of psychic, gelastic semiology since childhood. She had no history of continued febrile seizure, but had 3 admissions for 3 episodes of status epilepticus in last 3 years. She experienced acute generalized dyskinesia (torticollis, oromandibular dystonia, spasmodic dysphonia, right lower limb eversion plantarflexed type feet dystonia) soon after oxcarbazepine (OXC) therapy from last episode of status epilepsy on 15 April 2013 with similar semiology. We failed to explain the considered infectious, non-convulsive state and hyponatremic extra pyramidal syndrome. We used the Naranjo adverse drug reaction probability scale and stopped OXC. After state intravenous diazepam 2 nd day, she was starting to improve and over a period of 4 days she was asymptomatic. We shifted on clonazepam, sodium valproate for further. She was asymptomatic until 1 month follow-up.

Ciprofloxacin induced fixed drug eruption

Fixed drug eruption (FDE) is a clinical entity occurring in the same site or sites each time the drug is administered. Acute lesions appear as sharply marginated erythematous plaques, which are usually found on lips, genitalia, abdomen, and legs. The eruptions usually occur within hours of administration of the offending agent and resolves spontaneously without scarring after few weeks of onset. Most common drugs causing FDE are sulfonamides, tetracyclines, salicylates, barbiturates, doxycycline, fluconazole, clarithromycin, etc. Ciprofloxacin, a widely used fluoroquinolone antimicrobial, induces cutaneous adverse drug reactions (ADRs) in about 1-2% of treated patients. Urticaria, angioedema, maculopapular exanthems, and photosensitivity are the most frequently documented cutaneous adverse reactions. In this case report, the patient soon after taking ciprofloxacin tablets, developed itching in the lips, palms and in scrotal region. On continuing the treatment, the next day he developed fluid filled lesions over palm, knuckle, and hyperpigmentation. He gives a history of severe itching and rashes in scrotal region. He gives a history of similar complaints in the previous month after taking ciprofloxacin medication. There was no history of intake of any other medication. On examination, bullous lesions and pustules in finger webs, hyperpigmentation on knuckles, and scrotal erosions were seen. In the present case report, the patient presented with FDE immediately after oral administration of ciprofloxacin and got completely cured after stopping the drug and taking adequate treatment. According to the Naranjo’s ADR probability scale (score=8), this ADR is categorized as a “probable” reaction to the drug.

Toxic epidermal necrolysis: a retrospective analysis of 17 cases from central Tunisia.

Toxic epidermal necrolysis (TEN), also known as Lyell's syndrome, is a rare, life-threatening and wide-spread exfoliative disease of the skin and mucous membrane that is most commonly drug-induced. We retrospectively reviewed the charts of 17 patients who suffered from TEN in Farhat Hached University Hospital, Sousse, Tunisia over a 19-year period from January 1994 to January 2013. Causality for suspected drugs was assessed by means of the Naranjo adverse drug reaction (ADR) probability scale. Antibiotics, mainly ß-lactams, were the most common implicated drugs, followed by nonsteroidal anti-inflammatory drugs, anticonvulsants, and allopurinol. The interval between drug intake and onset of the first symptom ranged between few hours and 19 days with a mean period of 6.11 days. There was extensive skin detachment, averaging 66.17% of total body surface area (range 40-95%). The most major complication was infection, occurring in 9 patients (53%). Seven patients died with a mortality rate of 41%.

Dyke-Davidoff-Masson syndrome: A study of clinicoradiological variability in hemiplegia, hemiatrophy and epilepsy patients

Context: Clinicoradiological variability expansion in Dyke-Davidoff-Masson syndrome (DDMS) or hemiplegia, hemiatrophy and epilepsy (HHE) patients. Aims: To explore clinicoradiological features, associated abnormalities and refractoriness issues to antiepileptic drugs (AED) on such kind of epilepsy syndrome. Settings and Design: Prospective and retrospective observational hospital based cohort study. Materials and Methods: Thirty-two patients of HHE were enrolled and interviewed. They were divided into 4 groups congenital versus acquired and seizure control group (SCG) versus seizure refractory group (SRG). We used Naranjo adverse drug reaction (ADR) probability scale for analyzed phenytoin and other drugs adverse reaction. All patients underwent clinicoradiological examination, electroencephalograms, magnetic resonance imaging for parenchymal and skeletal changes. Statistical Analysis Used: Fisher's exact and Student's t-test applied for P value. Results: A total of 32 patients (21 males, 11 females) out of 1182 epilepsy patients were enrolled with mean age of 26.84 ± 9.71 (range: 8-42) years. Twenty-eight patients presented with DDMS, three Rasmussen encephalitis and two HHE syndromes. Congenital type and seizure refractory groups were common presentation. Left lateralization with holo-hemispheric atrophy, cerebellar atrophy, calvarial thickening with frontal sinus hyperpneumatization were significant (P < 0.05) magnetic resonance imaging (MRI) findings. Epileptiform activity was concordant to lesion. Phenytoin adverse effects were significantly (P < 0.03) associated with HHE patients. Remarkable findings of our study included cerebral hemispheric plus cerebellar atrophy (28.12%), hippocampal sclerosis (16%), dystonia, hemiparkinsonism, mirror movement and Dandy-Walker syndrome (DWS). Conclusions: DDMS/HHE can present protean clinicoradiological manifestation, cerebellar atrophy, hippocampal sclerosis and phenytoin intolerance may be one of them.

Fluoxetine-Induced Atypical Serotonin Syndrome with Hallucinations Masquerading as a Parkinsonian Syndrome

Objective: To report a unique case of fluoxetine overdose leading to serotonin syndrome with auditory and complex visual hallucinations. This case also demonstrates serotonin syndrome may mimic a Parkinsonian syndrome, which is poorly described in the literature. Case Summary: A 65-year-old gentleman, undergoing evaluation for possible Parkinsonian syndrome with bradykinesia and rigidity presented to the emergency department with additional complaints of weakness, fatigue, flushing, and complex visual and auditory hallucinations. Chart review revealed he was unintentionally overdosed with fluoxetine to a total daily dose of 160 mg. Examination revealed tachycardia, diaphoresis, significant mydriasis, and visual hallucinations. Initial workup was unremarkable. Poison control recommended discontinuation of the fluoxetine and in follow up he reported resolution of all symptoms. Discussion: This case describes serotonin syndrome as the result of chronic fluoxetine overdose masquerading as a Parkinsonian syndrome. This patient also experienced auditory and visual hallucinations that resolved with cessation of fluoxetine, adverse effects which are relatively uncommon. The likelihood the patient’s symptoms were the result of fluoxetine intoxication is probable, as assessed by the Naranjo Adverse Drug Reaction (ADR) probability scale. Conclusions: Chronic fluoxetine overdose can lead to serotonin syndrome, as well as, several rare adverse effects including a Parkinsonian syndrome, complex visual, and auditory hallucinations. A high index of suspicion is necessary for diagnosis of serotonin syndrome, particularly in mild cases. Most cases can be prevented with careful medication reconciliation.

Syndrome of inappropriate antidiuretic hormone associated with aripiprazole

A probable case of aripiprazole-induced syndrome of inappropriate antidiuretic hormone (SIADH) is reported. A 65-year-old Caucasian man arrived in the emergency department (ED) with dizziness, headache, abdominal pain, nausea, and vomiting. There had been no recent additions or changes to the patient's medication regimen except for an increase in the daily dose of aripiprazole (from 10 to 20 mg) about two months prior. On admission, the patient's serum sodium concentration was 108 meq/L, prompting discontinuation of aripiprazole use and fluid restrictions. Over the next 72 hours, the serum sodium level increased to a near-normal concentration (127 meq/L), and the man was discharged back to a nursing facility. Three days later, the patient was readmitted to the ED with recurrent symptoms and a serum sodium concentration of 118 meq/L, a serum osmolality of 254 mOsm/kg, a urine osmolality of 575 mOsm/kg, and a urine sodium concentration of 101 meq/L. It was learned that aripiprazole use had been inappropriately resumed at the nursing facility. Aripiprazole was again discontinued, and fluid restrictions were imposed, with subsequent abatement of hyponatremia over four days. Application of the adverse drug reaction probability scale of Naranjo et al. in this case yielded a score of 7, indicating probable aripiprazole-associated SIADH. A 65-year-old man developed severe hyponatremia after an aripiprazole dosage increase. Hyponatremia resolved promptly with the discontinuation of aripiprazole. After discharge from the hospital, the patient inadvertently received aripiprazole again and was subsequently readmitted with another episode of severe hyponatremia.

A Case Report of Probable Neuroleptic Malignant Syndrome

Objective: To report a case of probable neuroleptic malignant syndrome (NMS) of unknown origin. Case Summary: A 32-year-old Caucasian man was found unconscious by emergency services. On presentation to the emergency department, he had a temperature of 107.5°F (41.9°C) and a Glasgow Coma Scale rating of 3 (range = 3-15). Fluids were administered and cooling blankets applied. He was admitted to the intensive care unit. Supportive measures decreased his temperature to 101.7°F (38.7°C). Arterial blood gas, comprehensive metabolic panel, complete blood count, and cardiac risk panel results were within normal limits; urinalysis and urine and serum drug screens were negative. He had been discharged on the following medications: benztropine, citalopram, chlorpromazine, divalproex, haloperidol, and hydroxyzine. Based on the medication discharge list and clinical presentation, the Naranjo Adverse Drug Reaction Probability Scale was applied. The criteria scoring indicated a probable relationship (8 of 12) between the medications prescribed and symptoms consistent with NMS. Discussion: NMS has been reported with antipsychotics (APs) and other medications with dopaminergic activity. The etiology is poorly understood. Risk factors (ie, recent initiation or dose increase of an AP, dehydration, or genetic susceptibility) may increase the potential. The differentiation between the diagnosis of NMS and other factors, such as serotonin syndrome or hyperthermia, includes laboratory and clinical presentation characteristics. The potential contributions of anticholinergic agents, psychiatric comorbidities, and other risk factors were identified for this patient. Conclusions: We report the case of a patient found unresponsive and comatose. A variety of assessment measures were used to identify potential causes. Based on evaluations, clinical presentation, the medication list, and criteria for an adverse drug event, a diagnosis of NMS was given. Health care providers may not be fully aware of the potential severity for this medication-related effect in patients with multiple risk factors.

Hyperkalemia and Rhabdomyolysis With Succinylcholine Used for Rapid Sequence Intubation

Objective: Succinylcholine, a depolarizing neuromuscular blocker used during intubation, has a black box warning for use in pediatric patients due to the risk of rhabdomyolysis, hyperkalemia, ventricular arrhythmias, and cardiac arrest in patients with skeletal muscle myopathy. Though the warning does not exist for adult patients, succinylcholine is commonly used in adults, who may still be at risk for the same complications. Our objective is to present the case of an adult patient experiencing rhabdomyolysis, hyperkalemia, and cardiac arrest after the administration of succinylcholine for rapid sequence intubation. Case Summary: We describe the hospital course of a 58-year-old patient admitted for the placement of a biventricular implantable cardioverter defibrillator. The patient received etomidate, fentanyl, isoflurane, midazolam, and succinylcholine during rapid sequence intubation. During intubation for the procedure and shortly after the administration of succinylcholine, the patient went into asystole and arrested. After several arrhythmias and periods of cardiac arrest, the patient was stabilized, and the procedure completed. Shortly after the procedure, the patient developed hyperkalemia, rhabdomyolysis, and acute kidney injury and ultimately expired. Discussion: Though reports of adverse reactions to succinylcholine are less common in adults without underlying muscular disorders, this phenomenon has been reported in the literature. There is the potential that this patient may have had an underlying myopathy that was previously undiagnosed or could have experienced malignant hyperthermia. The Naranjo adverse drug reaction probability scale for this case is 5, which is considered probable. Conclusions: Though uncommon, succinylcholine is a potential cause of hyperkalemia, rhabdomyolysis, and cardiac arrest in susceptible adult patients.

Risk factors associated with adverse drug events among older adults in emergency department

BackgroundLittle is known about the emergency department (ED) visits from drug-related injury among older adults in Taiwan. This study seeks to identify risk factors associated with adverse drug events (ADEs) leading to ED visits. MethodsWe prospectively conducted a case–control study of patients 65years and older presenting to the ED. ED visits between March 1, 2009 and Feb 28, 2010 identified by investigators for suspected ADEs were further assessed by using the Naranjo Adverse Drug Reaction probability scale. For each patient with an ADE, a control was selected and time-matched from the ED population of the study hospital. The association between the risk of adverse drug events and triage, age, gender, serum alanine transaminase (ALT), serum creatinine, number of medications, and Charlson Comorbidity Index scores were analyzed using logistic regression. ResultsOf 20,628 visits, 295 ADEs were physician-documented in older adults. Independent risk factors for ADEs included number of medications (adjusted odds ratio [OR]=4.1; 95% confidence interval [CI] 2.4–6.9 for 3–7 drugs; adjusted OR=6.4; 95% CI 3.7–11.0 for 8 or more drugs) and increased concentration of serum creatinine (adjusted OR=1.5; 95% CI 1.1–2.2). Diuretics, analgesics, cardiovascular agents, anti-diabetic agents and anticoagulants were the medications most commonly associated with an ADE leading to ED visits. ConclusionsThis study suggests that prevention efforts should be focused on older patients with renal insufficiency and polypharmacy who are using high risk medications such as anticoagulants, diuretics, cardiovascular agents, analgesics, and anti-diabetic agents.

Inadvertent Exaggerated Anticoagulation Following Use of Bismuth Subsalicylate in an Enterally Fed Patient Receiving Warfarin Therapy

We report a case of an inadvertent increase in the international normalized ratio (INR) after the addition of bismuth subsalicylate for the treatment of diarrhea in an enterally fed patient receiving warfarin therapy. A 56-year-old Caucasian female presented to the trauma intensive care unit (ICU) with multiple lower extremity fractures. Warfarin was initiated for deep vein thrombosis prophylaxis due to the patient's inability to ambulate. The target INR was 2-3. Continuous intragastric enteral feeding was withheld 1 hour before and 1 hour after intragastric administration of warfarin. Bismuth subsalicylate 30 mL every 4 hours was prescribed for diarrhea. Within 3 days after starting bismuth subsalicylate therapy, the patient's INR increased from 2.56 to 3.54 and minor bleeding was noted from the patient's tracheostomy site. No significant change in warfarin dosage, variability in vitamin K intake, or medications that potentially alter warfarin metabolism were present during the unexpected rise in INR. When the bismuth subsalicylate was discontinued, the patient's INR stabilized into the target range on the same warfarin dose given at the time of the supratherapeutic INR. Salicylate displaces warfarin from plasma protein binding sites and may result in a significant increase in INR secondary to redistribution of warfarin to the free active form. Evaluation of this case report using the Drug Interaction Probability Scale and Naranjo Adverse Drug Reaction Probability Scale yielded scores consistent with a probable adverse drug interaction. Bismuth subsalicylate exaggerates warfarin's anticoagulant response and its concurrent use during warfarin therapy should be avoided.

Herbal drug related warfarin intoxication

Warfarin is a widely used antithrombotic drug in prevention of both arterial and venous thrombosis. Glucosamine is a popular dietary supplement used in symptomatic treatment of osteoarthritis. The interaction mechanism between these two drugs is not known yet. 63 year old woman, who was taking warfarin therapy 5 mg /day for 5;months for pulmonary embolism (therapeutic INR range:2.0–3.0), visited the emergency room with haematuria and rash. She had synchronous breast and colonic tumours for which right mastectomy and right hemicolectomy were done 5 months ago. Her INR (Internatıonal Normalized Ratio) values were highly increased (12.5) due to consumption of a herbal drug involving glucosamine hydrochloride 250 mg , boswellia extract and grapefruit extract at that day for arthralgia. Boswellia extracts are used in management of osteoarthritis. Naranjo adverse drug reaction probability scale score was 6, which indicated a probable relationship between the patient’s elevated INR and use of two drugs (warfarin and herbal drug) at the same time. After discontinuation of both drugs, two units of fresh frozen plasma were given. Her INR reduced to 2.5; as a result haematuria and rash regressed. This case report suggests a potential interaction between warfarin and both glucosamine and grapefruit extract. The inhibitory effect of grapefruit extract on cytochrome P450 isoenzymes is combined with the effect of glucosamine. Clinicians should be aware of patients taking herbal medicines with such drugs like warfarin which has narrow therapeutic index.

Acute hypokalemic periodic paralysis possibly precipitated by albuterol

An episode of acute hypokalemic paralysis associated with the use of inhaled albuterol is described. A 34-year-old woman admitted to the emergency department reported the development of pain and diffuse paralysis of the extremities and torso shortly after using an albuterol inhaler. At age 18, she had been diagnosed with hyokalemic periodic paralysis (HPP), a disorder of muscle membrane excitability caused by serum potassium depletion that can lead to life-threatening neuromuscular and cardiovascular complications. After a 15-year period of episodically recurring HPP symptoms despite long-term acetazolamide use, she was switched to spironolactone therapy and had experienced no HPP exacerbations for about 1 year. On her arrival in the emergency department, the patient's serum potassium concentration was 1.8 meq/L and she was mildly tachycardic (heart rate of 125 beats/min). After careful supplementation to gradually increase the serum potassium concentration to 5.4 meq/L, the patient slowly regained movement and strength in her extremities. Application of the adverse drug reaction probability scale of Naranjo et al. to this case yielded a score of 3, indicating that albuterol was possibly the cause of the patient's HPP exacerbation. Beta-2-adrenergic agonists and several other medications can affect serum potassium levels; although the potential risks posed by the use of such drugs in patients with a history of HPP are unclear, cautious use in the context of known HPP is advised. A patient previously diagnosed with HPP experienced an exacerbation of HPP possibly induced by inhaled albuterol treatment.