Hematologic effects of thrombophilia.

The hematologic effects of thrombophilia are subtle, and when recognized may provide clues for the diagnosis of hypercoagulation in patients. This article identifies aberrant, routine test results associated with the diagnosis of thrombophilia. The future expansion of laboratory testing for thrombophilia detection is presented in summation.     

Hematologic effects of heavy metal poisoning

Heavy metal poisoning can cause a variety of hematologic disorders. Exposure to heavy metals is ubiquitous in the industrial environment and must be considered in the differential diagnosis of many types of anemia. The heavy metals most commonly associated with hematologic toxicity are arsenic and its derivative arsine, copper, gold, lead, and zinc. A few distinctive clinical features characterize the hematologic manifestations of many occult heavy metal poisonings. These features have a limited differential diagnosis. A knowledge of these clinical features can assist the astute clinician in making the correct diagnosis.     

Hematologic effects of linezolid: summary of clinical experience

Linezolid has been associated with reversible myelosuppression. Clinical trial data were evaluated for anemia, thrombocytopenia, and neutropenia. Thrombocytopenia and a slight increased risk for anemia were evident at > or =2 weeks of linezolid treatment. Hematologic abnormalities were consistent with mild, reversible, duration-dependent myelosuppression. Appropriate monitoring is warranted with linezolid use.     

New anticonvulsants--new adverse effects

Ongoing refinements in pharmacology continue to provide new medications for the treatment of seizure disorders and other neurologic conditions. The authors present the cases of two children who developed relatively uncommon adverse effects to new anticonvulsant medications, including metabolic acidosis with topiramate and hyponatremia with oxcarbazepine. In one of our two patients, intraoperative acidosis related to topiramate was noted. Appropriate investigation with documentation of normal serum lactate resulted in the exclusion of other potentially serious causes of acidosis and in the identification of topiramate as the causative agent. In our second patient, hyponatremia and status epilepticus resulted from therapy with oxcarbazepine. Prompt recognition of hyponatremia, fluid restriction, and cessation of oxcarbazepine therapy resulted in prompt correction of the hyponatremia. We review previous reports of these adverse effects with topiramate and oxcarbazepine, describe the pathophysiology of these metabolic alterations, provide treatment strategies, and make suggestions for monitoring patients during therapy with these anticonvulsant medications.     

Management of adverse drug effects

Adverse drug reactions (ADRs) are still considered one of the main problems of drug therapy. ADRs are associated with considerable morbidity, mortality, decreased compliance and therapeutic success as well as high direct and indirect medical costs. Several considerations have to come into play when managing a potential ADR. It is critical to establish an accurate clinical diagnosis of the adverse event. Combining information about drug exposure together with considering other possible causes of the reaction is crucial to establish a causal relationship between the reaction and the suspected drug. Identification of the underlying pathogenesis of an ADR together with the severity of the reaction will have profound implications on continuation of drug therapy after an ADR. Since spontaneous reports about ADRs are a key stone of a functioning post-marketing surveillance system and therefore play a key role in improving drug safety, health care professionals are highly encouraged to report ADRs to a local or national organization. However, because the majority of ADRs is dose-dependent and therefore preventable, individualization of pharmacotherapy may have a major impact on reducing such events.     

Psychiatric adverse effects of corticosteroids

Psychiatric adverse effects during systemic corticosteroid therapy are common. Two large meta-analyses found that severe reactions occurred in nearly 6% of patients, and mild to moderate reactions occurred in about 28%. Although disturbances of mood, cognition, sleep, and behavior as well as frank delirium or even psychosis are possible, the most common adverse effects of short-term corticosteroid therapy are euphoria and hypomania. Conversely, long-term therapy tends to induce depressive symptoms. Dosage is directly related to the incidence of adverse effects but is not related to the timing, severity, or duration of these effects. Neither the presence nor the absence of previous reactions predicts adverse responses to subsequent courses of corticosteroids. Corticosteroid-induced symptoms frequently present early in a treatment cycle and typically resolve with dosage reduction or discontinuation of corticosterolds. In severe cases or situations in which the dose cannot be reduced, antipsychotics or mood stabilizers may be required. This review offers an approach to identifying and managing corticosteroid-induced psychiatric syndromes based on the type of symptoms and anticipated duration of corticosteroid treatment.     

Desired effects and adverse effects of cannabis use

Although the use of cannabis shows no pronounced acute toxicity, acute psychological and psychomotor disturbances are observed occasionally after intake of single doses. Cannabis use can result in relevant impairment of driving ability. The risk is enhanced by concomitant use of alcohol. This augments the effect of cannabis significantly. After chronic use, significantly more psychotic symptoms become manifest, and there is a risk for developing psychological and physical dependence. Young age and pre-existing psychological disturbances increase the risk of these adverse effects. Chronic marijuana smoking is associated with increased toxicity and the risk of cancer of the respiratory tract. There is evidence of disturbance of the immune system and teratogenic effects of chronic cannabis use.     

A screening study of drug-drug interactions in cerivastatin users: an adverse effect of clopidogrel

An analysis of a case-control study of rhabdomyolysis was conducted to screen for previously unrecognized cytochrome P450 enzyme (CYP) 2C8 inhibitors that may cause other clinically important drug-drug interactions. Medication use in cases of rhabdomyolysis using cerivastatin (n = 72) was compared with that in controls using atorvastatin (n = 287) for the period 1998-2001. The use of clopidogrel was strongly associated with rhabdomyolysis (odds ratio (OR) 29.6; 95% confidence interval (CI), 6.1-143). In a replication effort that used the US Food and Drug Administration (FDA) Adverse Event Reporting System (AERS), it was found that clopidogrel was used more commonly in patients with rhabdomyolysis receiving cerivastatin (17%) than in those receiving atorvastatin (0%, OR infinity; 95% CI = 5.2-infinity). Several medications were tested in vitro for their potential to cause drug-drug interactions. Clopidogrel, rosiglitazone, and montelukast were the most potent inhibitors of cerivastatin metabolism. Clopidogrel and its metabolites also inhibited cerivastatin metabolism in human hepatocytes. These epidemiological and in vitro findings suggest that clopidogrel may cause clinically important, dose-dependent drug-drug interactions with other medications metabolized by CYP2C8.     

Central adverse effects of methylxanthines]

Methylated xanthines are responsible of minor and major side effects on the central nervous system specially seizure. A review of the literature shows that it is related in adult to different promoting factors whereas the relationship between toxicity and excessive theophylline concentration is more clear in child. Other side effects on the gastrointestinal system, sleep and cerebral circulation are discussed.     

Managing adverse effects of hormonal contraceptives

Adverse effects of hormonal contraceptives usually diminish with continued use of the same method. Often, physi- cians only need to reassure patients that these symptoms will likely resolve within three to five months. Long-acting injectable depot medroxyprogesterone acetate is the only hormonal contraceptive that is consistently associated with weight gain; other hormonal methods are unlikely to increase weight independent of lifestyle choices. Switching com- bined oral contraceptives is not effective in treating headaches, nor is the use of multivitamins or diuretics. There are no significant differences among various combined oral contraceptives in terms of breast tenderness, mood changes, and nausea. Breakthrough bleeding is common in the first months of combined oral contraceptive use. If significant abnormal bleeding persists beyond three months, other methods can be considered, and the patient may need to be evaluated for other causes. Studies of adverse sexual effects in women using hormonal contraceptives are inconsistent, and the pharmacologic basis for these symptoms is unclear. If acne develops or worsens with progestin-only contra- ceptives, the patient should be switched to a combination method if she is medically eligible. There is insufficient evidence of any effect of hormonal contraceptives on breast milk quantity and quality. Patient education should be encouraged to decrease the chance of unanticipated adverse effects. Women can also be assessed for medical eligibility before and during the use of hormonal contraceptives.     

Management of common opioid-induced adverse effects

Opioid analgesics are useful agents for treating pain of various etiologies; however, adverse effects are potential limitations to their use. Strategies to minimize adverse effects of opioids include dose reduction, symptomatic management, opioid rotation, and changing the route of administration. Nausea occurs in approximately 25 percent of patients; prophylactic measures may not be required. Patients who do develop nausea will require antiemetic treatment with an antipsychotic, prokinetic agent, or serotonin antagonist. Understanding the mechanism for opioid-induced nausea will aid in the selection of appropriate agents. Constipation is considered an expected side effect with chronic opioid use. Physicians should minimize the development of constipation using prophylactic measures. Monotherapy with stool softeners often is not effective; a stool softener combined with a stimulant laxative is preferred. Sedation and cognitive changes occur with initiation of therapy or dose escalation. Underlying disease states or other centrally acting medications often will compound the opioid's adverse effects. Minimizing unnecessary medications and judicious use of stimulants and antipsychotics are used to manage the central nervous system side effects. Pruritus may develop, but it is generally not considered an allergic reaction. Antihistamines are the preferred management option should pharmacotherapy treatment be required.     

Analysis of antiretroviral drugs-induced adverse effects

In 1999, The Regional Center of Pharmacogilance and the Department of Infectious Disease of the Toulouse University Hospital set up a system to improve the data collection about antiretroviral-induced adverse reactionss (ADRs). From November 1999 to April 2003, a resident of pharmacovigilance collected ADRs reported with antiretroviral drugs during 2 weekly medical consultations. A total of 613 ADRs corresponding to 428 patients were reported, classified as "non serious" in 88.6% of cases and required the withdrawal of suspected drugs in 57% of cases. Our data show an improvement of antiretroviral drug-induced ADRs reporting.     

Perceived adverse effects of antiretroviral therapy

Adverse effects from antiretroviral therapy (ARV) for HIV are associated with medication nonadherence. The purposes of this study were to explore group differences in the reporting of adverse effects, identify individual adverse effects that are linked to nonadherence, and to explore the role of coping in the relationship between adverse effects and adherence. Cross-sectional interviews of 2,765 HIV-positive adults on ARV therapies in four U.S. cities were performed using a computerized assessment of self-reported adverse effects, coping self-efficacy, and adherence. There were no gender differences in the rate or severity of adverse effects reported. Latino respondents reported more adverse effects than either White or African Americans. Those taking a protease inhibitor (PI) reported a higher rate and greater severity of adverse effects. Older participants reported fewer adverse effects despite being more likely to be on a regimen containing a PI. Respondents with less than 90% adherence reported greater numbers and severity of adverse effects overall. In multivariate analyses, nausea, skin problems, vomiting, and memory adverse effects were independently related to less than 90% adherence over the prior three days. Coping moderated the relationship between nausea and adherence such that individuals who reported lower coping self-efficacy and experienced nausea were at increased risk for nonadherence, regardless of the length of time on the current ARV regimen. Women and men are similar in their overall reports of adverse effects, and Latinos report more adverse effects to ARVs than White or African American patients. Specific adverse effects (skin problems, memory problems, vomiting, and nausea) are more likely than others to be associated with missing ARV medications. Increasing adaptive coping self-efficacy among patients experiencing nausea may be a particularly effective strategy in increasing medication adherence.     

Mechanisms of adverse effects during hemapheresis

For over 20 years blood components have been collected from normal donors by automated hemapheresis. Cell separators have become increasingly sophisticated, and relatively pure component “concentrates” can be obtained quite safely. Cytapheresis donors are monitored carefully, and serious reactions are very rare. In contrast, therapeutic apheresis procedures may be technically demanding and frequently are performed on very sick patients. Large volumes of blood are rapidly removed from the patient, anticoagulated, and separated into components by the automated cell separator. The blood component containing the pathogenetic factor (e.g., plasma containing an antibody) is retained outside of the body, and the remaining components (e.g., red cells, white cells, and platelets) plus the replacement fluid are reinfused. Complications can occur in normal cytapheresis donors because of the technical challenges of the procedure (e.g., extracorporeal circuit to be filled, use of citrate anticoagulant, need for large bore intravascular access, and rapid blood flow rates). All of these factors apply also to therapeutic patients plus the additional requirement for replacement fluids, and the clinical features of the underlying illness for which each patient is being treated. Fortunately, even with therapeutic patients, most complications are of modest severity and are easily managed with only temporary slowing or interruption of the hemapheresis procedure. © 1996 Wiley-Liss, Inc.