Cutaneous side effects of doxycycline: a pediatric case series

Objective: Brucellosis is highly endemic in Turkey and doxycycline is commonly used for its treatment. The present study aimed at documenting the cutaneous side effects of doxycycline in pediatric brucellosis patients in Turkey.

Materials and methods: Pediatric patients with brucellosis that were treated between February 2014 and January 2016 were analyzed retrospectively, and those that developed doxycycline-related cutaneous side effects were identified. Demographic data, epidemiological history, physical examination findings, laboratory test results, anti-brucellosis treatment regimen, duration of follow up and outcome were recorded.

Results: Among the 189 brucellosis patients, 141 treated with doxycycline plus rifampicin. Seven patients (5%) (two female and five male) developed doxycycline-related cutaneous side effects. Mean duration of treatment before the onset of cutaneous side effects was 9.5 weeks. Doxycycline therapy was continued in five of these patients and was changed in two patients. In the patients that continued to receive doxycycline the cutaneous side effects gradually improved.

Conclusions: Cutaneous side effects of doxycycline should always be a consideration, especially in regions in which brucellosis is endemic and doxycycline is commonly used to treat it.     

Increased morphine analgesia and reduced side effects in mice lacking the tac1 gene

Background and purpose:

Although morphine is a very effective analgesic, its narrow therapeutic index and severe side effects limit its therapeutic use. Previous studies indicated that the pharmacological responses of opioids are modulated by genetic and pharmacological invalidation of tachykinin receptors. Here we address the role of substance P and neurokinin A, which are both encoded by the tachykinin 1 (tac1) gene, as modulators of opioid effects.

Experimental approach:

The analgesic and side effect potential of morphine was compared between wild-type and tac1 null mutant mice.

Key results:

Morphine was a more potent analgesic in tac1 null mutant mice, that is, in the absence of substance P/neurokinin A signalling. Interestingly, the most serious side effect of acute morphine, that is respiratory depression, was reduced in tac1^−/− animals. Comparing the addictive potential of morphine in wild-type and knockout animals we found that morphine preference was similar between the genotypes. However, the aversive effect of withdrawal precipitated by naloxone in morphine-dependent animals was significantly reduced in tac1 knockout mice. Behavioural sensitization, the underlying mechanism of addiction, was also significantly lower in tac1^−/− mice.

Conclusion and implications:

The analgesic potential of morphine was increased in tac1 knockout mice. In contrast, both the ventilatory suppressing effect and the addictive potential of morphine were reduced. These results suggest that reducing activity of the tachykinin system may be a possible strategy to improve the pharmacological potential of morphine.     

Muscular side effects of statins

Lipid lowering has been shown to be effective in preventing primary and recurrent cardiovascular events and to save life. Statins almost exclusively used for this purpose meanwhile became one of the most widely prescribed families of drugs world-wide. Myopathies--mainly not well characterized--are the major group of side effects. We here review different types of clinical appearances, localizations, symptoms and the biochemical background. The data indicate that severe muscular side effects are rare. Patients and their doctors, however, easily overlook mild ones. Myopathic symptoms without any known biochemical correlate are not rare. No general guideline exists about exact diagnosis and differential diagnosis. Strict adherence to the measures of life-style change and performance of regular exercise can even further enhance significantly these side effects. Much more research should be directed onto the pathophysiological (genetic?) background to finally evaluate possible therapeutic consequences rather than simply to withdraw or change the respective statin.     

Long-term side effects of glucocorticoids

ABSTRACT

Introduction: Glucocorticoids represent the standard therapy for reducing inflammation and immune activation in various diseases. However, as with any potent medication, they are not without side effects. Glucocorticoid-associated side effects may involve most major organ systems. Musculoskeletal, gastrointestinal, cardiovascular, endocrine, neuropsychiatric, dermatologic, ocular, and immunologic side effects are all possible.

Areas Covered: This article analyzes English-language literature and provides an update on the most recent literature regarding side effects of systemic glucocorticoid treatment.

Expert Opinion: The risk/benefit ratio of glucocorticoid therapy can be improved by proper use. Careful monitoring and using appropriate preventive strategies can potentially minimize side effects.     

Gastrointestinal side effects of drugs

Drugs can have adverse effects on any part of the gastrointestinal (GI) tract from mouth to colon. It is essential that a detailed and accurate drug history is taken in patients presenting with GI complaints. Many drug-induced effects will regress or heal on cessation of treatment. NSAIDs are usually associated with gastric and duodenal ulcers but are also recognised to cause lichen planus in the mouth, oesophageal inflammation and strictures, and small bowel and colonic ulcers and strictures. A newer class of anti-inflammatory drugs, the cyclooxygenase-2 (COX-2)-selective inhibitors, have been developed and have a more favourable GI safety profile than standard NSAIDs. Acute diarrhoea, relapse of inflammatory bowel disease (IBD), microscopic colitis and acute pancreatitis are also induced by ingestion of standard NSAIDs. The calcium antagonists, phenytoin and cyclosporin, induce gum hyperplasia, particularly in patients with poor oral hygiene. Alendronate, a bisphosphonate, has been associated with development of oesophageal ulcers, and specific recommendations are now given to reduce this complication. Of the many different forms of colitis associated with drug ingestion, the most frequent is pseudomembranous colitis. This is a complication of antibiotics and is caused by the toxin produced by Clostridium difficile. Many drugs have been associated with the development of acute pancreatitis, although a definite cause and effect relationship has been shown for only a few drugs. These include didanosine, furosomide, corticosteroids, azathioprine and sodium valproate.     

Mucocutaneous side effects of antineoplastic chemotherapy

All structures of the skin may be affected by side effects of antineoplastic chemotherapy. The most commonly described effects concern skin adnexes, especially hair with alopecia. Nails are also frequently involved. Eccrine sweat or sebaceous gland involvement is more rarely reported. Mucous membranes, particularly in the mouth, are frequently altered by several mechanisms; direct cytotoxicity, infection, and a decrease in polymorphonuclear or platelet counts. Among cutaneous side effects, hyperpigmentation is very common and may have different clinical patterns; generalised, figurated, or localised. Acral erythema is another cutaneous side effect that is relatively specific to chemotherapy and is often dose-related. Some cutaneous side effects are related to an interaction between chemotherapy and radiation, particularly phototoxicity, recall phenomenon, and radiation enhancement. Miscellaneous, less frequent, side effects are described; sclerodermiform dermatitis, Raynaud's phenomenon, and hypersensitivity syndrome. In some cases, cutaneous side effects are relatively specific to one type of drug. Capillary leak syndrome is most often related to taxanes. Hydroxyurea is responsible for some peculiar cutaneous side effects (ulcerations, pseudo-dermatomyositis), perhaps due to long-term administration of the drug. Although mucocutaneous side effects of chemotherapy are frequent and sometimes severe, interruption of the culprit drug is rarely mandatory. However, adaptation of the dosage or prevention of some of these side effects remains necessary. Antineoplastic chemotherapies are widely used in many therapeutic protocols and may be responsible for numerous mucocutaneous side effects, either specific or more unusual. In rare cases, the severity of these side effects may require interruption of therapy. They may involve skin adnexes, mucous membranes or the skin itself. This review discusses cytotoxic antineoplastic drugs only, not cytokines, monoclonal antibodies or transduction factors used in the treatment of cancer.     

Mucocutaneous side effects of antineoplastic chemotherapy

All structures of the skin may be affected by side effects of antineoplastic chemotherapy. The most commonly described effects concern skin adnexes, especially hair with alopecia. Nails are also frequently involved. Eccrine sweat or sebaceous gland involvement is more rarely reported. Mucous membranes, particularly in the mouth, are frequently altered by several mechanisms; direct cytotoxicity, infection, and a decrease in polymorphonuclear or platelet counts. Among cutaneous side effects, hyperpigmentation is very common and may have different clinical patterns; generalised, figurated, or localised. Acral erythema is another cutaneous side effect that is relatively specific to chemotherapy and is often dose-related. Some cutaneous side effects are related to an interaction between chemotherapy and radiation, particularly phototoxicity, recall phenomenon, and radiation enhancement. Miscellaneous, less frequent, side effects are described; sclerodermiform dermatitis, Raynaud’s phenomenon, and hypersensitivity syndrome. In some cases, cutaneous side effects are relatively specific to one type of drug. Capillary leak syndrome is most often related to taxanes. Hydroxyurea is responsible for some peculiar cutaneous side effects (ulcerations, pseudo-dermatomyositis), perhaps due to long-term administration of the drug. Although mucocutaneous side effects of chemotherapy are frequent and sometimes severe, interruption of the culprit drug is rarely mandatory. However, adaptation of the dosage or prevention of some of these side effects remains necessary. Antineoplastic chemotherapies are widely used in many therapeutic protocols and may be responsible for numerous mucocutaneous side effects, either specific or more unusual. In rare cases, the severity of these side effects may require interruption of therapy. They may involve skin adnexes, mucous membranes or the skin itself. This review discusses cytotoxic antineoplastic drugs only, not cytokines, monoclonal antibodies or transduction factors used in the treatment of cancer.     

莫西沙星与多西环素治疗女性非淋菌性宫颈、尿道炎的疗效比较

目的比较莫西沙星和多西环素治疗非淋菌性宫颈、尿道炎的临床疗效。方法采用随机分组对照方法,将130例入选患者分为：治疗组66例,用莫西沙星400mg,po,qd,疗程12d;对照组64例,用多西环素200mg,po,bid,疗程12d。对2组治疗的有效率和病原体清除率进行比较。结果治疗组与对照组有效率分别为85．9％及72．6％（P〈0．05）,病原体清除率分别为86．6％及73．8％（P〈0．05）。结论莫西沙星对女性非淋菌性宫颈、尿道炎的临床疗效较好,优于多西环素。     

Antibody-mediated side effects of recombinant proteins

This brief review is focused on the unwanted clinical effects mediated by antibodies against genetechnologically produced drugs. While many antibodies binding biotech-drugs may not be harmful, others may have deleterious clinical effects exposing patients to high risks. These antibodies can cause either lack of efficacy or hypersensitivity reactions. Examples for antibody-mediated lack of efficacy are inhibitors in hemophiliacs treated with Factor VIII, evidence of decreasing therapeutic efficacy of beta-interferons in MS-patients and pure red cell aplasia (PRCA) in patients with chronic renal failure treated with erythropoietin. Antibody-mediated hypersensitivity reactions have to be expected with all recombinant proteins. The mechanisms and causes of antibody production against biotech-drugs in patients are discussed.     

Cardiac side effects of psychiatric drugs

This review describes the common effects of psychotropic drugs on the cardiovascular system and offers guidance for practical management. Selected reports from the literature describing common side effects associated with psychotropic drugs are reviewed, and suggestions for further reading are given throughout the text. Orthostatic hypotension is the most common adverse autonomic side effect of antipsychotic drugs. Among the atypical antipsychotics the risk of orthostatic hypotension is highest with clozapine and among the conventional drugs the risk is highest with low potency agents. Rarely, orthostatic hypotension may result in neurocardiogenic syncope. QTc prolongation can occur with all antipsychotics but an increased risk is seen with pimozide, thioridazine, sertindole and zotepine. QTc prolongation is a marker of arrhythmic risk. Torsade de pointe, a specific arrhythmia, may lead to syncope, dizziness or ventricular fibrillation and sudden death. Heart muscle disease presents most commonly in the elderly as chronic heart failure, but myocarditis and cardiomyopathy, although relatively rare, are devastating, but potentially reversible complications of psychotropic drug therapy have been particularly linked to clozapine treatment. Patients with severe mental illness (SMI) are a 'high risk' population with regard to cardiovascular morbidity and mortality. It is probable that many patients accumulate an excess of 'traditional' risk factors for the development of cardiovascular disease, but other mechanisms including psychotropic drugs may also be influential in increasing risk in this vulnerable group. These risks need to be seen in the context of the undoubted therapeutic efficacy of the psychotropic armamentarium and the relief that these drugs bring to those suffering from mental disorder.     

Increased clozapine plasma concentrations and side effects induced by smoking cessation in 2 CYP1A2 genotyped patients

Clozapine, an atypical antipsychotic, depends mainly on cytochrome P4501A2 (CYP1A2) for its metabolic clearance. CYP1A2 is inducible by smoking, and lower plasma concentrations of clozapine are measured in smokers than in nonsmokers. Case reports have been published on the effects of discontinuing smoking in patients receiving clozapine, which might lead to elevated plasma concentrations and severe side effects. We present 2 cases on the consequences of smoking cessation in patients receiving this drug. In the first patient, smoking cessation resulted, within 2 weeks, in severe sedation and fatigue, with an approximately 3-fold increase of plasma clozapine concentrations. In the second patient, a very high plasma concentration of clozapine (3004 ng/mL) was measured 6 days following a 16-day stay in a general hospital, during which smoking was prohibited. In the latter patient, the replacement of omeprazole, a strong CYP1A2 inducer, by pantoprazole, a weaker CYP1A2 inducer, could have contributed, in addition to smoking cessation, to the observed strong increase of plasma clozapine concentrations. Genotyping of the 2 patients revealed that they were carriers of the AA genotype for the -164C>A polymorphism (CYP1A2*1F) in intron 1 of CYP1A2 gene, which has previously been shown to confer a high inducibility of CYP1A2 by smoking. Thus, at the initiation of clozapine treatment, smoking patients should be informed that, if they decide to stop smoking, they are encouraged to do so but must inform their prescriber beforehand. Also, because of the increased use of no-smoking policies in many hospitals, studies examining the consequences of such policies on the pharmacokinetics/pharmacodynamics of drugs metabolized by CYP1A2, taking into account different CYP1A2 genotypes, are needed.     

Genotoxic and cytotoxic effects of doxycycline in cultured human peripheral blood lymphocytes

Doxycycline (DOX) is a broad-spectrum tetracycline antibiotic used in the treatment of many infections. In this study, the genotoxic and cytotoxic effects of DOX in cultured human peripheral blood lymphocytes were investigated by measuring chromosome aberrations (CAs), cytokinesis-block micronucleus (CBMN) assay, mitotic index (MI), and nuclear division index (NDI). Cultures were treated with DOX at three concentrations (2, 4, and 6 μg/mL) for 48 hours. Mitomycin C (MMC) was used as a positive control. All the tested concentrations of DOX for MI and the higher concentrations (4 and 6 μg/mL) for NDI significantly decreased mitotic activity. However, there are no significant differences between negative control and all the tested concentrations of DOX for CA and MN frequencies. In conclusion, our results indicate that DOX has a cytotoxic effect, but not a genotoxic effect, on human peripheral blood lymphocyte cultures. Further detailed studies, especially about the cell-cycle kinetics of DOX, are required to elucidate the decreases in dividing cells and make a possible risk assessment on cells of patients receiving therapy with this drug. Further, if the specific cytostatic and cytotoxic potential of DOX to different types of cancer cells is investigated in detail, it may also have been used as an antitumoral drug.     

Genotoxic and cytotoxic effects of doxycycline in cultured human peripheral blood lymphocytes

Doxycycline (DOX) is a broad-spectrum tetracycline antibiotic used in the treatment of many infections. In this study, the genotoxic and cytotoxic effects of DOX in cultured human peripheral blood lymphocytes were investigated by measuring chromosome aberrations (CAs), cytokinesis-block micronucleus (CBMN) assay, mitotic index (MI), and nuclear division index (NDI). Cultures were treated with DOX at three concentrations (2, 4, and 6 µg/mL) for 48 hours. Mitomycin C (MMC) was used as a positive control. All the tested concentrations of DOX for MI and the higher concentrations (4 and 6 µg/mL) for NDI significantly decreased mitotic activity. However, there are no significant differences between negative control and all the tested concentrations of DOX for CA and MN frequencies. In conclusion, our results indicate that DOX has a cytotoxic effect, but not a genotoxic effect, on human peripheral blood lymphocyte cultures. Further detailed studies, especially about the cell-cycle kinetics of DOX, are required to elucidate the decreases in dividing cells and make a possible risk assessment on cells of patients receiving therapy with this drug. Further, if the specific cytostatic and cytotoxic potential of DOX to different types of cancer cells is investigated in detail, it may also have been used as an antitumoral drug.     

Ocular side effects associated with isotretinoin

Isotretinoin is used for severe recalcitrant nodular acne and has a variety of associated ocular side effects. This review classifies these ocular side effects according to World Health Organization (WHO) criteria and reviews the existing literature as well as 2449 spontaneous case reports collected from around the world. Ocular sicca, decreased dark adaptation and intracranial hypertension are identified as "certain" side effects from isotretinoin and clinicians are provided guidelines for care and follow-up.