Az aminokinolinok egy régóta használt gyógyszercsoport, amely napjainkban is elengedhetetlen számos kórkép, különösen szisztémás gyulladásos kórképek terápiájában. Az éles látásért felelős retinarész, a macula klorokin és hidroxiklorokin által okozott toxikus károsodása már jól ismert mellékhatás volt a múlt században is. Az ilyen gyógyszert hosszú távon szedő krónikus betegek szemészeti szűrése azóta visszatérő kérdéskör, mely az újonnan megjelenő evidenciák által folyamatosan megújuló vizsgálati protokollokban nyilvánul meg. Tanulmányunkban áttekintjük a jelenleg érvényes nemzetközi irányelveket, kitérve arra, hogy az ezekben újonnan történő változtatások milyen új adatokon alapszanak. Ismertetjük a korszerű szemészeti szűrés műszereit (automata látótérvizsgálat, optikaikoherencia-tomográfia [OCT], fundus-autofluoreszcencia [FAF], multifokális elektroretinográfia [mfERG]), valamint a klorokint vagy hidroxiklorokint szedő betegeknél azonosított rizikófaktorokat, melyek hajlamosítanak a maculopathia kialakulására. Végezetül egy hazai viszonyokra adaptált szűrési protokollt szeretnénk bemutatni. Orv Hetil. 2024; 165(30) 1147–1153.

The incidence and mortality of cancer are increasing, making it a leading cause of death worldwide. Conventional treatments such as surgery, radiotherapy, and chemotherapy face significant limitations due to therapeutic resistance. Autophagy, a cellular self-degradation mechanism, plays a crucial role in cancer development, drug resistance, and treatment. This review investigates the potential of autophagy inhibition as a therapeutic strategy for cancer. A systematic search was conducted on Embase, PubMed, and Google Scholar databases from 1967 to 2024 to identify studies on autophagy inhibitors and their mechanisms in cancer therapy. The review includes original articles utilizing in vitro and in vivo experimental methods, literature reviews, and clinical trials. Key terms used were \"Autophagy\", \"Inhibitors\", \"Molecular mechanism\", \"Cancer therapy\", and \"Clinical trials\". Autophagy inhibitors such as chloroquine (CQ) and hydroxychloroquine (HCQ) have shown promise in preclinical studies by inhibiting lysosomal acidification and preventing autophagosome degradation. Other inhibitors like wortmannin and SAR405 target specific components of the autophagy pathway. Combining these inhibitors with chemotherapy has demonstrated enhanced efficacy, making cancer cells more susceptible to cytotoxic agents. Clinical trials involving CQ and HCQ have shown encouraging results, although further investigation is needed to optimize their use in cancer therapy. Autophagy exhibits a dual role in cancer, functioning as both a survival mechanism and a cell death pathway. Targeting autophagy presents a viable strategy for cancer therapy, particularly when integrated with existing treatments. However, the complexity of autophagy regulation and the potential side effects necessitate further research to develop precise and context-specific therapeutic approaches.

UNASSIGNED: Hydroxychloroquine (HCQ) and chloroquine (CQ) are foundational treatments for several systemic autoimmune rheumatic diseases, including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Concerns regarding the risk of cardiac arrhythmia and death have been raised, yet the burden of HCQ and CQ-related cardiac toxicities remains unclear. A systematic literature search was conducted in the MEDLINE and Embase databases for articles published between the earliest date and April 2023 reporting cardiac conduction abnormalities in patients with systemic autoimmune rheumatic diseases taking HCQ or CQ. Meta-analysis was performed to calculate the difference in mean corrected QT (QTc) interval and odds ratio of prolonged QTc interval in those taking HCQ or CQ versus not. Of 2673 unique records, 34 met the inclusion criteria, including 70,609 subjects. Thirty-three studies reported outcomes in HCQ and 9 in CQ. Five studies reported outcomes in RA, 11 in SLE, and 18 in populations with mixed rheumatic diseases. Eleven studies reported mean QTc and OR for prolonged QTc for meta-analysis, all reporting outcomes in HCQ. There was a significant increase in mean QTc (10.29 ms,  P  = 0.458) among HCQ users compared to non-HCQ users in patients with RA. There was no difference in mean QTc between HCQ and non-HCQ users in other systemic autoimmune rheumatic diseases. When rheumatic diseases were pooled, HCQ users were more likely to have prolonged QTc compared to non-HCQ users (odds ratio 1.57, 95% CI, 1.19, 2.08). The results of this study suggest that clinicians should be aware of potential adverse cardiac events of HCQ and consider QTc monitoring for patients on HCQ for the treatment of systemic autoimmune rheumatic diseases.

OBJECTIVE: To evaluate whether hydroxychloroquine (HCQ) or chloroquine (CQ) are effective for the treatment of oral lichen planus (OLP).
METHODS: A literature search was conducted in four databases. Clinical studies investigating the effect of HCQ/CQ in patients with OLP were included.
RESULTS: Eleven studies were included. Four were RCTs and seven quasi-experimental studies. The studies included 390 patients diagnosed with OLP, of which 326 and 7 received HCQ and CQ, respectively. 46 patients received topical dexamethasone, 5 placebo and 6 griseofulvin as controls. Five studies assessed pain, and all of them obtained pain reduction with the use of HCQ. Six studies reported objective clinical improvement of OLP with the use of HCQ. Five studies that used a subjective scale obtained that 24%-100% of the patients achieved a complete/almost complete improvement of OLP lesions and its symptomatology. The most frequent side effects were vision problems, gastric discomfort, rash, nauseas, headaches, skin pigmentation, and elevated kidney function. 17 patients had to withdraw from the studies.
CONCLUSIONS: Current evidence is scarce to confirm HCQ as a therapeutic option for OLP. More RCTs are needed to compare its efficacy with topical corticosteroids and to evaluate whether HCQ reduces relapses of OLP.

The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a serious threat to global public health and there is currently no effective antiviral therapy. It has been suggested that chloroquine (CQ) and hydroxychloroquine (HCQ), which were primarily employed as prophylaxis and treatment for malaria, could be used to treat COVID-19. CQ and HCQ may be potential inhibitors of SARS-CoV-2 entry into host cells, which are mediated via the angiotensin-converting enzyme 2 (ACE2), and may also inhibit subsequent intracellular processes which lead to COVID-19, including damage to the cardiovascular (CV) system. However, paradoxically, CQ and HCQ have also been reported to cause damage to the CV system. In this review, we provide a critical examination of the published evidence. CQ and HCQ could potentially be useful drugs in the treatment of COVID-19 and other ACE2 involved virus infections, but the antiviral effects of CQ and HCQ need to be tested in more well-designed clinical randomized studies and their actions on the CV system need to be further elucidated. However, even if it were to turn out that CQ and HCQ are not useful drugs in practice, further studies of their mechanism of action could be helpful in improving our understanding of COVID-19 pathology.

OBJECTIVE: Chloroquine and its analog hydroxychloroquine are derivatives of 4-aminoquinoline and are regularly used in the treatment of malaria and autoimmune diseases. Among the side effects of these drugs, alterations associated with the auditory system are frequently mentioned. Thus, the aim of this systematic review is to systematically review publications on hearing disorders and chloroquine or hydroxychloroquine use.
METHODS: Inclusion criteria were observational or interventional studies on audiological assessment in participants who were using chloroquine or hydroxychloroquine. The methodological quality was independently assessed by two reviewers using the Meta-Analysis of Statistics: assessment and review Instrument. The certainty of the evidence was assessed using the GRADE tool.
RESULTS: A total of 1,372 non-duplicate papers were screened, out of which 17 were included in the final qualitative synthesis, and 5 studies in the meta-analysis. The odds ratio for the two subgroups evaluated did not show significance with no heterogeneity between the effects observed between the different diseases (I2=0%) and obtaining the global estimate of 0.76 (95% confidence interval [CI]=0.41-1.39; p>0.05). Despite the inclusion of papers with different disease samples, the heterogeneity observed in the analysis was low (I2= 0%) and prediction interval (95% PI=0.32-1.80; p>0.05) remained close to that estimated by the CI (95% CI=0.41-1.39; p>0.05). The certainty of the evidence assessed by the GRADE tool was considered very low due to the risk of bias, indirect evidence, and imprecision.
CONCLUSIONS: The findings of this study suggest that the use of chloroquine/hydroxychloroquine is not associated with hearing disorders.

Malaria is a potentially fatal parasitic disease transmitted by the Anopheles mosquito. A resurgence in locally acquired infections has been reported in the U.S.
This narrative review provides a focused overview of malaria for the emergency clinician, including the epidemiology, presentation, diagnosis, and management of the disease.
Malaria is caused by Plasmodium and is transmitted by the Anopheles mosquito. Disease severity can range from mild to severe. Malaria should be considered in any returning traveler from an endemic region, as well as those with unexplained cyclical, paroxysms of symptoms or unexplained fever. Patients most commonly present with fever and rigors but may also experience cough, myalgias, abdominal pain, fatigue, vomiting, and diarrhea. Hepatomegaly, splenomegaly, pallor, and jaundice are findings associated with malaria. Although less common, severe malaria is precipitated by microvascular obstruction with complications of anemia, acidosis, hypoglycemia, multiorgan failure, and cerebral malaria. Peripheral blood smears remain the gold standard for diagnosis, but rapid diagnostic tests are available. Treatment includes specialist consultation and antimalarial drugs tailored depending on chloroquine resistance, geographic region of travel, and patient comorbidities. Supportive care may be required, and patients with severe malaria will require resuscitation. Most patients will require admission for treatment and further monitoring.
Emergency medicine clinicians should be aware of the presentation, diagnosis, evaluation, and management of malaria to ensure optimal outcomes.

Chloroquine (CQ) is the drug of choice for treating uncomplicated Plasmodium vivax (P. vivax) malaria in India. The knowledge about the exact burden of CQ resistance in P. vivax in India is scarce. Therefore, this systematic review aimed to assess the prevalence of CQ resistance in reported P. vivax cases from India.
PubMed, EMBASE, and Web of Science, were searched using the search string: \'Malaria AND vivax AND chloroquine AND (resistance OR resistant) AND India\'. We systematically reviewed in-vivo and in-vitro drug efficacy studies that investigated the CQ efficacy of P. vivax malaria between January 1995 and December 2022. Those studies where patients were followed up for at least 28 days after initiation of treatment were included.
We identified 12 eligible CQ therapeutic efficacy studies involving 2470 patients, Of these 2329 patients were assessed by in-vivo therapeutic efficacy methods and the remaining 141 were assessed by in-vitro methods. CQ resistance was found in 25/1787 (1.39%) patients from in-vivo and in 11/141 (7.8%) patients from in-vitro drug efficacy studies.
Based on the available studies, the prevalence of CQ resistance in P. vivax was found to be relatively lower in India. However, continued surveillance and monitoring are crucial to identify the emergence of CQ resistance.

UNASSIGNED: We aimed to evaluate the high-quality literature on the frequency and nature of major adverse cardiac events (MACE) associated with either hydroxychloroquine (HCQ) or chloroquine (CQ).
UNASSIGNED: We searched Medline, Embase, International Pharmaceutical Abstracts, and Cochrane Central from 1996 onward using search strategies created in collaboration with medical science librarians.
UNASSIGNED: Randomized controlled trials (RCTs) published in English language from January 1996 to September 2022, involving adult patients at least 18 years of age, were selected. Outcomes of interest were death, arrhythmias, syncope, and seizures. Random-effects meta-analyses were performed with a Treatment Arm Continuity Correction for single and double zero event studies.
UNASSIGNED: By study drug, there were 31 HCQ RCTs (n = 6677), 9 CQ RCTs (n = 622), and 1 combined HCQ-CQ trial (n = 105). Mortality was the most commonly reported MACE at 220 of 255 events (86.3%), with no reports of torsades de pointes or sudden cardiac death. There was no increased risk of MACE with exposure to HCQ-CQ compared with control (risk ratio [RR] = 0.90, 95% CI = 0.69-1.17, I2 = 0%).
UNASSIGNED: These findings have important implications with respect to patient reassurance and updated guidance for prescribing practices of these medications.
UNASSIGNED: Despite listing as QT-prolonging meds, HCQ-CQ did not increase the risk of MACE.

Pyronaridine-artesunate was recently strongly recommended in the 2022 update of the WHO Guidelines for the Treatment of Malaria, becoming the newest artemisinin-based combination therapy (ACT) for both uncomplicated Plasmodium falciparum and Plasmodium vivax malaria. Pyronaridine-artesunate, available as a tablet and paediatric granule formulations, is being adopted in regions where malaria treatment outcome is challenged by increasing chloroquine resistance. Pyronaridine is an old antimalarial agent that has been used for more than 50 years as a blood schizonticide, which exerts its antimalarial activity by interfering with the synthesis of the haemozoin pigment within the Plasmodium digestive vacuole. Pyronaridine exhibits a high blood-to-plasma distribution ratio due to its tendency to accumulate in blood cells. This feature is believed to play a crucial role in its pharmacokinetic (PK) properties and pharmacological activity. The PK characteristics of pyronaridine include rapid oral absorption, large volumes of distribution and low total body clearance, resulting in a long terminal apparent half-life. Moreover, differences in PK profiles have been observed between healthy volunteers and malaria-infected patients, indicating a potential disease-related impact on PK properties. Despite a long history, there is only limited knowledge of the clinical PK and pharmacodynamics of pyronaridine, particularly in special populations such as children and pregnant women. We here provide a comprehensive overview of the clinical pharmacology of pyronaridine in the treatment of malaria.