Quinacrine Therapy Research Articles

Calf Thymus DNA Exposed to Quinacrine at Physiological Temperatures and pH Acquires Immunogenicity: A Threat for Long Term Quinacrine Therapy.

Quinacrine is an Acridine derivative with two potentially reactive groups; a diamino butyl side chain and an Acridine ring both capable of interacting with DNA but in different ways. This is an antimalarial drug approved by FDA for long term clinical trials and for the treatment of other diseases as well. The study evaluates the physicochemical interactions of quinacrine with DNA (calf thymus DNA) through characterizations of quinacrine DNA adduct (Q-DNA) by various techniques. It was observed that quinacrine induces stability in the structure of DNA, as the onset of melting was found to be increased by 6°C in the melting temperature profile of Q-DNA supported by other data obtained during study, deviation from the native structure of DNA was analyzed by FTIR that showed specific shifts in the region of 1707-1400cm-1.The study also probed the antigenicity of Q-DNA compared to its non antigenic native counterpart (N-DNA), by using both as antigens in female New Zealand White rabbits. Q-DNA was found to be antigenic with antibody titer > 1:6400. IgG was isolated and characterized to check for binding specificity. These antibodies were found to be promiscuous capable of cross reacting with other cellular molecules. Analysis of the data obtained suggested that intracellular accumulation of quinacrine and its ability to cross nucleus may allow the drug to interact with DNA. This may bring about significant structural perturbations in the macromolecule triggering an immunogenic response at the site where anti Q-DNA antibody and Q-DNA complex accumulates.

A case of hyperpigmentation induced by hydroxychloroquine and quinacrine in a patient with systemic lupus erythematosus and review of the literature.

Hydroxychloroquine (HQ) and quinacrine are widely used antimalarials for systemic lupus erythematosus (SLE) and other autoimmune diseases. We report a case of antimalarial-induced hyperpigmentation in a 57-year old African-American woman. The patient had a long-standing history of SLE that was treated with HQ and quinacrine in varying doses for 16 years. The disease improved considerably and entered remission; however, the patient subsequently developed severe, disseminated hyperpigmentation on her face, trunk, upper and lower extremities. A malar facial biopsy revealed numerous perivascular and scattered interstitial, heavily pigment laden dark brown to black macrophages. The Fontana Masson staining was positive for melanin, and Perl’s stain for iron was negative. This staining pattern, to our knowledge, has only been reported once before in the literature. Our patient represents a rare case of severe recalcitrant hyperpigmentation induced by combination HQ and quinacrine therapy for SLE.

Prevalence and risk factors of hyperpigmentation induced by hydroxychloroquine in lupus patients

<p class="abstract"><strong>Background:</strong> Antimalarials including hydroxychloroquine (HCQ) have been used in the treatment of systemic lupus erythematosus (SLE) for more than 50 years. Few cases of hyperpigmentation attributed to HCQ have been reported in the literature from different geographical areas. However, no case reports or local studies from Saudi Arabia estimated the magnitude of HCQ adverse effect. This study aimed to estimate the prevalence of HCQ-induced hyperpigmentation and to investigate the possible risk factors related to this condition.</p><p class="abstract"><strong>Methods:</strong> This retrospective study was conducted at King Abdulaziz University Hospital. All SLE patients on HCQ treatment, aged 18 years or above who visited Rheumatology and Dermatology Clinics were included. Those with the previous history of hyperpigmentation before starting HCQ treatment, or on chloroquine or quinacrine therapy were excluded. Medical records from September 2005 until June 2016 were reviewed.<strong></strong></p><p class="abstract"><strong>Results:</strong> Out of 199 cases, 98 (49.2%) cases had hyperpigmentation, only 13 (13.3%) cases reported resolution. The main sites affected were the hands 46 (23.1%), followed by face 45 (22.6%), then feet 18 (9.0%), leg and whole body equally 12 (6.0%). There was a significant association between hyperpigmentation and receiving medications, history of ecchymosis, sun exposure, the presence of mucous membrane pigmentations (p<0.0001, p=0.012, p<0.0001, p=0.022 respectively).</p><strong>Conclusions:</strong> HCQ-induced pigmentation is considered uncommon adverse effect of HCQ, with a prevalence rate of 49.2% indicated in this study. Furthermore, history of bruising, sun exposure, and the presence of mucous membrane pigmentation are possible predisposing factors.

Bull's-eye maculopathy associated with quinacrine therapy for malaria

PurposeTo report a side effect of quinacrine therapy for malaria. DesignCase report. MethodsReview of clinical chart and photographs. SettingPrivate retina practice. ResultsA patient developed a bilaterally symmetric bull's-eye maculopathy 45 years after taking quinacrine for 18 months as prophylaxis against malaria. Progression of the clinical picture was documented over 15 years of follow-up. The clinical picture was identical to that of chloroquine and hydroxychloroquine maculopathy. ConclusionsLow dosages of quinacrine used for malaria prophylaxis can be associated with a delayed, severe maculopathy indistinguishable from chloroquine maculopathy in certain patients.

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Hydroxychloroquine (HQ) and quinacrine are widely used antimalarials for systemic lupus erythematosus (SLE) and other autoimmune diseases. We report a case of antimalarial-induced hyperpigmentation in a 57-year old African-American woman. The patient had a long-standing history of SLE that was treated with HQ and quinacrine in varying doses for 16 years. The disease improved considerably and entered remission; however, the patient subsequently developed severe, disseminated hyperpigmentation on her face, trunk, upper and lower extremities. A malar facial biopsy revealed numerous perivascular and scattered interstitial, heavily pigment laden dark brown to black macrophages. The Fontana Masson staining was positive for melanin, and Perl’s stain for iron was negative. This staining pattern, to our knowledge, has only been reported once before in the literature. Our patient represents a rare case of severe recalcitrant hyperpigmentation induced by combination HQ and quinacrine therapy for SLE.

Severe Giardiasis in a Patient with Cystic Fibrosis

A 20‐year‐old male patient with cystic fibrosis (CF) is described, who acutely developed hypoalbuminemia concurrently with giardiasis. Hypoalbuminemia could not be explained by the usual causes seen in patients with CF, but resolved with quinacrine therapy. Subsequently, asymptomatic giardiasis was sought but not found by either the string test or stool exam in any of 15 patients with pancreatic insufficiency who were examined in a prospective manner. Although pancreatic insufficiency is felt to be able to act synergistically with giardiasis to accentuate malabsorption, patients with pancreatic insufficiency per se are not necessarily at greater risk for colonization with Giardia.

Quinacrine Skin Discoloration Is Associated with Fluorescence of `Y' Chromosome in Male Cells and Malarial Parasites in Malaria

Sokol et al reported yellow discoloration in a child treated with quinacrine for giardiasis. This, as the authors suggest, is a well known harmless side effect of quinacrine. During work with quinacrine fluorescence of the "Y" chromosome, we observed that malarial parasites within red cells of blood smears also fluoresced brightly. At that time we examined a smear of a Nigerian adult male with malaria, who had yellow discoloration due to quinacrine therapy. Not only did we demonstrate quinacrine fluorescence of "Y" chromosomes in white cells of his unstained blood smear but fluorescent malarial parasites were still present in some red cells.

Fatal aplastic anemia following quinacrine therapy in chronic discoid lupus erythematosus.

The use of quinacrine (Atabrine) has declined considerably since the introduction of newer antimalarials. However, recent new indications for the drug have revived its use. Page reported on the treatment in 18 cases of chronic discoid lupus erythematosus with quinacrine with striking results. Only one patient failed to improve considerably, and in a few cases all the lesions completely disappeared within six weeks of the start of treatment. In two patients associated changes of rheumatoid arthritis disappeared as the skin condition improved. This latter finding was extended by Freedman and Bach, who treated 23 arthritic patients with quinacrine, of whom all but one were said to have improved. Pain subsided, soft tissue swelling decreased, and movement became free and more vigorous. Six to 10 weeks of therapy were necessary before all signs of joint inflammation disappeared. In this series only one side-reaction, a macular eruption, developed in a patient who

HEMATOLOGICAL CHANGES FOLLOWING THE ADMINISTRATION OF LARGE DOSES OF QUINACRINE HYDROCHLORIDE

AbstractThe administration of quinacrine to rats, mice, rabbits, hamsters, guinea-pigs, dogs, monkeys, chickens, and ducks results in definite hematological changes. Peculiar basophilic inclusions, usually associated with vacuoles, appear in the cytoplasm of lymphocytes of all nine species following drug therapy. Inclusions of a similar nature are seen in erythrocytes of the rat, mouse, and hamster and rarely in monocytes of the rat.The rat shows an anemia, polynucleosis, lymphopenia, and monocytosis after quinacrine dosing. None of the other species develop a leukocytosis or monocytosis, but they sometimes show a polynucleosis and lymphopenia after quinacrine therapy. Leukopenia occurs in the monkey and occasionally in the dog following the use of this drug.

TOXICITY OF QUINACRINE (ATABRINE) FOR THE CENTRAL NERVOUS SYSTEM

A METHOD of detecting and measuring the toxic effects of drugs on cerebration and its use in a preliminary investigation of the toxicity of quinacrine (atabrine) are presented. The procedure is simple and consists in principle in comparing the intellectual functioning of subjects while taking the drug and when free of the drug. Groups of subjects receiving different doses of quinacrine hydrochloride and with varying serum levels of the drug were tested to gain an approximate estimate of the dose which tends to be toxic for human subjects. The study was undertaken when it was observed, during the treatment of many thousands of patients for malaria, that the most serious toxic effect of quinacrine was the occurrence of toxic psychoses. This complication was seen most often after excessive doses. Massive quinacrine therapy had been instituted on the island on which we were stationed to determine whether the production and maintenance

TOXIC PSYCHOSES ASSOCIATED WITH ADMINISTRATION OF QUINACRINE

EVER VER since quinacrine hydrochloride was introduced into the therapyof malaria, it has been considered a most valuable addition to the series of antimalarial drugs, owing to its well established effectiveness, together with its relatively low toxicity. This evaluation of the drug has not changed, even though reports of toxic effects after therapeutic doses and, in particular, of mental disorders following treatment with the drug were described as early as 1933. In that year Conoley1gave an unpublished report on psychosis following treatment with quinacrine. In 1934 Kingsbury,2utilizing observations of his own, as well as of others (Cameron,3Green,4Hoops,5McSwan,6Quaife7), collected a series of 12 cases of psychoses associated with quinacrine therapy, with the records available, which had been observed in the Malay States. Six more cases were published by Banerjee8in 1936, from India. Decherd,9in 1937,

MEDICINE AND THE WAR

<h3>QUINACRINE HYDROCHLORIDE (ATABRINE) FOR MALARIA</h3> On May 31, 1944 the Board for the Coordination of Malarial Studies adopted the following resolution concerning the relative value to the armed forces of quinacrine hydrochloride, U. S. P. (atabrine), quinine and totaquine, U. S. P. On the basis of controlled quantitative studies in civilian, Army and Navy establishments, the evidence at hand justifies the following statement: In the Suppressive Therapy.—Quinacrine (atabrine) has proved to have all the antimalarial properties ascribed to quinine in the suppression of malaria during and subsequent to exposure to infected mosquitoes. Effective suppression can be accomplished over long periods of time by proper use of quinacrine. Available evidence indicates that this end may be achieved without danger to the individual. Earlier reports indicated a significant incidence of gastrointestinal disturbances in certain groups of men receiving suppressive quinacrine therapy. For practical purposes these adverse reactions can be avoided by