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REVIEW ARTICLE • J. Bras. Patol. Med. Lab. 57 • 2021 • https://doi.org/10.5935/1676-2444.20210014   copy

Interference of medicines in laboratory exams

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Objective:

Conduct a survey on the interference of drugs in laboratory tests.

Methodology:

To identify the interference of each medication in laboratory tests, the Municipal List of Essential Medicines (Remume) of a medium-sized municipality in the state of Minas Gerais was used along with the following sources of information: Dynamed, Micromedex® and Nursing Reference Center.

Results:

We observed that the majority (67.7%) of Remume drugs can interfere in one or more laboratory tests; among them, the main classes of drugs are diuretics, beta blockers, ß-lactams, sulfonamides, macrolides, tricyclic antidepressants and selective serotonin reuptake inhibitors antidepressants.

Conclusion:

It is extremely important to disseminate knowledge about these interferences so that health professionals are alert and know how to identify the possible changes, reducing analytical errors and subsequently misdiagnosis and erroneous monitoring. Continued education on drug interference in laboratory tests is equally important.

Key words:
generic drugs; clinical laboratory techniques; diagnostic errors

RESUMEN

Objetivo:

Llevar a cabo una encuesta acerca de la interferencia de los medicamentos en las pruebas de laboratorio.

Métodos:

Usamos la Relación Municipal de Medicamentos Esenciales (Remume) de una municipalidad mediana en el estado de Minas Gerais y las siguientes fuentes de información: Dynamed, Micromedex® y Nursing Reference Center.

Resultados:

Observamos que la mayor parte (67,7%) de los medicamentos de Remume puede interferir en una o más pruebas de laboratorio; entre ellos, las principales clases son los diuréticos, beta bloqueadores, betalactámicos, sulfonamidas, macrólidos, antidepresivos tricíclicos y antidepresivos inhibidores selectivos de la recaptación de serotonina.

Conclusión:

Es muy importante divulgar el conocimiento respecto a esas interferencias para que los profesionales de la salud puedan identificar las posibles alteraciones en las pruebas, reduciendo errores analíticos y diagnósticos y monitoreos equivocados. Por lo tanto, es necesaria una educación continuada acerca de las interferencias de medicamentos en las pruebas de laboratorio.

Palabras clave:
medicamentos genéricos; técnicas de laboratório clínico; errores diagnósticos

RESUMO

Objetivo:

Realizar um levantamento sobre a interferência dos medicamentos nos exames laboratoriais.

Métodos:

Utilizamos a Relação Municipal dos Medicamentos Essenciais (Remune) de um município de médio porte do estado de Minas Gerais e as seguintes fontes de informações: Dynamed, Micromedex® e Nursing Reference Center.

Resultados:

Observamos que a maioria (67,7%) dos medicamentos da Remune pode interferir em um ou mais exames laboratoriais; entre eles, as principais classes de medicamentos são os diuréticos, betabloqueadores, betalactâmicos, sulfonamidas, macrolídeos, antidepressivos tricíclicos e antidepressivos inibidores seletivos da recaptação de serotonina.

Conclusão:

É muito importante divulgar o conhecimento a respeito dessas interferências para que os profissionais da área da saúde possam identificar as possíveis alterações nos exames, reduzindo erros analíticos e diagnósticos e monitoramentos equivocados. Portanto, faz-se necessária a educação continuada sobre as interferências de medicamentos nos exames laboratoriais.

Unitermos:
medicamentos genéricos; técnicas de laboratório clínico; erros de diagnóstico

INTRODUCTION

Medicines are major sources of variation in laboratory test results, and not always they can be discontinued for the conduction of those tests11 Ceará. Secretaria de Saúde. Laboratório Central de Saúde Pública do Estado. Manual de coleta, acondicionamento e transporte de amostras. 5 ed. Fortaleza: SESA; 2019.. Some drugs can produce false-negative or false-positive results; having access to this item of information is very important in laboratory routine, as well as in clinical practice and pharmaceutical care, because it deals with change in the clinical laboratory diagnosis and interference in the monitoring and evaluation of patient prognosis22 Ferreira BC, Santos KL, Rudolph SC, Alcanfor JDX, Cunha LC. Estudo dos medicamentos utilizados pelos pacientes atendidos em laboratório de análises clínicas e suas interferências em testes laboratoriais: uma revisão da literatura. Rev Eletrônica de Farmácia. 2009; 6(1): 33-43..

Thus, it is essential to obtain data about medications and their time of use by the patient for the last 10 days before collecting biological material for the conduction of a laboratory test. Commonly, patients forget reporting some medicines they use to the laboratory personnel, therefore it is necessary to be attentive to any abnormality in the tests33 Santos PCJL, Silva AM, Marcatto LR, et al. Interferência de medicamentos utilizados nos exames laboratoriais para monitoramento de dislipidemias e diabetes mellitus. Unisanta Health Science; 2017; 1(1): 18-32..

Numerous medicines can cause biological (in vivo) and analytical (in vitro) interferences that affect laboratory tests. When a medication produces the change of a biological marker by means of a physiological or pharmacological mechanism, there is the in vivo interference or adverse drug reaction. For example, the changes in serum uric acid, which can be caused by the use of enalapril and hydrochlorothiazide22 Ferreira BC, Santos KL, Rudolph SC, Alcanfor JDX, Cunha LC. Estudo dos medicamentos utilizados pelos pacientes atendidos em laboratório de análises clínicas e suas interferências em testes laboratoriais: uma revisão da literatura. Rev Eletrônica de Farmácia. 2009; 6(1): 33-43.. On the other hand, in vitro interference of a drug or its biotransformation product can happen at an analytical step in which those tests can interact with the substances of the employed chemical reagents, producing a false result of the analysis22 Ferreira BC, Santos KL, Rudolph SC, Alcanfor JDX, Cunha LC. Estudo dos medicamentos utilizados pelos pacientes atendidos em laboratório de análises clínicas e suas interferências em testes laboratoriais: uma revisão da literatura. Rev Eletrônica de Farmácia. 2009; 6(1): 33-43.. As an example, the reduction that the ascorbic acid can cause in plasma levels of glucose when measured by the method of glucose oxidase33 Santos PCJL, Silva AM, Marcatto LR, et al. Interferência de medicamentos utilizados nos exames laboratoriais para monitoramento de dislipidemias e diabetes mellitus. Unisanta Health Science; 2017; 1(1): 18-32..

Given the above, it is important that both professionals working in clinical laboratories and those involved in the care of patients know how to recognize the types of interference drugs can cause on laboratory tests, as they can alter some markers and interfere in the conduct of health professionals. Besides, care must be greater with patients treated with several medicines concomitantly for a prolonged time, because the chances of interference are higher.

The objective of this work was to conduct a survey on the interference on laboratory tests by the medicines present at the Municipal List of Essential Medicines (Remume) of a medium-sized municipality of the state of Minas Gerais, in order to warn and spread this knowledge to the population and health professionals.

METHODS

The present study used the last version of Remume (130 medicines belonging to different classes) of a medium-sized municipality of the state of Minas Gerais (234,937 inhabitants44 Instituto Brasileiro de Geografia e Estatística. Perfil dos municípios brasileiros. 2017. Available at: https://www.divinopolis.mg.leg.br/sobre-divinopolis/geografia. [Accessed on: 20 July 2019].
https://www.divinopolis.mg.leg.br/sobre-... ), made available by the Municipal Office of Health (Semusa) in 2019. From the obtained data, we carried out a search about the interference each medication can cause in laboratory tests, by means of the site Saúde Baseada em Evidências (Evidence-Based Health), using the databases Dynamed, Micromedex® and Nursing Reference Center. The names of medicines in English were searched as key words. Later, medicines were classified according to the Anatomical Therapeutic Chemical Code (ATC), which distributes the active substances in different groups, pursuant to the organ or system in which they act and their therapeutical, chemical and pharmacological properties55 World Health Organization. Essential medicines and health products. Anatomical Therapeutic Chemical (ATC) classification. Available at: https://www.who.int/medicines/regulation/medicines-safety/toolkit_atc/en/. [Accessed on: 16 Dec 2019].
https://www.who.int/medicines/regulation... . From this search, a table was built to be used as a material for rapid consultation by all health professionals involved in patient care.

RESULTS

The medications present at Remume used in basic attention were distributed according to ATC classification regarding the treatment of: disorders of the digestive system and metabolism and food supplements; diseases of the blood and blood-forming organs; cardiovascular diseases; skin conditions; genitourinary tract disorders, sex hormones and immunoglobulins; inflammatory processes and hypothyroidism; systemic infectious diseases; musculoskeletal disorders; nervous system diseases and sleep disorders; parasitic diseases; respiratory diseases. The interference of those medicines in laboratory tests is represented in the Table according to the group they belong to.

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Interferences in laboratory testing caused by medications Treatment of disorders of the digestive system and metabolism and food supplements

We observed that most (67.7%) medicines of Remume can interfere in one or more laboratory tests. Among them, the main classes of medicines are diuretics, which change especially electrolyte balance; betablockers, which affect lipid profile; beta-lactams and sulfonamides, which cause change in blood count; macrolides and tricyclic antidepressants, which alter hepatic enzymes; and selective serotonin reuptake inhibitors antidepressants, which affect glucose and uric acid levels. The main tests suffering interference were: liver function (46 medicines), blood glucose test (31 medicines), and electrolyte panel (29 medicines).

DISCUSSION

We verified that the medicines atenolol, propranolol, carvedilol, hydrochlorothiazide, carbamazepine, haloperidol, clopidogrel, medroxyprogesterone, prednisolone, and prednisone can cause alteration of the lipid profile as the major biological interference. Thus, it is important to monitor the lipid profile of the patients taking those drugs, as the increased serum levels of triglycerides and the low-density lipoprotein cholesterol (LDL-c) and the reduced serum levels of the high-density lipoprotein cholesterol (HDL-c) are associated with the increased risk of development of cardiovascular diseases66 Sociedade Brasileira de Cardiologia (SBC). V Diretriz Brasileira sobre Dislipidemias e Prevenção da Aterosclerose. Departamento de Aterosclerose da Sociedade Brasileira de Cardiologia. Arquivos Brasileiros de Cardiologia. 2017; 4(2Supl. 1): 1-76..

Acetylsalicylic acid, atenolol, carvedilol, clonidine, furosemide, hydrochlorothiazide, propranolol, simvastatin, prednisolone, prednisone, amoxicillin, amoxicillin + clavulanic acid, azithromycin, benzathine penicillin, cefalexin, nitrofurantoin, baclofen, ibuprofen, amitriptyline, clomipramine, phenytoin, fluoxetine, imipramine, levodopa + benserazide, levodopa + carbidopa, nortriptyline, paracetamol, promethazine, ciprofloxacin, and carbamazepine are associated with alterations in the metabolism of glucose by means of decreased insulin secretion or action. As they increase blood glucose as a biological interference, it is important to monitor the glycemic levels of patients who use them. Besides, in case patients suffer from diabetes mellitus, it may be necessary to adjust the dose of the antidiabetic agent77 Sociedade Brasileira de Diabetes (SBD). Diretrizes da Sociedade Brasileira de Diabetes 2017-2018. São Paulo: Clannad; 2017..

The main medicines that cause biological interference in the hepatic function are omeprazole, acetylsalicylic acid, clopidogrel, enoxaparin, heparin, captopril, losartan, methyldopa, simvastatin, ketoconazole, medroxyprogesterone, clotrimazole, amoxicillin + clavulanic acid, azithromycin, benzathine penicillin, cefalexin, clarithromycin, doxycycline, erythromycin, fluconazole, metronidazole, nitrofurantoin, sulfamethoxazole + trimethoprim, allopurinol, baclofen, diclofenac sodium, ibuprofen, valproic acid, amitriptyline, carbamazepine, clonazepam, clomipramine, chlorpromazine, phenytoin, fluoxetine, levodopa + carbidopa, nortriptyline, thioridazine, topiramate, albendazole, ivermectin, mebendazole, ceftriaxone, ciprofloxacin, pyridoxine, and paracetamol. Some of those medicines are hepatotoxic, being important to monitor liver function by measuring the hepatic enzymes alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyltransferase (GGT), and alkaline phosphatase (ALP), as well as bilirubins of the patients who use them. Moreover, in case the patient presents a liver disease, it may be necessary to adjust the dose of the medicine88 Lunardelli MJM, Becker MW, Blatt CR. Lesão hepática induzida por medicamentos: qual o papel do farmacêutico clínico? Rev Bras Farm Hosp Serv Saúde São Paulo. 2016; 7(4): 31-35..

The medicines that cause biological interference in renal function, with the risk of increased levels of urea and creatinine and reduction of creatinine clearance, are: clopidogrel, atenolol, captopril, carvedilol, spironolactone, furosemide, hydrochlorothiazide, losartan, methyldopa, propranolol, acyclovir, azithromycin, cefalexin, clarithromycin, nitrofurantoin, sulfamethoxazole + trimethoprim, allopurinol, diclofenac sodium, ibuprofen, carbamazepine, fluoxetine, levodopa + carbidopa, mebendazole, acyclovir, ceftriaxone, and sulfadiazine. Some of these medications are nephrotoxic99 Lucas GNC, Leitão ACC, Alencar RL, Xavier RMF, Daher EF, Junior GBS. Aspectos fisiopatológicos da nefropatia por anti-inflamatórios não esteroidais. J Bras Nefrol. 2019; 41(1): 124-30., consequently, for prevention of chronic kidney disease it is relevant to monitor renal function by means of the assessment of glomerular filtration rate and albuminuria1010 Porto JR, Gomes KB, Fernandes AP, Domingueti CP. Avaliação da função renal na doença renal crônica. Rev Bras Análises Clínicas. 2017; 49(1): 26-35.. Besides, some of those medications are contraindicated or must have the dose adjusted in patients who already present kidney disease99 Lucas GNC, Leitão ACC, Alencar RL, Xavier RMF, Daher EF, Junior GBS. Aspectos fisiopatológicos da nefropatia por anti-inflamatórios não esteroidais. J Bras Nefrol. 2019; 41(1): 124-30..

Linagliptin, acetylsalicylic acid, clopidogrel, atenolol, carvedilol, spironolactone, furosemide, hydrochlorothiazide, methyldopa, and propranolol have as biological interference the increased levels of uric acid, being important to monitor serum levels of this analyte in patients who use those medications due to the risk of development of gout - a disease characterized by accumulation of crystals of urate in joints, synovial tissue, bones, skin, and kidneys -, regardless of the presence or absence of clinical manifestations1111 Azevedo VF, Lopes MP, Catholino NM, Paiva ES, Araújo VA, Pinheiro GRC. Revisão crítica do tratamento medicamentoso da gota no Brasil. Rev Bras Reumatol. 2017; 57(4): 346-55..

Electrolytes are essential for basic life functioning, such as maintenance of electrical neutrality of cells, generation and conduction of action potentials in nerves and muscles1212 Shrimanker I, Bhattarai S. Eletrólitos. [Updated on: 3 May, 2019]. In: StatPearls [Internet]. Ilha do Tesouro (FL): StatPearls Publishing; 2019. Available at: https://www.ncbi.nlm.nih.gov/books/NBK541123/.. The drugs that alter the levels of electrolytes (sodium, potassium, magnesium, calcium) are aluminum hydroxide + magnesium hydroxide, recombinant human insulin (NPH), regular human insulin, omeprazole, enoxaparin, heparin, atenolol, captopril, carvedilol, enalapril, spironolactone, furosemide, hydrochlorothiazide, losartan, methyldopa, propranolol, prednisolone, azithromycin, benzathine penicillin, sulfamethoxazole + trimethoprim, ibuprofen, carbamazepine, lithium carbonate, fluoxetine, oxcarbazepine, topiramate, salbutamol, and itraconazole. High or reduced levels of electrolytes can cause an imbalance in the body, interrupting the normal body functions, with risk of complications such as death; therefore, it is important to monitor serum levels in patients who are treated with these medications1212 Shrimanker I, Bhattarai S. Eletrólitos. [Updated on: 3 May, 2019]. In: StatPearls [Internet]. Ilha do Tesouro (FL): StatPearls Publishing; 2019. Available at: https://www.ncbi.nlm.nih.gov/books/NBK541123/..

Acetylsalicylic acid, amiodarone, phenytoin, and medroxyprogesterone are able to interfere biologically in the levels of hormones triiodothyronine (T3) and thyroxine (T4), responsible for metabolism regulation, and also in the levels of the thyroid stimulating hormone (TSH), produced and released by the anterior pituitary gland and responsible for regulating the secretion of thyroid hormones1313 Ferreira FC, Costa SHN, Costa IR. Prevalência de disfunções tireoidianas em pacientes atendidos no Laboratório Clínico do Hospital da Polícia Militar do Estado de Goiás no período de 2015 a 2016. 2018; 50(1): 57-64.. Thus, it is of utmost importance to monitor thyroid hormones of patients in use of the mentioned drugs. Besides, dose adjustment can be necessary in patients with hypothyroidism who are treated with levothyroxine1414 Barros ACS, Xavier EM, Reis IS, Carvalho PRB, Oliveira RS, Pacheco FK. Farmacêutico Bioquímico: uma abordagem voltada para o TSH e doenças da tireoide. Rev Saúde e Desenvolvimento Humano. 2018; 6(1): 67-74..

Some drugs can even cause blood count alterations: dabigatran, hydralazine, amoxicillin, amoxicillin + clavulanic acid, benzathine penicillin, diclofenac sodium, ibuprofen, chlorpromazine, clomipramine, levodopa + carbidopa, thioridazine, mebendazole, ceftriaxone, ciprofloxacin, and silver sulfadiazine. They reduce the levels of hemoglobin, causing anemia. Metformin, pyridoxin, pyrimethamine can also cause reduction in the levels of vitamin B12 and/or folic acid, resulting in megaloblastic anemia1515 Sinco HBC, Peñafiel COR, Sánchez AS, Jaloma JC, Murillo CM, Figueiroa EM. Megaloblastic anaemia: folic acid and vitamin B12 metabolism. Rev Med Del Hospital General de México. 2015; 78(3): 135-43.. Captopril, enalapril, hydralazine, silver sulfadiazine, amoxicillin, amoxicillin + clavulanic acid, azithromycin, benzathine penicillin, cefalexin, ibuprofen, valproic acid, alprazolam, carbamazepine, clomipramine, chlorpromazine, phenytoin, haloperidol, levodopa + carbidopa, thioridazine, albendazole, ivermectin, mebendazole, promethazine, ceftriaxone, ciprofloxacin, and pyrimethamine can cause interference in the leukocyte levels. If patients use any of these drugs, it is important to monitor them by means of blood count1616 Ferreira AL, Rocha CP, Vieira LM, Dusse LMSA, Junqueira DRG, Carvalho MG. Alterações hematológicas induzidas por medicamentos convencionais e alternativos. Rev Bras Farmácia. 2013; 94(2): 94-101..

Regarding blood clotting, medications that interfere with the levels of platelets are heparin, hydralazine, silver sulfadiazine, amoxicillin, amoxicillin + clavulanic acid, azithromycin, cefalexin, allopurinol, ibuprofen, valproic acid, carbamazepine, clomipramine, chlorpromazine, phenytoin, levodopa + carbidopa, thioridazine, mebendazole, ceftriaxone, ciprofloxacin, pyrimethamine. As the acetylsalicylic acid, methyldopa, azithromycin, paracetamol, and ceftriaxone can cause alterations in prothrombin time, it is fundamental to monitor patients that use these drugs by means of laboratory assessment of coagulation panel. Besides, in case the patient uses the oral anticoagulant, drug dose adjustment may be necessary1717 Wolf JM, Wolf LM. A review on oral anticoagulant therapeutics in the management of thrombosis. Rev Saúde Biologia. 2017; 12(1): 66-78..

Metformin, omeprazole, captopril, clonidine, spironolactone, hydralazine, methyldopa, nifedipine retard, amoxicillin + clavulanic acid, benzathine penicillin, cefalexin, doxycycline, erythromycin, nitrofurantoin, norfloxacin, sulfamethoxazole + trimethoprim, valproic acid, bupropion, carbamazepine, chlorpromazine, phenytoin, phenobarbital, levodopa + benserazide, levodopa + carbidopa, paracetamol, sertraline, thioridazine, promethazine, ceftriaxone, ciprofloxacin, and pyridoxine are medications that can cause analytical interference, leading to false increase or false reduction of the following markers: antinuclear antibody (ANA), 5-hidroxi-indoleacetic acid, uric acid, amphetamine, tricyclic antidepressants, barbiturates, benzodiazepines, bilirubin, catecholamines, ketone, creatinine, digoxin, phenylketonuria, glucose, human chorionic gonadotropin (hCG), methadone, methotrexate, opiates, pentobarbital, perphenazine, salicylate, and tetrahydrocannabinol (THC). The false positive results can produce erroneous interpretations about patents’ affection by a health problem they do not present or mean therapeutic failure, whereas false negative results can cause the nontreatment of a health problem that can aggravate, creating future complications to patients, physicians and laboratories. Therefore it is essential that health professionals understand alterations that each medicine can cause in tests33 Santos PCJL, Silva AM, Marcatto LR, et al. Interferência de medicamentos utilizados nos exames laboratoriais para monitoramento de dislipidemias e diabetes mellitus. Unisanta Health Science; 2017; 1(1): 18-32..

CONCLUSION

Laboratory tests are essential for clinical diagnosis to be correctly established by the physician and the therapeutic choice to be appropriate. An incorrect test involves erroneous treatment, what can cause complications in patients’ health in the future. Besides, some drugs can promote alterations in laboratory tests due to adverse effects; that is why it is so important to monitor laboratorial the patients who use them.

In this study we observed that most (67.7%) medications of Remume interfere in one or more laboratory tests. Therefore, this survey bears great relevance, because it promotes dissemination of knowledge about the interference medications cause in laboratory tests, so that pharmacists, physicians and other health professionals are attentive and learn how to identify possible interference during analysis, leading to reduction of wronged diagnoses and unsuccessful monitoring.

REFERENCES

  • 1
    Ceará. Secretaria de Saúde. Laboratório Central de Saúde Pública do Estado. Manual de coleta, acondicionamento e transporte de amostras. 5 ed. Fortaleza: SESA; 2019.
  • 2
    Ferreira BC, Santos KL, Rudolph SC, Alcanfor JDX, Cunha LC. Estudo dos medicamentos utilizados pelos pacientes atendidos em laboratório de análises clínicas e suas interferências em testes laboratoriais: uma revisão da literatura. Rev Eletrônica de Farmácia. 2009; 6(1): 33-43.
  • 3
    Santos PCJL, Silva AM, Marcatto LR, et al. Interferência de medicamentos utilizados nos exames laboratoriais para monitoramento de dislipidemias e diabetes mellitus. Unisanta Health Science; 2017; 1(1): 18-32.
  • 4
    Instituto Brasileiro de Geografia e Estatística. Perfil dos municípios brasileiros. 2017. Available at: https://www.divinopolis.mg.leg.br/sobre-divinopolis/geografia [Accessed on: 20 July 2019].
    » https://www.divinopolis.mg.leg.br/sobre-divinopolis/geografia
  • 5
    World Health Organization. Essential medicines and health products. Anatomical Therapeutic Chemical (ATC) classification. Available at: https://www.who.int/medicines/regulation/medicines-safety/toolkit_atc/en/ [Accessed on: 16 Dec 2019].
    » https://www.who.int/medicines/regulation/medicines-safety/toolkit_atc/en/
  • 6
    Sociedade Brasileira de Cardiologia (SBC). V Diretriz Brasileira sobre Dislipidemias e Prevenção da Aterosclerose. Departamento de Aterosclerose da Sociedade Brasileira de Cardiologia. Arquivos Brasileiros de Cardiologia. 2017; 4(2Supl. 1): 1-76.
  • 7
    Sociedade Brasileira de Diabetes (SBD). Diretrizes da Sociedade Brasileira de Diabetes 2017-2018. São Paulo: Clannad; 2017.
  • 8
    Lunardelli MJM, Becker MW, Blatt CR. Lesão hepática induzida por medicamentos: qual o papel do farmacêutico clínico? Rev Bras Farm Hosp Serv Saúde São Paulo. 2016; 7(4): 31-35.
  • 9
    Lucas GNC, Leitão ACC, Alencar RL, Xavier RMF, Daher EF, Junior GBS. Aspectos fisiopatológicos da nefropatia por anti-inflamatórios não esteroidais. J Bras Nefrol. 2019; 41(1): 124-30.
  • 10
    Porto JR, Gomes KB, Fernandes AP, Domingueti CP. Avaliação da função renal na doença renal crônica. Rev Bras Análises Clínicas. 2017; 49(1): 26-35.
  • 11
    Azevedo VF, Lopes MP, Catholino NM, Paiva ES, Araújo VA, Pinheiro GRC. Revisão crítica do tratamento medicamentoso da gota no Brasil. Rev Bras Reumatol. 2017; 57(4): 346-55.
  • 12
    Shrimanker I, Bhattarai S. Eletrólitos. [Updated on: 3 May, 2019]. In: StatPearls [Internet]. Ilha do Tesouro (FL): StatPearls Publishing; 2019. Available at: https://www.ncbi.nlm.nih.gov/books/NBK541123/.
  • 13
    Ferreira FC, Costa SHN, Costa IR. Prevalência de disfunções tireoidianas em pacientes atendidos no Laboratório Clínico do Hospital da Polícia Militar do Estado de Goiás no período de 2015 a 2016. 2018; 50(1): 57-64.
  • 14
    Barros ACS, Xavier EM, Reis IS, Carvalho PRB, Oliveira RS, Pacheco FK. Farmacêutico Bioquímico: uma abordagem voltada para o TSH e doenças da tireoide. Rev Saúde e Desenvolvimento Humano. 2018; 6(1): 67-74.
  • 15
    Sinco HBC, Peñafiel COR, Sánchez AS, Jaloma JC, Murillo CM, Figueiroa EM. Megaloblastic anaemia: folic acid and vitamin B12 metabolism. Rev Med Del Hospital General de México. 2015; 78(3): 135-43.
  • 16
    Ferreira AL, Rocha CP, Vieira LM, Dusse LMSA, Junqueira DRG, Carvalho MG. Alterações hematológicas induzidas por medicamentos convencionais e alternativos. Rev Bras Farmácia. 2013; 94(2): 94-101.
  • 17
    Wolf JM, Wolf LM. A review on oral anticoagulant therapeutics in the management of thrombosis. Rev Saúde Biologia. 2017; 12(1): 66-78.

Publication Dates

  • Publication in this collection
    14 May 2021
  • Date of issue
    2021

History

  • Received
    30 Jan 2020
  • Reviewed
    11 Feb 2020
  • Accepted
    29 Apr 2020
  • Published
    20 Mar 2021
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