Journal of Pharmacy and Pharmacology 10 (2022) 131-138

doi: 10.17265/2328-2150/2022.04.004
D DAVID PUBLISHING

Alterations in the Results of Biochemical Laboratory

Tests Due to the Administration of Antihypertensive
Drugs

Cleiton Fantin, Patrí

cia Dabila Moraes Aparecido, Pedro Kazuya de Arruda Takano, Thairineda Silva Jucáand
Luciana dos Santos Viana
Human Genetics Laboratory, State University of Amazonas, Manaus, Amazonas 69065-001, Brazil

Abstract: Objective: Perform a literary review of the interference in the results of biochemical laboratory tests caused by
antihypertensive drugs. Methods: This is a review of the scientific literature with descriptive research performed according to the
PRISMA model using the databases PUBMED, SCIELO, MEDLINE, LILACS, and searches of Brazilian Ministry of Health and
Federal Pharmacy Council publications, reagent kits and package inserts approved by ANVISA. Literature and papers in Portuguese
and English were selected, prioritizing the years 2010 to 2020. Results: The diuretic class of antihypertensive drugs causes decreases
glucose tolerance, thus resulting in an increase in triglycerides. In long-term use, the drug captopril can increase serum levels of
potassium, creatine kinase and decreases blood sodium. Methyldopa causes an increase in AST levels. Propranolol is associated with
an increase in triglyceride levels and a decrease in HDL and glucose levels. The constant use of losartan results in an increase in
HDL, a decrease in uric acid levels and a slight and transient increase in transaminases. In the Gold Analisa, Bioclin and Labtest
reagent kits, most of the alterations occur due to the increase in levels of serum biomarkers according to the class of the
antihypertensive drug. Conclusions: Biochemical alterations in serum can result in false-positive or false-negative reports, since it
can be observed that most of the dosages caused increases due to the physiological effect of the drugs. The antihypertensive drugs
that showed the highest incidence of interference were captopril, atenolol, losartan and propranolol.

Key words: Antihypertensives, captopril, biochemical markers, losartan, propranolol, diagnosis and laboratory tests.

1. Introduction Non-pharmacological therapy is the first option; it is

low cost and is linked to the modification of the
Cardiovascular diseases occur due to pathological
patient’s lifestyle. Pharmacological therapy is always
changes in the heart and blood vessels, among which
associated with non-pharmacological therapy and,
we can cite arterial hypertension, which corresponds to
depending on the patient’s needs, has a high cost [3].
increased blood pressure, and is asymptomatic in the
Pharmacological treatment aims to reduce morbidity
majority of the population [1, 2]. There are two forms
and mortality and, according to its mechanism of
of arterial hypertension, primary and secondary, and
action, is classified into diuretics, adrenergic
these are determined by risk factors such as heredity,
inhibitors (centrally acting beta-blockers and
age and race. These predisposing factors are usually
alpha-blockers), direct vasodilators, calcium channel
associated with being overweight, smoking, excessive
blockers, angiotensin-converting enzyme inhibitors,
salt intake, sedentary lifestyle, alcoholism and stress
angiotensin II AT1 receptor beta-blockers and direct
[1].
renin inhibitors [4].
The treatment for arterial hypertension is divided
Some of these classes of antihypertensive drugs
into pharmacological and non-pharmacological types.
may interfere with the analytical determinations of
Corresponding author: Cleiton Fantin, PhD, research fields:
laboratory clinical practices. Such impairments are
genetics and cytogenetics. caused due to the ability of the drug to increase,
132 Alterations inthe Results of Biochemical Laboratory Tests Due to the
Administration of Antihypertensive Drugs
decrease laboratory test results, or even lead to false
negative or positive ones [5]. Commonly, the
interferences, as well their nature, are caused by
physiological mechanisms (in vivo); though, most of
the mechanisms of interference have not been fully
clarified [4].
The biochemical laboratory tests that have the
highest interference index as a result of the
antihypertensive drugs are those of uric acid, aspartate
aminotransferase, alanine aminotransferase, calcium,
glucose, urea, bilirubin, high-density lipoprotein
(HDL) and low-density lipoprotein (LDL),
triglycerides, sodium, potassium, creatinine, creatine
kinase and alkaline phosphatase [4, 6-10]. The action
of antihypertensive agents on such laboratory tests
may present variability according to the prescribed
dose, the therapeutic scheme, the administration route,
the individual physiological response, as well as
depending on the serum level at the time of collection
[11].
Considering the relevance of the proposed topic,
this study aims to address the importance of the need
to understand the factors that cause alterations in the
test results, as well as an analysis of the interferences
caused by antihypertensive drugs in laboratory tests
and, through a review of descriptive scientific
literature, emphasize which biochemical tests may
suffer alterations due to the use of these drugs.
2. Materials and Methods
This is a review of the scientific literature using the
PRISMA model, with descriptive research, using the
databases: PUBMED, SCIELO, MEDLINE, LILACS;
and a search of Brazilian Ministry of Health and
Federal Council of Pharmacy publications, reagent
kits and antihypertensive drug package inserts
approved by ANVISA that are related to the theme
“alterations in the results of laboratory biochemical
tests due to the administration of antihypertensive
drugs”.
The following descriptors were used for the
bibliographic research: antihypertensive drugs;
Captopril; biochemical markers; losartan; propranolol;
diagnosis and laboratory tests. The searches were
carried out using the following combinations:
antihypertensive (DeCS) AND biochemical markers
(DeCS) OR captopril (DeCS) OR losartan (DeCS) OR
propranolol (DeCS); biochemical markers (DeCS)
AND captopril (DeCS) OR losartan (DeCS) OR
propranolol (DeCS); antihypertensive (DeCS) and
biochemical markers (DeCS) AND laboratory tests
(DeCS); losartan (DeCS) and biochemical markers
(DeCS) OR laboratory tests (DeCS)1.
Papers in Portuguese and English were selected
from the literature, considering the classes of
antihypertensive drugs that are widely used by
Brazilians and alterations in laboratory biochemical
tests, for the period 2010 to 2020.
Editorials outside the established period and
publications that did not address the topic or that did
not meet the inclusion criteria were excluded.
This research was conducted between February and
June 2020. All the studies that met the inclusion
criteria established at the beginning of the
methodological protocol guided this review.
3. Results and Discussion
A total of 2,166 papers were found from the
combination of the DeCS descriptors. In accordance
with the inclusion and exclusion criteria, 25 papers
were selected for this review using the scheme in
Flowchart 1.
For public health, systemic arterial hypertension
(SAH) is a relevant problem, with the most affected
group being the elderly.Prevalence is calculated
between 52% and 63% in this group. The high
1
DeCS is part of the LILACS Methodology and is an
integrating component of the Virtual Health Library. Available
in: https://decs.bvsalud.org/en/about-decs/.
 Alterations inthe Results of Biochemical Laboratory Tests Due to the 133
Administration of Antihypertensive Drugs

incidence of SAH can lead to cardiovascular risk and the
use of multiple drugs in drug therapy, which increases the
likelihood of interference in laboratory tests [12].
According to the Regional Council of Pharmacy of
the state of São Paulo, laboratory tests must give
accurate results of various normal or pathological
parameters, assign essential indicators to designate
diagnoses, measure the severity and provide
information on the stage of existing pathologies, guide
the choice of the most appropriate drug therapy and
aid in assessing the effectiveness of the treatment used
[13].

Databases: PUBMED, SCIELO, MEDLINE and LILACS.

Languages: English and Portuguese.
Document type: Paper.
Period: 2010-2020.
Search of the BVS database, using “Antihypertensives” and
“Biochemical markers” or “Captopril” or “Losartan” or
“Propranolol” or “Biochemical markers” and “Captopril” or
“Losartan” or “Propranolol” (n = 2,166)

Papers selected after reading of the abstract (n = 81) Papers deleted after reading of
the title (n = 2,085)
Papers selected for full reading (n = 52)

Papers selected for Excluded papers: Due to duplicity (n = 17); Did

revision (n = 25) not fit the eligibility criteria (n = 10)
Flowchart 1 Papers found on antihypertensives and then selected after application of the inclusion and exclusion criteria.
BVS–Virtual Health Library.

According to Guimarães et al [12], approximately
70% of clinical diagnoses are based on the results of
laboratory tests, and these results are able to influence
between 60 and 70% of hospital admissions or
discharges, as well as in the choice of drug therapy.
The following laboratory tests are used in the
routine evaluation of the hypertensive patient: analysis
of urine, plasma uric acid, total cholesterol and
fractions, plasma creatinine, fasting blood glucose,
plasma potassium and triglycerides [14].
Currently, due to the wide use of drugs, regardless
of the route of administration, the interference in the
analytical methods of laboratory biochemical tests can
be described through physical, chemical and/or
metabolic pharmacological mechanisms [15].
The identification of such interferences is of
paramount importance in the laboratory routine, as it
helps in the understanding of the interfering factors in
the clinical diagnosis. These modifications can result
in false positive or false negative results,
pseudo-increases or pseudo-decreases in the reference
values of biochemical markers, thus causing risks to
the patient’s health, and making it necessary to request
new tests, which results in additional costs [7].
The effect of the drug on clinical analyses can occur
via two basic mechanisms, either via biological effects
(in vivo) or via analytical interference (in vitro). When
the constituents of the analytical reagents interact with
the drug at any stage of the analytical process and
promote a physical or chemical reaction that will
result in a false result of the analysis, this is known as
in vitro interference [16].
In vivo interferences are considered alterations
caused by a physiological, toxicological or
pharmacological mechanism that result from the main
action of a drug or its secondary metabolites, which
134 Alterations inthe Results of Biochemical Laboratory Tests Due to the
Administration of Antihypertensive Drugs

are responsible for the modifications of biological Table 1 describes the mechanisms of action of
components. These are also known as adverse antihypertensive drugs according to their
reactions according to the World Health Organization pharmaceutical class.
(WHO), because this occurrence in the biochemical According to the graph shown in Figure 1, the
parameter can be a response that is harmful or antihypertensive drugs most noted for promoting
undesirable and unintentional [7]. interference in laboratory biochemical tests were
According to Silva and Ramos [17], in Brazil, the captopril (57.14%), which is from the angiotensin
classes of antihypertensive drugs that are most sold converting enzyme inhibitor class; propranolol
are adrenergics, calcium channel blockers, angiotensin (57.14%) which is from the pharmaceutical class of
II AT1 receptor blockers, diuretics, direct vasodilators, β-blockers; enalapril (42.85%); and losartan (28.57%)
angiotensin converting enzyme (ACE) inhibitors and which are from the angiotensin I receptor antagonist
direct renin inhibitors. In accordance with Silva [4], class [18].
Table 1 Mechanism of action of the antihypertensive drugs.
Drug class Mechanism of action
Diuretics Action related to natriuretic effects.
Centrally acting, these act by stimulating presynaptic alpha-2-adrenergic receptors in the central
Adrenergic inhibitors
nervous system.
Beta-blockers: These act by reducing cardiac output, renin secretion and catecholamines in nerve
synapses.
Alpha-blockers: These act as a competitive antagonist of postsynaptic α1-receptors. Direct
vasodilators are represented by hydralazine and minoxidil and act by relaxing the arterial smooth
Calcium channel blockers
muscles.
These act primarily by reducing peripheral vascular resistance as a consequence of the decrease
in the amount of calcium inside the smooth muscle cells of the arterioles, which results from the
blocking of calcium channels in the membranes of these cells.
Angiotensin-converting Their main action is the inhibition of the angiotensin I converting enzyme, thus preventing the
enzyme inhibitors transformation of angiotensin I into angiotensin II, and have vasoconstrictive action.
These antagonize the action of angiotensin II by means of the specific blockade of AT1
Angiotensin II AT1 receptor
receptors, and are responsible for the vasoconstrictive, proliferative and stimulating actions of
beta-blockers
aldosterone release, which is typical of angiotensin II.
Aliskiren, the only representative of the class available for clinical use, promotes direct inhibition
Direct renin inhibitor
of renin action with consequent decrease in angiotensin II formation.
Source: Elaborated by the authors based on Silva [4].

60% 57.14% 57.14%

50%
42.85%
40%
28.57%
30%

20%

10%

0%
Propranolol Enalapril Captopril Losartan

Fig. 1 Antihypertensive drugs most cited in the papers reviewed (Source: Paula, L. L. et al. [18]).
 Alterations inthe Results of Biochemical Laboratory Tests Due to the 135
Administration of Antihypertensive Drugs

According to the parameters analyzed in some Since most laboratory biochemical tests are
studies, the diuretic class of antihypertensive agents performed in an automated manner, usually by
acts on the decrease of glucose tolerance, and results spectrophotometry, in vitro interferences occur by
in the increase of triglycerides; though, these effects altering the plasma or serum staining of the samples
are dependent on the dose administered [19]. after chemical reactions, and/or when a drug is
According to Marco et al [20], in the case and recognized as an analyte due to its structural similarity,
control studies performed with biochemical dosages, thus changing the quantitative dosage to be measured
relevant changes in uric acid levels were observed due [24].
to the administration of antihypertensive drugs. In According to the most commonly used reagent kits,
view of this, the class correlated with the alterations in most of the alterations occur as a result of the increase
the patients studied was the class of diuretics. in serum levels of biomarkers. This is presented in the
During prolonged use of angiotensin converting labtest package leaflet, in which it states that thiazide
enzyme inhibitors, such as captopril and enalapril, in diuretic drugs will raise the levels of uric acid,
patients with renal deficiency, these drugs can raise amylase, calcium and triglycerides, and that
creatinine by up to 30% [19, 21]. In blood sodium chlorothiazide increases the serum levels of AST and
results, ACE inhibitors may cause decreased serum ALT, and methyldopa only of AST. As described by
levels and in methyldopa use these levels increase [22]. Labtest and Gold Analisa, due to the use of
First generation drugs such as atenolol and spironolactone and amiloride, hyperkalemia can occur.
propranolol, especially if associated with diuretics, in According to Bioclin, methyldopa, furosemide and
addition to assisting in the onset of diabetes, can propranolol raise serum urea levels and the thiazide
provide a negative impact on the lipid profile, raising diuretics raise amylase levels [25-27].
LDL and lowering HDL [23]. Table 2 summarizes the interference of drugs in
According to Santos et al [5], patients with renal laboratory tests considering the drugs used, the main
insufficiency under regular use of captopril have a laboratory tests, and the alterations caused in the
greater predisposition to elevated serum potassium results and the prediction of these interferences in the
levels (hyperkalemia). package insert.
Table 2 Laboratory tests affected by the use of antihypertensive drugs.
Antihypertensive drugs Tests Alteration type Found in Package insert
Uric acid
Increase in serum level
Total cholesterol
--
HDL cholesterol Decrease in serum level
Atenolol Potassium Increase in serum level
Unusual alterations/Increase in serum Sandoz do Brasil Indústria
AST/ALT
level Farmacêutica Ltda.
Triglycerides Increase in serum level --
Uric acid Decrease in serum level --
Amylase --
Increase in serum level
Bilirubin Geolab S/A
Total cholesterol Decrease in serum level --
HDL cholesterol Increase in serum level --
Captopril Neo Química - Brainfarma
Creatinine Indústria Química e Farmacêutica
S.A.
Alkaline phosphatase Increase in serum level Laboratório Teuto
GGT --
Glucose --
136 Alterations inthe Results of Biochemical Laboratory Tests Due to the
Administration of Antihypertensive Drugs

Table 2 continued
Potassium Laboratório Teuto
Increase in serum level Sandoz do Brasil Indústria
AST
Captopril Farmacêutica Ltda.
Transient elevation of blood urea Laboratório Pharlab Indústria
Urea
levels Farmacêutica S.A.
Uric acid Decrease in serum level --
Amylase Increase in serum level --
Laboratório Sandoz do Brasil Ind.
Creatinine Increased blood creatinine
Enalapril Farm. Ltda.
Potassium Increase in serum level --
Laboratório Sandoz do Brasil Ind.
Urea Increase in serum level
Farm. Ltda.
Uric acid Decrease in serum level --
HDL cholesterol No
Increase in serum level MSD - Merck Sharp & Dohme
Creatinine
Farmacêutica Ltda
Glucose Increased blood glucose level Laboratório Teuto
Losartan
Vitamedic-Indústria Farmacêutica
Potassium
Ltda.
AST/ALT Increase in serum level Laboratório Teuto
Legrand Pharma
Urea
Indústria Farmacêutica Ltda
Bilirubin Increase in serum level --
Creatinine Alteration/interference in dosage EMS S/A
Methyldopa Potassium Increase in serum level --
Alterations/increase using the
AST EMS S/A
colorimetric method
Total cholesterol Pharma Lab S/A
PHARLAB Indústria
Alkaline phosphatase
Farmacêutica S.A.
Metoprolol Glucose Increase in serum level --
PHARLAB Indústria
AST
Farmacêutica S.A.
ALT EMS S/A
Uric acid
Bilirrubina
Increase in serum level
Calcium
--
Total cholesterol
HDL cholesterol Decrease in serum level
Creatine kinase Increase in serum level
Increases or reduces glucose through
Propranolol CIMED indústria de
Glucose a physiological effect on the glycemic
medicamentos Ltda
curve
Potassium
AST/ALT
--
Thyroxine Increase in serum level
Triglycerides
Urea Laboratório Neo Química
Source: Elaborated by the authors based on Ferreira et al [11]; Brito [6]; Moura [7]; Pagana et al [22]; Bezerra and Malta [8]; Souza et al [10]; Silva [4]; Salve
et al [28].

ascertained that the majority of the dosages obtained

4. Conclusions
According to the studies presented, the
corresponding changes such as the increase or
decrease in biochemical serum levels may result in
false-positive or false-negative results, and it can be
altered results with increases due to the physiological
effect of the drugs. The antihypertensive drugs that
presented higher incidence of interference were
captopril, atenolol, losartan and propranolol, and most
of the interference occurred due to a physiological
 Alterations inthe Results of Biochemical Laboratory Tests Due to the
Administration of Antihypertensive Drugs
mechanism (in vivo) or other mechanisms that have
not yet been fully elucidated.
However, laboratory tests are key parts in the
formulation of the diagnosis, so anamnesis is essential
in the pre-analytical phase, especially with the drugs
used, since an incorrect result will cause a series of
complications, such as increasing the amount of
consultations, requesting of new tests, personal strain
and greater costs.
Through these results, there is still a need to carry
out new experimental scientific studies in this area,
with a view to improving information on interference
by drugs on laboratory tests, in light of technological
advances. It is important to disseminate knowledge
and update the knowledge of health professionals, as
well as their training so that it is possible to achieve a
decrease in the percentage of analysis errors.
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