The Dosage Issue #1 (English)

EDITION #1

SEPTEMBER 2021

THE DOSAGE

A PARO PHARMACY EDUCATION MAGAZINE

Preface The constant updates in information regarding new health concepts, including new research and evolution of new therapies need a summary of the main research topics in order to guarantee a cohesive interpretation. This allows the dissemination of accessible information from reliable sources and has a special emphasis on academics in health courses.

This need becomes more and more necessary given the delicate moment of the pandemic that the world faces, where the race for the vaccine and for constantly updated treatment guidelines often leads to a loss of important information.

Therefore, due to the massification of content it is necessary to adapt the reality of publications of new studies to a routine of practice of exchange of information.

This context exists in pharmaceutical practice, where innovation goes hand in hand with training, updated with the perception of the performance of this professional and its value for breaking its own paradigms, becoming responsible for maintaining knowledge and ensuring the promoting the rational use of medicines, which is a practice that can be achieved by sharing recurring and necessary information.

Index 05

07

Snakes can Save our lives Marck Leiva Méndez

The effects of COVID in pregnancy and the recommended care Vanessa Anton Muñoz & María Belén Salguero

Chemistry of ACE2 receptors (Angiotensin converting enzymes) and relationship to SARS-CoV-2

09

Rebeca Mamani Sosa, Hanxi Xu

COVID Vaccine Distribution in Latin America

11

Priscila Malavasi Conejo, Sonia Elena Avendaño Pinto, Aron Francisco Cortez Quispe

Rotary Evaporator

17

Melissa Núñez Mora

Index

Skills in a Young Pharmacist

19

Ruth Elizabeth Meza y Fernanda Saito Matsuhira

Challenges to the use of Medications in Space

21

Libni Melissa Pérez & Rubí Calderón

Pharmacogenetics in Cardiovascular Diseases: Important Focus Today

23

Luis Andrés Núñez Alpízar

SNAKES CAN SAVE OUR LIVES Marck Leiva Méndez 1,2 1. Facultad de Farmacia, Universidad de Costa Rica, Costa Rica, marck.leiva@ucr.ac.cr.

2. Escuela de Ciencias Naturales, Universidad Nacional, Costa Rica

The search for new therapeutic options with

Casewell et al. mention that some PLA2 isoforms

greater efficacy and fewer adverse effects has led

have shown a high ability to stimulate insulin

to the exploration of new areas of research. The

release in in vitro models of BRIN-BD11 cells,

diversity of proteins and other bio-composites

making it a possible avenue for the treatment of

present in the venom of different species of snakes

type 2 diabetes mellitus [4]. Phospholipase A2

are of great interest, because they mostly have

BnSP-6 obtained from

biological effects [1].

the ability to induce genotoxicity and cytotoxicity in cancer

breast

Bothrops pauloensis

cells,

in

addition,

has these

Due to the vast composition of biomolecules in

phospholipases showed greater affinity for these

snake venoms, such as proteins and peptides of

cancer cells compared to healthy cells, causing

which many have enzymatic activity, different

damage to the DNA of cancer cells, so the study

molecules

and characterization of these molecules could help

are

studied

metalloproteinases,

as

phospholipases,

deintegrins,

for

their

promising applications in medicine. Deintegrins

the development of biotechnological drugs for the treatment of breast cancer [5].

have been shown to possess anticoagulant activity by inhibiting platelet aggregation, as well as their

The antibacterial activity of some proteins present

ability

in snake venom is of great medical importance, just

to

block

metastasis

or

angiogenesis

processes in cancer [2].

as several studies have shown the ability to fight large-positive bacteria [6], including against some

Studies have demonstrated the cytotoxic activity

antibiotic-resistant

of different enzymes Phospholipases A2 (PLA2) in

Pseudomonas aeruginosa

cancer cells using in vitro

interest

and invivomodels, as

today,

microorganisms

given

such

as

[7]. This is of great

the

increasing

rate

of

well as the inhibition of cell proliferation and

antimicrobial resistance worldwide, both in human

tumor growth [1]. In addition, in vitro studies show

medicine

that Phospholipases also have antiangiogenic

importance lies in the fact that these biomolecules

properties

with antibacterial activity could be used in the

by

inhibiting

the

proliferation

of

and

endothelial cells, this effect is of great importance

treatment

for

multiple drugs.

future

treatments

in

different

diseases,

of

veterinary

microbial

medicine

infections

[8].

resistant

The

to

including cancer [3].

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References 1. Kalita, B., Saviola, A. J., & Mukherjee, A. K. From venom to drugs: a review and critical analysis of Indian snake venom toxins envisaged as anticancer drug prototypes. Drug Discovery Today, 2021 00(00), 1–13. https://doi.org/10.1016/j.drudis.2020.12.021 2. Schönthal, A. H., Swenson, S. D., Chen, T. C., & Markland, F. S. Preclinical studies of a novel snake venom-derived recombinant disintegrin with antitumor activity: A review. Biochemical Pharmacology,

2020,

181(May),

114149.

https://doi.org/10.1016/j.bcp.2020.114149 3. Polloni, L., Azevedo, F, Teixeira, S., Moura, E., Costa, T., Gimenes, S., Correia, L., Freitas, V., Yoneyama, K., Rodrigues, R. S., Lopes, D., & Rodrigues, V. de M. Antiangiogenic effects of phospholipase A2 Lys49 BnSP-7 from Bothrops pauloensis snake venom on endothelial cells: An in vitro and ex vivo approach. Toxicology in Vitro, 2021, 72(January). https://doi.org/10.1016/j.tiv.2021.105099 4. Casewell, N., Conlon, J., Attoub, S., & Musale, V. Toxicon : X Isolation and characterization of cytotoxic and insulin-releasing components from the venom of the black-necked spitting cobra Naja

nigricollis

(Elapidae)

Toxicon

X

2020

6

100030,

https://doi.org/10.1016/j.toxcx.2020.100030 5. Silva, M., Lopes, D., Teixeira, S., Gimenes, S., Azevedo, F., Polloni,

Figure 1. Stages of the research process in which drugs derived from snake venoms are found. [9]

L., Borges, B. C., da Silva, M., Barbosa, M., Oliveira Júnior, R., Elias, M. C., da Silva, C., Yoneyama, K.,, Rodrigues, V. de M., & Rodrigues, R. Genotoxic effects of BnSP-6, a Lys-49 phospholipase A 2 (PLA 2) homologue from Bothrops pauloensis snake venom, on MDA-

It

is

important

to

continue

researching

and

characterizing the biomolecules present in snake venom, because only about 0.01% of the known

MB-231 breast cancer cells. International Journal of Biological Macromolecules,

2018,

118,

311

–

319.

https://doi.org/10.1016/j.ijbiomac.2018.06.082

bioactive components have been studied their

6. Mehrdar, M. Two proteins from snake venom have potent

mechanisms of action, and many compounds may

antibacterial effects against bacillus anthracis and streptococcus

have pharmacological activity, and their ideal

pneumoniae. Iranian Journal of Toxicology, 2020 14(3), 139–144.

characteristics such as high selectivity by cellular

https://doi.org/10.32598/ijt.14.3.634.1

receptors are of great interest to researchers,

7. Saber, S., Mohamed, A., El-fiky, A., & Eldaly, H. In Vitro

because they can be used both for the treatment

Evaluation of Antibacterial Potential of Cerastes Vipera Venom

and diagnosis of diseases [10].

against Gram-Positive and Gram-Negative Bacterial Strains. 2019

In conclusion, the study and characterization of the

8. Palma, E., Tilocca, B., & Roncada, P. (2020). Antimicrobial

biomolecules present in snake venoms is of great

resistance in veterinary medicine: An overview. International

importance

Journal

because

the

77(October), 5804–5816.

molecules

currently

known have properties of great interest and utility

of

Molecular

Sciences,

21(6),

1–22.

https://doi.org/10.3390/ijms21061914

in medicine, and there are still many molecules to

9. Pérez-Peinado, C., Defaus, S., & Andreu, D. (2020). Hitchhiking

be analyzed, finally it is necessary to carry out

with nature: Snake venom peptides to fight cancer and

research in this field because they could have

superbugs. Toxins, 12(4). https://doi.org/10.3390/toxins12040255

multiple applications in this and other areas.

10. El-Aziz, T., Soares, A., & Stockand, J. Snake venoms in drug discovery: Valuable therapeutic tools for life saving. Toxins, 2019 11(10), 1–26. https://doi.org/10.3390/toxins11100564

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THE EFFECTS OF COVID IN PREGNANCY AND THE RECOMMENDED CARE María Belén Salguero1, Vanessa Anton Muñoz2 1 . Facultad de Ciencias Químicas y Farmacia, Universidad de San Carlos de Guatemala, Guatemala, mariabelensal@gmail.com 2 . Facultad de Farmacia y Bioquímica, Universidad Nacional Mayor de San Marcos, Lima-Perú, vanessa.anton@unmsm.edu.pe

INTRODUCTION:

Faced with the big question, can a pregnant woman with COVID-19 transmit the disease to her

Coronavirus disease 2019 (COVID-19) is caused by

baby? Recent studies have shown a small increase

severe acute respiratory syndrome coronavirus 2

in the risk to the mother of SARS-CoV-2 infection.

(SARS-CoV-2) and was declared a pandemic in

Transplacental transmission of SARS-CoV-2 from

March 2020 by the World Health Organization

mother to fetus may occur, but the immediate and

(WHO)[1]. Since then, several questions have arisen

long-term effects on the newborn remain unclear

about

unresolved.

[4]. They also mention that the risk of neonatal

However, what has become clear is that this virus

transmission is low and that neonatal disease most

poses a particular threat to

commonly varies from asymptomatic to mildly

the

disease

that

remain

vulnerable people,

that is, those who are most at risk of contagion

symptomatic [5].

and death, for example: the elderly, people with pre-existing

conditions,

as

well

as

pregnant

For now, the evidence for this new infection is

women, especially in their third trimester of

contradictory and the long-term sequelae are

gestation

[2]. For now, we'll focus on the latter

uncertain

and

group, so if you're pregnant in times of pandemic,

Therefore,

physicians

relax! we have the latest updates on the subject.

judgment

hypothetical

when

should

assessing

at

this

use the

time

their

[6].

clinical

need

for

hospitalization and treatment in their pregnant According to the WHO, pregnant women with

patients, as many COVID-19 symptoms mimic those

suspected or confirmed COVID-19 who have been

associated

treated in hospitals are usually less likely to

during pregnancy [7].

with

normal

physiological

changes

experience fever or muscle aches, but if they contract a severe form of the disease they are

Recommendations for care during pregnancy

more likely to need intensive care than nonpregnant women with COVID-19. Pregnant women

Measures to prevent COVID-19 during pregnancy

with COVID-19 who have pre-existing conditions,

are regularly the same as those used for the general

such as diabetes or chronic hypertension, or older

population. These include wearing a proper mask,

or overweight people, are more likely to suffer

washing

serious health complications due to COVID-19 [3].

importantly, avoiding crowded areas and parties,

your

hands

frequently,

and

most

such as baby showers.

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Among the most common recommendations during pregnancy are some such as: maintain a safety distance of 1 to 2 meters, avoid crowded areas, public transport and sick people.

[2] Elsaddig M, Khalil A. Effects of the COVID pandemic on

pregnancy outcomes. Best Pract Res Clin Obstet Gynaecol.

2021;73:125–36.

Disponible

en:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969862/

You must attend the health centers only before already scheduled and essential visits, and with only one companion, at most. But, the consultation should be

[3] Gracias a nuevas investigaciones se conocen mejor los

efectos de la COVID 19 ‎en las embarazadas y sus bebés [Internet]. Who.int. [citado el 25 de julio de 2021]. Disponible en: https://www.who.int/es/news/item/01-09-2020-new-research-

maintained between week 11-14 for screening in the

helps-to-increase-understanding-of-the-impact-of-covid-19-for-

first trimester, week 20 for morphological ultrasound

pregnant-women-and-their-babies

and the third trimester for fetal growth control.

Otherwise, telematic control is ideal. Postpartum, for post-caesarean and postpartum wounds, telematic image control is also recommended (Sankaran et al., 2021).

Also, the question about the safety of vaccines

[4] Parums DV. Editorial: Maternal SARS-CoV-2 infection and

pregnancy outcomes from current global study data. Med Sci Monit. 2021;27:e933831.

[5] Barrero-Castillero A, Beam KS, Bernardini LB, Ramos EGC,

Davenport PE, Duncan AR, et al. COVID-19: neonatal-perinatal perspectives. J Perinatol. 2021;41(5):940–51.

designed to prevent infection and decrease symptoms and their use during pregnancy and lactation exists in some places.

[6] Cavalcante MB, Cavalcante CT de MB, Sarno M, Barini R,

Kwak-Kim J. Maternal immune responses and obstetrical outcomes of pregnant women with COVID-19 and possible health

In December 2020, a blog said it was concerned that antibodies from the vaccine could affect the placenta, as well as other rumors that it causes infertility. It should be noted that it is not the first vaccine of which such comments are made. However, during clinical

risks

of

offspring.

J

Reprod

Immunol.

2021;143(103250):103250.

[7] Hapshy V, Aziz D, Kahar P, Khanna D, Johnson KE, Parmar MS.

COVID-19

and

pregnancy:

Risk,

symptoms,

diagnosis,

and

treatment. SN Compr Clin Med. 2021;3(7):1–7.

trials, a part of the sample became pregnant, thus

[9] S

discarding the hypothesis that the application of the

[9] Male, V. (2021). Are COVID-19 vaccines safe in pregnancy?.

vaccine prevents pregnancy [9].

https://doi.org/10.1038/s41577-021-00525-y [10] Sankaran, D., Nakra, N., Cheema, R., Blumberg, D., &

On the other hand, it has been shown that the vaccine

Lakshminrusimha, S. (2021). Perinatal SARS-CoV-2 Infection and

does not cause increased risk during pregnancy and it

Neonatal COVID-19: A 2021 Update. NeoReviews, 22(5), e284-

remains a personal decision whether or not to apply it during

pregnancy

and

lactation,

after

e295. https://doi.org/10.1542/neo.22-5-e1001

discussing

individual risks, as recommended by the American

Rich, M. (2020). Consejos para el embarazo durante la

College of Obstetricians and Gynecologists and the

pandemia de la enfermedad por coronavirus (COVID-19).

Society of Maternal-Fetal Medicine [10].

https://www.unicef.org/es/coronavirus/consejos-para-embarazo-

References

Wastnedge, E. A. N., Reynolds, R. M., van Boeckel, S. R., Stock, S. J.,

durante-pandemia-coronavirus-covid19.

Denison, F. C., Maybin, J. A., & Critchley, H. O. D. (2021). Pregnancy

[1] González-de la Torre H, Rodríguez-Rodríguez R, Martín-Martínez

A.

Recomendaciones

y

manejo

and

COVID-19.

Physiological

Reviews,

101(1),

303–318.

https://doi.org/10.1152/physrev.00024.2020

práctico de la gestante con COVID-19: scoping review.

Enferm Clín (Engl Ed). 2021;31:100–6. Disponible en: https://doi.org/10.1016/j.enfcli.2020.05.009

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CHEMISTRY OF ACE2 RECEPTORS (ANGIOTENSIN CONVERTING ENZYMES) AND RELATIONSHIP TO SARS-COV-2 Rebeca Mamani Sosa1, Hanxi Xu2.

1 . Facultad ciencias de la salud, Escuela de Farmacia y Bioquímica, Universidad Nacional Jorge Basadre Grohmann, Tacna-Perú. rmamanis@unjbg.edu.pe 2 . Facultad de Ciencias Farmacéuticas, Universidad de São Paulo, Sao Paulo-Brasil. nancy@usp.br

The current 2019 coronavirus disease (COVID-19) outbreak is a global emergency due to its rapid spread and high mortality rate that have caused severe disruption.1 The pollution outbreak quickly spread around the world and left the health networks of several countries on the verge of collapse.2 The SARS-CoV-2 virus, like other coronaviruses, is introduced into lung cells by attaching to the angiotensin-converting enzyme II (ACE-2), which is found in different tissues such as the myocardium, kidney, respiratory tract and vascular level3. Unlike the classic ACE, ACE-2 degrades angiotensin II (Ang II), It seems that the main regulation of ACE2 on angiotensin II would be direct degradation, since it has been estimated that this effect is 400

Figure 1. Structure of the SARS-CoV-2 viral particles.The viral protein S (spike protein) fits into the ACE-2 like a key in a lock.

times greater than the one it has on angiotensin For SARS-CoV-2 viral entry, infection begins with a

I2.

ligand-receptor interaction, in which glycoprotein S Different structural components form the viral

binds to the host's angiotensin-converting enzyme

particle (Figure 1), among which are: a single-

(ACE2) receptor 2. The S1 subunit contains a

stranded RNA molecule (+), the nucleocapsid (N),

receptor binding domain (receptor binding domain

the envelope (E), membrane proteins (M), peak

or RBD) that binds to ACE2 (Figure 2) and is

glycoproteins (S) and the hemagglutinin-esterase

responsible for binding the virus to the host cell;

(HE) dimer.4

while the S2 subunit performs the fusion of the viral particle with the cell membrane. Protein and

ACE-2 is part of a biochemical pathway involved in

transcription expression (mRNA) analyses related to

the regulation of processes such as inflammation

the ACE2 receptor showed that intestinal, testicular,

or blood pressure and its usual function is to

and thyroid cells also express ACE2 during infection

modulate

caused by SARS-CoV-2, in contrast to the absence

the

activity

of

counteract its harmful effects.

angiotensin

2

to

of expression in blood cells.4

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To ACE-2 is formed by 2 domains: the catalytic

In conclusion, ACE-2 (angiotensin-converting enzyme

aminoterminal

its

2) is the receptor that allows coronavirus to enter

plasma

cells. ACE-2 in its full form is a membrane-bound

complete

and

form

it

the is

carboxyterminal,

anchored

in

the

In

membrane, while its shortened (or soluble) form circulates at low levels in the blood. 7 On the other hand, ACE-2 by degrading angiotensin II and

generating

angiotensin

1-7,

exerts

negative

regulation through the actions of the receptor that is coupled to G proteins and has actions contrary to angiotensin II. 7Preliminary studies in cell culture indicate that inhibitors of these pathways inhibit virus replication.6

enzyme, while its shorter (soluble) form circulates in the blood at very low levels.

References: 1. Yang, L., Liu, S., Liu, J. et al. COVID-19: immunopathogenesis and Immunotherapeutics. Sig Transduct Target Ther 5, 128 (2020). https://doi.org/10.1038/s41392-020-00243-2.

2. Pereira, André, et al. “PRINCIPAIS ASPECTOS DO NOVO CORONAVÍRUS

SARS-CoV-2:

UMA

AMPLA

REVISÃO.”

Arquivos Do Mudi, vol. 25, no. 1, 16 Apr. 2021, pp. 73–90,

periodicos.uem.br/ojs/index.php/ArqMudi/article/view/55455, 10.4025/arqmudi.v25i1.55455.

3. Patel A.B., Verma A. COVID-19 and angiotensin-converting

Given that ACE-2 is the SARS-CoV-2 receptor and that

enzyme inhibitors and angiotensin receptor blockers: What is the evidence? JAMA. 2020 doi: 10.1001/jama.2020.4812.

its binding allows the virus to enter the target cell, it is

4. Donoghue M., Hsieh F., Baronas E., Godbout K., Gosselin M.,

very important to know how ACE-2 levels can be

Stagliano N. A novel angiotensin-converting enzyme-related

modulated. ACE-2 levels can be modulated by: 1) ACE-

carboxypeptidase

2 polymorphism and by inhibition of the classical renin-angiotensin preclinical inhibitors

system

models, have

the

been

pathway; drugs

and

ARA-II

observed

to

2)

and

increase

in ACE the

(ACE-2)

converts

angiotensin

I

to

angiotensin 1-9. Circ Res. 2000;87:E1–E9 5. Ziegler C GK, et al. SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues. Cell.

2020. Doi: https://doi.org/10.1016/j.cell.2020.04.035 6. Tolosa, A. (18 de Mayo de 2020). Coronavirus SARS-CoV-2:

expression and/or activity of ACE-2. 6

estructura, mecanismo de infección y células afectadas.

Genotipia,

pág.

1.

https://genotipia.com/genetica_medica_news/coronavirusestructura-infeccion-celulas/ 7. Díaz-Barreiro LA, Cossio-Aranda J, Verdejo-Paris J, et al.

COVID-19 y el sistema renina, angiotensina, aldosterona. Una relación compleja. Cardiovasc Metab Sci . 2020;31(Suppl: 3):182-189.

doi:10.35366/93945.

https://www.medigraphic.com/cgi-bin/new/resumen.cgi?

IDARTICULO=93945&id2= 8. Ramírez-Sagredo, Andrea, Ramírez-Reyes, Andrés, Ocaranza, María Paz, Chiong, Mario, Riquelme, Jaime A, Jalil, Jorge E., & Lavandero, Sergio. (2020). Antihipertensivos en pacientes con

Figure 2. Molecular interaction between glycoprotein S and the ACE-2 receptor. (A) The S1 and S2 subunits of the S glycoproteins are shown, which form the peaks of SARSCoV-2: S1 in magenta and S2 in red. (B) The binding of glycoprotein S, portion S1, to the ACE-2 receptor in host cells is demonstrated. The ACE-2 receptor is indicated in blue and is part of a complex with the amino acid transporter B0AT1 (in green). Source: adapted from PDB (protein data bank): http: //pdb101.rcsb.org/motm/246.

COVID-19. Revista chilena de cardiología, 39(1), 66-74. Epub 01

de

abril

de

2020.

https://dx.doi.org/10.4067/S0718-

85602020000100066 9. Crackower, M. A., Sarao, R., Oudit, G. Y., Yagil, C., Kozieradzki, I., Scanga, S. E., Oliveira-dos-Santos, A. J., da Costa, J., Zhang, L., Pei, Y., Scholey, J., Ferrario, C. M., Manoukian, A. S., Chappell, M. C., Backx, P. H., Yagil, Y., & Penninger, J. M. (2002). Angiotensin-converting enzyme 2 is an essential regulator of heart function. Nature, 417(6891), 822–828. https://doi.org/10.1038/nature00786

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COVID VACCINE DISTRIBUTION IN LATIN AMERICA Priscila Malavasi Conejo1, Sonia Elena Avendaño Pinto2 , Aron Francisco Cortez Quispe3 1 . Facultad de Farmacia y Bioquímica, Universidad de Costa Rica, San José-Costa Rica, primalavassi@gmail.com 2 . Escuela Profesional de Farmacia y Bioquímica, Universidad Nacional Jorge Basadre Grohmann, Tacna-Perú. savendanop@unjbg.edu.pe 3 . Escuela Profesional de Farmacia y Bioquímica, Universidad Nacional San Luis Gonzaga de Ica, Ica-Perú. aroncortezquispe@gmail.com

Good Distribution Practices:

Good distribution practices (BPD) refer to the

For the proper distribution of vaccines, the

quality assurance part that ensures that a

relevant

authorities

should

pharmaceutical product is maintained through

distribution

proper control of the numerous activities that

regulatory body should be in a position to grant

take place in the distribution process (Pan

import permits quickly. As far as possible,

American Health Organization, 2008).

immediate

practices

customs

ensure

and

the

clearance

good

national

should

be

facilitated. On the other hand, all entities Different

distribution

pharmaceuticals

are

models

used

in

for

different

relevant to controls should coordinate their activities

with

the

improving

example in the public and private sectors.

vaccines. Caution should be exercised with

BPDs should apply to all individuals and

administrative

companies involved in the distribution of

customs

pharmaceuticals, from manufacturing facilities

potential conflicts in advance (World Trade

to the point of supply to patients in healthcare

Organization, 2020).

example,

private

processes

clearance

and

and

accelerating

for

import

of

countries or within the same country, for

facilities,

the

aim

clearance

that

processes

may and

of

delay resolve

pharmacies,

hospitals and clinics. On the other hand,

On the other hand, an important aspect to

governments,

assess is the shortage of specialized cold chain

international

policy-making donor

bodies,

organizations

and

agencies, certification bodies, as well as all parties that include health workers interested in any aspect of the trade and distribution of pharmaceutical

products

must

also

implement it.

prevent the distribution of falsified and belowmedicines.

storage containers. This situation could be made worse by slow or ineffective border clearance procedures. The obligation to deposit guarantees or financial bonds for cold chain equipment could delay the re-export of these

These guidelines can be used as a tool to standard

equipment, in particular reusable refrigerated

It

should

be

noted,

however, that these are general guidelines that

items and their timely reuse in the transport of additional

vaccines,

thewise

slowing

down

distribution on a global scale (World Trade Organization, 2020).

can be varied to adapt to the situations and conditions prevailing in different countries (Pan American Health Organization, 2008).

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The distribution of vaccines in each country varies

Countries:

according to a series of variables, among which is

The

the dispatch at the border. Where countries have

requested, complications with this, comply with

taken steps where customs and other agencies

BPD, internal distribution of the country, for whom

involved at the border, to speed up clearance

it is directed.

distribution,

to

which

industry

it

was

procedures. Among these is that establishments give priority in customs clearance to goods related

Costa Rica:

to COVID-19, simplification of forms, acceptance of for

In Costa Rica, vaccination is the main strategy

others.

envisioned by international and national public

Depending on the country, it may be necessary to

health authorities, in order to reduce the number

take

proper

of cases of COVID-19, and contain the current

distribution, in order to make access to vaccines as

emergency currently caused by COVID-19, thus

easy as possible (World Trade Organization, 2020).

reducing care and hospitalizations, since it would

the

electronic

processing

presentation

prior

additional

to

of

arrival,

measures

to

documents among ensure

complement Statistics:

the

other

non-pharmacological

measures that are already being used to prevent the transmission of the disease. and to return little

Argentina, Chile, Costa Rica and Mexico were the

by little, in the medium-term future, to the

first countries to start vaccination, in the last week

normality of all sectors of the country. Costa Rica

of December 2020, in Latin America. Most countries

purchased three million doses of the Pfizer-

began vaccination over the course of 2021.

BioNtech vaccine and one million doses of the

Chile

currently

leads

the

number

of

people

vaccinated with 43.91% of the population with the

AstraZeneca vaccine (Ministry of Public Health Costa Rica, 2021; Ugarte, 2021b, 2021a).

two doses and 58.26% with one dose. Chile is followed by Uruguay with 30.73% of the population

Vaccination in Costa Rica is segregated into five

vaccinated with two doses and 55.75% with one

groups. The first group are first responders, workers

dose (Horwitz & Zissis, 2021).

in long-stay power stations and elderly people who inhabit them; in the second group there are people over 58 years of age and in the third group there are people between 12 and 58 years old with some risk factor. In the fourth group are officials of the Ministry of Public Education, officials of shelters of the National Children's Trust (PANI), prisoners, workers of the Judiciary and 9-1-1. As the fifth and final group are health science students and related technicians in clinical fields of CCSS and the population

without

any

risk

described

above

(Brenes, 2021; Ministry of Public Health Costa Rica, 2021; Ugarte, 2021).

Figura 1. Datos de vacunación América Latina.

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12

Peru:

In Peru, the vaccination system is one of its priorities due to the great mortality that has arisen from Peruvians as foreigners who reside in the nation, so the Directorate General of Medicines, Supplies and Drugs (DIGEMID) of the Ministry of Health replied that so far, the only vaccines against COVID-19 that have conditional sanitary registration or exceptional authorization are those of the laboratories BioNTech

Pfizer, has

Sinopharm

joined;

and

and its

currently accredited

representatives, reaching a supply of 7,065,700 doses.

The vaccines that have arrived in Peru and that will continue to arrive in the coming months will be: AstraZeneca: 14 million doses already agreed that will arrive from September 2021.Covax Facility: through this mechanism 13.2 million doses will arrive. 400 thousand of AstraZeneca in July 2021, subsequently

Peru

continues

to

carry

out

negotiations to be able to acquire more vaccines for its population, developing since April 16 begins the

new

vaccination

approach, professionals

strategy

with

territorial

prioritizing vaccination to frontline (health

personnel),

against

the

coronavirus, within this group is considered all citizens over 18 years old and foreigners living in the country, being one of the first to be vaccinated the population at risk over 50 years, pregnant women, children with down syndrome and autistic people so far carried out in vaccination centers located at strategic points near their places of residence.

The strategy seeks to provide a more efficient response with the coverage of vaccination against COVID-19 in the country, adding important allies such as Es Salud, the Health Of the Armed Forces and Police, and the integrated health networks that depend directly on the Ministry of Health(MINSA). being this one that has confirmed that vaccination centers must be open to all citizens, according to their age range, without distinction of any kind, and according to their places of residence for the good of the Peruvian population.

Brazil:

In Brazil, the vaccine is considered a synonym of hope in the face of the Covid-19 pandemic, so the Ministry of Health reaffirms its commitment to the lives of all Brazilians for a vaccinated homeland and defeat the coronavirus.

Brazil being one of the countries with the highest acquisition

of

vaccines

AstraZeneca-Oxford,

Covishield, J & J, Pfizer-BioNTech, Sinovac, Sputnik V with a current amount of 109,266,944 doses distributed throughout the country, being applied until June 10 an amount of 74,812,794 vaccines, between the first dose 51,465,240 vaccines and in second dose 23,347,554 vaccines, with surveillance of the Ministry of Health safeguarding the life of the population in the application for priority groups making use of the vaccination portfolio called "Coecte SUS" (Unified Health System) and digital services.

A

vaccination

card

has

been

implemented

available through a QR code, which works as identification before public and private health services,

that certifies vaccinated persons who

have

official

an

record

and

functions

as

a

vaccination passport with data such as information on

the

type

of

vaccine

applied,

batch

of

manufacture and date on which the dose or doses were administered. In case of second dose, the application also shows the exact day when you should receive it and currently it has been possible to vaccinate more than 47% of the Brazilian population currently.

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13

Until May 2021, it was aimed at vaccinating people 60 years or older and remaining health personnel, where 69% of older adults were vaccinated, equivalent to 10,068,013.

The

third

stage

of

the

vaccination

process,

continued in May 2021 until June 2021, was aimed at vaccinating people aged 50 to 59 years and pregnant women aged 18 years and over from the third month of pregnancy, where 58% of the total México:

population of adults between 50 and 59 were vaccinated, equivalent to 7,424,714.

In Mexico, the COVID-19 pandemic, in terms of lethality, may show that socioeconomic inequalities

The

of the population can affect the development of

continued in June 2021 until July 2021, will be

worst scenarios, so the government has taken

aimed at vaccinating people aged 40 to 49 years,

concrete measures to improve the quality of life

where currently it has been possible to vaccinate

and equip itself with essential elements to face the

6% of the total population of adults between 40

current health emergency, such as vaccination to

and 49 years, equivalent to 953,666.

fourth

stage

of

the

vaccination

process,

mitigate morbidity and mortality.

The fifth stage of the Vaccination process, which The strategy that has been implemented for

will begin in July 2021 until March 2022, will be

vaccination is through a web page implemented by

aimed at vaccinating the rest of the population.

the Ministry of Health of the Government of Mexico, which is: http://mivacuna.salud.gob.mx. In this the

Guatemala:

personal data of the patient are entered, following the

proposed

stages,

for

their

respective

vaccination in the corresponding place.

In Guatemala, the vaccine, provided by the state, is considered the hope and response they asked for in the face of the scourge of Covid 19. The

The following vaccines are being used: BioNTech,

government

Pfizer-CanSino- Corona Vac- Oxford Astrazeneca-

vaccination

Sputnik V.

implementation of measures, with the priority objective

The first stage of the Vaccination process, which

of

is

facing

systems reducing

this

pandemic

and the

the mortality

through constant of

the

population.

began in December 2020 until February 2021, was aimed at vaccinating frontline health personnel, covid-19 control, where 92% of the total population of health personnel were vaccinated, equivalent to 1,101,972.

The second stage of the Vaccination process continued in February 2021.

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14

So Guatemala became the third country in the region of the Americas (after Colombia and Peru) to receive the vaccine, through the COVAX Mechanism. The first shipment was 81,600 doses of the AstraZeneca vaccine approved for use in emergencies by the World Health Organization (WHO), which arrived on March 11, 2021. These doses are the first shipment of the purchase that the Ministry of Public Health and Social Assistance (MSPAS) of a total of 6.6 million doses that are expected to receive this year to immunize 20% of the Population, Using the resources approved in Decree 1-2021 of the Congress of the Republic of Guatemala, Law for the Financing and Acquisition of Vaccines against the Coronavirus COVID - 19. (March 10, Ministry of Public Health and Social Assistance).

Guatemala will be carried out through a system of appointments,

appropriate

to

the

conditions of the target groups, through a web page implemented by the Ministry of Public Health and Social

Assistance:

https://registrovacunacovid.mspas.gob.gt/mspas/login.

In this the personal data of the patient are entered, following the phases proposed by the Government, for their respective vaccination in the corresponding premises.

the health system, and for the effectiveness in fulfilling this, it has been divided into subphases. First, Health facility workers who care for COVID-19 patients on the front line. Second, Workers from health facilities not included in the above subphase and community support, including midwives, volunteer promoters and therapists.

Third,

Students

of

Health

Sciences and related who carry out internships in health establishments. Fourth, firefighters, paramedics, funeral home workers and staff working in nursing homes. Fifth, Older adults interned in nursing homes.

Sex,

burden

of

severe

disease,

and

for

the

effectiveness in complying with this, it has been divided into subphases. First, Adults Over 70 and older. Second, Adult from 60 to 69 years old. Third, Adults from 50 to 59 years old. Fourth, Adults 18 or older with the following conditions: High blood pressure requiring medication, diabetes mellitus, chronic

lung

disease,

cardiovascular

chronic

and

kidney

disease,

cerebrovascular

diseases,

(HIV,

use

cancer,

of

immunosuppressants) or obesity. Fifth, Workers in the education sector (including teachers and professors

at

the

pre-primary,

primary,

basic,

diversified and university levels) who have not been included in the previous subphases.

The

Third

Phase

is

aimed

socioeconomic

impact

continuity

basic

of

at

and services,

reducing

protecting and

for

the the the

effectiveness in the fulfillment of this, it has been divided into national

subphases. First, workers in the

security

sector

(including

PNC,

PMT,

military and prison system personnel). Second,

The First Phase is aimed at maintaining the integrity of

traditional

and

immunosuppression

The National Vaccination Plan of the Government of staggered

The Second Phase is aimed at reducing mortality

Health

sector

workers

(administrative)

included in the first two subphases.

not

Workers registered in municipalities and entities that provide essential services of electricity, water, garbage collection, customs and migration. Third, Authorities Ministry

of

and

other

public

Education

and

servants workers

of

the

of

the

Universities of the Country. Fourth, Justice sector workers, (includes judges, court staff, prosecutors, assistants, prosecutors and investigations of the Public Prosecutor's Office).

The Fourth Phase, the latter is aimed at reducing the burden of disease, and for the effectiveness in complying with it, it has been divided into subphases. First, Adults from 40 to 49 years old.

Second, Adults from 18 to 39 years old.

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15

References:

Brenes, L. (2021). ¡Inició la vacunación! Ministerio de Salud

Costa

Rica.

https://www.ministeriodesalud.go.cr/index.php/centro-

Horwitz, L., & Zissis, C. (2021, junio 7). Timeline: Tracking Road

to

Vaccination.

Ministerio

de

Salud

Costa

Rica.

https://www.ministeriodesalud.go.cr/index.php/centro-

vacunacion America’s

factores de riesgo, incorporados al plan de vacunación contra COVID-19.

de-prensa/noticias/741-noticias-2020/2020-inicio-la-

Latin

Ugarte, K. V. (2021c). Personas de 12 a 16 años, con y sin

AS/COA.

https://www.as-coa.org/articles/timeline-tracking-latin-

de-prensa/noticias/746-noticias-2021/2109-personas-de12-a-16-anos-con-y-sin-factores-de-riesgo-incorporadosal-plan-de-vacunacion-contra-covid-19

americas-road-vaccination Ministerio de Salud Pública Costa Rica. (2021). LS-SS-013.

Lineamientos sobre la vacunación contra el virus SARSCoV-2

para

la

prevención

de

la

COVID-19.

https://www.ministeriodesalud.go.cr/sobre_ministerio/pre nsa/docs/lineamientos_vacunacion_contra_covid19_v2_2 5012020.pdf

CMSBlueTheme. Ministerio de Salud Pública y Asistencia Social - Fase IV [Internet]. Gob.gt. [citado el 12 de junio de 2021]. Disponible en: https://www.mspas.gob.gt/covid19/vacunacion-contra-covid-19/fases-vacunacion-covid19/fase-4-vacunacion-covid-19.html

Organización Mundial del Comercio. (2020, diciembre).

Desarrollo y Distribución de Vacunas Contra la COVID-9 en

Todo

el

Mundo.

https://www.wto.org/spanish/tratop_s/covid19_s/vaccine_r eport_s.pdf Organización Panamericana de la Salud. (2008). Red Panamericana de Armonización de la Reglamentación Farmacéutica.

https://www.paho.org/hq/dmdocuments/2008/VConferen cia_ANEXOS.pdf Ugarte, K. V. (s. f.). Comisión Nacional de Vacunación y Epidemiología aprobó el uso de vacuna contra COVID-

Guatemala recibe primeras vacunas del Mecanismo COVAX [Internet]. Paho.org. [citado el 12 de junio de 2021]. Disponible en: https://www.paho.org/es/noticias/113-2021-guatemala-recibe-primeras-vacunas-mecanismocovax Saludpublica.mx. [citado el 12 de junio de 2021].

Disponible

en:

https://saludpublica.mx/index.php/spm/article/view/1227 8/12092

19 de AstraZeneca en Costa Rica. Ministerio de Salud

Costa

Rica.

Recuperado

10

de

junio

de

2021,

de

Vacuna Covid – Sitio Informativo [Internet]. Gob.mx.

https://www.ministeriodesalud.go.cr/index.php/centro-

[citado

de-prensa/noticias/746-noticias-2021/2084-comision-

http://vacunacovid.gob.mx/wordpress/

el

12

de

junio

de

2021].

Disponible

en:

nacional-de-vacunacion-y-epidemiologia-aprobo-el-usode-vacuna-contra-covid-19-de-astrazeneca-en-costa-rica vacunas

COVID-19: Resumen de las principales medidas, acciones

Pfizer/BioNTech contra Covid-19 es por $36 millones.

y políticas implementadas por los Estados miembros del

Ministerio

SELA [Internet]. Sela.org. [citado el 12 de junio de 2021].

Ugarte,

K.

V.

(2021a).

de

Compra

Salud

de

Costa

Rica.

https://www.ministeriodesalud.go.cr/index.php/centro-

Disponible

de-prensa/noticias/746-noticias-2021/2026-compra-de-

documentacion/base-de-datos-

vacunas-pfizer-biontech-contra-covid-19-es-por-36-

documental/bdd/62873/covid-19-resumen-de-las-

millones

principales-medidas-estados-miembros-sela

en:

http://www.sela.org/es/centro-de-

Ugarte, K. V. (2021b). Costa Rica firma acuerdo con AstraZeneca para suministro de vacuna candidata contra el

SARS-CoV-2.

Ministerio

de

Salud

Costa

Rica.

https://www.ministeriodesalud.go.cr/index.php/centrode-prensa/noticias/741-noticias-2020/1982-costa-ricafirma-acuerdo-con-astrazeneca-para-suministro-devacuna-candidata-contra-el-sars-cov-2

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16

ONE DAY AT LAB: ROTARY EVAPORATOR Melissa Núñez Mora1 1. Facultad de Farmacia, Universidad de Costa Rica, Costa Rica, melissa.nunezmora@ucr.ac.cr.

Have you ever thought about how a flower's compound

can

be

part

of

essential

oils,

a

medicines' composition, or even a cooking recipe?

To answer this question, you have to think about the several separation and purification techniques made in organic chemistry or pharmaceutical laboratories. Most of these methods, such as recrystallization and chromatography, must be done in conjunction with a solvent – a substance that helps to dilute reagents – which most of the time is not part of the desired compound. (1,2) Therefore,

to

remove

the

solvent,

another

technique must be applied.

as it is efficient, quick, and easy to use. A rotary also

known

the final product will be a mixture of cinnamon's essential oil and some remains of water. During the extraction, these two substances are separated with the

help

of

another

solvent,

in

this

case,

dichloromethane. Once this is done, you have a solution

of

dichloromethane

and

cinnamon

essential oil. At this point, the main characters' role is for the RE. Start by placing the solution in the distilling flask. Next, turn on the motor to start the rotations and then the vacuum pump to reduce the pressure. (1,3,4) Both compounds have very different boiling points, 246 °C for cinnamon essential oil and 40 °C for dichloromethane. As a result, it is easy to

Rotary evaporation (RE) is the most common one evaporator,

In the first one, you will use water as a solvent, and

as

"rotavap,"

is

the

laboratory instrument that makes it possible to apply this process. It has a distilling flask, where the solution – the wanted substance and the solvent – is placed. Connected to the flask is the glass joint of the vapor tube, which makes the flask rotate. There is also a vacuum attached to the

separate them by evaporation; however, as the RE lowers the systems' pressure, the compounds' boiling

points

decrease

too,

making

the

evaporation, condensation, and collection of the solvent easier. (1,3,5,6) Simultaneously, the rotations increase the surface area of the solvent, raising the evaporations' rate. As a final result, the cinnamon's essential

oil

is

successfully

purified

from

the

cinnamon sticks. (1,3)

flask through the vapor tube. A condenser and a solvent collector are part of it too. (1,3,4) In simple words, this machine produces a reduced pressure distillation. (2) The big question here is how this instrument can separate different substances. The

.

RE principle explanation may get a little tricky, so using an example makes it more accessible.

Imagine that you want to obtain the cinnamon essential oil. Before using the rotary evaporator, you

have

to

follow

two

processes:

steam

Figure 1. Representation of a rotary evaporator. (3)

distillation and extraction.

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17

This

technique

has

other

applications,

such

as

1- Make sure the rotavap is turned off, clean, and

preparing samples and synthesizing. Even recycling

the flasks are empty.

solvents is possible. In the pharmaceutical field, it is

2- Prepare a cooling bath and locate it in the

crucial for discovering, fabricating, and optimizing

solvent collector to prevent volatile solvents from

drugs. (7) For instance, by RE, a way of preparing an

evaporating. You can also use a dry-ice condenser.

amorphous solid dispersion (ASD) of acetyl-11-keto- β-

3- Connect the vacuum pump but do not turn it on.

boswellic acid (AKBA) – a compound with anti-

4- Connect the distilling flask with the solution

inflammatory and oncological properties, extracted

inside it to the vapor tube and attached it.

from the flower Boswellia serrata – was successfully

5- Hold it softly. Even though it is already attached

done. Because this drug's water-solubility is poor and

to the rotavap, sometimes the distilling flask might

so affects its bioavailability, a group of researchers

fall. Hence, support it while the evaporation is

decided to develop an ASD of AKBA to improve these

done.

characteristics

6- Turn on the vacuum pump.

since

ASDs

are

capable

of

supersaturating and increasing dissolution rates. (8)

7- Turn on the motor and start the rotations.

8- By moving the whole assembly, bring the flask

RE is such a well-designed method that it has even

towards the water bath or vice versa – depending

reached the kitchen of many well-known chefs around

on

the world. With the rotary evaporator's help, a lot of

Remember, you must not exceed the solvent's

chefs have improved the quality of their recipes by

boiling point.

concentrating,

9- The solvent will start to evaporate.

extracting,

and

separating

juices,

the

rotavap

model

–

and

start

heating.

colors, sugars, acids, flavors, and more. The now called

10- Once all the solvent is collected, stop de

"molecular cooking" has been expanding worldwide

rotation, release the vacuum and take out the

since this new kind of food tastes and smells

distilling flask from the water bath.

completely different. (9)

11- Clean the rotavap and the flasks.

When Lyman C. Craig created RE, he had no idea of the enormous legacy he left to humankind. (10) It has become not only an incredible tool for scientists but

Bibliography

also many other areas outside of a laboratory. Since it

Connections A How-To Guide for Organic Chemistry Lab Techniques.

1.

Padías AB. Chapter 3: Purification Techniques. En: Making the

has helped create medicines, purify the unique flavors

United States of America: Hayden HM McNeil; 2007. p. 107-74.

and odors of nature, and even brought new ways of

2. Nichls L. Overview of Rotary Evaporation [Internet]. 5.6A: Overview of

understanding cuisine, it truly has reached the goal of

Rotary

improving people's lives.

Evaporation.

2021.

Disponible

en:

https://chem.libretexts.org/@go/page/95729 3. Pravia L D, Gary M. L, George S. K, Randall G. E. Part 6: The Techniques.

En: A Small Scale Approach to Organic Laboratory Techniqes. Third.

Canada: Brooks/Cole. Cengage Learning; 2011. p. 545-959.

4.

Labrotovap. What is the usage of a rotary evaporator (rotovap)?

[Internet]. Well-Known. Disponible en: https://www.labrotovap.com/whatis-true-about-usage-of-a-rotary-evaporator-rotovap/

Figure 2. Chemical structure of acetyl-11-keto--boswellic acid (AKBA). (8)

5. National Center for Biotechnology Information. PubChem Compound Summary for CID 6344, Dichloromethane [Internet]. National Center for Biotechnology

Information.

2021.

Disponible

en:

https://pubchem.ncbi.nlm.nih.gov/compound/Dichloromethane 6. National Center for Biotechnology Information. PubChem Compound

Remember! You have to be careful!

Summary for CID 637511, Cinnamaldehyde [Internet]. National Center for

A rotavap is a costly machine, so you have to follow specific instructions to use it properly: (1,4)

Biotechnology

Information.

2021.

Disponible

en:

https://pubchem.ncbi.nlm.nih.gov/compound/Cinnamaldehyde

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18

SKILLS IN A YOUNG PHARMACIST - Fernanda Saito Matsuhira, USP, Farmacia, Brasil.1 E-mail: fernandasmat@yahoo.com.br - Ruth Elizabeth Meza, Facultad de Ciencias Químicas y Farmacia, Universidad San Carlos de Guatemala, Guatemala2 E-mail: elizaeliza16garsa@gmail.com - Solange t. O. Saito- Farmacéutica, AQIA. Brasil.3 - Alberto Keidi Kurebayashi - Farmacéutico-Bioquímico - FCF- USP; Especialización en Dermato-Cosmética en la Universidad de Vrije - Bélgica 4

We have always been led to believe that what is

The World Health Organization (WHO) published a

truly valuable is on the report card, on an exam

document entitled "The role of the pharmacist in

note, on the passing of a course. However, the

health care" ("The role of the pharmacist in the

reality in the Industry is different.

health system") in which seven qualities that the professional must present, which was then calleda

Speaking a little about the educational field from

7-star pharmacist, are highlighted, these qualities

the primary levels of schooling, for many years we

being:

have been instructed or guided consciously or unconsciously to obtain high grades or scores

1. Pharmaceutical service provider in a health team

being that a reflection of a "prosperous future", "a

2. Able to make decisions

good student", "level of intelligence", simply, the

3. Communicator

score, was a way or is currently the way to

4. Leader

categorize students 1.

5. Manager 6. Permanent update

Over time, different ways of learning, types of

7. Educator

intelligence, have been discovered and classified, we go from objectives to competences, because

>>SOLANGE, COMMENT<<

the desire is no longer the "knowing" but, the knowing "being", to be competent in life2 .

The pharmacist has a very wide field of activity. You

We would like that together we can perceive

can work in a pharmaceutical, cosmetic, food and

Education as something integral, although a good

chemical industry, either in the manufacture of

average is important what really makes it valuable

pharmaceutical inputs or products. Within the

is the -PROCESS- 2.

industry, there are different areas in which you can work:

Research

and

Development,

Innovation,

A good professional must "know how to be",

Application, Quality Control, Processes, Regulatory,

empathetic,

Supply Chain, Marketing and Sales.

upright,

enthusiastic,

generous,

proactive, be able to work as a team, and we call all these characteristics and personal skills soft

"The growth of the pharmacist, within

skills (Castro R., 2020).

of an industry, depends on factors such as: Predisposition to Continuous Learning"

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19

To be a Capable Professional, it is necessary that from our beginning in university education we get involved in activities that strengthen our Skills2.

We

can

see

that

it

is

not

References

Castro, R. (19 de Noviembre de 2020). Dpersonas.

Obtenido

enough

for

future

Pharmacists to dedicate themselves only to the subjects of the Curriculum, what will make a big difference at the time of an interview will be to have a Proactive Profile3.

A proactive profile has complementary activities, practices, participation in events or academic centers from the beginning of his University training, which allows him to be an Integral Professional3.

de

https://dpersonas.com/2020/01/31/habilidadesblandas-que-son-y-por-que-sonimportantes/#:~:text=Las%20competencias%20bla ndas%20(soft%20skills,habilidades%20sociales%20 o%20habilidades%20interpersonales.

González Pech, Harim Ernesto, Scior, Thomas Rainer F., & Vries, Wietse De. (2019). La profesión del farmacéutico

mexicano,

una

comparación

internacional. Perfiles educativos, 41(165), 148-164.

Epub

16

de

abril

de

2020.https://doi.org/10.22201/iisue.

>>KUREBAYASHI, COMMENTS<<

24486167e.2019.165.59101

Currently, with this new scenario in which we find ourselves in the home office, there is a great opportunity for future Pharmaceutical Professionals, still in graduate, to look for courses, talks, webinars to expand their horizons of knowledge4.

"Much success for all future graduation colleagues"

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20

CHALLENGES TO THE USE OF MEDICINE IN SPACE Libni Melissa Pérez1,, Rubí Calderón2

1 . Facultad de Ciencias Químicas y Farmacia, Universidad de San Carlos de Guatemala, Guatemala, prezlibni37 @gmail.com Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Perú, rubi.calderon@upch.pe

In a changing world, human beings must adapt to

and there is resupply from the International Space

different situations in their environment. It is

Station (ISS), a kit is not the solution for longer trips,

estimated that since 1910, the year in which

as is the three-year mission to Mars. Because of

arsphenamine, discovered by Paul Erlich, began to

these challenges, scientists have been researching

be used for the treatment of the then deadly

and developing new methods and technologies to

syphilis, the average life expectancy of a human

facilitate

extended by more than 23 years [1], reaching 72.6

supplies. In this way, it is sought that trips and stays

years in 2019 [2]. Therefore, advances in medicine

are less invasive and that they do not threaten the

have been exceptional tools to prolong life on

health of individuals for long periods of time.

access

to

medicines

and/or

medical

Earth, but what happens outside of it?

One of the biggest challenges is radiation, as it One of the great advances of modern science has

would not only affect astronauts, but also the

been space travel that increasingly seeks to

stability of medicines. At a greater distance from

explore and discover beyond. In fact, until the

Earth, the protection provided by Earth's magnetic

beginning of 2020, more than 560 people have

fields is getting smaller and smaller. Consequently,

made trips to space of varied duration, from 15

it increases exposure to galactic cosmic radiation,

minutes to 437 days [3]. However, there is one

which is composed of high-energy ions that travel

persistent problem and that is the fact of how

almost at the speed of light, ionize virtually

these trips affect the health and quality of life of

everything in their path [6] and cause DNA damage

the men and women who carry out these

that is difficult to repair [7]. Since the radiolytic

missions.

species that are generated can react with the active

The

medical

and

environmental

challenges astronauts face vary according to the

ingredients

and

excipients

and

alter

the

length of travel, the type and time they stay out of

physicochemical and pharmacological properties.

Earth's atmosphere [4].

Some studied ways to protect drugs are the use of polymeric packaging of low atomic number and

Due to the limited capacity to carry supplies on

microemulsions,

as

well

as

the

inclusion

of

each flight, astronauts are provided with medical

antioxidants and radioprotective excipients (such as

kits whose drug and device contents are pre-

mannitol and pyridoxine) in formulations [8].

established. While the drug content is quite robust (a single kit can contain more than 117 types of medications!) [5]

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An even more striking option contemplated is the use

In practice, the "organ-on-a-chip" system has not

of

active

yet been used to study microgravity, but it has

molecules in the same space. Currently, it is being

been used to observe the neurovascular effects

studied whether the highly stressful environment of

that cosmic radiation has at the level of the blood-

space can activate secondary metabolic pathways in

brain barrier [13].

radiation-resistant

Aspergillus

nidulans,a

fungi

to

produce

filamentous

fungus

whose

genome was sequenced in 2016 [9].

In conclusion, much remains to be known about

Another challenge is microgravity, which is defined as that condition in which "gravitational acceleration is one hundredth to one millionth of the gravitational acceleration present on the Earth's surface" [10].

objects appear to be weightless and float. The effects

that

microgravity

has

on

astronauts are known almost for sure: redistribution of fluids,

reduction

of

muscle

mass

and

that have been implemented for its study are increasingly innovative. It would come as no surprise if in the future drugs could be produced in the same space, so that astronauts have immediate

In other words, in microgravity conditions, people and physiological

the behavior of drugs in space. The technologies

strength,

alteration of gastric emptying and intestinal transit, alteration of cytokine production and modification of

access to them during long-duration missions.

References 1. Hutchings M, Truman A, Wilkinson B. Antibiotics: past, present and future.

Current Opinion in Microbiology. 2019;51:72-80. https://doi.org/10.1016/j.mib.2019.10.008 2. World Population Prospects 2019: Highlights | Multimedia Library - United Nations Department of Economic and Social Affairs [Internet]. 2019 [citado 2021

Jun

10].

Disponible

en:

https://www.un.org/development/desa/publications/world-population-

the activity of transmembrane proteins, ion channels

prospects-2019-highlights.html

and enzymes [11].

space?. Expert Opinion on Drug Metabolism & Toxicology. 2020;16(5):353-356.

3. Eyal S. How do the pharmacokinetics of drugs change in astronauts in https://doi.org/10.1080/17425255.2020.1746763

However, there is still a large knowledge gap about

4. Stepanek J, Blue R, Parazynski S. Space Medicine in the Era of Civilian Spaceflight. New England Journal of Medicine. 2019;380(11):1053-1060.

how microgravity affects the absorption, distribution,

https://doi.org/10.1056/NEJMra1609012

metabolism and excretion of drugs. Compared to the

5. Eyal S, Derendorf H. Medications in Space: In Search of a Pharmacologist’s

traditional models of "head-down bed rest" (HDBR)

https://doi.org/10.1007/s11095-019-2679-3

Guide to the Galaxy. Pharmaceutical Research. 2019;36(10).

and immersion in water used to simulate microgravity

6. Perez J, Dunbar B. Why Space Radiation Matters [Internet]. NASA. 2019

conditions on Earth, an interesting possibility that has

space-radiation-matters

been contemplated is that of conducting automated research on the same spacecraft through the use of "organ-on-a-chip" systems [3]. These systems, based on microfluidic technology, simplify the organism, but

[citado 2021 Jun 10]. Disponible en: https://www.nasa.gov/analogs/nsrl/why7. Elgart S, Little M, Chappell L, Milder C, Shavers M, Huff J et al. Radiation Exposure and Mortality from Cardiovascular Disease and Cancer in Early NASA Astronauts. Scientific Reports. 2018;8(1). https://doi.org/10.1038/s41598-018-25467-9 8. Mehta P, Bhayani D. Impact of space environment on stability of medicines: Challenges and prospects. Journal of Pharmaceutical and

have the advantage of being portable and accurately

Biomedical Analysis. 2017;136:111-119.

simulating the physiological environment of human

9. Wang C. Experiment Details: Influence of microgravity on the production

organs,

since

parameters

such

as

concentration

gradients and shear forces, among others, can be controlled [12]. In this way, "organ-on-a-chip" systems could

be

useful

extrapolations [3].

for

performing

in

vitro-in

vivo

https://doi.org/10.1016/j.jpba.2016.12.040 of Aspergillus secondary metabolites (IMPAS) – a novel drug discovery approach with potential benefits to astronauts’ health [Internet]. Nasa.gov.

2021

[citado

2021

Jun

10].

Disponible

en:

https://www.nasa.gov/mission_pages/station/research/experiments/explorer/I nvestigation.html?#id=1164 10. Carrillo Esper Raúl, Díaz Ponce Medrano Juan Alberto, Peña Pérez Carlos Alberto, Flores Rivera Oscar Iván, Ortiz Trujillo Adriana, Cortés Antonio Osvaldo et al . Efectos fisiológicos en un ambiente de microgravedad. Rev. Fac. Med. (Méx.) [revista en Internet]. 2015 [citado 2021 Jun 10] ; 58( 3 ): 13-24.

Disponible

en:

http://www.scielo.org.mx/scielo.php?

script=sci_arttext&pid=S0026-17422015000300013&lng=es.

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PHARMACOGENETICS IN CARDIOVASCULAR DISEASES: IMPORTANT FOCUS TODAY Luis Andrés Núñez Alpízar Facultad de Farmacia de la Universidad de Costa Rica, Costa Rica, luis.nunezalpizar@ucr.ac.cr.

As is well known, genetics is one of the most

Due to the large number of enzymes in humans

important branches of biology, since it describes

that are responsible for the metabolism of drugs, it

the characteristics obtained from our ancestors,

was found that there are polymorphisms that act

whether they are the distinctive physical traits of

differently in each patient, so they raise the amount

each human being, or the physiological activity in

of medication remaining in the body (which could

our body. At present, many factors have changed

cause toxicity) or reduce this amount of medication

in society, and thus new genetic variations have

to an ineffective level, therefore, the doses used for

appeared in humans, so this affects the desired

each patient are adapted separately, thus giving

aspects in medicines, since it has been seen the

greater

different reactions that patients have specifically

pharmacogenetics is the area that is responsible for

when ingesting medicines. It is interesting and

looking for the genetic values of each patient and

important, since, in the variation of a single base, it

see if these generate a change in the enzymes and

can

the

proteins that are responsible for the metabolism of

intermediate proteins of the process, so it is

the drug, thus generating a change in the response

reflected in a change in the efficacy of the drug or

time of the drug and, therefore, its desired effect.

even reaching a high level of toxicity of the drug.

(2)

trigger

an

unwanted

reaction

with

follow-up

to

the

variation.

Basically,

(1) Of course, the side effects of a drug are not only The beginning of pharmacogenetics occurs after

due to genetic factors, since there are other

the great project already known called Human

characteristics in each human being that differ in

Genome, which managed to decipher that each

different

human being is constituted by at least 30,000

medications and even the consumption of alcohol,

different genes, in which, about 10% can present

tobacco and other substances,

ways,

such

as

age,

sex,

additional

alterations, which are known as SNP, or single nucleotide

polymorphisms,

where

a

single

nucleotide is altered in the DNA chain and this is the

one

that

causes

the

greatest

incidents

observed with medications. In the clinical area, it seeks to perform individual genetic profiles for

.

patients who show unexpected results in specific drugs.

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23

These are extremely important to prevent and treat in

There are several cases where the activity of

time, since in most of the time they are silent and

genetic polymorphisms is observed, such as, for

appear when they are least expected.

example, in the use of Warfarin, this is a drug used as an anticoagulant and must have a regulated and

They are recognized for being one of the largest

individualized prescription, since depending on the

causes of death in the world, so in recent years

dose can cause serious bleeding problems. This

research has increased to find more efficient solutions

drug is metabolized by a liver enzyme called

and try to raise awareness in society a balanced care in

CYP2C9, which has two NSP-type polymorphisms

the diet of each one, as well as the practice of sports

called CYP2C9 *2 and CYP2C9 *3, responsible for

and avoid the consumption of tobacco. In addition,

the decrease in warfarin metabolism, so a previous

there are factors which cannot be changed, such as

genetic examination of the patient should be done

age, sex and genetic inheritance of each one, so if

to decrease the dose as necessary. In addition, an

there is any suspicion of being prone to these diseases,

enzyme called epoxide K reductase (VKOR) is also

the aforementioned preventions should be applied

known, which has a variation called VKORC1 that

with greater care. (3)

affects the sensitivity of Warfarin and therefore

Later, it was determined that there is a relationship between the drugs used for cardiovascular diseases and genetics, so pharmacogenetics began to take on more importance in the field of research. To analyze pharmacogenetics from the beginning, you have to initially know the types of patients there are, since each one has a different metabolism. Starting with the slow metabolizers, they are those patients who generate a minimum response of the drug due to a genotypic variation, altering the side effects of the drug and, therefore, forcing the medical manager to increase the required dose. Intermediate metabolizers have more pronounced side effects as do slow ones, however, they are not as strong effects.

Extensive

metabolizers

are

normal

patients, who admit the drug in the expected way, resulting in the desired therapeutic effect. Finally, there are ultrafast metabolizers, which metabolize metabolizing

enzymes in double or even triple amounts. (4) addition,

these

emergence

of

bad

practices

common

cardiovascular diseases.

It is known that most drugs are metabolized by the enzymes of the CYP3A family, having these two common isoforms: CYP3A4 and CYP3A5. It is known that there is an NSP in CYP3A4, which does not allow the metabolism of some cardiovascular drugs of the statin type, such as lovastatin, simvastatin and atorvastatin.

In the case of atorvastatin, a change in the differences in LDL cholesterol levels (commonly called ''bad'' cholesterol) was observed, so the doses of patients who present the polymorphism in the CYP3A4 genotype should be adjusted. (1)

considered

drugs too quickly, as they produce

affects the desired result. (2)

attribute

diseases,

to

In the

including

Drugs such as clopidogrel act in the same way as the previous ones, with an enzyme called CYP2C19, which contains an NSP called CYP2C19 *2, which can cause bleeding in some patients as in the previous case with Warfarin. In this case, the patient's dose must be adapted to a more stable one in order to obtain the benefit over the desired patient. (5)

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References

All these cases have been investigated in various locations around the world, where these differences

1.

have been shown, however, in Latin America these

FARMACOGENÉTICA

polymorphisms have not been investigated so much,

(Ribeirão Preto). 30 de diciembre de 2006;39(4):535-

since the population is a racial mixture since ancient times and this hinders the research processes, so it seeks to raise interest in this topic and encourage the student and professional population to carry out more formal research on the subject in order to help the Latin American population in a more efficient way. (6) Knowledge in this area is extremely important in each pharmacy professional, since each patient is different and may or may not have these genetic variations previously mentioned, so knowing them can mean a successful treatment, without aggressive side effects

Sandrim VC, Rezende VB, Tanus-Santos JE. CARDIOVASCULAR.

Medicina

42.

2.

Fernández

APLICACIONES

JM. EN

FARMACOGENÉTICA: LA

ENFERMEDAD

CARDIOVASCULAR. :34.

3.

García Riesco N. Prevención de enfermedades

cardiovasculares desde atención primaria: revisión bibliográfica

[Internet]

[info:eu-

repo/semantics/bachelorThesis]. 2020. Disponible en: http://uvadoc.uva.es/handle/10324/41967 4.

Stein

R,

Beuren

T,

Cela

LR,

Ferrari

F.

Farmacogenômica e Doença Cardiovascular: Onde Estamos e Para Onde Vamos. Arquivos Brasileiros de Cardiologia. 13 de octubre de 2020;115(4):690-700.

(main objective in taking medications), or a treatment

5.

with strong and harmful adverse effects for the patient

Hilal-Dandan R, Knollmann BC, editores. Goodman &

and being even worse, cause the death of the patient.

Gilman’s: The Pharmacological Basis of Therapeutics,

Because of this, knowing the pharmacogenetics has

13e [Internet]. New York, NY: McGraw-Hill Education;

important advantages for the patient, such as, for

2017 [citado 6 de mayo de 2021]. Disponible en:

example,

accesspharmacy.mhmedical.com/content.aspx?

obtaining

more

effective

therapeutic

Roden DM. Pharmacogenetics. En: Brunton LL,

benefits and in less time, as well as reducing the cases

aid=1162533468

of poisoning present in this type of drugs.

6.

Scudeler

FARMACOGENÉTICA

MM, NA

Rodrigues-Soares AMÉRICA

F.

LATINA.

2020;3(2):17.

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E D I T O R I A L CREATOR OF THE MAGAZINE

SR. GREIVIN ÁLVAREZ VEGA Pharmacy Education Subcoordinator PARO 2020-21

GENERAL SUPERVISOR SRA. LAURA PÉREZ Regional Projects Officer PARO 2020-21

EDITORIAL DESIGN SR. MAURICIO ABEL MIRANDA CH. Regional Media and Publications Officer PARO 2020-21

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