USMP

UNIVERSITY OF

SAN MARTIN DE FORRES

FACULTY OF
HUMAN MEDICINE

PRACTICE OF
PHARMACOLOGY
VI Cycle of Studies Academic Semester 2020-II

ROUTES OF ADMINISTRATION AND

PHARMACOKINETIC PARAMETERS
Members
Majuan Pintado Luis Fernando: University code: 75320516

Medina Concha Norbil Harly: University code: 70103323

Mejía Delgado Elizabeth Esther. University code: 74394344

Mendoza Malca Sadith Araceli University code: 72215744
Monsalve Perez Alexander Alberto University code: 71038419

Mundaca Palomino Flavio Erick University code: 73444100

Orozco Delgado Liz Katherine. University code: 75020481

Pachas Amaringo Cynthia Tatiana University code: 75494571

teacher

Rodríguez Salinas, Juan Ismael

Cluster
03

NORTH SUBSIDIARY

Chiclayo – Peru
2020
 INDEX

Content

ROUTES OF ADMINISTRATION AND PHARMACOKINETIC PARAMETERS..............1

INTRODUCTION.......................................................................................................................3
II.OBJECTIVES:.........................................................................................................................4
III. MAP.......................................................................................................................................5
IV. EXPERIMENTS...................................................................................................................6
V.CONCLUSIONS OF THE EXPERIMENTS:.......................................................................22
INTRODUCTION

Clinical pharmacokinetics is a multidisciplinary science very interested in health,

whose main objective in healthcare practice is to individualize dosage or optimize
pharmacotherapy to achieve the greatest therapeutic effect and the lowest
incidence of adverse reactions. The relationship between some pharmacokinetic
and pharmacodynamic parameters, such as the maximum concentration achieved
(Cmax), the area under the curve (AUC) and the minimum inhibitory concentration
(MIC), play a decisive role in determining the choice of drugs and their dose.
Drug administration is the procedure of administering drugs to patients to achieve a
certain effect. The drug can be administered by different routes. Pharmacological
treatment requires that drugs reach their specific targets in the tissues that carry out
their actions. Typically, the drug will be introduced into the body (drug delivery
process), in some cases outside the target area. It must enter the blood (absorption
process) and be transported to the target area where it must work (distribution
process). Some medications are chemically modified by the human body (metabolic
processes) before they work, other medications are metabolized later, while others
are not metabolized at all. The final stage includes excretion of the drug and its
metabolites (elimination process). Many factors, including a person's weight,
genetic makeup, and kidney or liver functionality, can infl uence these kinetic
processes. Changes due to aging also affect the way the body processes drugs .
It is important to remember that each drug is prepared to be administered in a
certain way so that it works most effectively. The doctor is responsible for
prescribing the necessary dose for the patient, and the nurse or auxiliary nursing
technician will be responsible for administering the medication.
III. MAPII.OBJECTIVES:
ROUTES OF ADMINISTRATION AND PHARMACOKINETIC PARAMETERS

1. Recognize the influence of administration routes on the pharmacokinetic P

PHARMACOKINETICS
parameters of drugs.

2. Identify factors that can influence the pharmacokinetics of drugs.

Phases
Pharmacokinetic p
Bioavailability (BD

3. Calculate and determine pharmacokinetic parameters

Plasma protein

binding

Volume of
distribution (Vd)

Metabolism

Elimination half-lif

(t'ó)

Renal clearance
(0)

Dermal
IV. EXPERIMENTS

EXPERIMENT Nº 1: Action of the routes of administration on the effects of drugs.

ASK:

In which of the administration routes will we have a better result with respect to
intensity?

HYPOTHESIS:

If the same drug is administered, in this case Diazepam, through different

routes, the latency period will be shorter in the intraperitoneal route, resulting in
greater intensity.

MATERIALS:

■ Drug: Diazepam, sol. 10 mg in 2 ml.

Diazepam
■ Species: Mouse. Diazepam

Piazepam
■ Software: Virtual Pharmacology Lab Software.
■ Methodology: Simulation using software –
vide
PROCEDURE:

■ Diazepam 10 mg/kg body weight was administered to each mouse.

2. Subcutaneous – under the skin of the back.
following ways: 1. Oral. - Using a metal cannula

3. Intramuscular. – in the muscle

quadriceps
4. Intraperitoneal. - Lower left
quadrant of the abdomen

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 5. Rectal. - through a cannula

RESULTS:
1. Oral 2.
Subcutaneous

3. Intramuscular. 4. Intraperitoneal.

5. Rectal.

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 Dose (ml) Lateritial Period (minutes) Intensity
Oral O.O5 10 2
S.C. 0.052 4 3
I.M. 0.048 2 3
IP 0.054 1 4
GO 0.058 15 1

Experiment oN°1: Action of the routes of administration on the effects of drugs, data collection matrix
Mouse N Weig Dose Via Effect intensity Observations
Latency Period (minutes)
ht(g)
mg my Basal Change

1 25 0.05
pra 10 0 ++
Started with sedation, and his respiratory rate
y decreased.
He became excited , and his respiratory rate
2 26 0.052 HE 4 0 +++
remained increased.
He was sedated, and his respiratory rate
3 24 0.048 I.M. 2 0 +++
decreased.
I present transient excitement, and then deep
4 27 0.054 IP 1 0 ++++
hypnosis.
5 29 0.058 GO 15 0 + No other effects occurred.
Effect intensity: No effect- 0. Sedenle= +. Hypnotic: ++ Deep Hypnosis: +++ Lists Respiratory: ++++.
DISCUSSION :

Diazepam is a drug that is administered orally, rectally and parenterally. It is the

benzodiazepine that is absorbed the fastest after being ingested. When
administered rectally it is absorbed very well, with a bioavailability of almost 90%.

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The effects usually begin to be noticed after the 1st dose, being muscle relaxation
and anticonvulsants. In an intramuscular dose the time for it to take effect is 2 – 5
minutes. The metabolism of diazepam is mainly hepatic and its half-life is 30 – 60
hours.
A drug was dosed to a group of 5 mice. The drug selected on this occasion was
Diazepam in a solution of 10 mg in 2 ml. Through this experiment, we sought to
affirm the effectiveness of changing the basal state to the intensification of the
side effects of the previously mentioned drug. For this reason, a dosage was
applied to each of the mice according to their weight, particularly the route of
administration.

In the attached table, the pathway of each of these and confirmation of the
intensity of the effect is clearly seen.
• In mouse number 1, the oral route was chosen. This pathway is recognized as
the most frequent in humans, especially in children. Unfortunately, the
effects of the drug were of a low intermediate level in the intensity of the
effects.
• In mouse #2 , the injectable was applied subcutaneously under the skin of
the back. The results in intensity were greater compared to the oral route.
Concluding that it is an intermediate way to visualize the effects of the drug.
• In mouse number 3, the intramuscular route was used in the quadriceps
muscle. The selection of the anatomical area is due to the fact that it must
be a richly irrigated muscle, such as the gluteus in men. The intensity of the
effects is similar to the subcutaneous route on this occasion.
• In mouse #4 , dosing was intraperitoneal. It should be noted that this route is
very similar to the intravenous route in humans. The only difference is
second. If a categorization was made of which had the greatest magnitude
in results, it would be stated that this one. It has an intensity of 4 compared
to the rest.
• In mouse #5, an irregular route was used through a cannula. This route is in
the rectal area, which is characterized by being infrequent due to the
epithelium of the mucosa and irrigation. It had the least effect on what
would become the intensity of the drug's effects.

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Experiment No. 2: Action of the vehicle, on the effect of medications

PROCEDURE:

Based on the class videos, in this practice 3 mice will be used (white, head, back)
and calculations will be made to present the respective results in the proposed
tables and complete it with the doses of the administered substances, to finally
make a discussion about the effect of the vehicles on the observed drug.

Strychnine (SC) + 0.30 ml of

distilled water

Strychnine (SC) + gelatin in sol.

15 %.

Strychnine (SC) + 1 o/oo

adrenaline

STEP 1: Calculate the dose of Strychnine to be administered

A mouse (White / 35 g) was injected subcutaneously with a dose of

1st WHITE MOUSE:
strychnine (1.8 mg/Kg. by weight, 0.1% sol, plus 0.30 ml. of distilled water).

A second mouse (Head / 30 g) was injected with the same drug, at the
2nd MOUSE HEAD:
same dose and by the same route, but replacing the distilled water with the
vehicle gelatin in sol at 15%.

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 A third mouse (Lomo / 33 g) was administered the same drug, by the
3rd LOMO MOUSE:
same route and at the same dose, but this time using a 1% adrenaline solution as
a vehicle.

Answer:
It corresponds to 0.0594 ml
of Strychnine.

STEP 2: We complete the table with the data obtained

EXPERIMENT Nº 2: Action of the vehicle, on the effect of medications, data collection matrix
Mouse Drugs and dosage mg ml Effect intensity Observation

Latency period
(sec.)
White Strychnine 0.063 0.363 +++
15 It began with an
increase in
Distilled water 0.3 0.3
respiratory rate,
followed of
convulsions (+++)
and tetany.
Head +++ Start showing
Strychnine 0.054 0.354 360 increase in

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0
 Jelly 0.3 0.3 respiratory rate,
hyperreflexia

and
Loin +++ seizures (++).
Beginning
Strychnine 0.0594 0.3594 180 presenting an
0.3 0.3 increase in
Adrenalin respiratory rate,
followed by
hyperreflexia,
convulsions (+++)
and tetany.
Effect intensity: No effect = 0. Hyperreflexia = +. Seizures = ++. Seizures = +++. Respiratory paralysis = ++++.

STEP 3: Latency period

Latency Period

STEP 4: Discussion

In the present experiment, the drug used is Strychnine, which is an alkaloid,

analgesic, opioid, and proconvulsant.
This alkaloid excites all portions of the central nervous system, but this effect is
not a consequence of direct synaptic excitation but rather of the blockade of
postsynaptic inhibition mediated by glycine.
Glycine is an important inhibitory transmitter of motor neurons and interneurons in
the spinal cord and central nervous system, and strychnine acts as a selective and
competitive antagonist of it.
Strychnine is rapidly absorbed from the gastrointestinal tract and the first
symptoms appear 10 to 20 minutes after ingestion. This toxin is preferably
eliminated by the liver, although more than 20% of the ingested amount can be
excreted in the urine.
Strychnine and Distilled Water: The reaction is evident in 15 seconds, which is less than in the
other 2 mice.

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1
Strychnine
Time and Gelatin: Gelatin
Plasma is a colloid
and its characteristic
concentration is to absorb40
Case 1: propranolol ormg/kg
otherwise
- POfix
strychnine
(min) colloid(ng/ml)
micelles to its micelles, and also causes a decrease in the
-
permeability
0 of the blood
0 capillaries through which the substances are absorbed.
The 30
reaction is evident Adult
63.819in 360 seconds, which is greater than in the 2 mice.
60 60.458
90 40.145
120and Adrenaline: Adrenaline
Strychnine 30.522 is a vasoconstrictor that will cause a reduction in blood
flow 180 in the capillaries.
22.354 Therefore, when administering the drug with adrenaline, it
will 240
decrease blood flow causing a decrease in the distribution capacity of the
18.344
drug, 360 delaying its effect.
13.055
420 11.052
480 9.358
It is because of this that the latency period is moderately slow. In the case of
distilled water, the latency period and the intensity of the response are considered
as a standard to compare these magnitudes with the results of the other mice. The
other vehicles in which strychnine is administered (gelatin and adrenaline) do slow
its absorption rate, which is evidenced by the prolongation of the latency period
and a less intense effect.

Experiment N°3: Pharmacokinetic parameters

MATERIAL

Drugs: Propranolol / Ampicillin.

Species: Male.
Software: Microlabs Software, Dr Henk van Wilgenburg, Dept. of Pharmacology,
University of Amsterdam.

PROCEDURE

Below, 8 cases are presented, the results of which are found in the experiment
results table.
Line graphs with X/Y axis should be constructed for all cases, delimiting the
pharmacokinetic and pharmacodynamic clinical parameters.
Case 1 - An adult individual was administered orally propranolol at a dose of 40 mg/kg.

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 Latency period: 15 min approx.
Tmax: 30 min
Cmax: 63,819 mg/ml
t1/2: 120 min
Duration of effect: 360 – 15 = 345 min
MCE (Minimum Effective Concentration) 13.055
MEC (maximum effective concentration): 30.522
ABC: It is not possible to
Therapeutic window: calculate
Does not have
CMT (minimum toxic concentration): -

- Propranolol was administered orally to an elderly individual at a dose of 40

Case 2
mg/kg.

Plasma concentration
Case 2: Propranolol 40 mg/kg - V0 - Adult
Time (min) (ng/ml)
0 0 elderly
30 112.744
60 97.054
90 66.282
120 58.074
180 46.804
240 41.426
360 34.119
420 31.077
480 28.312
1020 12.249
1080 11.16

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 Latency period: 600 min
Tmax: 30 min
Cmax: 103,431 mg/ml
t1/2: 120 min
Duration of effect: -
MCE (Minimum Effective Concentration) 11.375
MEC (maximum effective concentration): 66.282
ABC: It is not possible to
Therapeutic window: calculate
Does not have
CMT (minimum toxic concentration): -

Propranolol was administered orally to an adult individual with a diagnosis of

Case 3 -
renal failure at a dose of 40 mg/kg.

plasma concentration
Time (min) (ng/ml) Case 3: Propranolol 40 mg/kg - PO
0 0 -
30 103.431 Adult
60 73.487
90 66.282
120 37.1
180 27.171
240 22.298
360 15.868
420 13.434
480 11.375
540 9.632 700
600 8.156
Latency period: 10 min approx.
Tmax: 30 min
Cmax: 112,744 mg/ml
t1/2: 120 min
Duration of effect: 1020 – 10 = 1010 min
MCE (Minimum Effective Concentration) 12.249
MEC (maximum effective concentration): 97.054
ABC: It is not possible to
Therapeutic window: calculate
Does not have
CMT (minimum toxic concentration): -

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4
 Propranolol was administered orally to an adult individual with a diagnosis of
Case 4 -
liver cirrhosis at a dose of 40 mg/kg.

plasma concentration
Time (min) (ng/ml) Case: propranolol 40 Mg/kg - PO - Adult
0 0
30 211.171
60 150.036
90 75.745
120 55.474
180 45.524
240 38.307
480 23.224
540 19.665
840 8.562
900 7.25
Latency period: 60 min
Tmax: 30 min
Cmax: 211,171 mg/ml
t1/2: 120 min
Duration of effect: -
MCE (Minimum Effective Concentration) 11.375
MEC (maximum effective concentration): 66.282
ABC: It is not possible to
Therapeutic window: calculate
Does not have
CMT (minimum toxic concentration): -

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 Propranolol was administered orally to an individual with a diagnosis of liver
Case 5 -
cirrhosis at a dose of 120 mg/kg.

Time (min) plasma concentration

0 0 Case 5: Propranolol 120 mg/kg - PO
30 590.851 -
60 419.797 Adult
90 278.751
120 211.932
180 155.214
240 127.376
480 64.979
540 55.023
840 23.956
900 20.286
1000 15.29
1100 11.525
1300 6.657
Latency period: 10 minutes
Tmax: 30 min
Cmax: 590,851 mg/ml
t1/2: 295.4255
Duration of effect: 1100 min
MCE (Minimum Effective Concentration) 11.525
MEC (maximum effective concentration): 590.851
ABC: It is not possible to
Therapeutic window: calculate
Does not have
CMT (minimum toxic concentration): -

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 Ampicillin was administered orally to an adult, considering a gastric pH of 2, at
Case 6:
a dose of 500 mg/kg.

Time (min) plasma concentration

0 0

60 6257.648

120 3458.025

180 1906.291

240 1050.97

300 579.506

360 319.619

480 97.37

600 29.8
Latency period:
Tmax: 60 min
Cmax: 6257.648 mg/ml.
t1/2: 3128.824
Duration of effect
MCE (Minimum Effective Concentration) -
MEC (maximum effective concentration): 6257.648 mg/ml
ABC: It is not possible to
Therapeutic window: calculate
Does not have
CMT (minimum toxic concentration): -

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 It was administered to an adult individual orally, considering a gastric pH of
Case 7:
3.5. Ampicillin at a dose of 500 mg/ml.

Time (min) plasma concentration Case 7: Ampicillin 500 mg/kg- Oral

0 0
route-
Adult gastric pH 3.5
60 2729.737

120 1508.474

180 831.57

240 458.459

300 252.794

360 139.426

480 42.475
Plasma concentration
600 12.999
Latency period:
Tmax: 60 min
Cmax: 729.737mg/ml.
t1/2: 1364.8685
Duration of effect:
MCE (Minimum Effective Concentration) -
MEC (maximum effective concentration): 6257.648 mg/ml
ABC: It is not possible to
Therapeutic window: calculate
Does not have
CMT (minimum toxic concentration): -

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 Ampicillin was administered orally to a patient with renal failure in a dose of
Case 8:
500 mg/ml.

Case 8: Ampicillin 500mg/Kg

Time (min) plasma concentration VO- Adult-R

0 0

60 8724.918

120 7902.845

180 7145.824

240 6461.478

300 5842.816

360 5283.518

480 4320.732

600 3533.736

Latency period:
Tmax: 60 min
Cmax: 8724.918 mg/ml.
t1/2: 362.459
Duration of effect:
MCE (Minimum Effective Concentration) -
MEC (maximum effective concentration): 8724.918 mg/ml
ABC: It is not possible to
Therapeutic window: calculate
Does not have
CMT (minimum toxic concentration): -

DISCUSSION EXPERIMENT 3:
Propranolol is a medication that is mostly ingested orally and is characterized by
having a high affinity for binding plasma proteins. It has a half-life between 3-
5hrs, and the determined time to reach its maximum effect is 1h to 1h30min. It is
characterized by: reducing heart rate, increasing renin activity in plasma and
inhibiting lipolysis.
In the data analysis, there are limitations in being able to find some
pharmacokinetic parameters (AUC, therapeutic window) since the software was
not available or the effects were not mentioned in some cases.

: Propranolol was administered to an adult without a specific pathology. It

In case 1
was observed that the kinetics of the drug coincide with what was described in
paragraph 1. We must consider that beta blockers are a group of drugs that
undergo first-pass metabolism, which is why they must be administered in

1
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higher doses.
In case 2 : the administration of the drug was to an older adult, where the Cmax. is
higher than that of case 1, it means that the drug entered the circulation in
higher concentrations. This particularity could be explained by the fact that first-
pass metabolism and the enzymes involved in it are reduced in older adults.
In case 3 : the drug Propranolol was administered orally at a dose of 40 mg/ml to an
adult with a diagnosis of renal failure. As a consequence, an increase in the
effect of the drug can be seen, due to an alteration in renal failure.
In case 4 and 5 : the drug Propranolol was administered to an adult with a diagnosis of
liver cirrhosis. Here it can also be seen that the Cmax is high, due to an
alteration of the CYP340 system, a product of liver failure, therefore, the
duration of the effect is also longer if we compare it with case 1 (base case).
Ampicillin has an oral absorption of 35 to 50% reduced by consumption with
food. It is stable in the presence of gastric acid with good absorption in the
gastrointestinal tract. It has low protein binding, 17 to 20%. Hepatic Metabolism:
Ampicillin is 12 to 50% metabolized in the liver. Elimination: renal, 25-60%
unchanged.
The limitation in the case analysis is here, because the effects corresponding to
ampicillin are not specified in the case table.
In cases 6 and 7 : it was administered to an adult individual orally considering different
gastric pHs. We sought to see the concentration of the drug in the plasma in
relation to the minutes that passed until the effect of the drug wore off.
In case 8 : Ampicillin was administered orally at a dose of 500 mg/ml in a patient with
renal failure. Because the elimination routes occur via urine, bile and breast
milk, we can deduce that plasma concentrations of ampicillin will decrease
slowly.
Therefore, in experiment 3, it is evident how the action of drugs works in
different organisms and with different pathologies; taking into account that both
propranolol and ampicillin follow first-order kinetics.

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0
V.CONCLUSIONS OF THE EXPERIMENTS:

Experiment 1:

- Each of these routes has demonstrated the variability of absorption that

the drug can have from the visualization of the effects that the drug
characteristically had. Although not all of them have illustrated the same
intensity, it can be seen how the route used influences the consequence
of the xenobiotic.
- We can see that it was reaffirmed that the most effective route is the
intraperitoneal route, similar to the intravenous route in humans.
Likewise, it would be considered that the last option to apply a drug would
be the rectal area, both because of the infrequent location and because
of the appreciation of its consequences.

Experiment 2

- We were able to corroborate the different mechanisms of action of

Strychnine such as its participation in the interference in postsynaptic
inhibition mediated by glycine, it acts as a selective and competitive
antagonist to block the inhibitory effects on all glycine receptors, an
important inhibitory transmitter of motor neurons. , and interneurons in
the spinal cord. The result is contractions of several muscle groups at the
same time.
Experiment 3

- It is made evident how the action of drugs works, taking into account that
they follow first-order kinetics.
- In case 5 an antiarrhythmic effect could be seen when the concentration
was higher and lower. Among these effects we could see other
consequences of the drug, such as muscle weakness, fatigue,
hypotension and asthma attacks.
- We came to understand the different pharmacokinetic parameters since
the 8 cases were carried out in which we calculated and determined
different values.

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1
CONCLUSIONS

- We understood that some medications, due to their chemical

composition, their physical state, must be administered in different ways
and in some patients due to various diseases, physical state, medications
must be administered by different routes than the common ones. Also,
we conclude that the dose and other factors such as pH alter the effects
of the drugs.
- It was concluded that the factors that influence the action of the drugs are
age (in children and the elderly the kidney and liver significantly change
their functionality), weight (the higher the weight, the higher the dose),
sex (hormones), factors genetics, presence of diseases, timing of
administration (greater absorption on an empty stomach), and
environment (e.g., psychiatric medications).
- We understood that the relationship of some pharmacokinetic and
pharmacodynamic parameters such as the maximum concentration
achieved (Cmax), the area under the curve (AUC) and the minimum
inhibitory concentration (MIC) are determinants in decision making to
select the drug and its dosage. According to these parameters, antibiotics
are classified as time-dependent and concentration-dependent. The
former (beta-lactams, glycopeptides) may require adjustments in the
infusion time and the concentration-dependent ones (aminoglycosides,
fluoroquinolones) are based on Cmax/MIC.

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