FAR 142 Basic Pharmacology and

Biochemistry
ROUTES OF DRUG ADMINISTRATION

NAME
A)
MATRIC NUMBER

: LOW KAH JUN

: 127920

DATE

: 15TH APRIL 2016

LECTURER

: Dr. YAP MUN FEI

(GROUP

AIM:
To compare the influence of the route of administration on the onset and
duration of action in response to a hynoptic drug, sodium pentobarbitone
(40mg/kg), in mice.

EQIUPMENTS AND MATERIALS:

Please kindly refer to the Pharmacology Practical Manual page 16
METHOD:
Please kindly refer to the Pharmacology Practical Manual pages 16 19

RESULTS:

Body
weight
(gm)
Volume of
drug
solution
(ml)
Time of
drug
administra
tion
(hour,min)
Time of
loss of
righting
reflexes(h
our,min)
Duration
taken for
onset of
drug
action
(min)
Time able
to stand
on fours
again

Routes of administration of sodium pentobarbitone

p.o
s.c
i.m
i.p
i.v
27.0
24.9
27.6
32.6
32.4

0.27

0.25

0.28

0.33

0.34

9.57 a.m.

10.06 a.m.

10.14 a.m.

10.25 a.m.

11.06 a.m.

10.00 a.m.

10.07 a.m.

10.21 a.m.

10.28 a.m.

11.06 a.m.

11.43 a.m.

12.30 p.m.

11.34 a.m.

12.03 p.m.

11.46 a.m.

(hour,min)

Duration
of action
(min)

103

143

73

95

40

DISCUSSION:
1. The onset of drug action refers to the time it takes for the drug to
show a therapeutic response. The duration of action can be defined
as the time a drug concentration is sufficient to elicit therapeutic
response. It means the duration of time that the drug impose a
therapeutic response on the body, in this case, the mice.
2. Based on the results we got from the experiment, the duration taken
for the onset of drug action of sodium pentobarbitone for different
routes of administration is as follow:
Intravenous < Subcutaneous < Oral = Intraperitoneal <
Intramuscular
3. Theoretically, the duration taken for the onset of drug action based
on different routes of administration should be as follow:
Intravenous < Intraperitoneal < Intramuscular < Subcutaneous <
Oral
4. In this experiment, the dose to be given to each mouse is calculated
based on their weight. This is because different weight will affect the
distribution of drugs in the body.
5. Parenteral routes provide shorter durations of action because they
dont need to go through the first-pass metabolism but directly
diffuse into the blood capillaries and into the blood circulation to the
site of action. Whereas oral administration will go through first-pass
metabolism. The drug has to pass through gastrointestinal tract
(GIT), only then to diffuse into the blood circulation, slowing its
onset of action. It will be metabolized by GIT and liver enzymes, so
this reduces amount of drug thatultimately reaches the systemic
circulation.

6. There are a few factors influencing the rate of absorption and

bioavailability that are needed to be considered before deciding on
the route of administration:
a) Viscosity and nature of drug
b) Rate of dissolution of drug
c) Volume and concentration of the drug
d) pH of the gastrointestinal tract (for oral administration)
e) Gastric motility (for oral administration)
f) Total relative surface area of the depot and the drug available
for absorption into capillary membranes
g) Splanchnic blood flow
h) First-pass metabolism
7. From the experiment, it is found that the duration of action for
sodium pentobarbitone is as follows:
Intravenous < Intramuscular < Intraperitoneal < Oral <
Subcutaneous
8. The duration of action of a drug depends on its bioavailability, rate
of it being metabolized and rate of it being excreted. Bioavailability
is the amount of administered drug that reaches the systemic
circulation following administration by any route. For instance, in the
case of oral administration, the drug will be metabolized by GIT and
liver enzymes, so this reduces amount of drug that ultimately
reaches the systemic circulation.
QUESTIONS:
1. Discuss the basis of differences in the duration taken for the
onset of drug action and the duration of action for the various
routes of drug administration in this experiment.
Intravenous
For intravenous administration, the onset of drug is the fastest
because drug is administered directly into the tail vein of the rat. It
doesnt need to go through diffusion through the endothelium of the
blood vessel. Therefore it is the fastest in reaching the blood
circulation. Also, because it doesnt go through first-pass metabolism,
its bioavailability is almost 100%, meaning that all the drugs
administered were effective. However, its duration of action is
relatively short because of its thorough and fast distribution in the
blood circulation, it completely dissolute in the blood stream, causing
it to be metabolized relatively fast.
Intramuscular

In the case of intramuscular administration, the onset of action is

theoretically proven to be slower than intraperitoneal but faster than
subcutaneous. The absorption of the drug is diffusion-controlled but it
is faster of the high vascularity of the muscle tissue. However, the
rate of absorption is affected by physiological factors such as the
blood circulation of the muscle and the state of muscular activity. In
this experiment, intramuscular is found to have the slowest onset of
action. During administration, the drug might be injected into the
area which is less vascularized, or the needle is not inserted deep
enough into the muscle, resulting in the drug being administered only
into the subcutaneous area, reducing its bioavailability. Therefore, its
duration of drug action is relatively low. However, it was situated the
second fastest among the others. This may because the dose or
concentration of drug given is quite high for the mice.
Intraperitoneal
For intraperitoneal administration, the onset of drug is the second
fastest theoretically because the centre of the abdomen has a large
network of blood vessels and it has a large absorbing surface area to
be absorbed into the portal vein, which was quickly taken up by the
blood circulation. It has to diffuse through the endothelium of the
blood vessel, thus it works slower than intravenous route. However,
we found that intraperitoneal is the third fastest of onset of drug.
Some of the drug may have been transported into the GIT instead
and is metabolized there, reducing its bioavailability. The duration of
action is the third longest maybe because of the large surface area of
abdomen ensure constant release of drug into the blood circulation.
Oral
Through oral administration, the drug is administered directly into the
stomach of the mice. The onset of drug is same with intraperitoneal.
In the stomach, it undergoes degradation due to the digestive
enzymatic activity. Then it is transported into the small intestine, in
which it is further degraded, absorbed into the blood capillaries,
enters the liver via the hepatic portal vein, and finally is distributed
throughout the blood circulation in the body. In the liver, some of the
drug is being metabolized and excreted. This is called the first-pass
metabolism. Due to its long pathway to reach the blood circulation, it
took a long time to onset its therapeutic response. Its bioavailability
is left with 50% due to it being metabolized in the GIT and the liver.
Therefore, it has the shortest duration of action theoretically.
However, it is the second longest among the others. This might

caused by its pH of gastrointestinal tract which near to neutral or its

low gastric motility.
Subcutaneous
In this experiment, the subcutaneous injection placed the second
highest of onset of drug. Subcutaneous injection has a relatively low
onset of action theoretically due to its poor vascularization in the
subcutaneous layer compared to the rest of the parenteral routes.
The rate of absorption is difficult to control from the subcutaneous
deposits like fatty tissues. The rate of diffusion of drug is therefore
decreased. However, pentobarbital is highly lipid soluble and fat
content may alter the distributive qualities of the drug. Some of the
drug will be trapped in the layer for a longer period of time. So the
onset of action is slower. The deviation of the result from experiment
with the theory might cause by the relatively high concentration of
drug given. However, due to its constant and prolonged release into
the blood circulation, the duration of action is relatively long.

2. Explain why pentobarbitone and drugs of its kind are no more

used as anxiolytics and hypnotics.
A hypnotic drug is used primarily to induce sleep, treat insomnia and
for anesthetic use while an anxiolytic drug is used for the treatment
of anxiety and its related psychological and physical symptoms.
Sodium pentobarbitone is a very potent drug and its margin of safety
is very narrow. The therapeutic index is low, thus overdose happens
very easily. Overdose may be fatal or result in a coma. Tolerance
occurs upon prolonged used, and this results in high liability of drug
abuse. Psychological and physical dependence may develop with
repeated use. A suddenly withdrawal of pentobarbitone will cause
convulsion, coma and even death.

3. List routes of drug administration other than those stated in

this experiment. Give one example of drug administered via
each route given and the rationale for choosing the named
route.
a) Inhalation: Inhalation is used for rapid onset of drug action to act on
the lungs, as the drug only takes 7 10 seconds to reach the brain. Its
function is for systemic delivery of potent drugs like general

anesthetics during surgery. It is also administered for local delivery of

drugs like epinephrine for asthma relief.
b) Transdermal route: This route is used for patients who are unable to
take oral medication. The drug like nicotine is disseminated
systemically through a patch on the skin. It is also effective for local
action for drugs such as analgesics and antibiotic creams.
c) Mucousal route
(i)
Sublingual route: A small amount of drug administered below the
tongue for rapid absorption of the drug into the small blood
vessels which lie just beneath the tongue, without first-pass
effect, mainly for the systemic delivery of potent drugs.
Nnitroglycerin is administered sublingually for angina relief.
(ii) Nasal route: Drug is transformed into tiny droplets in air
(atomized), then breathed in and absorbed through the thin
mucous membrane that lines the nasal passages. Once absorbed,
the drug enters the bloodstream. It is mainly for local delivery of
drugs like antihistamine for anti-inflammatory
(ii)

(iii)
(iv)

Ocular route: It is used for local delivery of drugs to treat eye

diseases like pupil dilation and cataracts. Carbachol is
administered ocularly to constrict the pupils during cataract
surgery
Vaginal route: It is used for local delivery of drugs like
prostaglandin mainly to induce labour.
Rectal route: Drug is usually administered in the form of a
suppository to the rectum for patients who have difficulties in
swallowing medication or nausea. It is also used for systemic
delivery of potent drugs because the rectum's wall is thin and its
blood supply rich, so the drug is readily absorbed; or for local
delivery of drugs like analgesics for relieve of pain due to
hemorrhoid. For example, a suppository named Voltaren
(diclofenac sodium) is used to relieve stomach upset.

d) Intrathecal route: Intrathecal is the space under the arachnoid

membrane of the brain or spinal cord route. A drug is introduced into
the fluid surrounding the brain and spinal cord (cerebrospinal fluid) by
injecting into the subarachnoid space. This route will bypass the bloodbrain barrier and for rapid and local effects on the central nervous
system, usually for analgesic effect. For example, Ziconotide which is a
conotoxin-derived peptide used for chronic pain therapy is
administered intrathecally.

4. Discuss
the
possibilities
of
administering
sodium
pentobarbitone via intrarectal, inhalation and topical routes.
a) Intrarectal: The amount of drug absorbed into the blood circulation is
not accurately known if its intrarectally administered because rectal
doses are very erratic when suppositoriesare dissolved by the rectal
fluid and diffuse into the blood circulation. This may result in an
underdose or overdose. So administration intrarectally is not advised.
b) Inhalation: Administration through inhalation is not appropriate as
the sodium pentobarbitone molecules are directed into the lungs
instead of the brain, which is the site of action. Thus the drug will not
impose its effect, that is hypnotic and anxiolytic.
c) Topical routes: Topical administration only produces localized effect.
Sodium pentobarbitone is a water-soluble salt, and if applied to the
skin, will not be able to penetrate the hydrophobic skin layer into the
body. The drug will not be able to reach the central nervous system.
PRECAUTIONS:
1. Make sure that the oral-feeding needle is inserted through the
oesophagus and advanced into the stomach. Breathing difficulties
indicate that the needle has been mistakenly inserted into the
trachea.
2. Make sure there is no air bubble in the syringe to prevent venous air
embolisms.
3. Gentle pressure is applied to the injection site after parenteral
administration to ensure that the drug is not leaking out.
CONCLUSIONS:
1. Based on experiment, the duration taken for the onset of drug action for different
routes of administration of sodium pentobarbitone is as follows:
Intravenous < Subcutaneous < Oral = Intraperitoneal <
Intramuscular
2. Theoretically, the duration taken for the onset of drug action based
on different routes of administration should be as follows:
Intravenous < Intraperitoneal < Intramuscular < Subcutaneous <
Oral
3. Based on the experiment, the duration of drug action for different
routes of administration of sodium pentobarbitone is as follows:

Intravenous <
Subcutaneous

Intramuscular

<

Intraperitoneal

<

Oral

<

4. The onset of sodium pentobarbitone depends on the rate of

absorption of the drug into the blood circulation to its site of action
and its bioavailability; its distribution throughout the body; its rate
of being metabolised and excreted.
5. Parenteral routes provide a quicker effect to the body than oral
administration due to its high rate of absorption into the blood
circulation.

REFERENCES:
1. http://wiki.answers.com/Q/Why_is_pentobarbitone_and_drugs_of_its_
kind_are_no_more_used_as_anxiolytics_and_hypnotics
2. http://professional.cancerconsultants.com/ccj_pain.aspx?id=23792
3. http://www.ncbi.nlm.nih.gov/pubmed/15737247
4. http://www.merckmanuals.com/home/sec02/ch011/ch011b.html
5. Kewal K. Jain (2007). Drug Delivery System. Humana Press.
6. Pharmacology Practical Manual (2013). School of Pharmaceutical
Sciences, Universiti Sains Malaysia.