Transcript intramuscularly

Experiment 2: Factors Affecting Drug
Action
A. INFLUENCE OF ROUTE OF ADMINISTRATION
2A – Med
Subsection A2
Anacta, Klarizza
Andal, Charlotte Ann
Ang, Jessy
Ang, Joanne Marie
Ang, Kevin Francis
Ang, Kimberly
Aningalan, Arvin
Antonio, Abigaille Ann
Aquende, Hershe
Aquino, Arnold Cedric
Aquino, Unica
Aramburo, Jan Christian
Arcilla, Juan Martin
Argana, Desiree
Aribon, Pamela Ann
Arquiza, Paula
Asuncion, Gewelene
Atienza, Vyron
Austria, Mary Martha
1
Objectives

General Objectives
◦ To determine how the route of administration
influences the action of ketamine
hydrochloride
2
Objectives

Specific Objectives
◦ To determine the latency (sec) and duration of
effect (sec) of ketamine hydrochloride when
administered intravenously and intramuscularly
◦ To statistically determine if there is a significant
difference between the (a) latencies and (b)
durations of effect of ketamine hydrochloride in the
IV and IM group
◦ To determine the effect of route of administration
in the absorption and efficacy of ketamine
hydrochloride
3
Definition of terms:

Latency/Time to Peak Effect - Time between initial
administration and onset of the maximum expected effect.

Duration of Effect - Length of time peak effect can be
expected to last after a single administration of an
anesthetic dose.

Righting reflex - A reflex resulting in the body or a body
segment tending to regain its former body position when it
is displaced.

ESSENTIALS FOR ANIMAL RESEARCH:
A PRIMER FOR RESEARCH PERSONNEL
Second Edition
Marilyn J. Brown, D.V.M., M.S
http://dcminfo.wustl.edu/education/primer_chap4.htm
4
METHODOLOGY
5
Ketamine hydrochloride
Preparation : 50mg/mL
Dosage
: 5mg/Kg
2-(O-chlorophenyl)-2-(methylamino) cyclohexanone hydrochloride
6
Ketamine hydrochloride
water-soluble
 white crystalline
 pKa=7.5
 commercially available pharmaceutical
form is in aqueous solution

7
Ketamine
2-(2-chlorophenyl)-2-(methylamino)-cyclohexanone
8
Ketamine
anesthetic drug
 blocks the N-methyl-D-aspartate
(NMDA) glutamate receptor = noncompetitive NMDA-receptor
antagonist
 inhibits activation of NMDA receptor
by glutamate
 reduces presynaptic release of
glutamate
 potentiates effects of GABA

9
Experimental Animal: Rabbit
1
2
1
2
3
4
3
4
SECTION A
SECTION B
1
2
1
2
3
4
3
4
SECTION C
SECTION D
10
Weighing
11
Dosage
Dosage of drug
=(weight of rabbit)(5mg/kg)(1mL/50mg)
e.g.:
(1.5kg)(5mg/kg)(1mL/50mg) = 0.15mL
12
Intramuscularly (IM)
1
3
13
Intravenously (IV)
2
4
14

Time of injection

Time the righting reflex was lost

Time the righting reflex was regained
15
Righting reflex
“static reflex”
 bring the body into normal position in
space
 resist forces acting to displace the
body out of normal position
 turns a falling animal's body in space
so that its paws or feet are pointed at
the ground; hence, returns the animal
to sternal recumbency after being
placed on its back or side

16
Rabbit with no righting reflex
17
RESULTS and DISCUSSION
18
Tabulation of results- Route of Administration
SECTION
Latency
Duration of Effect
Intramuscular
(seconds)
Intravenous
(seconds)
Intramuscular
(seconds)
Intramuscular
(seconds)
1
335
11
472
876
2
129
10
322
1112
3
170
31
172
371
4
217
30
147
361
5
76
7
852
995
6
150
9
517
1357
7
232
5
906
880
8
193
9
898
662
187.75
14
535.75
826.75
SD
72.632207
9.68245837
296.19873
325.552511
Variance
5275.4375
93.75
87733.6875
105984.438
A
B
C
D
Mean
19
Actual Results
L atenc y
tim e (s ec .)
400
300
intramus c ular
200
intravenous
100
0
0
1
2
3
4
5
6
7
8
9
ra bbit no.
20
Actual Results
time (sec.)
Duration
1600
1400
1200
1000
800
600
400
200
0
intramuscular
intravenous
0
1
2
3
4
5
6
7
8
9
rabbit no.
21
Actual Results

Latency (Mean)
◦ Intravenous = 14 seconds
◦ Intramuscular = 187.75 seconds

Duration (Mean)
◦ Intravenous = 826.75 seconds
◦ Intramuscular = 535.75 seconds
22
Hypothesis

Ho: there is no significant difference in
the latency/duration between
intramuscular and intravenous
administration

H1: there is significant difference in the
latency/duration between
intramuscular and intravenous
administration
23
Formula for calculating independent
t statistics
Test statistic

Its value is used to decide whether or not the null hypothesis should
be rejected in our hypothesis test
= difference between
population means
= Pooled standard deviation
24
Latency
Count
mean
variance
Standard
deviation
Intramuscular
8
187.75
5275.44
72.63
Intravenous
8
14
93.75
9.68
t=
(187.75 – 14) – 0
= √ 5275.44(8-1) + 93.75(8-1)
51.81 √1/8+1/8
√
= 51.81
8+8-2
= 7.00
25
Critical region

Set of values of the test statistic for
which the null hypothesis is rejected in
a hypothesis test
df = n1+n2 -2
 df = 14
 Critical region = 1.7613

26
t = 7.00
 Critical region = 1.76

Fail to
reject
Ho
Reject Ho
1.76
7.00
27
Duration
Count
mean
Intramuscular
8
535.75
Intravenous
8
826.75
t=
(535.75 – 826.75) – 0
311.22√1/8+1/8
variance
Standard
deviation
87733.69
296.20
105984.44
325.55
Sp= √ (8-1) 87733.69 + (8-1) 105984.44
8+8-2
Sp =311.22
= -2.64
28
Duration
t = -2.64
Critical region : 1.7613
Reject Ho
Fail to
reject
Ho
1.76
29
Actual Results: Statistics
Student t test
t test for two independent variables
Significance level = 0.05
Latency
Intramuscular vs Intravenous
P value 0.00017991< 0.05
There is significant difference
Duration
Intramuscular vs Intravenous
P value 0.05115812 > 0.05
There is no significant difference

30
Expected results

IV route has faster onset of action than
IM route

Duration of action is greater in IM than
the IV route
31
Intravenous Drug Administration
Intravenous (IV) [drug administered
directly into the bloodstream]
 Avoids first pass metabolism
 Rapid and complete absorption
[100% Bioavailability]
 Fastest rate of drug delivery and
onset of action

32
Intravenous Drug Administration
Maximal degree of control over drug
circulating levels
 No way to stop response to drug
(no recall)

33
Intramuscular Drug Administration

Intramuscular (IM)
- Rapid absorption and onset of action
• Uptake of drug dependent on blood flow at the
injection site and solubility of the drug.
34
IV versus IM Drug Administration

Onset of action
is indeed faster
in the IV route.
35
DURATION OF ACTION
36
Sources of Error

Human Error:
◦ The administration of drug was done by
different experimenter
◦ The time of observation of latency and
duration was done by different people
37
CONCLUSION
38
Onset of action
IV route has faster onset of action than
IM route
 The onset of action is dependent on the
route of administration

39
Duration of action
Duration of action in the intramuscular
route is dependent on the solubility of
the drug
 The IM route has a longer duration of
action than the IV route

40
References

Howland, Richard and Mycek, Mary. Lippincott's
Illustrated Reviews. Lippincott Williams and Wilkins,
2006.

Katzung, Betram G. Basic and Clinical Pharmacology,
10th ed. The McGraw-Hill Companies, Inc, 2007.
41
THANK YOU!
42
Tolerance

Repeated use of ketamine
 users can develop a tolerance and/or dependence to the
drug.
 Rises quickly with regular use and lasts about three days

Can be very high and develop rapidly to the point where after
a period of time users will no longer experience the
dissociative effects they first began using

Chronic use can cause development of a very high, almost
permanent, tolerance to the drug.
43
Ketamine Absorption
Ketamine is rapidly absorbed when administered
through the intramuscular (Tmax 5-15 min), nasal
(Tmax 20 min) or oral route (as a solution) (Tmax
30 min).
 Bioavailability is low when ketamine is given orally
(17%) or rectally (25%). Extensive first pass
metabolism in liver and intestine is largely
responsible for this effect. Bioavailability after nasal
administration is approximately 50% (Malinovsky et
al., 1996)

44
Ketamine Distribution
•
Ketamine has a high lipid solubility and low
plasma protein binding (12%), which
facilitates rapid transfer across the bloodbrain barrier.
 Initially it is distributed to highly perfused
tissues, including the brain, to achieve
levels 4-5 times those in plasma
(distribution half-life after i.v. 24 sec.).
 CNS effects subside, following redistribution
to less well-perfused tissues (re-distribution
half-life 2.7 min.).
45
Ketamine Metabolism

Biotransformation primarily takes place in the liver.
The most important pathway is N-demethylation to
norketamine. When administered orally or rectally,
initial plasma norketamine concentrations are
higher than those of ketamine are, but the plasma
area under the curve (AUC) for norketamine is
similar for all routes of administration. Norketamine
has one-third the anaesthetic potency of ketamine
and has analgesic properties. Norketamine may be
metabolised through multiple pathways, but the
majority is hydroxylated and subsequently
conjugated.
46
Ketamine Elimination

The predominant route of elimination
is by liver metabolism. The high
extraction rate (0.9) makes ketamine
clearance susceptible to factors
affecting blood flow. The conjugated
hydroxy metabolites are mainly
excreted renally. Terminal elimination
half-lifes are ranging from 100-200
minutes.
47