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EXPERIMENT NO.

2
FACTORS AFFECTING DRUG
ACTION

INFLUENCE OF ROUTE
ADMINISTRATION
Drug Administration
• the giving of a drug by one of several
means
• When a drug is introduced to the body, it
moves into the bloodstream and is then
transported to the target site where its
action is desired to take place
• Drug’s pharmacokinetic properties
(absorption, distribution, metabolism,
and elimination) are greatly influenced
by the route of administration
ROUTES OF
ADMINISTRATION
 Topical
 the
substance is directly applied to the area
where its action is desired to take place
and includes epicutaneous, inhalational,
enema, eye and ear drops, and intranasal
 Enteral
 thesubstance is given via the digestive
tract and can be oral or rectal
 Parenteral
 thesubstance is administered by injection,
which can be subcutaneous, intramuscular,
intravenous, and intrathecal
 Reasons for using a certain route depend
on convenience, drug’s ability to
maximize its action at the target site,
ability to prolong its duration of
absorption, and in order to avoid the
first-pass effect
 Each route then has specific purposes,
advantages, and disadvantages
GENERAL OBJECTIVE
 To determine the influence of the route
of administration, namely intravenous
(IV) and intramuscular (IM), on the effect
of drug action.
SPECIFIC OBJECTIVES
 To determine latency and duration of
ketamine HCl administered IV
 To determine latency and duration of
action of ketamine HCl administered IM
 To compare latency and duration of
action of ketamine HCl between IM and
IV routes using appropriate statistical
test
MATERIALS
 Animals:
Rabbits (4)
 Instruments:
Rabbit cage
Animal weighing scale
Tuberculin syringe
Stopwatch
 Drug:
Ketamine Hydrochloride
Preparation: 50 mg/mL
Dosage: 5mg/kg
METHODOLOGY
 Rabbits were weighed separately to
compute for the dosage of drug
(Ketamine HCl) to be given.
 For the first set of rabbits (2), 0.19mL
and 0.16 of Ketamine HClwas given
intramuscularly. This was done by
injecting the drug through the thigh of
the hind leg.

 --- doses are dependent on weights


 The following parameters were noted
and recorded:
- time the drug was administered
- time the righting reflex of the rabbit
was lost (in secs) (latency)
-time the righting reflex was regained (in
secs) (duration of action)
Righting reflex
 ability to assume an optimal position or
to bring the body into normal spatial
position when there has been a
departure from it
 For the second set of rabbits(2),
Ketamine HCl was given intravenously
through the lateral vein in the rabbit’s
earlobe.
 The same parameters were also
observed (time drug was administered,
latency, and duration of drug action)
 The onset and duration of effect of
Ketamine HCl administered
intramuscularly and intravenously were
compared using statistical test.
RESULTS
 Dosage Computation
 Drug: Ketamine Hydrochloride
 Preparation: 50 mg/mL
 Dosage: 5mg/kg
Dosage Computations
 IM
 Rabbit 1: 1.9kg
Volume of ketamine to be administered =
5mg/kg (1.9kg)
= 9.5mg * (1mL/50mg)
= 0.19 mL
 Rabbit 2: 1.6kg
= 0.16mL
Drug Computations
 IV
 Rabbit 1: 1.7kg
= 0.17mL
 Rabbit 2: 1.9kg
= 0.19mL
INTRAMUSCULAR INTRAVENOUS
LATENCY 179.250 53.500
DURATION 824.625 532.625
INTERPRETATION OF
RESULTS
 ACTUAL RESULTS(IM vs IV)

 DURATION
 Paired t-test showed no significant difference ( p
= 0.110)

 LATENCY
 Paired t-test showed significant difference (p=
0.017)
INTERPRETATION OF
RESULTS
 EXPECTED RESULTS
 Intravenous route should have shorter
latency compared to intramuscular route.
 Duration for both IM and IV is the same.
KETAMINE HYDROCHLORIDE
 dissociative anesthetic for use in human
and veterinary medicine
 usually injected intravenously or
intramuscularly, but it is also effective
when insufflated, smoked, or taken
orally
 suppresses breathing much less than
most other available anaesthetics
 may be used in small doses (0.1–0.5
mg/kg/h) as a local anesthetic,
particularly for the treatment of pain
associated with movement and
neuropathic pain
 Occasionally used as a short-acting
general anesthetic for children and
elderly patients
 block afferent impulses associated with
the affective-emotional component of
pain perception within the medial
medullary reticular formation, to
suppress spinal cord activity, and to
interact with several central nervous
system (CNS) transmitter systems
 arylcyclohexylamine, chemically related
to tiletamine and PCP
 non-competitive glutamate inhibitor at
the NMDA receptors
 reduces presynaptic release of
glutamate and potentiates effects of
gamma-aminobutyric acid
 highly lipophilic drug and is rapidly
distributed into highly vascular organs
 molecular weight is 283 g/mol and is
partially water soluble at pH 7.4 (pKa
7.5)
 Its bioavailablity (IM) is 93%, while
orally, it is 17%
 metabolized in the liver and excreted
into the urine (>90%)
 Half-life is less than15 minutes
INTRAVENOUS
 100% bioavailability
 done by inserting a needle directly into a
vein
 A drug given intravenously is
immediately delivered to the
bloodstream and tends to take effect
more quickly than when given by any
other route
 effect of a drug given by this route tends
to last for a shorter time
 offers the best way to deliver a precise
dose quickly and in a well-controlled
manner throughout the body
 drug avoids the GI tract and, therefore,
first- pass metabolism by the liver
 also used for irritating solutions, which, if
given by subcutaneous or intramuscular
injection, would cause pain and tissue
damage
INTRAMUSCULAR
 75 to <100 % bioavailability
 is preferred when larger volumes of a
drug product are needed
 longer needle is used since it would pass
through the skin and fatty tissues before
penetrating the underlying muscles
 usually injected into muscle in the upper
arm, thigh, or buttock
 rate of absorption of the drug into the
bloodstream depends on the blood
supply to the muscle
 The sparser the blood supply, the longer
the drug takes to be absorbed.
REASONS FOR
DISCREPANCIES
 inaccurate dosage of the given drug
 inability to administer the drug at the
appropriate route (like missing the vein
and injecting the drug subcutaneously
instead of having it administered
intravenously)
 improper assessment of loss and gain of
the righting reflex of the test animal
CONCLUSION
 Intramuscular vs Intravenous
 Significant difference in LATENCY
 No significant difference in DURATION
References
 Lippincott Williams and Wilkins (2005).
Clinical Pharmacology.
 Beers, M., et al. (2003). The Merck
Manual of Medical Information 2nd ed. NJ:
Merck & Co., Inc.
 Katzung, B. (2004). Basic and Clinical
Pharmacology 9th ed. Singapore: The
McGraw-Hill Companies, Inc.
 Ketamine. Available at:
http://www.rxlist.com/cgi/generic3/ketamine
, 2005.
 Ketamine Hydrochloride. Available at:
http://
www.drugs.com/MMX/Ketamine_Hydrochlori
. Accessed July 29, 2005.
 Route of Administration. Available at:
http://
en.wikipedia.org/wiki/Route_of_administratio
. Accessed July 29, 2005.
Results of the Experiment

INTRAMUSCULAR INTRAVENOUS
SECTION LATENCY (s) DURATION LATENCY (s) DURATION
A (s) (s)
123 1196 46 851
A 239 680 3 1138
B 192 724 69 184
B 388 195 34 389
C 147 383 52 237
C 73 671 38 106
D 174 1716 156 756
D 98 1032 30 600
Intravenous

 an intravenous dose of 2 mg/kg (1 mg/lb)


of body weight (for surgical anesthesia)

Latency: within 30 seconds after


injection
Duration: 5-10 minutes
Intramuscular
 in a range of 9 to 13 mg/kg (4 to 6 mg/lb)
usually produce surgical anesthesia with:

Latency: 3-4 minutes following


injection
Duration: 12-25 minutes
Paired Sample s Statistics

Std. Error
Mean N Std. Deviation Mean
Pair imlat 179.2500 8 99.59310 35.21148
1 ivlat 53.5000 8 45.55687 16.10679
Pair imdur 824.6250 8 481.30416 170.16672
2 ivdur 532.6250 8 365.24901 129.13503
Paire d Sample s Corre lations

N Correlation Sig.
Pair 1 imlat & ivlat 8 -.107 .801
Pair 2 imdur & ivdur 8 .459 .252
Paired Samples Test

Paired Differences
95% Confidence
Interval of the
Std. Error Difference
Mean Std. Deviation Mean Lower Upper t df Sig. (2-tailed)
Pair 1 imlat - ivlat 125.75000 113.86929 40.25887 30.55289 220.94711 3.124 7 .017
Pair 2 imdur - ivdur 292.00000 451.13793 159.50134 -85.16074 669.16074 1.831 7 .110

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