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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.
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
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