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 substance is given via the digestive tract and can be oral or rectal

Enteral
 the

Parenteral
 the

substance 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 2: 1.9kg

0.17mL 0.19mL

 Rabbit

INTRAMUSCULAR LATENCY DURATION 179.250 824.625

INTRAVENOUS 53.500 532.625

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

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 Mean 179.2500 53.5000 824.6250 532.6250 N 8 8 8 8 Std. Deviation 99.59310 45.55687 481.30416 365.24901 Std. Error Mean 35.21148 16.10679 170.16672 129.13503

Pair 1 Pair 2

imlat ivlat imdur ivdur

Paire d Sample s Corre lations N Pair 1 Pair 2 imlat & ivlat imdur & ivdur 8 8 Correlation -.107 .459 Sig. .801 .252

Paired Samples Test Paired Differences 95% Confidence Interval of the Difference Std. Error Mean Std. Deviation Mean Lower Upper imlat - ivlat 125.75000 113.86929 40.25887 30.55289 220.94711 imdur - ivdur 292.00000 451.13793 159.50134 -85.16074 669.16074

Pair 1 Pair 2

t 3.124 1.831

df

Sig. (2-tailed) 7 .017 7 .110