* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download intramuscularly
Survey
Document related concepts
Polysubstance dependence wikipedia , lookup
Psychopharmacology wikipedia , lookup
Plateau principle wikipedia , lookup
Compounding wikipedia , lookup
Neuropsychopharmacology wikipedia , lookup
Pharmaceutical industry wikipedia , lookup
List of comic book drugs wikipedia , lookup
Prescription costs wikipedia , lookup
Prescription drug prices in the United States wikipedia , lookup
Pharmacognosy wikipedia , lookup
Intravenous therapy wikipedia , lookup
Pharmacogenomics wikipedia , lookup
Drug discovery wikipedia , lookup
Theralizumab wikipedia , lookup
Drug design wikipedia , lookup
Neuropharmacology wikipedia , lookup
Drug interaction wikipedia , lookup
Transcript
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