Iv Infusion PDF

IV INFUSION Prepared by: Dr.Rahila Bano Assistant Professor Pharmaceutic, DCOP, DUHS LEARNING OBJECTIVES At the end of this lecture students will be able to  Define IV infusion  History of IV infusion  Explain the purpose for intravenous therapy  Explain types of intrav...

IV INFUSION Prepared by: Dr.Rahila Bano Assistant Professor Pharmaceutic, DCOP, DUHS LEARNING OBJECTIVES At the end of this lecture students will be able to  Define IV infusion  History of IV infusion  Explain the purpose for intravenous therapy  Explain types of intravenous fluids (IV bolus and infusion)  Calculate the flow rate for an infusion  Advantages of IV infusion Intravenous Infusion  Drug administration through the intravenous route at a constant rate over a determined time interval.  Intravenous is the term means “into the vein”  Infusion is a slow injection of a substance into a vein History of IV Infusion  Intravenous technology started from studies on cholera treatment in 1831  It was further developed in 1930s but was not widely available until the 1950s Purpose of IV Infusion  Maintenance of stable plasma concentration  Avoidance of periods of low drug concentration  Dosage adjustments  Maintain or replace body store  Restore acid base balance  Administer medication  Provide nutrition  IV solution may be given either as  A bolus dose  An Infused slowly through a vein into the plasma at a constant or zero order rate  Intravenous Bolus Administration  IV bolus administered drugs, the entire dose enters the bloodstream directly. This is followed by distribution of the drug through the circulatory system to all the tissues in the body.  Concentration of the drug in various tissue organs or the process of drug distribution in the body will occur depending on the blood flow to the tissue, the molecular weight of the drug, the drug lipophilicity, plasma protein binding, and the binding affinity of the drug toward certain tissue.  Mostly, drugs are eliminated from the body either through the kidney and/or the liver following drug metabolism.  The first pharmacokinetic parameter that arises is the apparent volume of distribution, VD, which is the volume in which the drug is distributed on it within the body  The elimination rate constant, k, is the second pharmacokinetic parameter which governs the rate at which the drug concentration in the body declines over time.  IV (dose)-----------DB, Vd----------K----------- Elimination IV Infusion  This can be obtained by high degree of precision by infusing drugs IV, a drip  The body is considered as a single, kinetically homogeneous unit.  This route applies only to those drugs that distributes rapidly throughout the body.  Drugs move dynamically in an out of this compartment  Drugs administered by constant IV infusion show a zero-order input process,  during which the drug is introduced into the bloodstream while the elimination process for most drugs is first-order.  The rate of input minus the rate of output represents the change in the amount of drug in the body at any given time (dDB/dt)  dDB / dt = R – k DB  If DB is the amount of the drug in the body, R is the rate of drug input (infusion rate) and k is the elimination rate constant.  The expression that best describes the process is: dD /dt = R- k Cp Vd  Integration of the last equation will give Cp = [ R/Vd K ] ( 1- e-kt )  At infinite time, t = α and e –kt will approach zero (at steady-state) and the last equation will be: Css = R /V k = R /Clearance  At steady-state, the rate of drug input (R) is equal to the rate of drug output (k DB)  so, R = k.DB and R = k. CP. VD CP = R / VD. K  At steady-state, CP = Css So, R = k.Css. VD Css =R / k.VD Css = R / Cl  Once the infusion stops either this achieved at or before steady- state is reached,  The drug concentration will decline according to first-order rate kinetics with the slope of the elimination curve that is equal to – k/2.3. Example  A desired steady-state plasma concentration of theophylline may be 15 mg/L. The average half-life of theophylline is about 4 hr and the apparent volume of distribution is about 25 liter. What is the necessary infusion rate? R = k.Css. VD R = 0.17/hr × 15 × 25 = 63. 75 mg/hr Steady-State Drug Concentration (CSS) and Time to Reach Steady-State  During administration of a drug by IV infusion, the plasma drug concentration starts to increase and the rate of drug elimination will also increase since the latter is concentration dependent.  Cp keeps increasing until a steady-state condition is reached at which the rate of drug input (IV infusion rate) equals the rate of drug output (elimination rate).  At this stage, a steady-state (CSS) is reached and the resulting plasma drug concentration is directly related to the rate of infusion and inversely related to the body clearance of the drug.  For drug administered by IV infusion, the therapeutic activity is observed when the concentration of the drug is close to the desired plasma concentration, which is usually the required steady-state drug concentration.  The time to reach steady-state could be determined by knowing the time to reach half the steady-state  which can be derived:  Since Css = R / VD.k = R / Clearance  At (t½); time to reach half the steady-state , CP = Css/2 Cp = [ R/Vd K ] ( 1- e-kt half ) = Css/2 Css ( 1- e-kt half ) = Css/2 (1- e-kt half ) = 1/2 - e-kt half = 1/2 - 1 - e-kt half = 0.5 Taking the ln to both sides, T1/2 = 0.693 / k Example  A septicemia patient was administered by constant IV infusion an antibiotic that has an elimination half-life (t½) of 6 hr. The rate of infusion was 2 mg/hr. At the end of second day of treatment, the serum drug concentration was 10 mg/L. Calculate the total body clearance ClT for this drug. Calculating Patient Elimination Half- Life Following Drug Infusion  The half-life for drug administered by IV infusion could be calculated from (0.693/k).  So, a mathematical expression that describes the elimination rate constant should first be determined. Cp = [ R/Vd K ] ( 1- e-kt ) since, Css = R / k.VD Cp =Css ( 1- e-kt ) Cp = Css – Css. e-kt Css. e-kt = Css – Cp e-kt = (Css – Cp) / Css Kt / 2.303 = log (Css – Cp) / Css K = ( -2.303/ t )× log (Css – Cp) / Css Example  A patient was administered an IV infusion of a certain antibiotic at an infusion rate of 15 mg/hr. Blood samples were taken from this patient at 8 and at 24 hr and the plasma concentrations for this drug were found to be 5.5 and 6.5 mg/L, respectively. Calculate approximately the elimination half-life of this drug. Loading Dose plus IV Infusion (Combined Infusion and Bolus Administration)  If we desire to achieve a quick therapeutic concentration, a loading dose by rapid intravenous injection (bolus injection) is first administered and then starts the slower maintenance infusion.  At this condition, the total drug concentration in the plasma is the function of both; the IV bolus and the infusion doses.  The concentration following IV bolus (C1) is described by: C1 = Loading dose (DL)/Vd e-kt = Coe-kt  The concentration following IV infusion at rate R is: C2 = [ R/Vd K ] ( 1- e-kt )  The total concentration Cp will be the sum of bolus and infusion: CP = C1 + C2  Cp = (DL)/Vd e-kt + [ R/Vd K ] ( 1- e-kt )  If the loading dose (DL) represents or equals the amount of drug in the body at steady-state,  so, DL =Css.Vd since Css = R /VD.k Css. V = R /k Therefore, DL = R/K Example  An anesthetic agent was administered by IV infusion at a rate of 2 mg/hr. The drug has an elimination rate constant of 0.1/ hr and a volume of distribution (one compartment) equals to 10 L. What loading dose is recommended if the physician wants the drug level to reach 2 μg /mL immediately? DL = Css.VD DL = 2μg /mL x10 x1000 = 20000μg = 20mg Or, DL = R/K = 2 / 0.1= 20mg Advantages of IV Infusion  An immediate therapeutic effect is achieved due to a rapid delivery of the drug/fluid to target sites.  If patient can not tolerate drug by oral route, iv route is applicable.  Pain and irritation caused by some substances when given intramuscular or subcutaneously is reduced. References Applied Biopharmceutics and Pharmacokinetic (Leon Shargel) Basic Pharmacokinetics (Sunil S jambhekar and Philips J Breen Biopharmceutics and pharmacokinetics (PL Madan and Jaypee)