IV INFUSIONS

1Intravenous infusion

INTRAVENOUS INFUSION

BAZLA SIDDIQUI


INTRAVENOUS INFUSION

"Drug administration through the intravenous route at a constant rate over a determined time interval.“

Intravenous: administering a solution into or within a vein

Infusion: slow injection of a substance into a vein or subcutaneous tissue


Cont…

IV solutions may be given either as :

a bolus dose

or infused slowly through a vein into the plasma at a constant or zero order

rate.



PURPOSE OF IV INFUSIONMaintenance of stable plasma concentration.

Avoidance of periods of low drug concentrations.

Maintenance of clinical effectiveness.

Dosage adjustments

Maintain or replace body store .

Restore acid base balance

Administer medication

Provide Nutrition6Intravenous infusion

ADVANTAGES OF IV INFUSION

An immediate therapeutic effect is

achieved due to a rapid delivery of the drug/fluid

to target sites

Pain and irritation caused by some

substances when given intra

muscularly or subcutaneously is

reduced.

if patient cannot tolerate drug by

oral route, iv route is

applicable.


ONE COMPARTMENT MODEL DRUGSIV INFUSION

• This can be obtained by high degree of precision by infusing drugs i.v. via a drip or pump in hospitals

• The body is considered as a single, kinetically homogeneous unit.

• This model applies only to those drugs that distributes rapidly throughout the body.

• -Drugs move dynamically in an out of this compartment


PLATEAU LEVEL OR STEADY-STATEONE COMPARTMENT MODEL

DRUGS•At steady state, the rate of drug leaving the

body is equal to the rate of drug (infusion rate) entering the body.

Rate of drug input= rate of drug output

• the rate of change in the plasma drug concentration

dC p/dt = 0


PLATEAU LEVEL OR STEADY-STATE

Drug accumulates in the body during an infusion as a function of the difference b/w drug in and drug out

In one compartment model, Infused drug follows:

•Zero order input

•First order output


Cont…

Css can be determined by the equation:

Css= ko/Cl or R/Cl

ko = Rate of constant intravenous infusion (mg/h)

R = infusion rate

Cl = Clearance




Example

• 1. An antibiotic has a volume of distribution of 10 L and k =0.2 hr-1. A steady-state plasma concentration of 10 g/mLis desired. The infusion rate needed to maintain this concentration can be determined as follows.

• Equation

Css= R/Cl

Cl= VD.k

R=CssVD.k

R=(10)(10)(1000)(0.2)

R=20mg/h


Example 2:A patient was given an antibiotic (t 1/2 = 6 hr) by constant IV infusion at a rate of 2 mg/hr. At the end of 2 days, the serum drug concentration was 10mg/L. Calculate the total body clearance Cl T for this antibiotic. Solution:

Equation used is:Css= R/Cl

So Cl=R/Css


LOADING DOSE PLUS IV INFUSION:

THE LOADING DOSE:

• Css achieved immediately

• obtain desired concentrations

IV INFUSION:

• loading dose is sustained by infusion rate.

Superimposition of two contributing processes to the plasma concentration at any time would produce a sustained plasma concentration.


LOADING DOSE PLUS IV INFUSION:


INCREASING THE INFUSION RATE :

If a drug is given at a more rapid infusion

rate, a higher SS drug concentration is obtained but the time to reach SS is

the same.


LOADING DOSE PLUS IV INFUSION:Cp LEVEL:

• If loading dose in body at time t is

e-kt

• Then steady state achieved by infusion is

1-e-kt

• Plasma concentration at steady state is

Cp= Css-(1-e-kt)


CP LEVEL

Plasma concentrations during the start of an infusion and after the infusion has been switched off once a steady state has been achieved.


EFFECT OF LOADING DOSES

In practice the solution is to give an

iv bolus loading dose at the start of

the infusion equal to the required therapeutic

concentration

Reason: time delay b/w start of infusion and attainment of pleateu level may not be desirable.

Sustained plasma concentration can

be achieved by exactly matching

the infusion rate to replace the drug loss

by elimination of loading dose.


DRUG PLASMA CONCENTRATION

• Total concentration at any time is:

• Sum of contributions made by loading dose and the infusion rate

• Equation for calculating plasma concentration at any time (Cpt) is:

• Contribution from loading dose + contribution from infusion

• Cpt= D/V .e-kt + ko/Cl.(1-e-kt)


CALCULATION OF ELIMINATION HALF LIFE OF DRUG

It is defined as time taken for the amount of drug in the body as well as plasma concentration to decline by ½ or 50% its initial value.

Css versus time relationship may be used to calculate k or indirectly elimination half life of drug in patient.

One or more plasma samples must be taken at a known time after infusion.

It is expressed in hrs or mins

t1/2 = 0.693/k 23Intravenous infusion

Cont…

•Half life is secondary parameter that depends upon the primary parameters clearance and volume of distribution

•Knowing the half life in the general population helps to determine if the sample is taken at steady state in the patient.


CLINICAL APPLICATION OF CONTINUOUS IV INFUSION:

• For drugs with a narrow therapeutic window, IV infusion maintains an effective constant plasma drug concentration by eliminating wide fluctuations between the peak (maximum) and trough (minimum) plasma drug concentration.

• Prevent toxicity that might occur if the drug is presented too quickly

• E.g:

• Immune reactions

• Hypotensive reaction

• Local damage to vein25Intravenous infusion

EXAMPLES OF CLINICAL APPLICATION

Insulin in hyperglycemic

coma

Heparin in acute

thrombosis

Liginocaine in acute

arrythmias

Isosorbide for vasodilation

Adrenergic agonists

Diazepam for antiepileptic

control


ANALOGUES OF THE INFUSION MODEL IN DRUG DELIVERY

Transdermaldrug delivery

depot implants/ injections

Oral controlled

release dose forms


EXTRAVASCULAR ADMINISTRATION

• Extravascular route:

• Oral, intramuscular, rectal, buccal.etc.

• Dosage form first has to release the drug which then has to be absorbed from the site of administration.

• For systemically acting drugs, absorbtion is prerequisite for therapeutic activity

• Bioavailabilty and absorbtion rate constant need to be considered.


INTRAVENOUS INFUSION OF TWO COMPARTMENT MODEL DRUGS

• Many drugs given by iv infusion follow two compartment kinetics

Example:

The drugs follow two compartment models are:

• Theophylline

• Lidocaine

Iv infusion requires a distribution and equilibration of the drug before a stable blood level is reached.


Cont…

• This compartment helps to explain distribution within the body which is not 'instantaneous', that is slow enough to see in the plasma concentration versus time curve.

• This shows up as a rapid drop at first with elimination and distribution, followed by a slower phase.

• During a constant infusion , drug in the tissue compartment is in distribution equilibrium with the plasma

• Constant Css level result in constant drug concentration in the tissue

• No net change in amount of drug in tissue occurs during steady state.


SUMMARY

Intravenous infusion 31

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IV INFUSIONS