Glasgow Royal InfirmaryPharmacy Department

PHARMACEUTICAL ASPECTS OF

INTRAVENOUS DRUG ADMINISTRATION

Differences IV ORAL route

IV administration leads to: Higher peak

concentrations Greater total quantity of

drug absorbed Avoids 1st pass

metabolism However requires more

training, knowledge, skills and precautions

time

Conc.

IV route - Advantages

Emergency situations / immediate response e.g. adrenaline in cardiac arrest.

Loading dose e.g.digoxin, phenytoin Patient unable to swallow or tolerate

other routes Sustained drug levels required Drug cannot be given by another route

because of its chemical property e.g. cytotoxics, cefotaxime

Less painful than I.M. injection. Administration can be stopped

quickly Allows dosing of unconscious,

uncooperative and uncontrollable patients.

To achieve effects unattainable by oral administration.

IV route - Disadvantages

Risk of toxicity Risk of embolism Risk of extravasation/phlebitis Fluid overload Problems with compatibility + stability Risk of microbial contamination Increased cost More training required

BOLUS 3-10 minutes

Quick/easy/economical Tendency to administer too quickly

causing damage to veins. Sudden anaphylactic reactions Only limited volumes can be

administered

Intermittent IV INFUSION 20-120 minutes

One-off or repeated doses E.g. Gentamicin, vancomycin,

erythromycin High plasma concentration

achieved rapidly over longer periods.

Continuous IV INFUSION

Delivers constant level of drug Used for drugs with a rapid elimination

rate or a very short half-life e.g. midazolam

BUT Fluid overload, incompatibility,

contamination, incomplete mixing, phlebitis and rate calculations can be problematic.

Formulation of I.V. drugs

Reconstitution required-Dry powder e.g. amoxicillin-Allows prolonged storage

BUT- Is time consuming- Risk of contamination, foaming, glass particles, pressurised vials.

Solutions needing further dilution

e.g. Ranitidine, Amiodarone No reconstitution necessaryBUT Time consuming Prone to vacuum/pressure problems Can cause glass breakage Risk of microbial contamination.

‘Ready to use’

No further dilution needed Come in bags/small volume amps/syringes e.g.

metoclopramide, adenosine, morphine PCAs Easy to use & time saving Minimal microbial contaminationBUT Microbial contamination Fluid overload

Factors influencing Stability & compatibility

A proportion of the drug will be lost between time of preparation and

entry into the bloodstream by degradation, precipitation or an

interaction.

Degradation

By hydrolysis in aqueous solution May be accelerated by pH change Minimised by using reccomended

diluent

Photodegradation Breakdown by light. e.g. Vitamin A,

sodium nitroprusside, liposomal amphotericin.

May not be clinically important provided direct exposure to strong daylight is avoided e.g. furosemide.

Precipitation Precipitates are inactive but harmful:

can block catheters, damage capillaries and cause emboli.

May be transparent or pale Affected by differences in pH Anions and cations mix to form ion

pairs Most drugs are more soluble as temp.

increases

Blinding of drugs to plastics

Most equipment made from plastic

Drug binding difficult to predict as it depends on:

Conc. Flow rate, vehicle, surface area, temp. pH and time.

Care with insulin, diazepam, nitrates....

Leaching of plasticisers Oils and surfactants contained in

PVC bags can leak out and affect compatibility and stability of drugs.

e.g. Ciclosporin infusion must be used within 6 hours as polyethoxylated castor oil in the solution causes phthalate to leach from PVC.

Summary

Add one drug at a time following manufacturers advice

Mix thoroughly to avoid layering Examine solution regularly Add most concentrated or most soluble

additive first Strongly coloured solutions will hide

reactions Observe patient for ADR’s

Intravenous AntibioticsState for each of the following:

Diluent & volume required for reconstitution

Volume required for doseType of injection

Gentamicin 260mg Erythromycin 750mgCo-amoxiclav 1.2g Metronidazole 500mg

Tazocin 4.5g

Example (1) How would you prepare and administer

Flucloxacillin 1g IV?

Each 1g vial should be reconstituted with 20ml WFI (SPC)Add 20ml reconstituted solution to 100ml NaCl 0.9% or glucose 5% (BNF)Can be given as an infusion over 30-60min. or bolus injection over 3-4 min. (BNF & SPC)

Example (2) How would you prepare & administer

Vancomycin 1250mg

Each 500mg vial should be reconstituted with 10ml WFI – Use 3 vials (BNF Appendix 6)Got 1500mg 30ml

1250mg 1250 x 30 / 1500 = 25mlConc. of infusion fluid must be ≤ 5mg/ml (BNF)Therefore put 25ml into 250ml of Nacl 0.9% or Glucose 5%Must be given as an infusion (SPC & BNF)

References to use BNF appendix 6 BNF monographs SPC (www.emc.medicines.org.uk) Technical leaflet JHO handbook Medusa I.V. drugs guidance manual (

www.medusa.wales.nhs.uk) Ward clinical pharmacist Medicines information (ext 24407)

How would you prepare and administer:

Gentamicin 260mgCo-amoxiclav 1.2gTazocin 4.5g Erythromycin 750mgMetronidazole 500mg

Answers Gentamicin 260mg

4 x 80mg/2ml vials. Withdraw 6.5ml and add to 100ml NaCl 0.9% or Glucose 5%. Give over 30-60 min.

Co-amoxiclav 1.2g1.2g vial reconstituted with 20ml WFI. Bolus (3-4min.) or infusion in 50-100ml NaCl0.9% given over 30-40min.

Answers (cont) Tazocin

4.5g vial reconstituted with 20ml WFI or NaCl 0.9%. Bolus (3-5min.) or infusion in 100ml NaCl 0.9% over 20-30min.

Erythromycin 750mg1000mg vial reconstituted with 20ml WFI. Withdraw 15ml (750mg) and add to 250ml NaCl 0.9%. (Cannot get 150ml bag!!) Infuse over 60min.

Answers (cont.) Metronidazole 500mg

100ml bag 5mg/ml = 500mg. Infuse over 20 min.