Glasgow Royal Infirmary

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PHARMACEUTICAL ASPECTS OF INTRAVENOUS DRUG
ADMINISTRATION

• Glasgow Royal Infirmary
• Pharmacy Department

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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

Conc.
time
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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

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• 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.

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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

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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

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Intermittent IV INFUSION 20-120 minutes

• One-off or repeated doses
• E.g. Gentamicin, vancomycin, erythromycin
• High plasma concentration achieved rapidly over
  longer periods.

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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.

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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.

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Solutions needing further dilution

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

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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 contamination
• BUT
• Microbial contamination
• Fluid overload

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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.

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Degradation

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

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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.

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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

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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....

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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.

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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 ADRs

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Intravenous Antibiotics

• State for each of the following
• Diluent volume required for reconstitution
• Volume required for dose
• Type of injection
• Gentamicin 260mg Erythromycin 750mg
• Co-amoxiclav 1.2g Metronidazole 500mg
• Tazocin 4.5g

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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)

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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 25ml
• Conc. 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)

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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)

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• How would you prepare and administer
• Gentamicin 260mg
• Co-amoxiclav 1.2g
• Tazocin 4.5g
• Erythromycin 750mg
• Metronidazole 500mg

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

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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 750mg
• 1000mg vial reconstituted with 20ml WFI.
  Withdraw 15ml (750mg) and add to 250ml NaCl 0.9.
  (Cannot get 150ml bag!!) Infuse over 60min.

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Answers (cont.)

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