1. Oxford University Hospitals NHS Trust Injectable medicines study day:
Claire Waghorn
Pharmacist

2. Kinetics oral vs IV
Stability and compatibility
Information sources
High risk medicines

3. Why do we use Injectable medicines?
If the oral route is unsuitable e.g. NBM
If medicines are destroyed by stomach acid e.g. insulin
If medicines are not absorbed orally e.g. heparin
If the IM route is inappropriate use IV medicines e.g. haemophilia
Provides flexibility:
To obtain high blood concentrations very quickly
For a rapid, continuous response
For a slow, continuous infusion, titrated according to response
Other examples eg gentamicin

4. Kinetics: oral dose vs. IV bolus
Single IV bolus dose profile

5. Multiple daily dosing vs. infusions
Why would you want to give intermittent infusions eg red man syndrome.
Speed shock – if given too quickly
Multiple daily dosing at steady state

6. Kinetics: IV bolus + infusion
Which drugs would you want to give loading dose?
Why?
Profile following a loading dose (bolus) and maintenance infusion

7. Relationship between plasma level & effect
= peak
Therapeutic range
= trough
Narrow therapeutic range – what does it mean?
Ask for examples – Theophylline, digoxin, gentamicin.
Vancomycin – just do trough levels (see MI bulletin)

8. Stability of Injectable products
After a medicine has been prepared, it starts to degrade. This results in by-products, which may be pharmacologically active, inactive or even toxic.
Incompatible medicines may:
Block venous access device
Introduce an embolus
These may reduce the effectiveness of treatment
Minimise risks by:
Adhere to compatibility information
Prepare immediately before use
Maximum expiry 24 hours after preparation
Prepare before use – injectables SOP
Check Embolus definition.

9. Mechanisms by which medicines degrade
pH dependent reactions (acid-alkaline)
Photo degradation (light)
Concentration dependent precipitation
Reaction with water (aqueous solutions)
Absorption of medicine by components of drug delivery system
pH dependent reactions – just some background wouldn’t expect you to work out if compatible.
Most drugs are weak acids – mix with fluids ??

10. pH Dependent Degradation
pH < 7: acidic
pH > 7: alkaline
Acidic and alkaline medicines or solutions may react with one another
Glucose 5% = pH 4-5
Sodium chloride 0.9% = pH 7
Mix like pH with like pH

11. pH Sensitive medicines- examples
Amphotericin = acidic
Fungizone brand: glucose 5% 4.2<pH<5.0
Use glucose 5% flushes
Phenytoin = alkaline always given in sodium chloride 0.9%, precipitation risk if pH<11.5
Epoprostenol (Flolan), Sodium fusidate (Fucidin), Terlipressin (Glypressin) all come with buffered solution for preparing these medicines: always use it.
Insulin comes buffered in solution of pH 7
Phenytoin – needs a filter because of risk of precipitation

12. Amphotericin and Terlipressin
Use the diluent supplied. Don’t give it away unless it is needed.

13. Photo-degradation Light is energy Promotes chemical reactions
May result in degradation
Light-sensitive medicines: brown ampoule for storage
Usual effect is change in colour e.g. dobutamine turns pink.
TPN cover bags to protect fat soluble vitamins
Sodium Nitroprusside:
Degrades to cyanide products on exposure to light
Wrap infusion bag and giving set with foil provided
Brown ampoules – vitamins, frusemide
Aminophylline – straw coloured to start with.

14. Emulsions Emulsions are very delicate balance of oil and water.
Upsetting this balance can cause cracking or splitting.
Identified by milky white appearance.
PN, diazepam emulsion, fat soluble vitamins, propofol.
Why is there a diazemuls product and a diazepam injection???

16. Concentration-dependent Precipitation
Medicines often poorly soluble in aqueous solution
Formulated as salts to increase solubility
May require minimum volume of dilution
e.g. cotrimoxazole: (75mL glucose 5% or 125ml sodium chloride 0.9% per 5mL ampoule)
Precipitation possible at low temp
(e.g. mannitol, 20% = supersaturated solution)
Calcium salts, magnesium salts, avoid mixing with other medicines, especially phosphates
Formulated in polyethylene glycol???
Correcting magnesium and calcium far more these days.

17. Adsorption by delivery system
Medicines may adsorb onto plastic, glass
PVC main problem
Insulin, glyceryl trinitrate, ciclosporin, isosorbide dinitrate
Leeching of phthalate plasticisers (ciclosporin)
Low sorption giving sets
Non-PVC bags
Short expiry times in PVC ?
Not a problem with insulin as titrating it to response.
Phthalates leached with cyclosporin – not a significant problem.

18. What can you do to ensure that incompatibilities are avoided?
Check if drugs are compatible with the infusion fluid and each other. Unless you have positive proof that they are do not give together.
Ideally do not infuse drugs at the same time through the same venous access device.
Where several drugs are given through the same device flush well with sodium chloride 0.9% (or glucose 5% if the injectable monograph advises) before, between and after administration to avoid mixing.
If any obvious change occurs to a solution DO NOT ADMINISTER IT – ask the pharmacist for advice.

19. Information sources Local medicines administration procedures
Injectable medicine monographs
BNF Appendix 6: intravenous additives
Product information leaflets (SPC)
Clinical Pharmacist on ward
Medicines Information department (Ext )
Extravasation Antidotes for different drugs
Plastic surgery reg
Hydrocortisone inj/cream
Diclofenac gel

20. Pharmacy Intranet site

26. High alert medicines
Increased risk of causing significant patient harm when used in error.
Knowing which medicines are high alert – remind you to use additional safety strategies.
Injectable examples: amiodarone, chemotherapy, vasoactive agents, heparin, opioids, insulin, opioids
Three ways to safeguard therapy:
Reduce or eliminate errors e.g. training, ready to administer solution
Make errors visible e.g. independent double checks, bar coding
Minimise consequences of error e.g. monitoring, antidote prescribed and available.
Dalteparin LMWH
Heaprin now ready to use
Cardiac monitoring for phenytoin.
Monitoring with PCAs

28. National Patient Safety Agency Alerts
March 2007 Promoting safer use of injectable medicines– competencies re: preparation, administration and monitoring of injectable medicines
March 2007 – competence re: preparing and administering Heparin therapy

29. Nov 2010 Preventing fatalities from loading doses
June 2010 Safer administration of insulin
Feb 2010 Injectable medicines in theatres
April 2008 Heparin flushes
March 2007 Promoting the safer use of injectable medicines
May 2006 High dose diamorphine and morphine
October 2002 Potassium solutions: risks to patients from errors occurring during intravenous administration

30. High Alert Medicines Potassium Ampoules -Store in CD cupboard
Max rate = 10-20mmol / hour
Max peripheral concentration = 40mmol / litre
Care with mixing
Amiodarone
Central administration if repeated doses
Max concentration for dilution
Phenytoin
Cardiac monitoring
Filter when administering as an infusion
Where are ampoules kept?
10 years ago research – lots of problems.
Mix thoroughly but generally use ready made solutions.
(with or without pump at 20mmols/L)