Oxford University Hospitals NHS Trust

Injectable medicines study day:

Claire Waghorn

Pharmacist

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

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

Kinetics: oral dose vs. IV bolus

Single IV bolus dose profile

Multiple daily dosing vs. infusions

Multiple daily dosing at steady state

Kinetics: IV bolus + infusion

Profile following a loading dose (bolus) and maintenance infusion

Relationship between plasma level & effect

Therapeutic range

= trough

= peak

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

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 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

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

Amphotericin and Terlipressin

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

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.

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

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 ?

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.

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. 21505)

Pharmacy Intranet site

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:1. Reduce or eliminate errors e.g. training, ready to

administer solution2. Make errors visible e.g. independent double checks,

bar coding3. Minimise consequences of error e.g. monitoring,

antidote prescribed and available.

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

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

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