Extemp Exam Flashcards
Where are CYP450s found? What do they do?
Found on cells smooth endoplasmic reticulum
Highest conc in liver and small intestine
Add oxygen atoms to molecules, makes them more water soluble
What’s the main aim of personalised medicine?
To ensure treatments meet the needs of INDIVIDUAL patients and to maximum efficacy of treatment, and significantly reduce the risk of undesirable side effects
10% of the population get little pain from codeine due to the enzyme _______
CYP2D6
What two variants are being tested to determine more accurate dosing of warfarin based on a patients genotype?
Gene variations for the CYP2C9 enzyme that metabolises warfarin
And in the gene for the vitamin K epoxide reductase enzyme
How can we personalise the treatment of cancer with Trastuzumab (Herceptin)?
Drug binds to HER2 proteins, it’s a monoclonal antibody
We can Test cancer patients to see if they have over production of HER2 BEFORE treating with this drug as these are the only patients who will benefit from it
Definition of a special?
A non-licensed medicine manufactured to fulfil the prescribers requirements
Manufactured under a ‘Special Manufacturing License’
Definition of an import?
A product that has a product license in its country of origin
Definition of extemporaneous preparation?
Made under the supervision of a pharmacist under section 10 of the Medicines Act 1968
Which regulations exempt the need for a MA for a relevant medicinal product, which is supplied to fulfill a ‘special need’?
HMR 2012 part 10: exception to requirements for a marketing authorisation
When can doctors give unlicensed medication?
If the licensed form is inappropriate for the patient
If there’s evidence the unlicensed form is SAFE
As long as they monitor and follow it up
Remember doctors are liable if the unlicensed med causes harm
It’s a legal requirements that specials products are _________ by the requesting pharmacist
Commissioned/ signed off
Any unlicensed meds must be made up in licensed premises, that is they’ve been inspected by the _____
MHRA
E.g Registered pharmacies under supervision of a pharmacist
What are some of the risks associated with extemporaneous dispensing?
Feisty Cats Like Rapping Songs Quite Loudly
F= Failure of Formulation : eg microbiological contamination, bioequivalence issues, dose uniformity (overdose or underdose), issues with stability C = Calculation errors L = Labelling errors R = Raw material contamination S = Safety and efficacy unknown Q = QA and GMP issues L= lack of standards and specifications
In extemporaneous dispensing there’s some risks to staff. What are these?
Liability, they have a lot of responsibility
May be exposed to harmful substances when crushing tablets or weighing and pouring etc
How can we minimise risk in extemporaneous dispensing?
Do risk assessments to ensure a safe outcomes
Record keeping to safeguard patients
Train staff
Patient information- make sure pharmacy staff communicate with patients
Correct equipment and facilities available
How can we comply with quality requirements in extemp?
Make sure premises comply with GMP
Follow QA systems, eg following pharmacopeia monographs
Make sure batch testing systems are in place
Certificates of analysis for batchs
Yellow card ADR reporting schemes
When using a product within its licence, liability lies with the manufacturer if it all goes wrong. When using an unlicensed product, who does liability lie with?
The pharmacist AND the prescriber
What’s an overall definition of specials and unlicensed medicines?
Medicinal products prescribed by doctors for specific indications for which a licensed product does not exist or is no longer available on the market.
Repackaged medicines are classed as specials/ unlicensed. Meds prepared by a manufacturer but aren’t available in UK are also classed as this (unlicensed). What about medicines prepared for a specific patient, to use with doctors instructions?
This is classed as specials
Does a pharmacy require a specials manufacturing license?
No, all suppliers and manufacturers of specials must have one apart from pharmacies, as the law recognises that pharmacists should have the knowledge to safely prepare and supply medicines without a manufacturers license.
If a patient experiences an adverse effect for a product that has been prescribed within its terms of license, who can they prosecute?
The manufacturer
Ie the ones who created the sPc
if it’s a special/ unlicensed then the prescriber gets the blame
Specials don’t need a Marketing authorisation, and can be given by a practitioner in the UK. Who may these practitioners be?
Doctor
Dentist
Nurse independent prescriber
Pharmacist IP or supplementary prescriber
Specials manufacturers can advertise their _______ but not their _______
Can advertise their services
But not their products!! Cannot advertise specials
HMR 2012 makes the exception that a pricelist of products they usually make can be published by manufacturers, can’t include bespoke products in this!
What does be-spoke mean?
Custom made, completely tailored to an individual patient!
The HMR 2012 requires anyone selling or supplying an unlicensed medicines to keep a record of supply for _______?
5 years
What are transmissible spongiform encephalopathys?
Also known as prion diseases, caused by prions (infectious agents composed of proteins in a mis-folded form)
Progressive conditions effecting brains and nervous system
What are the TSE guidelines?
Unlicensed medicines for human use (transmissible spongiform encephalopathies) safety regulations 2003
All manufacturers, importers AND exporters MUST comply with these, otherwise the import is not allowed.
If an unlicensed medication is supplied and proves a risk of TSE, those who manufactured and imported the medication should be held liable as they should have checked TSE guidelines have been followed in the manufacture.
When do TSE guidelines NOT apply?
Don’t apply to pharmacists making up unlicensed medicines in the pharmacy
What are chief pharmacists and superintendent pharmacists responsible for?
Responsible for making sure systems are in place to safeguard public health and the safety of patients being supplied unlicensed medication
What different things could a product be in order to be classified as hazardous?
Carcinogenicity (cancerous) Genotoxicity Organ toxicity (at low doses) Teratogenicity Reproductive toxicity
What’s the risk of cytotoxic chemotherapy agents to patients? Where’s the riskiest place to make up cytotoxics?
Secondary neoplasms in patients
Preparing chemo on the wards
What engineering control can we use in grade C rooms? What should we use for hazardous substances?
Use biological safety cabinets in grade C rooms
Use ISOLATORS when handling hazardous materials
What is composite air flow?
Where airflow comes down and protects product from contamination
It is double filtered air
What types of gloves offer best protection?
Nitrile and neoprene gloves
What is the best practice with needles?
Using luer-lock syringes
Using vented needles or filter needles- these normalise vial pressures and minimise aerosols
Use chemo mats: these will absorb any spill ages
__________ of needles is not permitted in a healthcare setting
Re-sheathing
What’s the process of decontamination?
Firstly remove organic matter using an aqueous cleaner or a detergent as this will inactive alcohol
Then do alcohol clean
Any biologics that may be present- denaturation is needed using liquid or gaseous chemicals
What will a PN bag contain?
Protein (AS AMINO ACIDS) Carbohydrate (AS GLUCOSE) Fat Electrolytes Trace elements Vitamins Water
What are micro nutrients?
Trace elements such as zinc
Vitamins
Water
Macro elements: Protein Carbohydrates Fats Electrolytes
What is the difference between a 2 in 1 TPN solution and a 3 in 1?
2 in 1: the aqueous mix (I.e amino acids and glucos etc) are in a seperate section to the lipids
3 in 1; the aqueous solution (amino acids, glucose etc) is in the same bag as the lipids, all ingredients in one
What’s a triple chamber TPN bag?
3 different sections
One for glucose, one for amino acids, one for lipids
What’s the problem with sunlight and TPN bags?
Sunlight can break down any vitamin A in the bag
Also if a lipid emulsion is exposed to both oxygen and sunlight, lipid peroxides may form which can be harmful
You need to be careful of oxidation of Amino acids in TPN bags. Why?
Tryptophan degradation products may cause cholestasis
If a solution is BROWN it usually means it has oxidised
Some trace elements may catalyse the breakdown of vitamins. What’s an example?
Copper catalysing the breakdown of vitamin C
Vitamin C in TPN bags will oxidise to oxalic acid. Unless you can get all your oxygen from out your bag which isn’t usually possible! Oxidation catalysed by copper ions and light
Oxalic acid will precipitate with calcium
The loss of vitamin C from the bag needs to be supplemented so need to calculate estimated loss
What’s the link between precipitation in TPN bags and pulmonary embolisms?
Precipitation results in particles in the TPN bag
These can block small capillaries in the human
Results in pulmonary embolisms
When adding strong injections of calcium/ magnesium/ phosphate to a TPN bag whys it so important to MIX between additions or to DILUTE the solutions before adding to the TPN bag?
If this occurs you will get precipitation (insoluble precipitate forms)
You will therefore see cloudiness
This results in a risk of EMBOLISM
With calcium phosphate this precipitate formation depends on 4 factors, what are these?
Salt Concentrations pH Other ingredients (Also temperature, as precipitates more likely to form at high temp, so store in fridge!!)
What should the final pH of TPN mixtures be maintained at?
pH 5.00 and above!
should definitely be below 6 to reduce precipitation
Increasing temperature can also make formation of precipitates more likely. What can we use to stop precipitates forming?
In-line filters
What’s the max concentration of glucose that should be used in peripheral veins? Why?
15%
This avoids phlebitis (inflammation of veins)
High concentrations destabilise fat emulsions (40-50% conc)
High concentrations cause hyperglycaemia
Why are lipid emulsion tiny droplets of fats immersed in water designed to be the same size as chylomicrons?
Chylomicrons are lipoprotein particles found naturally in the body, so we know these are an ok size and won’t block capillaries etc
What are the three stages of lipid instability that can happen with lipid emulsions in TPN bags?
1) fat droplets start to join (aggregation)
2) creamy layers are seen (Reversible with mixing)
3) cracking: oily layers sat on top of aqueous phase, not able to mix again. Cracking = danger to patient!! Lipid micro-embolisms
What causes destabilisation in lipid emulsions?
Electrostatic effects causing repulsion between lipid particles is GOOD- keeps lipid particles seperate
Some factors may interfere with this repulsion
Eg positive ions like Al +++ bring lipid particles together
Or pH; over 6 we can get precipitation
Glucose concentrations (40-50%)
Time (if we leave for a long time we get precipitation)
Amino acids act as a _______ in TPN bags
They therefore stabilise other constituents
And they ______ with metal ions
_____ pHs can cause precipitation of amino acids
Act as a buffer
Can chelate metal ions
Low pHs cause precipitation
What is the best type of TPN bag (container) to use? Why?
Multilayer
It’s a good barrier to oxygen
It reduces oxidation reactions and loss of ingredients and stabilises the formulation, doesn’t leach
Others
PVC; problems with leaching
EVA; problems with letting in oxygen
We should seperate vitamins and trace elements in TPN bags. How can we do this?
Put vitamins in the lipids (fat emulsion) bag
Put trace elements in the amino acid/ glucose bag
As copper may catalyse breakdown of vitamin C !
Whys it important to allow PN feeds to warm up to room temperature ONE HOUR before use?
Cold infusions may cause cardiac arrest
Why do we need to be extra careful when adding calcium / magnesium to inorganic phosphates in TPN bags?
Precipitates are likely to form eg calcium phosphate
To stop this we need to MIX between additions
Would be good to use an inorganic phosphate SALT where possible
It’s recommended that ALL PN bags are QC tested. What are some of the QC testing methods used?
Flame photometers
Atomic absorption
Electrolytes
Refractive index
Infusion bags may be needed for ____ drugs as in a syringe they’re very concentrated whereas in a bag they’re more dilute.
Irritant drugs
Infusion bags give the dose slower
What pH range do opthalmic solutions for the eyes need to be buffered at?
Need to be buffered in the pH range 4.5- 11.5
What TONICITY and osmolarity should be used for opthalmic solutions for the eye?
300 mOsm/ L is ideal
200-600mOsm/L is acceptable
TONICITY: 0.6- 1.8% sodium chloride is tolerated
Why should intrathecal formulations to be injected not really contain any other additives eg antimicrobials, antioxidants, pyrogens, preservatives?
They can be TOXIC to the CNS (intrathecal: going into spine)
Sodium chloride should be used as Tonicity agent
Particulates are ok (microspheres for slow release)
What is the ENDOTOXIN limit formula?
EL= K / M
K = max number of EU of endotoxin a patient may receive without suffering toxic reactions M= maximum dose of substance per person (or per kg) per hour
What are the two values of K in the ENDOTOXIN limit equation?
K= 350 per person for parenteral preparations K = 14 per person for intrathecal
This is because intrathecal injections are going into the spinal cord, therefore these will have a lower limit for endotoxins!! Don’t want these on your nerves–ouch!
Fentanyl citrate has a bacterial endotoxin limit of 5.0 mg/L. Work out the maximum dose of it you can give for a parenteral formulation?
EL= K / M M = K / EL
K for parenteral = 350 per person
350 / 5.0 = 70ml/ person/ hour
Fentanyl citrate has a bacterial endotoxin limit of 5.0 mg/L. Work out the maximum dose of it you can give for an intrathecal formulation?
EL = K / M
M = K / L
K for intrathecal = 14 per person
So M = 14 / 5,0 = 2.8 ml / person / hour
What does the orange guide set out?
Microbiological testing guidelines
Recommended limits for microbial contamination in rooms
Grade A = zero contamination, so that’s inside an isolator
Grade B= ?
Open fronted cabinets
Grade C= room containing an isolator (the isolator itself is grade A)
What’s grade D?
The room you get changed in
Settle plates are a passive technique using gravity to collect microbes. But they only represent 0.2% of the work surface. Contact plates are slightly better, the media includes a neutraliser, roll the plate on the surface for around __ seconds
5 seconds contact time
Why is sterility testing abit useless?
They take 14 days
Only tests the container for sampling
Poor indicators of low levels of contamination therefore no good for grade A rooms
