Chemistry of Drugs Week 19 Flashcards
What is the difference between a risk assessment and COSHH?
a risk assessment is used for PROCESSES e.g. use of autoclave, COSHH is used for harmful substances
How is COSHH approached (5 factors)?
- identify which harmful substances may be present
- decide how people might be exposed and harmed
- look at measure to put in place to prevent harm
- provide information, instruction and training
- provide health surveillance in appropriate cases
What are the 3 main steps to follow in a COSHH assessment?
- identify the hazards
- decide who might be harmed and how
- evaluate the risks and decide on precautions
How can you find out which substances are harmful?
reading product labels, safety data sheets (SDS) and suppliers catalogue information
Where is non-toxic aqueous solvent disposed of?
drains
Where is halogenated organic solvent waste disposed of?
halogenated bottles
Where is non-halogenated organic solvent waste disposed of?
non-halogenated bottles
What is disposed of in the glass bins?
glass materials, ceramic ware, cover slips, microscope slides, test tubes (uncontaminated), pasteur pipettes, thermometers
What is disposed of the sharps bins?
razor blades, scalpel blades, syringes with needles, lancets, pins, sharps
What goes in the biohazard bins?
ANY material that has been in contact with biological agents - blue roll, gloves, plastic pipettes, tips, cuvettes
What goes in the special waste?
crude oil, mercury etc - must be clearly labelled with component, concentration, volume and hazards and sealed
What goes in the general waste?
ALL UNCONTAMINATED waste - blue roll, bungs, cotton wool, plastic tubing etc
What must you contact the technical team for?
special material including solvent bottles, hard plastic, scrap metal etc
Which functional groups are particularly susceptible to degradation by hydrolysis?
esters and amides
What is needed for the synthesis of drugs?
REACTIVE functional groups
What do we tend to NOT have in drug molecules once made?
reactive functional groups
Why do we not want reactive functional groups in drug molecules?
we are nucleophilic, so don’t want electrophilic functional groups attacking enzymes, proteins, DNA etc
By which 2 processes do drugs usually degrade?
- photolytic degradation
- hydrolysis
What are the general steps of photolytic degradation (generally oxidation)?
- the molecule absorbs a photon from the IR, visible or UV light spectrum
- this causes the drug molecule to go from its ground state to an excited state
- the drug molecule can then spontaneously decompose or react
What are 2 examples of drug types that are susceptible to photo decomposition?
various corticosteroids and antimycotics
How is photolytic degradation avoided?
use of amber glass bottles, blister packs, fridges etc, use of a physical quencher
define physical quencher
a compound that causes physical decay of the excited state before decomposition occurs
How is photolytic degradation a positive?
it can be used to reduce the effect of pharmaceuticals on the environment in waste water etc
How can pharmaceuticals be eliminated from the environment?
photo-assisted wastewater treatment methods
Which groups are susceptible to hydrolytic degradation?
esters and amides - including their cyclic counterparts lactones and lactams
define lactone
a cyclic ester
define lactam
cyclic amide
Why do paediatric penicillin suspension need to be kept in the fridge?
- once made up, they are aqueous suspensions
- water molecules can hydrolyse the strained lactam ring
- refrigeration reduces hydrolysis
Why is the nitrogen bond in penicillin not very reactive?
its lone pair overlaps with the C=O bond due to resonance
What are repackaging of a medication, involving removal from its primary packaging examples of?
off-label of illegal use of a medicine
Why is this off-label use?
removal from its primary packaging invalidates the stability guarantee of the manufacturer
What is the MCA stability tool (for multi compliance aids)?
information on stability for tablets and capsules to help create MCAs for patients
What does a green label for MCA stability mean?
the drug is okay to be put in an MCA
What does a yellow rating on the MCA stability tool mean?
special measures are needed for that drug to prevent degradation
What does a red rating on the MCA stability tool mean?
do NOT use this drug in MCAs
What are the potential issues for use of proteins/biologicals as drugs?
- hydrolysis of the backbone
- oxidation of susceptible side chains e.g. cysteine and methionine
What could oxidation of cysteine result in?
formation of a disulfide bond between two cysteine side chains resulting in protein aggregation
What could oxidation of methionine result in?
oxidation to methionine sulfoxide
Which 2 main factors does the drug design process involve?
- pharmacological properties
- drug-like properties
What do pharmacological properties include?
interactions, Lipinski’s rules
What do drug-like properties include?
affinity and efficacy
Why are protein side chains important?
the nature of the groups influences how they react with functional groups on drug molecules
What does drug design rely on?
- pharmacological properties (good interactions between ligand and target) - hydrogen bonds, ionic bonds, lipophilic interactions etc
- having good drug-like properties - not metabolised too quickly, can reach site of action, high affinity and efficacy
