MP321 week 2 Flashcards
where do drug molecules come from
bacteria, plants, fungi, animals, inorganic (lab)
why would you use a broth micro dilution assay
cheap, reproducible and robust giving accurate results
define cytotoxicity assay
assay test to measure the ability of cytotoxic compounds to cause cell damage or cell death
what do antibacterial drugs do
kill or inhibit the growth of microbes at low concentrations
what is B-lactam mode of action
stop bacterial cell wall being formed, because human (host) cells do not have cell walls it does not affect the host
do antibiotics kill or inhibit growth of bacteria
kill only
name one difference between gram positive and gram negative bacteria
gram negative have a much thinner cell wall than gram positive thus making them more vulnerable
explain how enzymes are used to make the bacterial cell wall more rigid
enzymes called transpeptidases or penicillin binding proteins link 2 strands of sugars together forming a bridge that is more rigid
what is called peptidoglycan
the bacterial cell wall, this is because it is made of peptides and sugars
name the 4 classes of B-lactams
penicillin
cephalosporin
carbapenem
monobactam
describe the structure of a penicillin type B-lactam
cyclic amide is fused to 5 membered ring with sulphur atom inside
describe the structure of a cephalosporin type B-lactam
cyclic amide is fused to a 6 membered ring with sulphur atom inside
describe the structure of a carbapenem type B-lactam
cyclic amide is fused to 5 membered ring with sulphur atom on the side (NOT inside ring)
describe the structure of a monobactam type B-lactam
there is no ring attached to the cyclic amide
how to spot if the B-lactam has lost antibacterial properties
if there is no longer the N, C double bond O square functional group
in which kind of medium are B-lactams the most degradable
acidic medium- ie stomach
why can some B-lactams not be administered orally
they are very degradable in acidic medium- ie stomach and so have lost their antibacterial properties by the time they reach the bloodstream
describe the mode of action of B-lactams
inhibit cell wall synthesis of bacteria
B-lactam mimic natural substrate for bacteria
when B-lactam bind to bacterial enzyme this is irreversible and so the bacteria cannot bind with real substrate
because the bacteria then do not have a rigid cell wall to protect them they go into cell lysis and die
why are B-lactams highly reactive
they have a cyclic amide which unlike normal amides are not planer therefore the movement of electrons make B-lactam unstable and very reactive
define narrow spectrum
these target a specific class of bacteria, normally only working on gram positive
define broad spectrum
normally work on both gram positive and gram negative but not always on antipseudomonal
what are antipsudomonal penicillins
antimicrobial agents, which are used to treat pseudomonal infections- gram negative
name one penicillin that does not work on gram negative bacteria
benzylpenicillin
how to bacteria try to protect themselves against B-lactams
produce a chemical called B-lactamase which inactivates B-lactams
how do we try to combat B-lactams instability in acidic medium
attach an electronegative group to minimise neighbouring group attack on the B-lactam carbonyl
Which one is true?
1. Benzylpenicillin can be given orally
2. Amoxicillin and piperacillin are both effective against pseudomonas
3. Cefuroxime is B-lactamase resistant
4. Cefaclor cannot be taken orally
3
how is phenoxymethyl penicillin administered
orally
what is the most appropriate antibiotic to treat strep
phenoxymethyl penicillin
what kind of bacteria is flucloxacillin used to treat
gram positive
what kind of B-lactam must be administered with another antibiotic
B-lactamase inhibitors like tazobactam and clavulanic acid
name 2 antibiotic that work on gram positive and gram negative but not pseudomonas
amoxicillin and ampicillin
name 2 antibiotics that are active against pseudomonas
ticarcillin
piperacillin
name 4 antibiotics active against gram positive
cefalexin
cefradine
cefadroxil
cefaclor
what are cefotaxime, cefriaxone, cefixime and cefpodoxime all effective on
gram negative
B-lactamase resistant
name 2 cephalosporins that can be given orally
cefalexin and cefaclor
name 4 parenteral administration routes
Subcutaneous (under the skin)
Intramuscular (in a muscle)
Intravenous (in a vein)
Intrathecal (around the spinal cord)
which of the following is true
1- The peptidoglycan in Gram-positive bacteria is thicker than the one in Gram-negative bacteria
2- Ticarcillin is a cephalosporin with antipseudomonal activity
3- Amoxicillin is active against Pseudomonas aeruginosa
4- Flucloxacillin is degraded by beta-lactamases
A beta-lactamase inhibitor can only be given parenterally
1
name the 4 main structural classes of antifungals
polyenes
azoles
echinocandins
allylamines
name the main functional group in polyenes
alkene groups
name the main functional groups in imidazoles
ring with 2 nitrogens- called imidazole group
this is basic (can accept hydrogen)
the nitrogen that is attached to amide accepts hydrogen, the other nitrogen is making the ring aromatic
name the main functional group in triazoles
ring with 3 nitrogens (tri=3)
give one example of a polyene drug
nystatin
name an example of a imidazole drug
clotrimazole
miconazole
econazole
ketoconazole
name an example of a triazole drug
fluconazole
itraconazole
name a structural component of echinocandins
long lipophilic tail
name an example of an echinocandin
caspofungin
name an example an allylamine
terbinafine
describe the mechanism of action of polyenes
bind directly with ergosterol in the cell membrane causing leakage and cell death
describe the mechanism of action of azoles
competitively inhibits lanosterol (an enzyme involved in ergosterol biosynthesis
describe the mechanism of action of echinocandins
non competitively inhibit B-1,3-D-glucan biosynthesis in cell wall causing cell lysis and death
describe the mechanism of action of allylamines
inhibit squalene epoxidase required for ergosterol biosynthesis
describe the mechanism of action griseofulvin
binds to polymerised microtubules in nucleus and prevents mitosis
describe the mechanism of action of flucytosine
an antimetabolite which interferes with RNA and DNA synthesis in the cell nucleus causing cell death
where in the body is the imidazole ring sensitive to metabolism
the liver
structure governs what?
PK, PD, spectrum range, oral availability and preparation
what antibiotic would be most suitable for this case ?
Mrs CP brings her 8 year old daughter into her GP’s surgery. The child has a high temperature and a sore throat. No cough or runny nose is present. Swabs taken from the tonsils and the roof of the mouth are sent for culture and sensitivity. Streptococcal pharyngitis is diagnosed.
phenoxymethyl penicillin
what antibiotic would be most suitable for this case
Mrs AM has a high temperature and her knee is painful, red and swollen. A sample of knee aspirate is sent for culture and sensitivity testing. A diagnosis of septic arthritis is made and
Pseudomonas aeruginosa isolated.
ceftazidime
what is the purpose of streaking on an agar plate
allows you to see distinct colonies
do capsules form on flagella?
bacteria normally have one or the other
what is mutants
a species of the genus streptococcus causing dental plaque
will gram positive bacterium show on Mackey agar
growth of gram positive bacteria is inhabited on this medium
what is a nosocomial pathogen
one that is encountered and causes infection in hospitals
are gram negative bacteria more harmful than gram positive
no just much harder to treat
is flucloxacillin stable in acidic medium
yes
will phenoxymethylpenicillin be degraded by B-lactamases
yes
is phenoxymethylpenicillin broad or narrow spectrum
narrow spectrum
is amoxicillin B-lacatmase resistant
no
what is a way to tell if an antibiotic is can be used orally
look for an electronegative group on the left side chain- this generally means it can be used orally
how does phenoxymethylpenicillin work if it is degraded by B-lactamase
if b-lactamase is present it it no longer active
however it will work if the microbes do not produce B-lactamases
what is tazobactam
b-lactamase inhibitor
can tazobactam be given orally
only available for IV
would you use flucloxacillin on MRSA
no it doesn’t work
what is a good choice for MRSA
vancomycin
does cefalexin work on pseuodomonas?
no
how to tell from the structure if an antibiotic is effective on gram negative
if it has a bulky side chain it will not work
too big to get through the small porins
what is neighbouring group attack?
Neighbouring group attack is when the acyl side chain attacks the nearby b-lactam ring. The electrons in search of a positive centre (carbon of the carbonyl b-lactam) can come from the N (also from the O).
define algophobia
fear of pain
what percentage of working adults struggle to understand how to calculate a paracetamol dose for a child
43%
what do vaccines contain
a weakened or inactive antigen which can be live
name 3 common routes of administration for vaccines
injectable, oral or nasal
is active or passive immunity longer lasting?
active
name a medical procedure or treatment that means the patient must receive all childhood immunisations again
bone marrow transplant
name some pharmacy aspects of vaccination programmes
o Manufacturing
o Procurement
o Distribution
o Logistics of endpoint supply (final mile delivery)
o Storage
o Legal mechanism of administration – POM but no prescription is written- PGD
o Recording of administration and analysis of uptake
o Incident reporting/ handling
what can pharmacists do about vaccine hesitancy
provide correct information
cultural sensitivity
incentive programmes (like requiring vaccine to travel or attend events)
name some factors which contribute to vaccine hesitancy
misinformation
safety concerns
fear of needles
malpractice
vaccine myths
what would you do if it was thought a vaccine had been left out of the fridge or not stored at the correct temperature?
quarantine vaccines
find out how long they have been at the incorrect temperature
contact SPC- they will clarify storage and handling requirements
contact manufactures for further clarification
name some common childhood immunisations
6 in 1
MMR
who decides which vaccines go into programmes
JCVI (joint committee on vaccine and immunisation)
what is herd immunity
when the majority of a population is vaccinated it helps prevent the spread of a virus to those who are not vaccinated for whatever reason (too vulnerable, don’t have access, allergic etc)
define teratogenesis
failure to develop limbs correctly, congenital malformations
name a drug that was used and what it was used for that caused teratogenesis
thalidomide, used for morning sickness
define what a medicinal product is
- any substance or combination of substances presented as having properties of preventing or treating disease in human beings
- any substance or combination of substances that may be used or administered to human beings with a view to
- restoring, correcting or modifying a physiological function by exerting a pharmacological, immunological or metabolic action or
- making a medical diagnosis
- restoring, correcting or modifying a physiological function by exerting a pharmacological, immunological or metabolic action or
- things such as oxygen and testing strips are also medicinal products
POMs can only be supplied if:
- a person is lawfully conducting a retail pharmacy business
- the product is sold, supplied or offered for sale or supply on premises that are a registered pharmacy and
- if the transaction is carried out on behalf of the person by another person that other person is or acts under the supervision of a pharmacist
what does the general pharmaceutical council do
-registration and regulation of pharmacists and technicians
-restricts titles to practising pharmacists and technicians
-premises register/ inspection
-educational accreditation
-guidance
when may a pharmacist refuse supply
-when they reasonably believes the prescription is forged
-where to supply would be contrary to the pharmacists clinical judgement
-where the pharmacist or others on the premises are subject to or threatened with violence
-where the person presenting the prescription commits or threatens to commit a criminal offence
-where irregularities or deficiencies in a repeat dispensing service mean that a repeat supply is not appropriate
provision of pharmaceutical services- key points
- not allowed to accept Rx for dispensing that has been received by pharmacy not on pharmaceutical list
- can only supply a NHS Rx from registered pharmacy included in pharmaceutical list
- where details are missing from Rx (strength, dosage), pharmacist can supply medication considered most appropriate
- if no quantity, give up to 5 days supply or minimum pack size
define HSCP
health and social care partnerships
name the three stages of production of antibiotics at GSK
fermentaion
extraction
isolation
name the four stages of fermentation of antibiotics at GSK
spore preparation
seed fermentation
product fermentation
harvest
what is the ideal pH for fermenting antibiotics
6-7
name the five stages of extraction of antibiotics at GSK
ultrafiltration
reverse osmosis
resin
forward extraction
carbon
name the four stages of isolation of antibiotics at GSK
back extraction
tBA salt isolation
tBA salt converted to K salt of clav
pre mix blend
define the enzymatic stage of antibiotic production at GSK
penicillin G is converted to 6-APA by enzymatic cleavage of the amide side chain
