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What is the difference between intrinsic and acquired resistance in bacteria?
intrinsic = the bacteria is already like that
Acquired = It acquires the immunity either through horizontal or vertical transfer
Why are gram negative bacteria harder to treat?
because they have porins that only let small hydrophilic molecules go through
antibiotics e.g. amoxicillin are broad spectrum if they can go through the porin to reach the inner cell
Insert pic slide 6
What is an example of intrinsic resistance using gram negative bacteria and vancomycin antibacterial (glycopeptide)?
vancomycin is big and hydrophilic (insert pic slide 7)
Hydrophilic molecules can go through porins but vancomycin isn’t small enough to go through
This is intrinsic as there isn’t anything that can be done to change this and the bacteria didn’t do anything to cause this resistance
What is vertical transfer (acquired resistance)?
(Insert pic slide 8)
go from non-resistant pool of bacteria to a resistant pool of bacteria (think like a family tree)
Mother → daughter cells
What are the 3 methods of horizontal transfer (acquired resistance)?
From daughter → other cells
transformation - mutant bacteria dies and its free genetic info gets transferred to another cell → other cell receives the resistant mutation
Conjugation - close contact between cells results in plasmid being transferred → resistant mutation is transferred
Transduction - viruses called bacteriophages replicate inside the bacterial cell, virus takes some of the genetic info and transfers it to another cell → mutation is transferred using the bacteriophage as a vector
(Insert pic slide 9)
What are other ways that a bacterial cell is antimicrobial resistant?
effflux pumps, beta-lactamase produced, changes in structure of porins, enzymes that can alter antibacterials so that they stop working
(Insert pic slide 10)
What bacteria are part of ESKAPE?
Which one is gram positive?
enterococcus faecium, staphylococcus aureus, klebsiella, acinetobacter, pseudomonas aeruginosa, eneterobacter
Staphylococcus aureus
What is a problem with bacteria?
Keep mutating to become more resistant to more types of antibiotics so harder to treat
What does metallo-beta-lactamase (NDM1) degrade?
So what can treat it?
penicillins, cephalosporins and carbapenems
only monobactams
What does metallic-beta-lactamase (KPC) degrade?
What can be used to treat?
penicillins, cephalosporins, monobactams and cabapenems
Nothing → WERE FUCKED
What patients are at risk of infection?
immunocompromised
In intensive care or post operation
Malnourished
Cancer/diabetes
Elderly or infirm
Infants
What is bactericidal and bacteriostatic?
bactericidal = kills the bacteria
Bacteriostatic = immobilising the bacteria without killing them
How long should IV therapy be used for before you switch to oral therapy?
IV when you can’t control the infection and switch to oral therapy when patient is back within range
Why are doses in BNF different from doses used in practice for antibiotics?
would be too expensive for a clinical trial and because a lot of antibiotics have existed for a long time a lot of the doses that were originally in the BNF have since changed
What dose of penicillin is used in practice?
What dose of gentamicin is used in practice?
500mg to 1g QTD
5-7mg/kg
When should patient be monitored when they have infection?
throughout treatment not just after they have finished course
Safety net e.g. - if feel worse come back etc.
What are 80% of pharyngitis cases caused by?
What bacteria causes pharyngitis (other 20%)?
viral (Will get better itself)
Streptococcus pyogenes
What can cause otitis media and how can it be treated?
What is important for management of otitis media?
mostly viral so self limiting
If bacterial caused by haemophilus influenzae→ amoxicillin, clarithromycin if penicillin allergy
Pain management as pressure build up in ear = ouch
What are the 3 symptoms for COPD patients where 2/3 need to be met for patient to be treated with antimicrobials?
increased sputum volume
Increased shortness of breath
Purulent sputum
What patients cannot be given doxycycline and why?
What is a side efffect of doxycycline?
any patient under 12 because the medication affects bones
Causes photosensitivity
What should non-severe community acquired pneumonia (CAP) be treated with?
What is CURB-65 score for non-severe?
Amoxicillin, doxycycline, clarithromycin
0-1
What should severe community acquired pneumonia (CAP) be treated with?
What is CURB-65 score for severe?
If patient is confused what bacteria is likely to have caused CAP?
macrolide and penicillin, or penicillin with beta lactamase
>3
Legionella
What should not be given to pregnant people with UTI?
Why?
What trimester is it safer to use this drug?
trimethroprim
is teratogenic as can affect folic levels → spina biffida
In the 3rd trimester
What is cellulitis caused by?
What antibiotic?
s. Aureus or strep pyogenes
A narrow spectrum penicillin, if MRSA then vancomycin
What is treatment for necrotising fasciitis?
What causes necrotising fasciitis?
IV antibiotics to hold the infection back but surgery required to get rid of fascia that has been infected
strep pyogenes
When is the only time that vancomycin can be given orally?
Why?
when patient has a C diff infection
Vancomycin doesn’t enter the bloodstream from the GI so normally isn’t a good thing, but because C diff is in the GI its actually a good thing as the vancomycin stays at the site of infection
What are the main choices of dosage form?
oral/rectal administration
IV/IM administration
What are advantages and disadvantages of oral administration?
simplest, convenient and safest means of drug administration
Potentially irregular absorption of certain drugs
What is main advantages capsules have over tablets?
drug released faster using capsules than tablets
Shell that masks taste of drug (some tablets have but not all)
What are disadvantages of tablets?
poor bioavailability of some drugs
Local irritant effects to the GI mucosa
What are advantages and disadvantage of powder formulations (oral)?
faster dissolution rate than tablets or capsules
not suitable for the administration of drugs which are inactivated in the stomach (same as with capsules)
Less convenient to self administer
What are advantages and disadvantages of suspensions?
convenient when drug is not soluble in water and when non-aqueous solvent cannot be used
Disadvantages = risk of sedimentation
What is phenoxymethylpenicillin used to treat?
tonsillitis, otitis, rheumatic fever
What can be used to treat invasive aspergillosis?
tablet = voriconazole, suspension = posaconazole
What can amoxicillin be used to treat?
Lyme disease, h.pylori infection
What can tetracycline be used to treat?
acne
What are advantages of rectal formulations?
Good for drugs that get inactivated in GI when taken orally
Good route when patient is vomiting
Fast systemic response
What are disadvantages of rectal administration?
less patient compliance
Irregular drug absorption
What can be injected intravenously?
only solutions
What are differences between injections and infusions
injections are sterile solutions, emulsions or suspensions in water or non-aqueous liquid, injected in less than 15 mins
Infusions are aqueous solutions that are administered in large volumes 100-1000ml and are injected in more than 15 mins
What are depot preparations?
Where are they injected and what quantity?
What are pros/cons of depot preparations?
dispersion of the drug in an oily vehicle
Injected IM and max 5ml at a time into a large muscle to decrease pain and swelling
Slow release of the drug but can be quite painful
What are the components present in fungizone?
Amphotericin (polyene) and sodium deoxycholate (surfactant)
What is the problem with fungizone?
severe side effects
Renal toxicity
Haemotological toxicity
Cardiovascular toxicity
How does fungizone work to cause therapeutic effect?
Why does it result in toxicity?
Amphotericin binds to ergosterol presents in fungal cell = therapeutic effect
Toxicity because also targets cholesterol in mammalian cells
So non-specific/ not selective
Where is ambisome drug located in the liposome?
located within the liposome membrane (insert pic slide 30)
Why is ambisome better than fungizone?
passive targeting of the liposomes to the infected organs
Minimal exposure to non-target tissues (so don’t target mammalian cells)
What is structural differences between fungizone and ambisome in terms of targeting tissue and toxicity?
for ambisome the Amphotericin stays encapsulated in liposome (lipid bilayer) so less toxic effects and better at targeting just fungal cells and not mammalian cells
Fungizone, the Amphotericin leaks out of the micelle so it enters circulation, targets both fungal and mammalian cells = toxic effect
How much more toxic is fungizone than ambisome?
What is the main drawback of ambisome?
80 times more toxic
Way more expensive than fungizone ( £24 vs £821) per vial
What are the main choice of dosage form for mild infections?
topical administration
(Sometimes oral/rectal administration - dependant)
What is an ideal anti-microbial formulation?
effective against the targeted infection
Able to reach site of infection
Rapid onset and controllable duration
Free of undesirable side-effects
When is it that oral/rectal administration of a drug would occur when treating a mild infection?
if infection is more difficult to treat or is spreading fast
What is the advantage of topical administration?
What is the main barrier to this method of drug delivery?
results in location action
The stratum corneum (outermost layer of skin)
Composed of 15-20 layers of flattened, keratinised cells that must be crossed in order for drug to cause effect
What are the requirements for a suitable drug for topical administration?
have a low MW (less than 500 Daltons)
Moderately lipophilic logP between 1-4
Be effective at a low dose (less than 10mg/day)
Why do topical administrations need to have a lipophilicity between 1 and 4?
lipophilic enough to be able to penetrate the stratum corneum
If not lipophilic enough will not penetrate, too lipophilic and will stay in the stratum corneum and not travel to site of infection
What is Fick’s Law of Diffusion?
J = -D triangle C/triangle x
J = flux
D= diffusion co-efficient
C = concentration of diffusing drug
X = distance
What are the formulation types of topical administrations?
liquid formulations
Semi-solid formulations
Solid formulations
What is the advantages and disadvantages of liquid topical formulations?
Precise as can be applied directly to site of infection
Evaporation of the solvent leads to cool, soothing effect (good for treatment of acne)
poor residence time on skin
Low drug delivery
What are advantages of semi solid topical formulations?
Good patient acceptance and compliance
More viscous due to drug being in semi-solid base so good residence time on skin
What type of medication is liquid topical formulations?
single phase solutions and lotions (e.g. erythromycin solution and clindamycin lotion)
What are bases of semi-solid formulations?
hydrophobic bases = liquid paraffin, glycerides, waxes
Hydrophilic bases = polyethyleneglycol (PEG)
What drug types are semi-solid formulations?
ointments, creams and gels
What are ointments?
What are advantages of ointments?
hydrophobic, fatty preparations (extra lipophilic base)
highly occlusive, increase of transdermal drug flux, prolonged drug delivery
messy to use
What sort of lesions are ointments used for?
dry, flaky lesions e.g. impetigo (fusidic acid)
What are gels made of?
What is advantage of gels?
made up of a solution that gets excipients added to it to form a more viscous gel (excipients = PEG, polymers, gums)
Due to evaporation of alcohols, results in a soothing effect - relief for inflammation
What type of gel provides relief for patients with rosacea?
metronidazole gel
What are creams?
made of 2 phased emulsion: either water based tablet dispersed in oil phase or oil based tablet disperse in water phase
What are advantages and disadvantages of creams?
w/o emulsions less greasy than ointments, easier to apply than ointments, can be washed off the skin surface
less occlusive than ointments, less beneficial in treating dry skin conditions
What type of formulation are spray powders?
What is an example of a spray powder drug and what is it used for?
solid formulations
Miconazole nitrate - treats athlete foot
What is the nail made of?
So what component does the drug need to have?
Why is nail lacquer considered a solid formulation?
hard keratinised structure
Keratolytic components (e.g. urea) to increase diffusion of drug through the nail plate (think like is like)
Because it is a solution that dries to become a solid
What are barriers to drug absorption in the eyes?
formulation must be sterile, eyes blink and have tears so a lot of the drug gets removed from the eyes
What does homogenous mean in terms of drug formulations?
means that it is uniformly made so 1 drop would have the same quantity of each component as another drop (and every other drop)
What is a common viscosity enhancer used to make eye drops?
polyvinylalcohol
What excipients are used to make eye ointments?
petrolatum, lanolin
What are advantages of using eye ointments?
What are disadvantages of eye ointments?
reduce drug removal caused by tears and blinking
Increase of corneal residence time
Sustained drug release
more difficult to administer than solutions
More variable administered dose (not as homogenous)
causes blurring of vision
Patients don’t like to comply when it comes to any sort of thing going in eye
What are pessaries and ovules?
vaginal suppositories = pessaries
Vaginal capsules, shell pessaries = ovules
are both solid, single-dose formulations that are ovoid in shape but ovules are more elongated and larger in size
What are advantages and disadvantages to vaginal delivery route?
treatment of local infections requires lower dose than with oral administration
No need of absorption of drugs for local action
release of the drugs influenced by vaginal fluids
What does MCR stand for?
my chemic… medicines care review
What service did MCR replace?
CMS (chronic medication service)
What is the main aim of MCR?
to support people with long-term conditions in managing their medicines effectively (normally people who take multiple meds but not always)
Who is eligible for MCR?
How many pharmacies can the patient choose to register to?
patients registered with a Scottish GP who take regular long term medication
only one
What is a serial Rx?
How long can they last for?
a prescription issued by the GP
24, 48 or 56 weeks
What are the main components of MCR?
medication review
care plan
serial prescriptions
What is the benefit of a serial Rx (for a patient)?
don’t need to go to GP to get a new prescription every time, and can get it directly from the pharmacy you are registered to
What info is required from patient to sign them up for MCR service?
name
dob
address AND postcode
gender
CHI number
What additional things does patient need to confirm before they are part of MCR service?
they want to register for MCR service (so basically agreement/consent)
have a long-term condition
agree doctor and pharmacist can share info about meds
What year was the Humans Medicines Regulations put into play?
2012
What section/part of the Humans Medicines Regulations 2012 is “dealings with medicinal products”?
part 12
When can pharmacists refuse to provide service/supply to a patient?
if believe Rx if forged
where supplying to the patient is contrary to the pharmacist’s clinical judgement
where pharmacist or other on premises are subject to or threatened with violence
if person with Rx commits or threatens to commit a criminal offense
where irregularities or deficiencies in a repeat dispensing service mean that a repeat supply isn’t appropriate
What does it mean to be on the pharmaceutical list?
list of pharmacies approved to provide NHS services
Rx written by NHS can only be dispensed by a pharmacy on this list
What kind of pharmacies are allowed to supply NHS Rx?
only pharmacies included in pharmaceutical list
What happens if a pharmaceutical list pharmacy is given an Rx by a pharmacy not on the list (e.g. private pharmacy)?
are not allowed to dispense it as it goes against NHS rules
What does a pharmacist supply if no quantity is provided on an Rx?
up to a 5 day supply
or supply minimum pack size
What does “supply of products listed in Schedule 10” mean under the NHS Medical Services Regulations?
It refers to a blacklist of items that must not be supplied or reimbursed under the NHS in Scotland. These products are excluded due to limited clinical or cost-effectiveness. NHS pharmacies cannot dispense these items for NHS payment.
What must a pharmacy do about opening hours?
display the opening hours and MUST BE OPEN during the opening hours
What year were IP pharmacists legally implemented?
in 2006 (doesn’t mean all pharmacists became IP’s tho obvi)
What is the “Patient Rights Act” 2011?
aims to improve patient’s experiences using health services and to support people to become more involved in their health and healthcare
What is the “Equality Act” 2010?
116 legislations combined to make new act that provides a legal framework to protect the rights of individuals and advance equality of opportunity for all
What is the “Human Rights Act” 1999?
lets you defend your rights in UK courts and compel public organisations - including gov, police and local councils - to treat everyone equally, with fairness, dignity and respect
What is the “Data Protection Act” and when was it legislated?
access to patient data should be monitored and inappropriate usage = penalty (basically respecting confidentiality)
2018