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mpharm year 3 sem 1 > MP321 week 4 > Flashcards

MP321 week 4 Flashcards

1
Q

what patients are at risk of HAI

A

elderly
prolonged hospital admission (current or recent)
ICU/ HDU
invasive procedures
broad spectrum antibiotics
co-morbidity

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2
Q

how do C.diff infections occur (CDI)

A
  • patient, hospital environment and staff contaminated by spores
  • C.diff spores ingested
  • onset CDI usually after antibiotic therapy
  • 4 Cs antibiotics
  • spores ingested and produce toxins in the lower GIT which cause colitis
  • symptoms vary from mild diarrhoea to severe bloody diarrhoea
  • patients over 65 are at most risk
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3
Q

antimicrobials and C.diff infection

A

-Broad spectrum antibiotics disrupt natural bowel flora allowing pathogenic organisms such as C. difficile to flourish

-Narrow spectrum antibiotics that cause little disruption to the bowel flora are less likely to cause CDI

-Antibiotics are a risk factor for CDI but some patients reported with CDI will not have been exposed to any antibiotics

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4
Q

minimising the risk of C.diff when using antimicrobials

A
  • minimise use of 4Cs antibiotics (try to use a narrower spectrum antibiotic) unless very severe infection
  • balance between effectively treating current infection and not causing harm to both the patient and wider population (CDI, increased)
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5
Q

prevention and management of CDI (c. diff infection)

A

prevention
- standard infection control precaution
- antimicrobial stewardship

management
- isolation of patient
medication review (antibiotics, PPIs, laxatives)(stop laxatives) (stop PPI unless absolutely necessary)

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6
Q

key elements of antimicrobial stewardship

A
  • prescribing guidance
  • information about antibiotic use and antimicrobial resistance
  • audit of clinical practice
  • education of healthcare staff and patients/ public
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7
Q

what does SAPG do?

A

aim is to improve use of antibiotics throughout all health and care settings in Scotland.

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8
Q

what is SAPG

A

safeguarding antibiotics for Scotland

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9
Q

obstacles to antimicrobial stewardship

A

Physician loss of autonomy
Resistance to being told what to do
fear of antagonising patients or more senior clinicians

Lack of resources – needs management buy in and support

Poor IT infrastructure
electronic prescribing.
electronic data capture -audit
antibiotic usage data.

Measuring its impact is difficult – outcome and process measures rather than clinical outcomes

Lack of evidence for some aspects of stewardship

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10
Q

what does antimicrobial pharmacist do

A

Develops, reviews and implements policies and guidance

Evaluates antimicrobial use data

Audits compliance with policy and use of antibiotics

Provides education for medical, pharmacy and nursing staff

May have clinical role – Infectious Diseases ward, microbiology ward round

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11
Q

pharmacist roles

A

pharmacists in all settings have a role in antimicrobial stewardships

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12
Q

treatment for staph aureus and strep pyogenese skin and soft tissue infection

A

flucloxacillin - oral tablets 1g four times daily for 5 days

AND

phenoxymethyl penicillin- oral tablets 500mg four times daily for 5 days

if penicillin allergic
clarithromycin 500mg twice daily for 5 days

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13
Q

chicken pox treatment

A

if less than 72 hours from sport appearing- can give aciclovir- 400mg 4 times daily for 5 days

could also give antihistamine for itching- chlorphenamine 2mg every 3-4 hours- drowsy

cooling lotion like calamine- remind patient not to rub as this could break the skin and lead to a secondary infection

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14
Q

treatment for tonsillitis

A

phenoxymethyl penicillin - 500mg 4 times daily for 5 days

if penicillin allergic- clarithromycin 500mg twice daily for 5 days

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15
Q

tetracycline dose for exacerbation of COPD infection

A

200mg for first dose then 100mg for next 5 days

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16
Q

c.diff treatment

A

vancomycin capsules - 125mg four times daily for 10 days

metronidazole 400mg every 8 hours for 10 days - cannot drink ANY alcohol

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17
Q

volume of distribution units

A

litres

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18
Q

clearance units

A

litres / hour

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19
Q

elimination rate constant units

A

K (/h)

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20
Q

elimination half life units

A

hours

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21
Q

b-lactam PK/PD relationships

A
  • Glycopeptide antibiotics: vancomycin and teicoplanin
  • Active against gram positive organisms, used in patients with
    – penicillin allergy
    – methicillin resistant Staphylococcus aureus (MRSA)
  • PK/PD targets
    – traditionally regarded as “time-dependent”
    – AUC24/MIC ratio now accepted as more important for vancomycin
    – target AUC24 / MIC ratio >400 (AUC24 is the daily AUC)
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22
Q

vancomycin PK/PD relationships

A

Glycopeptide antibiotics: vancomycin and teicoplanin
Active against gram positive organisms, used in patients with
penicillin allergy
methicillin resistant Staphylococcus aureus (MRSA)
PK/PD targets
traditionally regarded as “time-dependent”
AUC24/MIC ratio now accepted as more important for vancomycin
target AUC24 / MIC ratio >400 (AUC24 is the daily AUC)

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23
Q

vancomycin toxicity

A

Vancomycin infusion reaction (flushing reaction)
Nephrotoxicity

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24
Q

Vancomycin infusion reaction (flushing reaction)

A

4 – 47% of patients, varying severity, soon after the start or end of an infusion - related to the infusion rate
Caused by histamine release following degranulation of mast cells and basophils
Erythematous rash spreads across face, neck and upper torso with burning and severe pruritus – for images, see https://www.frontiersin.org/articles/10.3389/fpubh.2014.00217/full
Patient may be hypotensive, dizzy, agitated and experience headache, chills, fever, paraesthesia, chest pain, dyspnoea
To reduce risk, doses are administered by infusion at a rate not greater than 500 mg/h (i.e. a 1000 mg dose is infused over 2 hours)

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25
Q

Nephrotoxicity

A

Mechanism unclear: oxidative stress, renal tubular ischaemia, acute tubulointerstitial damage
Associated with high trough concentrations
risk: low if <15 mg/L, medium >15 mg/L, high >20 mg/L
Associated with long duration of therapy
risk: low if <7 days, medium >7 days, high >14 days
Can potentiate aminoglycoside toxicity

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26
Q

Nephrotoxicity

A

Mechanism unclear: oxidative stress, renal tubular ischaemia, acute tubulointerstitial damage
Associated with high trough concentrations
risk: low if <15 mg/L, medium >15 mg/L, high >20 mg/L
Associated with long duration of therapy
risk: low if <7 days, medium >7 days, high >14 days
Can potentiate aminoglycoside toxicity

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27
Q

other less common vancomycin toxicity side effects

A

IgA mediated bullous dermatosis
Neutropenia, especially with longterm use
Thrombocytopenia

Anaphylaxis
Rare, associated with release of IgE

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28
Q

Infectious Disease Society of America (IDSA) March 2020

A

“Efficacy is best related to AUC24/MIC ratio; the target AUC24 is ≥400 mg.h/L, assuming an MIC of ≤1 mg/L
Troughs are not optimal surrogates for AUC­24
Aim for an AUC24 of 400–600 mg.h/L and steady state concentration during continuous infusion of 20–25 mg/L (equivalent to an AUC24 of 480-600 mg.h/L)”
But trough concentrations are currently used for routine monitoring of vancomycin given by intermittent infusion

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29
Q

Vancomycin – routes of administration

A

Oral administration is only used to treat C. difficile infections in the gut - there is no systemic absorption
Intravenous administration is always used for systemic infections and there are two options
Continuous infusion
Intermittent infusion

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30
Q

Design of vancomycin dosage regimens – targets for optimal efficacy and low toxicity

A

. Continuous infusion
Mainly used in critically ill patients in intensive care units
Cssaverage target 20 – 25 mg/L
AUC24 target 480 – 600 mg.h/L

  1. Intermittent infusion
    Easier to manage in general medical and surgical wards
    Trough target 10 – 20 mg/L
    AUC24 400 - 600 mg.h/L (assuming MIC <1 mg/L)
31
Q

for continuous infusions

A

start treatment with loading infusion (to achieve therapeutic concentrations quickly
then start the continuous infusion at the end if the loading infusion
after the infusion stops there is an exponential decline in the concentration

32
Q

intermittent infusion

A

loading infusion followed by the maintenance dosage regimen
- want troughs between 10-20 mg/l

33
Q

clinical applications of PK

A

A patient is admitted to your ward with a suspected gram positive infection and it is decided to start vancomycin.
As the clinical pharmacist
You could be asked to recommend a loading and a maintenance dosage regimen (continuous or intermittent infusion)
You would check if a prescribed dosage regimen is appropriate for a patient
You could be asked to interpret measured vancomycin concentrations and to recommend a dose adjustment

34
Q

how continuous infusions are prescribed in clinical practice

A

Daily dose rate (mg/24 h) = 22.5 mg/L x CL (L/h) x 24

The approach used varies among different hospitals
The daily dose is prescribed with the instruction to administer by infusion continuously over 24 hours, e.g. 2000 mg over 24 hours
The daily dose is split in two and prescribed with the instruction to administer as two 12 hour infusions, e.g. 1000 mg twice daily, each infusion given over 12 hours
- 24 hour infusions are difficult due to factors such as drug stability

35
Q

How intermittent infusions are used in clinical practice

A

Daily dose rate (mg/24 h) = 22.5 mg/L x CL (L/h) x 24
The daily dose is split into one (24 hourly), two (12 hourly) or three (8 hourly) equal doses
Ideally, the dosage interval should be less than one elimination half-life
Each dose must be administered at a maximum rate of 500 mg per hour, e.g. 1000 mg twice daily would be given as 1000 mg infused over 2 h every 12 hours

36
Q

Aminoglycosides PK/PD relationship

A

Efficacy: peak:MIC ratio, aim for a high peak, low trough
Different targets: Gm–ve sepsis and synergistic use (Gm+ve)
Administered by short IV infusion (30-60 minutes) or IV bolus

37
Q

penicillin PK/PD relationships

A

Efficacy: % time free concentrations >MIC (40-60% fT>MIC)
Wide therapeutic range, ideal profile is flat

38
Q

vancomycin PK/PD relationships

A

Efficacy depends on: AUC24/MIC ratio >400
Target concentrations: trough 10 - 20 mg/L, Cssaverage 20 – 25 mg/L
Loading infusion then intermittent IV infusion or continuous IV infusion

39
Q

metronidazole dose and counselling for c.diff infection

A

400mg every 8 hours for 10 days
stop 4C antibiotic that caused infection
cannot drink alcohol on this (causes abdominal pain and sickness)

40
Q

describe trimethoprim mode of action

A

blocks the reduction of dihydrofolate to tetrahydrofolate, the active form of folic acid, by susceptible organisms.

41
Q

UTI treatment, drug, dose, duration

A

trimethoprim 200mg twice daily for 3 days

42
Q

UTI treatment, drug, dose, duration- in pregnant woman

A

nitrofurantoin
100mg twice daily for 7 days

43
Q

UTI non drug advice

A

drink plenty fluids
don’t hold pee for too long
pee after sex
wipe front to back

44
Q

what advice must be given to everyone on antibiotics

A

FINISH THE COURSE !!!!

45
Q

what kind of drug is aciclovir

A

a nucleoside reverse transcriptase inhibitor

46
Q

how does aciclovir work (MOA)

A

-to make a strand of DNA we phosphorylate a nucleotide 3 times- the energy from these phosphates is then used by DNA polymerase to bind the nucleotide to the DNA strand
- phosphorylation is done by kinase enzymes
- when aciclovir enters a cell it is phosphorylated by viral kinases (once) then phosphorylated by host kinases the 2nd and 3rd time
-now that it is phosphorylated it looks very like guanine (a real nucleotide)
- viral DNA polymerase gets confused and adds aciclovir to the DNA chain
- this causes chain termination
- it does this because normally the next nucleotide in the chain would be joined on the OH group (however this is not present in aciclovir)
- this prevents the virus replicating

47
Q

what kind of drugs make good topical applications

A

negative log P so struggles to diffuse passively- in absence of uptake mechanism the cream helps encapsulate the drug and delivery it through the skin

48
Q

It is recommended to reconstitute a 500 mg vial of flucloxacillin with 10 ml water for injection. If the vial has a displacement value of 0.4 mL for 500 mg, how should the product be prepared?

A

9.6ml should be added to achieve a 10ml volume of solution

49
Q

what is a normal adult body surface area? (range)

A

1.4-2 m^2

50
Q

treatment for severe community acquired pneumonia with risk of sepsis

A

IV amoxicillin 1g every 8 hours for 5 days
should review daily and swap to oral when improving

51
Q

treatment for skin and soft tissue infection (cellulitis) in penicillin allergic patient

A

doxycycline 100mg twice daily for 5 days
counselling
—- dairy interaction, sun interaction- photosensitivity

52
Q

doxycycline counselling

A
  • dairy interaction
  • iron, magnesium, Gaviscon, stomach acid – avoid all – massive interaction
  • avoid the sun- photosensitivity, extremely severe
53
Q

treatment for skin and soft tissue infection (cellulitis) with no penicillin allergy

A

oral flucloxacillin 1g every 6 hours for 5 days

54
Q

normally how many half lives does it take to reach steady state concentration

A

5

55
Q

Gentamicin uses

A

Gram -ve sepsis: community or healthcare acquired, urinary tract, neutropenic, unknown source
relatively narrow spectrum, less risk of C. difficile overgrowth
sometimes used “synergistically” (low dose) with penicillins / vancomycin against Gram +ve organisms

56
Q

amikacin uses

A

Neutropenic sepsis, multi-resistant mycobacterial infections

57
Q

tobramycin uses

A

Exacerbations in patients with cystic fibrosis (Ps. aeruginosa)

58
Q

Aminoglycoside clinical pharmacokinetics

A

Absorption
highly polar, water soluble => low oral bioavailability, administered IV (or topically in ear/eye drops)

Volume of distribution
distributes into extracellular fluid 0.25 - 0.4 L/kg
 by oedema, ascites, burns, malnutrition
 by dehydration

Elimination route
90-100% renal excretion via glomerular filtration
clearance and dose requirements depend on renal function

59
Q

aminoglycosides - efficacy

A

Concentration-dependent kill rate
higher peaks (Cmax) produce a faster kill, more effective against bacteria

Energy dependent uptake into bacteria
reduced after exposure to antibiotic: temporary resistance

Post antibiotic effect
prolonged suppression of bacterial growth even when antibiotic concentrations fall below detection limit

60
Q

ahminoglycosides - nephrotoxicity

A

Acute tubular necrosis: uptake into proximal renal tubule
Saturable absorption into the kidney: risk lower with a large daily dose rather than lower doses given 8 or 12 hourly
Increased risk in patients who are elderly, have renal or hepatic impairment
Increased risk with other nephrotoxic agents: NSAIDs, diuretics, amphotericin, beta-lactams, vancomycin, cisplatin

Toxicity generally related to drug exposure
High trough concentrations
Long duration of therapy, cumulative area under the curve (AUC)

61
Q

aminoglycosides - ototoxicity

A

Vestibular toxicity (esp. gentamicin, tobramycin)
dizziness, vertigo, nystagmus, oscillopsia, tinnitus
linked to duration of therapy -rare if <6 days
Cochleotoxicity (esp. amikacin)
hearing loss, tinnitus
linked to genetic factors and age
Monitoring patients on an aminoglycoside
Question patient about dizziness and balance problems
STOP if the patient raises concerns

62
Q

ideal amino glycoside concentration - time profile

A

high peak and low trough, close to 0 before next dose is administered

63
Q

How do I check that a prescribed gentamicin dosage regimen is safe?

A

Identify the type of infection (sepsis or endocarditis) to define the target peak and trough concentrations

Identify the mode of administration (IV bolus or IV infusion) to determine the appropriate steady state equation (multiple doses)

Predict the steady state peak and trough concentrations and adjust the dosage regimen, if necessary

Measure concentration(s) and interpret the result(s)
Sepsis
measure a mid-dose concentration and plot on a nomogram
use two concentrations to calculate individual CL and V
Endocarditis
usually measure peak and trough concentrations
calculate individual CL and V

Adjust the dosage regimen, if necessary

64
Q

where are most antibiotics used

A

primary care (~80%)

65
Q

the 5 Rs for antibiotics

A

right choice
right dose
right frequency
right route
right duration

66
Q

what is a normal duration for acute otitis media

A

4 days

67
Q

what is a normal duration for acute sore throat/ pharyngitis/ tonsillitis

A

1 week

68
Q

what is a normal duration for common cold

A

7- 10 days

69
Q

what is a normal duration for acute sinusitis

A

2 and a half weeks

70
Q

what is a normal duration for acute cough/ bronchitis

A

3 weeks

71
Q

are antibiotics required in upper respiratory tract infections

A

in sore throats 90% will resolve in 1 week without the use of antibiotics
in acute otitis media 66% of children are better in 24 hours and antibiotics have no effect on symptoms

72
Q

when should antibiotics be used in upper respiratory tract infections

A

systemically very unwell (fever, chills, low bp, fast HR and breathing rate)
symptoms and signs of serious complications like pneumonia and sepsis
high risk of complications (over 65 with 2 of these symptoms or over 80 and one of these)-
hospitalisation in the last year
diabetic
cardiac failure

children under 2 with acute otitis media in both ears or children with discharge from the ear

acute sore throat- using fever pain- a score of 4 or 5

73
Q

what can we do to prevent over use of antibiotics

A

educate the public- when people want antibiotics for something that does not require it- reassure them they are ok and will get better on their own

educate healthcare staff- provide guidelines and policies to help staff make the right decision and b as specific as possible with the information known

mpharm year 3 sem 1 (10 decks)

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