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PHARMACOLOGY FRCA > antimicrobials and antifungals > Flashcards

antimicrobials and antifungals Flashcards

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1
Q

what different types of pathogens do you know?

A

pathogen is a micro-organism that causes disease
may be bacterial, virus, fungi, protazoa

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2
Q

what is the difference between gram positive and negative bacteria?

A

depends on structure of cell wall
gram staining includes applying stain to bacteria and washing it off. Gram positive bacterial retains the stain and appears purple, gram negative does not hold the stain and appears pink

gram negative - thin peptidoglycan wall, outer and inner membrane , lipopolysaccharides

gram positive - thick peptidoglycan wall

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3
Q

describe the structure of a bacteria..

A

cell wall
cell membrane
naked DNA , no nucleus
plasmids
30s and 50s ribosomes (40s and 60s in eukaryotes)
no mitochondria

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4
Q

describe the structure of a virus

A

genetic material - positive/ negative RNA, DNA
proteins
contained in protein shell = capside
sometimes enveloped

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5
Q

can you classify different bacteria

A

gram staining + rods/ cones

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6
Q

causes of atypical pneumonias..

A

mycoplasm
legionella
mycobacterium

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7
Q

can you classify viruses

A

DNA/ RNA, enveloped and non-enveloped

DNA enveloped = herpes, hep B
DNA non-enveloped = adenovirus
RNA enveloped = Measles, mumps , rubella
RNA non-env = polio, hep A

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8
Q

describe the general structure of fungi

A

eukaryotic cells
membranes differ from ours - contain ergosterol (not cholesterol)
have cell walls made of chitin

2 main groups - yeast (candida) and moulds (Asperigillus)

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9
Q

what is the size of bacteria, virus and eukaryotes

A

virus less than 0.3um
bacteria 2um
erykaryotes - 10-100um

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10
Q

what fungal infections do you know

A

candida albicans - thrush of mouth, vagina. can also cause disseminated disease in immunocompromised

asperigillus - lung infection in immunocompromised

cryptococcus - fungal menigitis assoicated with HIV

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11
Q

how can the antibiotics be classified?

A

By target
Cell wall
* B lactams
* glycopeptides

Protein synthesis
* 30S - aminoglycosides , tetracyclines
* 50S - macrolides, clindamycin, linezolid, chloramphenicol

Nucleic acid synthesis
* folate synthesis - trimethroprim, sulphonamides
* DNA gyrase - quinolones
* RNA polymerase - rifampicin

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12
Q

what is the difference between bacteriostatic and bacteriocidal.
can you give examples

A

some Abx work by killing bacterial = bacteriocidal e.g. B lactam and glycopeptides and aminoglycocides

others inhibit growth - macrolides, sulphonamides

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13
Q

what is meant by minimum inhibitory concentration and minimum bacteriocidal concentration?

A

MIC = lowest Abx conc to inhibit bacterial growth
MBC = lowest conc to kill bacteria in vitro

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14
Q

what pharmacokinetic parameters are important when assessing Abx efficiency

A

peak serum level
Trough serum level
Area under serum conc time curve

some Abx work via conc dependant killing - in this case the peak serum / MIC ratio shuld be high and the 24h AUC / MIC ratio should be high
(MIC = minimum inhibitory conc)

some Abx work via time dependant killing e.g. efficacy is determined by time above MIC. for these the time above MIC i.e percentage time spent above MIC during dose period, should be high.

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15
Q

give an example of Abx which are dose dependant and time dependant killing..

A

time dependant = b lactams

conc dependant e..g aminoglycosides

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16
Q

what is the general structure of a penicillin

A

B lactam ring + Thiazolidine ring + acyl chain

acyl chain varies between different penicillins

previous Q asked to draw this

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17
Q

which bacteria are penicillin used for?

A

gram positive - inhibit thick peptidoglycan wall
e.g. cellulitis, respiratory tract infection (streptococcus, pseudomonas)

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18
Q

how do penicillins work

A

bacteriocidal Abx
inhibition of cell wall synthesis
through inhibiting transpeptidase enzyme - normally responsible for cross linking peptidoglycan wall and hence allowing strength to develop
without this strength, weak wall and bacteria cell bursts due to osmotic damage.

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19
Q

what are the pharmacodynamics of the penicillins?

A

GI - diarrhoea and cholestatic jaundice
immune - anaphylaxis and hypersensitivity.
CNS - some can be pro convulsant (benzylpenicillin)

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20
Q

what are the pharmacokinetics of penicillins?

A

A: oral, IV. some only can be given IV e.g. benzylpenicillin and amoxicillin only oral
some can penetrate BBB when it is inflammed e..g benzylpenicillin

20% metabolised
mostly excreted unchanged by kidneys
hence renal adjustments necessary
short half life

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21
Q

tell me about penicillin resistance..

A

bacteria can develop resistance in a number of ways

B lactamases can be priduced by bacteria which breaks down B lactam ring, preventing penicillins acting.

altering transpeptidase target

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22
Q

how can the penicillins be classified?

Study These Flashcards
A

classified depending on their spectrum of uses….

narrow spec = flucloxacillin. NOT inhibited by B lactamases. good for staphylococcus

Broad spec = benzylpenicillin. howeever destroyed by B lactams and poor GI absorption. can cover gram positive and negative cocci

extended spec = amoxicillin. destroyed by B lactamases. good GI absorption. same as broad spec PLUS increased gram neg cover - bacilli too.

anti-pseudomonal = piperacillin, destroyed by B lactamases, poor GI absorption. broad spec PLUS pseudomonas

23
Q

how can B lactamase resistance be over come?

Study These Flashcards
A

combining penicillin with B lactamase inhibtor
e.g. co-amoxiclav = amoxicillin + clauvanic acid
e.g. Tazocin = piperacillin + tazobactam

24
Q

what are the cephalosporins

Study These Flashcards
A

bacteriocidal, B lactam antibiotics
B lactam ring like penicillin but no thiazolidine ring instead dihydrothiazine ring
mostly good for gram positive infections….

5 generations , each with improved spectrum of activity. common ones include cefuroxime (2nd gen) and cefotaxime and ceftriaxone (3rd gen). 5th generation ones have MRSA cover.

lipid solubility gives them good BBB penetration for CNS infections.

25
what abx belong to B lactam group
penicillins e.g. amoxicillin cephalosporins e.g. ceftriaxone carbapenems e.g. meropenem
26
which Abx should be used in caution in those with penicillin allergy?
cephalosporins - cross reactivity both have B lactam ring
27
tell me about the carbopenems
bacteriocidal Abx in B lactam group similar to penicillins and cephalosporins as all have B lactam ring. broader spectrum, gram positive and negative and anerobic cover. not susceptible to B lactamases
28
tell me about the glycopeptides..
glycopeptides are a class of Abx that work via inhibiting cell wall synthesis (non B lactams) includes vancomycin, teicoplanin they work by inhibiting the transpeptidase enzyme which is responsible for cross linking bacterial peptidoglycan cell wall. hence bacteria killed by osmotic pressure - bacterocidal. can be used for both aerobic and anerobic gram positive. pharmacodymanics * nephrotoxic * ototoxic * histamine release - red man syndrome + hypotension * allergy - teicoplanin is highest (NAP6) pharamcokinetics * no GI absorption - hence acts locally for C diff. can give intrathecally for CNS infection * excreted unchanged in urine * needs monitoring to maintain levels between 10-15mg/l
29
common uses of glycopeptides
- oral vancomycin for C diff - endocarditis - MSRA
30
how does ciprofloxacin work?
quinolone Abx DNA gyrase inhibition prevents DNA synthesis good for gram negative
31
which Abx penetrate BBB well
3rd gen cephalosporins rifampicin ciprofloxacin
32
how does rifampicin work and when is it used?
TB infection inhibits DNA dependant RNA polymerase - transcription bacteriocidal
33
Mechanism of metronidazole?
breakdown of bacterial DNA mostly works in anaerobes - mechanism involves free radical production that destroys DNA
34
which Abx should be avoided with alcohol?
metronidazole - nausea vomitting, headache (hangover)
35
how do macrolides work?
bacteriostatic 50S inhibition prevent protein synthesis
36
give an example of a macrolide
erythromycin clarithromycin azithromycin
37
what precautions should be taken with macrolides?
prolong QTc risk of rhabdo with statins cyp450 inhibitor - increases warfarin prokinetics - diarrhoea, N&V
38
give examples of aminoglycosides
gentamicin streptomicin
39
what bacteria are aminoglycosides most effective against. how do they work?
gram neg 30S inhibition
40
what precautions should be taken with aminoglycosides?
ototoxic and nephrotoxic can also cause muscle weakness by inhibiting nACHR presynaptically - bad for myasthenia gravis (prolong NMBA) needs monitoring - initially dose via height and weight and then by levels narrow therapeutic index hence contraindicated in MG
41
which Abx belong to tetracyclines. how do these work?
doxycycline 30S inhibition good for intracellular bacteria e.g. chlamydia
42
what are the side effects of tetracyclines
photosensitivity shouldnt be given to children - due to teeth and bone development
43
mechanism of clindamycin
50S inhibition
44
mechanism of trimethroprim
dihydrofolate reductase inhibitor - prevents folate and nucleic acid synthesis
45
what is meant by antimicrobial stewardship?
coordinated programme that promotes correct use of antibiotics to reduce risk of resistance devloping and improve patient outcomes. methods include - only when clinically indicated - use local guidelines - correct dose and duration - collect samples and target therapy to sensitivity - de-escalate from broad to narrow spec when possible - stop spread - PPE
46
what is meant by antimicrobial resistance
microbes are rapidly dividing within the population mutations will develop and some of these will be beneficial and provide resistance to Abx. these will be selected for and resistance will develop plasmids can also share resistance genes in the population mechanisms for mutation include - enzymes that destroy Abx - b lactamases - altering bacterial target - pumping Abx out of the cell
47
what factors are considered when starting Abx
patient factors * age e.g. avoid gentamicin in older people * allergies * renal function * pregnancy infection factors * culture and sensitivities * gram staining * location of infection - BBB needs penetrating local policies
48
what antivirals do you know?
viruses replicate within host cells hence hard to target without killing host. antivirals work by targeting virally infected cells selctively they may inhibit protein synthesis, viral release or DNA replication examples include aciclovir - inhibits nucleic acid syntheiss as it is a guanine analogue but only activated in virally infected cells. Tamiflu neuraminidase inhibitor prevents release of influenza HIV antivirals act via targetting reverse transcriptase
49
what antifungal agents do you know?
3 groups azoles, polyenes, echinocandins azoles = inhibit ergosterol synthesis - important component of fungal cell wall. e.g. fluconazole polyenes = bind ergosterol and create a pore within membrane - intracellular contents leak. e..g amphotericin , nystatin echinocandins - inhibit B1,3 glucan synthase - prevents synthesis of b-1,3 glucan which gives cell wall strength e.g. capsofungin
50
do you know any other mechanisms of antifungals?
inhibit DNA and RNA synthesis inhibit mitosis
51
tell me about amphotericin
polyene antifungal agent works via binding ergosterol and creating pores that allow leakage of fungal cell contents given IV for systemic fungal infections.
52
what are the side effects of azoles and polyenes
polyenes - nephrotoxic, electrolyte disturbance azoles * hepatic dysfunction * prolonged QT * CYP450 inhibitor
53
when are antifungals given prophylactically
immunocompromised patients e.g. transplanted patients, HIV
54
what are the risk factors for developing fungal disease?
immunocompromisation HIV, diabetes, chemo, transplant , long term steroid resp compromise - bronchiectasis , CF , prolonged mechanical ventilation

PHARMACOLOGY FRCA (16 decks)

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