Antibiotic Therapy Flashcards
1
Q
what is an antibiotic?
A
a drug used to treat or prevent an infection caused by micro-organisms (molecules that at small levels can inhibit or kill bacteria by reducing pathogenicity of bacteria/prokaryotes)
2
Q
what is bacteriostatic?
A
inhibition of the growth of bacteria
3
Q
what is bacteriocidal?
A
killing of bacteria (remeber as “cidal” like sui”cidal”)
4
Q
what is a narrow spectrum antibiotic?
A
one that kills only one group e.g. gram negative
5
Q
what is a broad spectrum antibiotic?
A
killing of lots of different group like gram - and gram + etc
6
Q
what is penicillin spectrum?
A
narrow spectrum = active against gram + bacteria
7
Q
what is tetracyline spectrum?
A
broad spectrum = active against many gram - and gram +
8
Q
what are ideal antibiotic components?
A
- selective toxicity/minimal toxicity
- cidal (kills bacteria
- long half life (low binding to plasma proteins)
- appropriate tissue distrubution
- no adverse drug interaction/side-effects
- oral & pareneteral preparations
9
Q
what is price of taking antibiotic?
A
effect on host natural microbiome, bacteria that gives host some protection
10
Q
what does it mean by selective toxicity/minimal toxicity to host in antibiotics?
A
idea that antibiotic molecule inhibits something in micro-organism that isn’t present in host e.g. peptidoglycan wall is unique so could target that
11
Q
what are antibiotic targets?
A
- cell wall structures e.g. petidoglycan synthesis
- ribosomes (protein synthesis)
-DNA replication (nucleic acid synthesis)
-DNA gyrases
-metabolic pathways (as different nutrients required, diffferent enzymes involved)
-cell membrane functions
=extra enzymes involved in these areas/functions could be targeted by antibiotic
12
Q
what does pharmodynamic mean?
A
how much of antibiotic you have, what activity etc
13
Q
what does pharmokinetic mean?
A
about delivery of antibiotic, how body deals with it & secretion is important
14
Q
what factors are involved in pharmodynamics?
A
MIC/MBC = minimum inhibitory/bacteriocidal concentration (in vitro)
time dependant action (in vitro/in vivo blood concentration)
spectrum (broad to narrow range) in vitro e.g. gram +, gram -, anaerobic bacteria
15
Q
what factors are involved in pharmokinetics?
A
absorption (peritoneal Vs IV, acid sensitivity)
distrubution (plasma binding proteins, GI/urinary tract, environment permissive for activity)
elimination (liver or kidney)
16
Q
what are cell wall antibiotics?
A
- penicillins (beta lactam)
-cephalosporins (beta lactam)
-glycopeptides (not beta lactam)
17
Q
what is beta-lactam?
A
structural element within molecules that look like component (terminal peptide amino acid) of bacterial cell wall
= flexible side chain & structure that can be altered to change spectrum & resistance
18
Q
what is lysis?
A
breakdown of cell wall as no new material is syntheisised so gap
19
Q
what is molecular mechanims of beta-lactam antibiotics?
A
beta lactam looks like terminal peptide amino acid so enzyme binds to beta lactam instead, but beta lactam doesn’t go anywhere and remains bound - when found it had radioactive penicillin bound to them so called it PBP (penicillin binding protein) - result of this is lysis going ahead without synthesis, weakening & bursting cell wall. as beta-lactam has bound and stuck so corss link side chain not holding cell wall together (irreversibly binds)
20
Q
what are target of beta lactam antibiotics?
A
penicillin-binding protein
21
Q
what would normal molecular mechanism be if no beta lactam for synthesis of cell wall?
A
terminal amino acid usually binds to enzyme, enzyme breaks it open and transfers energy and through series of chemical reactions forms chemical bridge an makes rigid cell wall
22
Q
what are positives of penicillin?
A
- Safe, very few side effects
- Variety, very flexible molecule with side groups & chains able to alter multiple
features - Range from narrow spectrum to broad spectrum i.e. empiric prescribing & can act on a wide range of bacteria, usually both Gram negative
& Gram positive organisms, but also some can be quite specific - Excreted (rapidly) via kidney
23
Q
what are the limitations of penicillin?
A
- resistance causes major issue, resistance was observed almost immediately
- certain group of patients tended to have hypersensitivty (allergy)
-rapid secretion by kidneys so requires frequent dosage
24
Q
what are the 3 principle compound of penicillin?
A
Benzylpenicillin = Penicillin G, Intravenous IV
Phenoxymethyl penicillin = Penicillin V, oral delivery too
Benzathine penicillin = long-acting, Intramuscular
25
what was discovered to help resistance?
that you can combine certain antibiotics with a second compound that inhibits the enzyme that would degrade them
e.g. beta lactamase inhibitor to inhibit beta lactamase so it doesn't degrade beta lactam
26
what are properties of co-amixclav?
amoxicillin & clavulanic acid
contains:
-b-lactam & b-lactamase inhibitor
* Clavulanic acid
* Inhibits the action of b-lactamase
* Microbial resistance enzyme
* Does NOT have antibiotic properties of its own
Combination extends range of bacteria that can be treated, similar for Piperacillin & tazobactam
27
what are some properties of flucloxacillin?
narrow spectrum antibiotic
* Useful for Staphylococci and Streptococci ONLY
* Replaced methicillin or meticillin (better tissue distrubution)
* MRSA is resistant to Flucloxacillin
* Reporting labs use oxacillin to report resistance
* Commonly prescribed antibiotic
* i.e. very common Staph and Strep skin infections
* Skin and soft tissue infection
* Wound infection
* Cellulitis (infection of the soft tissues under the skin)
- modify side chains allow beta lactam to resist degredation
28
what are the key clincical penicillins?
a) gram +?
b) gram -?
c) gram + and gram -?
a) flucloxacillin (IV, oral) & penicillin V
b) temocillin (IV only)
c) amoxicillin (IV, oral), co-amoxiclav (IV, oral)
29
what are beta lactams examples?
1. penicillins
2. cephalosporins
3. carbapenems
30
how frequently used is cephalosporins?
very restricted use in tayside as they kill off normal gut bacteria and allow overgrowth of c.difficiles so many hospitals try to avoid using them. each successive generation increases broad spectrum over next which means it just wipes out again and again which in this case isn't a good thing as it leaves nothing left (even good)
31
how is cephalosporins excreted?
via kidneys and urine
32
what makes B lactams the most successful group of antibiotics?
- pharmokinetics
-development of formulations with extended spectrum (pharmodynamics altered, can extend spectrum)
-development of less resistant forms insensitive to beta lactamases (carbapenems)
-development of beta lactamases inhibitors
33
describe some properties of carbapenems?
1. Broad spectrum Gm+ ve & Gm-ve
Resistant to b-lactamase
Abiot of last resort for some Gm-ve
e.g. Meropenem usually IV admina
(good for when you don’t know whats wrong with them as kills broad range. bad as wipes out everything including good bacteria)
34
what are penicillin binding proteins?
PBP = proteins that make cell wall structure rigid by cross linking side chains (they bind to D-alanine D-alanine)
-> it's what beta lactam antibiotics target
*PBP is a subgroup of transpeptidase
35
what are the side effects of cephalosporin antibiotics?
very few side effects (reduced allergy side effects)
- therefore safe in prgenancy
36
what is a negative of cephalosporins antibiotics?
generally they're more resistant to beta lactamases but gram - still has developed resisitance
37
How do cephalosporin act as antibiotic?
it's a beta lactam antibiotic that inhibits cell wall synthesis and bactericidal (cell wall targeting)
38
what are the side effects of penicillin?
safe - very few side effects
apart from allergy - certain groups of patients have hypersensitivity (allergy)
39
what is general penicillins spectrum?
range from narrow to broad - can act on wide range of bacteria
= you can subtly alter them to extend spectrum
40
how are penicillins excreted?
rapidly through urine - means has to be taken in frequent dosage
41
what are negatives of penicillin?
resistance is major issue, bacteria showed resistance very early on
(need lots of penicilllin in frequent doses as excreted quickly)
42
what is penicillin V spectrum?
narrow spectrum - mostly gram positive
43
how is penicillin V get into system?
absorbed through intestine
44
what is negative to penicillin V?
sensitive to stomach acid so have to co-ordinate doses with eating times which can be awkward and annoying
-it also takes longer for drug to get into blood system (30-60 mins)and doesn't stay there for very long (3--60 mins)
45
what does it mean by % of plasma binding for types of antibiotics?
the degree to which medications attach to blood proteins within the blood plasma. A drug's efficacy may be affected by the degree to which it binds. The less bound a drug is, the more efficiently it can traverse or diffuse through cell membranes
46
is lots of plasma protein binding good or bad?
bad as high binding means that the antibiotics don't diffuse into cells easily and are secreted quicker
47
what is plasma binding level for penicillin V?
75-90% binds to plasma proteins (not very good)
48
what types of bacteria do penicillin V tackle?
streptococci, straphylococci, clostridia, neisseria, treponema, listeria, bacillus
49
what are negatives of amoxicillin?
-effectiveness challenged by beta-lactamases
-disrupts gut flora as broad spectrum & absorbed through intestine
50
what are side effects of amoxicillin?
safe & well tolerated
51
what is plasma binding like in amoxicillin?
20% (low) plasma binding so good distrubution to tissues
52
why is amoxicillin good?
good absorption when given orally
-stable in presence of stomach acid so not inconvenient for eating times
53
what is amoxicillin spectrum?
extends to gram +ve and gram -ve
54
what is half life of antibiotics?
the time it may take for the strength or concentration of the medication to decrease by half of its original strength so you want a high half life for good effectiveness
55
what is half life of amoxicillin?
plasma half life = 60 minutes
56
what is half life like in cephalosporins?
longer half life (which is good)
57
what is co-amoxiclav?
a combination drug of amoxicillin & clavulanic acid
also contains: beta lactam & beta lactamase inhibitor
58
why did they want combination drug? e.g. co-amoxiclav
extends range of bacteria that can be treated (also includes beta lactamase to try and reduce resistance)
59
what is beta lactamase?
enzyme produced (by bacteria) to degrade beta lactam (from antibiotic) which is what gives resistance (when antibiotics don't work on bacteria due to resistance)
60
what is flucloxacillin spectrum?
narrow spectrum - straphylococci & streptococci ONLY
61
what is negative of flucloxacillin?
narrow spectrum & MRSA is resistant to it
62
when and how often if flucloxacillin prescribed?
commonly prescribed. for straph & strep infections
e.g. Skin and soft tissue infection
* Wound infection
* Cellulitis (infection of the soft tissues under the skin)
63
how does flucloxacillin try to resist beta lactam degredation?
by modifying side chains so beta lactamase can't bind/fit and degrade it
64
why did flucloxacillin replace methicillin?
better tissue distrubution
65
why is temocillin good?
beta lactamase resistant as targets beta lactamase producers
66
what is temocillin spectrum?
- largely restricted to coliforms (gram -) like GI tract and e.coli
-Active against ESBL-producing organisms
* Extended spectrum to b-lactamases producers
* Also resistant to ampC b-lactamases
67
what is problem with temocillin?
only given IV not orally
68
what is carbapenems spectrum?
broad spectrum = gram +ve and gram -ve
69
why is carbapenem good?
resistant to beta lactamase and can be a bit of a lost resort - if you don't know whats wrong with patient then kills broad range
70
what are 2 types of glycopeptide?
vancomycin
teicoplanin
(both IV)
71
what is action of glycopeptide?
it's not beta lactam antibiotic but still targets cell wall
=binds to end of peptide chain (D-alanine D-alanine) & prevent its incorporation into the cell wall.
= this block PBP from binding to cell so reduced cross linking so lysis and weakening of cell wall
(Also interferes with membrane & PG precursor carrier molecule (Lipid II))
72
how is glycopetide excreted?
via kidneys & urine
73
how can glycopeptide help cause kidney damage?
-toxic levels of vancomycin in blood can build up in patients who have kidney failure causing further kidney damage
74
what is glycopeptide spectrum?
Restricted activity means limited to bacteria with a Gram-positive cell wall
* Oral Vancomycin can target Gram+Ve GI microbes as builds up in intestine
* NO activity against Gram negative organisms
* Excluded by outer membrane
75
what is function of protein synthesis inhibitors?
they block different steps in protein synthesis with transient & permanent binding
76
what are protein synthesis inhibitors?
antibiotics that inhibit protein synthesis by attaching to bacterial ribosomes (which are STRUCTURALLY DIFFERENT from mammalian ribosomes)
77
what does it mean by bacteriostatic antibiotic & what are some examples?
bacteriostatic - when protein synthesis resumes after antibiotic antibiotic removed
examples = macrolides & tetracyclines
78
what does it mean by bacteriocidal antibiotics & what are some examples?
bacteriocidal = when binding of antibiotics is lethal and protein synthesis doesn't ever continue
example = aminoglycosides (gentamicin)
79
what are 3 key examples of protein synthesis inhibitors (the specific antibiotic & the group of antibiotics they're in)
1. gentamicin (in aminoglycosides group)
2. deoxycyline/minocycline (tetracycline group)
3. erythromycin (macrolide group)
80
how is gentamicin given?
IV only - not absorbed in the gut
(occasionally intramuscular)
81
how does gentamicin inhibit protein synthesis?
binds to ribosome 30S inhibiting protein sythesis
- it's irreversible binding & bacteriocidal (kills bacteria)
82
what is gentamicin active against?
mainly gram -ve aerobic organisms e.g. coliforms & pseudonomas aeruginosa
-> for people who are seriously ill (in hospital)
83
what is negative of gentamicin?
toxicity = causes damage to kidneys and VIIth carnial nerve (deafness & dizzyness) so blood levels need to be monitored of aminoglycosides complicating therapy
84
how is gentamicin excreted?
by urine
85
what is mode of action of tetracyline?
actively transported into cell
= binds to 30S subunit on ribosome & prevents attachment of tRNA to acceptor sites (stops chain elongation)
86
what is spectrum of tetracycline?
broad spectrum
= useful against intracellular bacteria & atypical bacteria e.g. chlamidyia
87
is there resistance against tetracyclins?
more resistance after each use
88
what are negatives of tetracyclins?
destruction of normal intestinal flora resulting in increased secondary infections
- staining & impairment of the structure of bone & teeth
- restricted use in infants, children & pregnancy
89
what tetracylins have more efficient absorption?
deoxcyclin & minocycline
(lower concentration in gut so less disturbance & higher concentration in serum)
90
are the following bacteriocidal or bacteriostatic?
a) aminoglycides (gentamicin)
b) tetracyclins
c) macrolides
a) bacteriocidal
b) bacteriostatic
c) bacteriostatic
91
when are macrolides commonly prescribed?
for penicillin allergy & intracellular pathogens
92
what is mode of action for macrolides?
bind to 50S subunit on ribosome and block translocation = no release of peptide
93
what are examples of macrolides?
- erythromicin
- clarythromicin (gram -ve)
- azithromycin (gram +ve)
94
how are macrolides excreted?
by the liver - biliary tract and into gut
(NOT URINE)
95
is erythromycin safe in pregnancy?
yes
96
what type of infections are macrolides useful for?
treating certain infections where intracellular bacteria “hide” from the host’s immune system
97
what are examples of antibiotics that target nucleic acid?
1. fluoroquinoles (gram - & +)
2. metranidazole (anaerobes & protozoa)
3. Trimethroprim = +/- sulphonamides (urinary tract infections)
98
what is main example of quinolones?
ciprofloxacin
99
what is mode of action of quinolones?
bind to the A subunit of DNA gyrases (topoisomerase) and prvent supercoiling of DNA
= indirectly inhibits DNA synthesis
100
are quinolones bacteriocidal or bacteriostatic?
bacteriocidal
101
what does DNA gyrase do?
catalase the supercoiling of DNA
- belong to group of enzymes called topoisomers
102
how is ciprofloxacin given?
IV or orally
103
what activity does ciprofloxacin target?
gram -ve activity e.g. e.coli, H.influenza, pseudonoma etc
104
what is spectrum of quinolones?
broad spectrum therefore use now severely restricted to reduce risk of c.difficile GI infection (especially in elderly)
105
what do you prescribe quinolones for?
- bones
- UTI's
- community acquired ammonia
-> severely restricted due to broad spectrum = risk for c.diff
106
what antibiotic group does metronidazole belong to?
nitroimadazoles
107
how can metronidazole be given?
IV or orally
108
what is metronidazole active against?
anaerobes (important to know)& parasites/protozoa
109
what is mode of action of metronidazole?
- drug activated by reduction process
- intracellular low Eh leads to reduction (found in anaerobes)
- forms toxic intermediate that induces DNA strand breakage
110
what is resistance for metronidazole like?
very rare
111
what are negatives for metronidazole?
adverse reactions are limited as long as alcohol is avoided
- complaints of metallic taste
- furred tongue
112
why would you want drugs to inhibit folic acid synthesis?
because then a key intermediate metabolism is blocked
- it's a pathway we don't use in eukaryotic cells
- folic acid vitamin is required for synthesis of key cellular components
113
what are 2 types of folic acid synthesis inhibitors?
1. sulphonamides
2. Trimethroprim
114
how is trimethroprim excreted?
in urine
115
when is trimethroprim commonly prescribed?
for acute UTI's e.g. e.coli
116
how can trimethroprim be given (hint = on it's own & in combination)?
on it's own = orally
in combination with a sulphonamide (sulphamethoxazole) (called co-trimoxazole) = orally or IV
117
what is trimethrprim spectrum?
some gram -ve and some gram +ve
118
why isn't trimethroprim used more often?
it's not used sytstemicly, beta lactam drug preferred over it
119
what is presumptive prescribing?
also called empiric prescribing
= without laboratory identification based on likely pathogens for infection under treatment
120
what is targeted prescribing?
-nature & extent
= Laboratory investigation (identification & sensitivity of pathogen)
121
what are considerations for when picking what antibiotic to prescribe?
-drug choice
- nature of infection
-dose route & frequency
- allergy
-interactions
-compliance
= prescribing should be limited but still prescribe as saves lives
122
what are COMMON side effects of antibiotics?
nausea, vomiting, diarrhoea
= all antibiotics interrupt gut bacterial flora
= may affect absorption of oral contraceptives
123
what is gentamicin main problems?
renal & VII nerve damage
124
what is ciprofloxacin main problems?
tendonitis - avoid use in pregnancy & breast feeding women
125
what is main problem with metronidazole?
interacts with alcohol
126
what are the 4C's?
high risk - restricted antibiotics
1. Cephalosporins
2. Co-amoxiclav
3. Ciprofloxacin
4. Clindamycin
= they kill a broad range of bacteria but means high c.diff risk
127
why are antibiotics sometimes given in combination? (reasons for)
1. To cover a broad range of possible infecting organisms, e.g. for the treatment of pneumonia
2. To prevent the development of resistance, e.g in the treatment of tuberculosis (TB)
3. For the synergistic (co-operation) effect of combination (1+1 = 3), e.g in the treatment of some cases of endocarditis (means they work together to get good outcome)
128
what should you never combine?
bacteriostatic & bacteriocidal e.g. protein synthesis inhibition with cell wall antibiotics - cell wall synthesis has stopped
