J Letchford Lec 3 B-lactams Flashcards
Penicillin G is a naturally occurring antibiotic. It is an asexual sporing structure of ______ mould.
Penicillium
B lactams include drugs with different nuclei as follows:
1) P______ nucleus (5 mem)
2) C_____ nucleus (6 mem)
3) C_____ nucleus (5 mem)
4) M_____ nucleus (4 mem)
Penicillin
Cephalosporin
Carbapenem
Monobactam
Bioavailability of penicillins depends on their _ group.
This could determine whether the drug is given IM, IV or PO
R group
The R group of penicillins determines:
S______ G+ve, G-ve, (Ps. aeruginosa)
S______ Na+ & K+ salts more soluble
S______ e.g Methicillin vs ampicillin in acid
B______ e.g benzylpen vs benzathin benzylpen
B-l_____ ______ e.g ampicillin vs flucloxacillin
Selectivity Solubility Stability Bioavailability B-lactamase resistance
Main types of penicillins:
1) B-______ sensitive
Benzylpenicillin (Pen _)
Benzathine benzylpenicillin
Phenoxymethylpenicillin (Pen _)
B-lactamase sensitive
Pen G
Pen V
Main types of penicillins:
2) B-lactamase resistant
Flucloxacillin: Co-fluampicil (____ active) - with ampicillin to broaden spectrum as fluclox is ____ spectrum
Temocilin - resistant to _-______ from G-ve
Orally
Narrow
B-lactamases
Main types of penicillins:
3) Broad - Spectrum
Am_____, Am____ (NOT Pseudomonas though)
Co-_____ (Augmentin)
All orally active
Amoxicillin
Ampicillin
Co-amoxiclav (amoxicillin and clavulonic acid)
Main types of penicillins:
4) Anti-pseudomonal
Pi____
Pi____ and tazobactam (_____)
Ticarcillin and clavulonic acid (_____)
Piperacillin
Piperacillin
Tazocin
Timentin
Benzylpenicillin (Penicillin G)
Mainly active against gram ____ but some gram ____.
It can/can’t be taken orally.
It is/isn’t sensitive to B-lactamases
Gram positive but some gram negative
It can’t be taken orally
It is sensitive to B-lactamases
Benzylpenicillin PKs
How is it given?
Is it toxic or non toxic?
Good diffusion into body tissues and fluids
Does it reach HIGH or LOW levels in the CSF?
What about in meningitis?
IM, slow IV injection or IV infusion
NON toxic (can reach high blood conc quickly)
Low levels in CSF as doesn’t cross BBB but weakness in BBB in meningitis so high levels in the CSF in these instances.
Benzylpenicillin has a long post _____ effect.
Antibiotic
Maintenance benzylpenicillin blood levels:
- Administer ____ doses.
- Give ____ doses.
- Combine with benzathine benzlpenicillin (slow release from IM site)
Dose:
- IM, Slow IV injection or IV infusion
- Endocarditis 2.4g every _ hrs therefore _ doses a day = __._g!
- Std dose 1.2g _DS
Large
Frequent
4 hourly
6 doses a day
14.4g a day! (in endocarditis)
Std dose is 1.2g QDS
Benzylpenicilin:
- Throat infections
- En_____
- _______ (keep IM injection in cabinet to admin)
- Pn_____
- Cel_____
- Osteomyelitis
Phenoxymethylpenicillin (Orally active) used in ____ infections.
Endocarditis
Meningitis
Pneumonia
Cellulitis
Throat
Meningitis is caused by…
N______ _______
S______ _______
H______ _______
You should use ______ immediately if meningitis suspected
Neisseria meningitidis
Streptococcus Pneumoniae
Haemophilus influenza
Benzylpenicillin
Oral penicillin: Amoxicillin
The R group makes it stable in ____.
Its peak blood conc is achieved after __ mins.
It achieves good ___ levels in meningitis
It can be used in conjunction with Clavulonic acid to produce __-_____.
Acid
90 mins
CSF
Co-amoxiclav
Amoxicillin is a ___ ____ antibiotic working against most gram +ve and -ve bacteria.
It is most commonly used to treat ___ infections, and ___. tract infections.
It is sometimes used to treat GIT infections and _____ meningitis alongside G_____.
Broad spectrum
Oral infections
Resp. tract infections
Listerial meningitis alongside Gentamicin
Resistance to amoxicillin is __& in E.coli, __% in H. Influenzae but mostly S_______.
40% in E.coli
10% in Haemophilus Influenzae
but mostly Staphylococci
Side effects of Penicillins:
H_______
1-10% = ___, fever
0.05% = _____
Neurotoxicity
Higher risk with ____ failure
Fits, ______, unconsciousness
____ failure
High ___ affects electrolyte balance
e.g injectables esp. ______ benzylpenicillin
_____ and pseudomembranous _____. (Due to C.diff infection - superinfection after treatment with broad spec antibiotics)
Hypersensitivity
Rash, Fever
Anaphylaxis
Renal failure (espesh in elderly) Hallucinations
Renal Failure
Salt
Benzathine BenzylPenicillin
Diarrhoea & pseudomembranous colitis
Oral broad-spectrum antibiotics kill ___ bacteria.
Resistant pathogenic ___ bacteria cause ____-_______.
This causes diarrhoea and _______ colitis: C.diff (spore)
Gut
Gut
Pseudomembranous colitis (inflame, debris, WBCs, pus, diarrhoea)
Cephalosporin C is isolated from Cephalosporium Acre_____.
This has no antimicrobial activity but is related to B lactams and its derivative provide useful antibiotics.
They have a _ membered ring.
Their specificity, s_____ and activity is determined by composition of _ groups 1&2
Cephalosporium Acremonium
They have a 6 membered ring
Selectivity
R groups 1 (antibacterial action) & 2 (Metab and PK)
Cephalosporins:
- Resistance to B-lactamases (NOT ____s)
- Active against both gram +ve and gram -ve after _____ have been produced
ESBLs
Derivatives (as only originally active against gram +ve)
Cephalosporins:
Activity against gram+ve bacteria:
Affinity for ___’s
Resistance to B-lactamases
Activity against gram-ve bacteria:
Penetration through ____ _______.
PBP’s
Outer membrane (pores need to be large enough for B lactam to get in)
Cephalosporins have a similar spectrum of activity to _______.
Used to treat:
Septicaemia, p______, men____, biliary-tract infections, per_____, UTIs
BUT cost and _.___ risk limit use
Penicillins
Septicaemia, pneumonia, meningitis, biliary-tract infections, peritonitis, UTIs
But cost and C.diff risk limit use
Cephalosporins have similar PKs to ______.
- Most given by . or . ______ or . ______
- Some ____
- LOW penetration into ___ (except ______)
- ____ excretion
Penicillins
I.M or I.V infusion or I.V injection
Oral
CSF except Meningitis
Renal
Side effects of Cephalosporins: H\_\_\_\_\_\_ 1-10% rash, \_\_\_\_ \_\_\_% anaphylaxis 0.5-6% \_\_\_\_\_ sensitive patients allergic to cephalosporins
Hypersensitivity
Fever
0.05%
Penicillin
Side effects of Cephalosporins:
- D______, N______, _.____ S____ I______
- RARE (0.1% patients)
- V______, headache, dizziness
- Renal toxicity, H______ (in early cephalosporins that used to destroy bacteria that produced vitamin K)
Diarrhoea
Nausea
C.Diff super infections
Vomiting
Haemorrhage
___ Generation Cephalosporins
e.g Cefazolin (inject) and Cefradine (oral)
Active against MOST G_ve cocci
except enterococci, MRSA, staph epidermis
Active against SOME G_ves
e.g E.coli, Klebsiella pneumonia, Proteus mirabilis
GENERALLY REPLACED
1st
G+ve
G-ves
2nd Generation Cephalosporins
____ spectrum compared to 1st generation.
Active against more G_ve bacteria
e.g Haemophilus influenzae, Enterobacter, Proteus mirabilis, E.coli, Klebsiella pneumoniae
More resistance to _-______.
Examples of 2nd generation are:
Cef_____ (injection, oral)
Cefaclor (oral)
Used in ____ infections and prevention of infection after surgery (p______)
Broader
G-ve
B-lactamases
Cefuroxime
Severe
Prophylaxis
3rd Generation Cephalosporins
_____ spectrum
Increased activity
Increased resistance to B-lactamases
e.g
Cef____ (injection)
Cef____ (injection) OD DOSING
FOR community acquired ______
Meningitis, infantile sepsis, gonorrhoea, hospital acquired infections
SUBSET active against P_____ A_____ (difficult to treat) e.g Cef______ (injection)
Broad
Ceftaxime
Ceftriaxone
Pseudomonas Aeruginosa
Ceftazidime
4th Generation Cephalosporins
Extended spectrum agents
More resistant to _-_______
Many cross the ___ even if the _____ are not inflamed
Reserved for use against difficult to treat P______ A______ and severe infections
e.g Cef____ (injection) and Cef_____ (injection)
B-lactamases
BBB
Meninges
Pseudomonas Aeruginosa
Cefepime
Cefpirome
Antibiotic inhibitors of cell wall synthesis: C_______.
e.g Imipenem, M_____, doripenem.
Highly resistant to _-_____ including ____s
Broad spectrum activity against +ve and -ve and _____.
Active against difficult to treat ______ ______.
Not active against M___ or E._____
Carbapenems
Meropenem
B-lactamases including ESBLs
Anaerobes
Pseudomonas Aeruginosa
MRSA or E.Faecium
Carbapenems PK, uses and SE’s:
- Similar to other B-lactams
- _._ for: Septicaemia \_\_\_\_\_ \_\_\_\_\_ pneumonia Intra-abdominal infections Skin and soft tissue infections Complicated \_\_\_
- Issues with emerging _____: NDM-1
I.V
Hospital acquired pneumonia
Complicated UTI
Resistance: NDM-1
Antibiotic inhibitors of cell wall synthesis: M______
e.g A_____
Have _ B-lactam ___
Active against G___ aerobes
NOT active against G___ or _____
Stable to most _-_______
Used for I.M or I.V septicaemia, complicated UTI
SE’s ____ likely to cause hypersensitivity
Aztreonam
1 Ring
G-ve
G+ve or anerobes
B-lactamases
Less likely to cause hypersensitivity
