Cell Wall Synthesis Inhibitors Flashcards
How do Beta Lactems work?
Bind to active site of transpeptidase enzyme (PBP) which catalyses cross linking of terminal peptide components of the linear polymer chains
Leads to weakening of the cell wall structure, build up in i travel pulse osmotic pressure and lysis of bacterial cells
What are 4 types of penicillins
- natural penicillins
- penicillinase resistant penicillins
- aminopenicillins (broad spectrum) + beta lactemase inhibitors
- anti pseudomonal penicillins (extended spectrum) + beta lactamase inhibitor
What are two types of natural penicillins?
Penicillin G and Penicillin V
What are 3 types of Penicillin G?
Pen G Potassium
Pen G Procaine
Pen G Benzathine
for natural pencilling, What is the
a) route of administration
b) main target organisms
c) penetration into CSF
d) excretion
e) distribution into storage tissue
a) Pen G Potassium = IV; Pen G Procaine = IM; Pen G Benzathine = IM; Pen V = Oral (better absorption than Pen V bc acid stable)
b) - gram positive, some gram neg (meningococci, gonococci), spirochetes (treponema pallidum *use pen G benzathine), beta lactamase negative strains
c) IV aqueous Pen G reaches higher concentrations than procaine or benzathine; penetration increased if meninges inflamed
d) renal (can be blocked by probenecid to prolong effect)
e) Pen G procaine and benzathine can distribute into storage tissues to be released slowly
4 examples of penicillinase-resistant penicillins?
a. methicillin
b. cloxacillin
c. oxacillin
d. flucloxacillin
4 examples of penicillnase resistant penicillins?
a. methicillin
b. cloxacillin
c. oxacillin
d. flucloxacillin
for penicillinase resistant penicillins, what is the
a) route of administration
b) main target organisms
c) penetration into CSF
d) Excretion
e) mechanism of action
a) IV, IM, Oral
b) gram positive penicillinase producing staphylococci and other gram positives
*ig organism is susceptible to pen G, less effective
c) does not achieve therapeutic levels
d) renal
e) bulky side groups confers protection from beta lactamases by limiting their accessibility to catalytic site of action
examples of 2 aminopenicillins
a. ampicillin
b. amoxicillin
For aminopenicillins,
a) route of administration
b) target organisms
c) penetration into CSF
d) excretion
e) Usually prescribed with what?
a) Ampicillin: Oral, IV; Amoxicillin: Oral (better than ampicillin)
b) Ampicillin & Amoxicillin: Gram positive & Gram Negatives (broad spectrum) EXCEPT pseudomonas + klebsiella;
c) IV yes, better in inflamed meninges
d) renal
e) Ampicillin + Sulbactem (unasyn); Amoxicillin + Clauvanate (augmentin)
example of antipseudomonal penicillin?
piperacillin
for antipseudomonal penicillins,
a) route of administration
b) target organism
c) penetration into CSF
d) excretion
e) usually combined with?
a) IV
b) Gram negs (including pseudomonas + klebsiella) + gram positives; anaerobes
c) good in inflamed meninges
d) renal
e) tazobactem (zosyn)
How do beta lactamase inhibitors work?
- Clauvanic Acid = suicide inhibitor of beta lactamase
- Sulbactem + tazobactem allosteric inhibitors
for beta lactamase combination drugs,
a) route of administration
b) main target organisms/ types of infection
c) penetration into CSF
d) excretion
a) Augmentin = oral, IV; Unasyn = IV; Zosyn = IV
b) Augmentin = Staph, H. influenzae, Gonococci, E .Coli/ Skin, lower respiratory tract infections, UTI; Unasyn = S. aureus, Gram neg aerobes, anaerobes/ skin. intra-abdominal, gynae infections; zosyn = broad af/ appendicitis, moderate to severe nosocomial pneumonia
c) clauvanic acid & tazobactem no; sulbactam need meningeal inflammation
d) renal
4 mechanisms of resistance to penicillin?
- PBP altered, reducing affinity for penicillins (MRSA expresses PBP2a, reduced affinity for penicillin)
- Production of beta lactamase resulting in hydrolysis of beta lactam ring
- Decreased ability of antibiotic to reach PBP when bacteria decreases porin production
- Presence of efflux pumps
adverse reactions of penicillins?
- allergy/hypersensitivity - SJS + TEN
- CDAD (ampicillin & augmentin)
- Neurotoxicity
- Hepatotoxicity
- Anosmia
- In patients with renal failure, high doses of penicillins can cause seizures
How are cephalosporins produced?
produced from 7-aminocephalosporanic acid; modification at position 7 of beta lactam ring alters anti bacterial activity;
substitution at position 3 of the dihydrothiazine ring alters the metabolism and PK properties of the drugs
first gen cephalosporin a) examples (2) b) useful spectrum
c) method of administration
a) cefazolin, cephalexin
b) gram positives (streptococci [except if penicillin resistant], staph [except if methicillin resistant]); cefazolin the 2nd line for staph for pt with allergic rxn to penicillins
c) oral except cefazolin (IV)
second gen cephalosporin a) example b) useful spectrum
a) cefuroxime
b) e. coli, klebsiella, proteus, h. influenzae
third gen cephalosporin a) examples b) useful spectrum
c) method of administration
a) ceftriaxone, ceftazidime
b) enterobacter, p. aeruginosa (ceftazidime only), n. gonorrhoaea (ie gram negs); s. aureus, s. pneumonia, strep. pyogenes (ie gram pos, comparable to first gen, ceftazidime not so good, cefotaxime good for gram pos)
c) parenteral
fourth gen cephalosporin a) examples b) useful spectrum
c) method of admin
a) cefepime
b) enterobacter, p. aeruginosa, n. gonorrhoaea; s. aureus, s. pneumonia, strep. pyogenes (same as third gen) + pseudomonas
c) parenteral
fifth gen cephalosporin a) examples b) useful spectrum c) method of admin
a) ceftaroline
b) MRSA, VRSA, s. pneumoniae, h. influenzae, moraxella catarrhalis
limitations of first gen to fourth gen cephalosporin?
no activity vs LAME = listeria, atypicals (mycoplasma, chlamydia, legionella), MRSA, enterococcus
limitation of 5th gen cephalosporins?
no activity vs ESBL
which gen of cephalosporin can cross CSF?
from 3rd gen onwards
which gen of cephalosproin resistant to beta lactamase?
1st gen no; 2nd gen moderate; 3rd gen onwards good
which gen of cephalosporin activity vs gram negs?
1st gen no; increases as go from 2nd gen to 4th gen
clearance of cephalosporins?
all renal EXCEPT ceftriaxone (hepatic)
caution with ceftriaxone?
do not mix with calcium containing product (ie ringers or hartmann solution) = will cause calcium precipitate
adverse reactions to cephalosporins?
- hypersensitivity - cross reactivity with penicillin (if got penicillin allergy. NO to cephalosporin)
- GIT - diarrhoae (ie CDAD)
- thrombophlebitis - pls give slowly and in diluted form rotate infusion site
Types of Carbapenems? (3)
- Imipenem (w/ cilastatin)
- Meropenem
- Ertapenem
How are carbapenems administered?
IV
How is imipenem prescribed? Why?
With cilastatin. Hydrolysed rapidly by DHP1 at the brush border of proximal renal tubule, thus DHP1 inhibitor cilastatin is added
For carbapenems:
a) main target organisms
b) excretion
a) Imipenem: Gram Pos (esp strep (including penicillin resistant s. pneumoniae), staph (including penicillinase producing strains), enterococci), Gram Neg, ANaerobes, Pseudomonas; meropenem: similar to imipenem, with less activity vs gram pos, but more vs pseudomonas aeruginosa (those strains unable to be covered by imipenem); ertapenem: NO vs pseudomonas & enterococci
b) all renal
types of infections to consider carbapenems?
1) nosocomial
2) intra-abdominal
c) skin
4) septicaemia
which carbapenem to use in meningitis?
meropenem
can use carbapenem for MRSA?
no
adverse effects of carbapenem?
- GIT
- Rashes
- Neurotoxicity
- Hypersensitivity - cross reactivity with penicillin
Example of a monobactem?
Aztreonam
For monobactem,
a) Useful spectrum/type of infection
b) Method of administration
c) adverse effects
d) excretion
a) gram negs only, (including beta lactamase producing gram negs - enterobacter, p. aeruginosa, n. gonorrhoae, h. influenzae/ UTI, Lower respiratory tract infection, intra-abdominal, septicaemia
b) Parenteral
c) Skin rash + transaminasemia
d) renal
Example of glycopeptide antibiotic?
Vancomycin
For glycopeptide antibiotic,
a) Method of administration/ type of infections
b) target organisms
c) mechanism of action
d) excretion
e) adverse reactions
f) how might resistance come about?
a) IV + Oral (for CDAD + AAPMC)
b) Gram Positive Only (includes penicillin resistant + MSSA + MRSA)/ Osteomyelitis, Endocarditis, CDAD
c) Binds to D-Ala-D-Ala trminus of NAM component of peptidoglycan, thus intefering with transglycosylation of the cell wall precursor units
d) Renal
e) Thrombophlebitis, Red Man Syndrome (rash above nipple line due to histamine release when vanc is infused too rapidly - pls prolong duration of infusion to 1-2h), Nephrotoxicity, Ototoxicity (esp when use with another nephrotoxic or ototoxic agent)
Cat B Pregnancy for Oral; Cat C for parenteral
f) enterococcal resistance - substitute D-ALa fpr D-lactate or D-serine, reducing vanc binding affinity; S. aureus may have reduced susceptibility to vanc
