L27- β-lactams: Penicillins Flashcards
list the cell wall synthesis inhibitors
β-lactams: penicillins, cephalosporins, carbapenems, monobactams
vancomycin
daptomycin
bacitracin
Cell wall synthesis inhibitors require (1) and (2) from bacteria in order to work well. Due to the nature of their target, (3) is an important advantage.
1- peptidoglycan cell wall [inactive for mycoplasma, protozoa, fungi, viruses]
2- actively proliferating cells (cell wall synthesis must be occurring
3- selectively toxic –> target not in humans, therefore minimal AEs
define:
- (1) peptidoglycan
- (2) PBPs
1- polysaccharide and polypeptide chains cross-linking to form cell wall
2- transpeptidases in bacteria involved in last step of cell wall synthesis –> target for β-lactams
- number varies with organism type
- resistance may develop if PBP mutates
list the β-lactams, include structure, MOA
- penicillins, cephalosporins, carbapanems, monobactams
- β-lactam ring
- Bactericidal: inhibits PBP, last step of cell wall synthesis –> activates autolytic enzymes –> lysis / cell death
(1) are bacterial enzymes that are responsible for the hydrolysis of β-lactams. (2) is the important bacteria species that is resistant to β-lactams due to presence of (1). Although (1) don’t work on (2), (3) will be effective even though MOA is similar. (4) may be given to assist β-lactams if bacteria have (1).
1- β-lactamases: penicillinases, cephalosporinases
2- S. aureus (penicillinase)
3- cephalosporins
4- β-lactamase inhibitors
β-lactamase inhibitors:
- (1) list drugs
- (2) definition
- (3) uses
1- clavulanic acid, sulbactam, tazobactam, avibactam (all are specific to one β-lactam)
2- agents with β-lactam, but no significant antibacterial activity
3- used in fixed combinations with specific drugs – binds most β-lactamases to prevent β-lactam inactivation
describe the advantage of β-lactam + protein synthesis inhibitor combination, include how to administer
(synergistic combination)
-β-lactam destroys cell wall –> allows other drugs to enter cell (facilitates movement through cell wall)
-must be infused separately (different IVs) or they will form inactive complex
Penicillins:
- (narrowly/widely) effective
- (high/low) toxicity
- (high/low) bacterial resistance
- (4) entry in Gram+ cells
- (5) entry in Gram- cells
1- widely effective
2- low toxicity
3- high / increasing levels of resistance
4- easily passes thru cell wall - more effective
5- must utilize outer membrane porins to enter cell - less effective
The ability for penicillins to ‘reach’ PBPs is determined by the following characteristics…
- size (smaller better)
- charge (neutral better)
- hydrophobicity (highly better)
list the mechanisms of Penicillin resistance by bacteria (hint- 4)
- inactivation via β-lactamases
- modification of PBPs
- impaired penetration of drug to target PBPs
- increased efflux via p-glycoprotein pumps
Penicillin G = (1):
- (2) route of administration
- active against (3) bacteria
- susceptible to (4)
1- benzylpenicillin
2- IV, IM (not oral)
3- Gram+ cocci/rods, Gram- cocci, most anaerobes
4- β-lactamase inactivation
Penicillin G is the drug of choice for….
(mainly Gram+ organisms)
-Syphilis, Treponema pallidum (benzathine penicillin G)
- Strep infections
- susceptible pneumococci
name and define the 2 repository penicillins (with G)
penicillin G procaine
penicillin G benzathine
-local anesthetics with penicillin given IM to prolong duration of action of penicillin G (dec dosing)
penicillin G procaine:
- (1) route of administration
- (2) half life
- (3) uses
1- IM (IV would => procaine toxicity)
2- 12-24hrs
3- seldomly used due to increased resistance
penicillin G benzathine:
- (1) route of administration
- (2) half life
- (3) uses
1- IM
2- 3-4 wks [NOTE- must check for possible hypersensitivty before use due to long duration]
3- Syphilis (T. pallidum), rheumatic fever prophylaxis (Strep. pyogenes)
Penicillin V:
- (1) and (2) are the main difference in comparison to penicillin G
- drug of choice for (3)
- also used for (4)
1- more acid stable –> given orally
2- less active against Gram- bacteria
3- Strep. pharyngitis
4- mild-moderate infections: pharyngitis, tonsilitis, skin infections (Strep. spp.)
Anti-staphylococcal Penicillins:
- (1) list drugs
- (2) key property, although inactive against (3)
- (4) uses
1- nafcillin, oxacillin, dicloxacillin
2- β-lactamase resistant
3- MRSA
4- β-lactamase producing staphylococci
list the anti-staphylococcal penicillins
nafcillin
oxacillin
dicloxacillin
Extended Spectrum Penicillins:
- (1) list drugs
- similar to actions to (2) agent, with additional (3) activity
- susceptible to (4) therefore activity enhanced with (5)
1- ampicillin, amoxicillin
2- penicillin G
3- Gram- activity
4- β-lactamases
5- β-lactamase inhibitor
______ is the penicillin with the highest oral bioavailability
amoxicillin (even over ampicillin)
______ is a common antibiotic prescribed for children and pregnant patients
amoxicillin
(1) is the drug of choice for prophylaxis after dog, cat, human bite
(2) is the drug of choice for infection after dog, cat, human bite
1- (augmentin) amoxicillin + clavulanic acid, oral
2- ampicillin + sulbactam, IM
discuss general clinical uses of Amoxicillin, include route of administration
- oral
- *URIs, acute otitis media, Strep. pharyngitis, pneumonia, skin infections, UTIs
discuss general clinical uses of Ampicillin, include route of administration
- IV (version of amoxicillin)
- acute otitis media, Strep. pharyngitis, pneumonia, skin infections, UTIs
Anti-pseudomonal Penicillins:
- (1) list agents
- effective against (2) bacteria
- usually used with (3)
1- ticarcillin, pipercillin
2- Gram+/- bacilli
3- β-lactamase inhibitor
Ticarcillin, Piperacillin are commonly used to treat (1) infections. (2) is the general main clinical use (include route of administration) for (3) infections.
(anti-pseudomonal penicillins)
1- Pseudomona Aeruginosa
2- IM for susceptible Gram- bacteria
3- moderate-to-severe infections of susceptible bacteria: un-/complicated skin infections, GYN / intra-abdominal infections, febrile neutropenia [mixed infections generally]
Penicillins Pharmacokinetics:
- (1) half-life, except for (2) types
- absorption via oral administration can be disrupted by (3); (4) penicillin oral bioavailbility is described as erratic
1- 30-60 mins
2- repository penicillins
3- food
4- nafcillin
Penicillins Pharmacokinetics:
- successfully distributed to (1) body fluids
- only (2) are found in bile
- (3) do not receive sufficient penicillin concentration; (4) is the exception
1- (most) pleural, pericardial, peritoneal, synovial fluids, urine
2- nafcillin, pipercillin, ampicillin
3- prostate, eye, *CSF
4- meningitis –> BBB is leakier
penicillins are mainly excreted via (1), (2) is the exception
1- kidney / urine (don’t use in CKD)
2- Nafcillin in bile
(1) is the main or perceived highest concern with use of penicillins, where (2) is the major determinant. (3)% of people ‘claim’ allergy to penicillin with (4) as symptoms. (5) reactions can also occur between β-lactam antibiotics.
1- hypersensitivity 2- penicilloic acid 3- 5% 4- ranges from rash to anaphylaxis 5- cross-allergic reactions
Penicillin AEs:
- (1) is most common
- (2) can cause pseudomembranous colitis
- (3) can cause maculopapular rash (not allergy)
1- GI disturbances: diarrhea
2- ampicillin
3- ampicillin, amoxicillin (rash if given to Pts with viral disease)
Penicillin AEs:
- (1) via methicillin
- (2) via nafcillin
- (3) via oxacillin
- (4) via ticarcillin
- (5) via penicillin G, V
- (6) in epileptics
- (7) development in general after use of any penicillin
1- interstitial nephritis 2- neutropenia 3- hepatitis 4- hematological toxicity 5- pos. Coombs test (Abs against RBCs) 6- neurotoxicity 7- secondary infections (eg. candidiasis)
