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MSKIII > Beta Lactams > Flashcards

Beta Lactams Flashcards

1
Q

What are the antibiotic molecular targets?

A

DNA synthesis

RNA Synthesis

Protein Syntheis

Peptidoglycan synthesis

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2
Q

What are the quick characteristics of a Gram positive?

A

Very thick murein (peptidogylcan cell wall)

No outer membrane

Teichoic acid

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3
Q

What are the quick characteristics of a gram negative cell wall?

A

Thin murein wall (peptidoglycan)

Contain outer membrane in addition to cytoplasmic

Porins

LPS

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4
Q

Describe the basic mechanism of peptidoglycan synthesis that can be interrupted by antibiotics.

A

Two peptidoglycan chains need to cross link to be a stable wall.

Attached to each NAM are a series of amino acids ending in D-Alanine - D-Alanine

A transpeptidase enzyme connects the first D-Alanine to the Lys of the adjacent peptidoglycan chain with a L-Glycine

The result is a D-Ala - L-Gly crosslink

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5
Q

What is the basic structure of penicillins?

A

A beta lactam ring with secondary amino group and a thiazolidine ring

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6
Q

What is the basic structure of cephalosporin?

A

Similar to penicillin but instead of a thiazolidine ring it has a 6 carbon ring

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7
Q

What is the mechainism of action of penicillin?

A

It inhibits transpeptidation reaction of cell wall synthesis

Beta lactams are structural analogs of natural D-alanyl-D-alanine substrate.

The beta lactam covalently binds to the active site of the transpeptidases

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8
Q

Why is penicillin considered bactericidal?

A

The interference of the cross linking increases the osmotic instability with the cell leading to cell lysis via osmotic pressure causing it to burst or activation of autolysins

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9
Q

What are autolysins?

A

Degenerative enzymes produced by many bacteria (particullar gram positive cocci) that participate in normal remodeling of the bacterial cell wall.

In the pressence of penicillins, the autolysisn continue in the absence of cell wall syntehsis and further degrade the cell wall.

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10
Q

What infectious agents are penicillins targeted for?

A

Only rapidly replicating bacteria with a cell wall.

No activity against mycobacteria, protozoa, fungi and viruses

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11
Q

What are the components of the cell wall?

A

Comprised of cross-linked polymers of:
polypeptides
peptidoglycans
polysaccharides: N-acetylglucosamine and N-acetylmuramic acid

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12
Q

What drugs are of the class Penicillin?

A

Penicillin G (benzylpenicillin)

Penicillin V

Benzathine

Procain penicillin G

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13
Q

Procaine Penicillin G

A

Procaine benzylpenicillin (rINN), also known as procaine penicillin, is a form of penicillin which is a combination of benzylpenicillin and the local anaesthetic agent procaine

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14
Q

Penicillin G

A

Benzylpenicliin or penicillin G (G referring to the Gold standard)

Non-beta-lactamase staphylococci

Streptococcus (pneumo,pyogenes, and viridans)

Gram (+) bacilli (Bacillus anthracis, corynebacterium diphtheriae)

Gonorrhea (neisseria gonnorrhoeae/meningitidis)

Syphilis (treponema palligum)

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15
Q

What are the class of extended-spectrum penicillins?

A

Amoxicillin

Ampicillin

Piperacillin

Ticarcillin

Ampicillin and Amoxicillin (identical spectrum and activity) active against:

Gram-positive bacilli (Listeria Monocytogenes)

Gram negative rods (Escherichia coli, Hameophilus influenzae, proteus mirabilis, salmonella typhi)

AMP AMOX good for Penicillin resistant pneumococci

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16
Q

What are the Anti-staphylococcal penicillins?

A

Beta-lactamase resistant

Nafcillin

Methicillin

Oxacillin

Cloxacillin

Dicloxacillin

OCD (PO) used for mild to moderate localized staphylococcal infections

NO (Nafcillin and Oxacillin; IV) for serious systemic staphylococcal infections (like MSSA - methicillin susceptible Staphylococcal Aureus)

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17
Q

What are the routes of administration for penicillins?

A

Oral - absorption is impaired by food (given 1-2 hours before or after meal)

Parenteral - absoprtion complete and rapid

IV preferred over IM

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18
Q

Which penicillin can be given with food?

A

Amoxicillin (an extended spectrum antibiotic)

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19
Q

Which penicillin when given intramuscularly are leached slowly?

A

Benzathine and procaine

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20
Q

How are most ‘Beta-lactamse resistant’ penicillins excreted?

A

both biliary and renal routes

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21
Q

What affect does treament of gout have on the role of penicillins?

A

Probenecid is use to treat gout.

Probenecid impairs renal tubular secretion of weak acids which increase blood levels of beta-lactams

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22
Q

How are most beta-lactams excreted?

A

All except for anti-staph (beta-lactamase resistant penicillins) are readily exreted through urine

Anti-staph are exreted via urine and biliary

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23
Q

What is the most determinant criteria for penicillin dosage?

A

Adjustments base on renal failure

24
Q

Can penicillins be used to treat menigitis?

A

Yes, the inflammed meninges allows for greater permeability of penicillin into the CSF

25
Q

Benzathine penicillin G (BPG) clinical use

A

Beta-hemolytic streptococcal pharyngitis (pyogenes ) or syphilis (treponema palidum)

Given IM yield low but prolonged drug levels

26
Q

Procaine penicillin G clinical use

A

former DOC for uncomplicated pneumococcal pneumonia or gonorrhea

Rarely used***low yield***

27
Q

Drug of choice for Listeria Monocytogenes

A

Ampicillin

28
Q

Ticarcillin and Piperacillin

A

Extended spectrum Penicillins

Antipseudomonals, other gram negative rods

UTIs

P. Aeruginosa can lead to pneumonia, UTIs and Bacteremia

(often given in comibnation with other antibiotics (aminogrlycosides or fluroquinolones) for infections outside the urinary tract)

29
Q

What are the beta-lactamase inhibitors?

A

Potent inhibitors of Beta-lactamases

* Clavulanic acid

* Sulbactam

* Tazobactam

Extends the activity of penicillins to include β-lactamase-producing strains of S. aureus and some strains of β-Lactamase-producing gram negative bacteria

30
Q

Augmentin

A

Amoxicilin (extended spectrum) and clavulanic acid (resemble beta-lactamase)

Synergistic

31
Q

Zosyn

A

Piperacillin (extended spectrum; antipseudomonas) + Tazobactam (resembles beta-lactam)

32
Q

What are the adverse effects of Penicillins?

A

Most common: Rash and Diarrhea

Serum sickness: urticaria (hives), fever, joint swelling, angioneurotic edema, intense pruritus and respiratory embarrassment
Nephritis: due to an autoimmune reaction to a penicilliin-protein complex
in patients with renal failure, penicillins may cause seizures

33
Q

What is the basic of methicillin resistance in staphlococci and penicillin resistance in penumoccoci and enterococci?

A

Modifications of the PBPs (transpeptidase)

34
Q

What is the most common ways for penicillin resistance?

What are the others

A

Most common: Inactivation by beta-lactamases

Others:

Modification of transpeptidases

Poor drug penetration to peptidases (gram negative species; alteration of porins)

Efflux pumps eject drugs from periplasmic space (gram negatives)

35
Q

What are the main differences of cephalosporins from penicillins?

A

Still beta lactams but have two R groups;

Have broader spectrum of activity

More stable to many bacterial beta-lactamases

Divided into generations that are determined by spectrum of activity

36
Q

What are the first generation cephlosporins?

A

Cef/Ceph_adroxil,azolin,alexin,or radine

Cefadroxil, Cefazolin, Cephalexin, Cephradine

Effective against: Gram-positive cocci except MRSA

Gram-negative activity: Proteus mirabilis, E.Coli, K.Pneimoniae (PEcK)

Anaerobic cocci activity: Peptococcuc and peptostreptococcus but NOT Bacteroides

Clinical Uses:

37
Q

What are the second generation cephalosporins?

A

Cef_aclor, furoxime, foxitin, otetan

Cefaclor

Cefuroxime

Cefoxitin#

Cefotetan#

Active against organisms inhibited by 1st generation PLUS extended gram negative activity

Gram positives: Streptococcus Pneumoniae, Streptococcus Pyogenes, Anaerobic streptococci (#)

Gram Negatives: Neisseria gonorrhea, enterobacter aerogenes, Escherichia coli, Hameophilus influenzae, Klebsiella pneumoniae, PRoteus Mirablilis

Cephamycins (#) have good anaerobe activity

38
Q

What are the third generation cephalosporins?

A

Cef_ Tax, Traix, or taz

Cefotaxime

Ceftazidime

Ceftriaxone

“Tax and Triax” can cross the blood brain barrier

Have expanded Gram-negative coverage compared to 2nd generation ( adds Pseudomonas aeruginosa)

39
Q

What are the fourth generation cephlasporins?

A

Cef_prime

Cefipime

Good activity against P. aeruginosa, enterobacteriaceae, S. aureus, and S. pneumoniae

Highly active against haemophilus and neisseria

Penetrates the CSF

40
Q

What are the clinical uses of second generation cephalosporins?

A

Cefuroxime (fur) - sinusitis, otitis, and lower respiratory tract infections (active against influenzae or Moraxella catarrhalis)

Community acquired pnbeumonia (H influenzae, K pneumoniae and peniccilin-resistant pneumococci)

Cefoxitin, Cefotetan (fox & tea) - mixed anaerobic infections (bacteroides fragilis)

41
Q

What is the empirical therapy for third geenration

A

Empirical therapy for sepsis of unknown cause:
Immunocompetent and immunocompromised

Treatment of infection where cephalosporins are the least toxic drug available

In neutropenic, febrile, immunocompromised patients, 3rd generation are used in combination with an aminoglycoside

42
Q

What are the excretion patterns of cephalosporins?

A

Renally and require a does adjustment in the case of renal insufficiency (except 3rd generation; ceftriaxone)

43
Q

What organisms are not cover by cephalosporins?

A

LAME

Listeria Monocytogenes

Atypicals (chlamydia, mycoplasma)

Methicillin-resistant staphylococcal aureus

Enterococci

Psuedomonas is covered by Cephs but NOT UNTIL 3rd generation (Ceftazidime and Cefoperazone are the only two with useful activity).

44
Q

What are the adverse effects of cephalosporins?

A

May induce hypersensitivity reactions identical to penicillins however, if no anaphylaxis, Individuals with penicillin allergies may tolerate cephalosporins

cefotetan can cause Hypoprothrombinemia and bleeding disorders (reaction with vitamin K which is needed for the clotting cascade

Avoid alcohol and alcohol containing medications

45
Q

Aztreonam

A

Specturm: Similar to 3rd generation cephalosporins

Resistant to most β-lactamases

Can be given to penicillin-allergic patients without reaction

Can treat pneumonia, meningitis and sepsis caused by Gram-negative pathogens

46
Q

Imipenem

A

Acts like penicillin

Resistant to most beta lactamases

Inactivated by dehydropeptidase in renal tubules

Administered with cilastatin to inhibit dehydropeptidase

Given to resistant strains of p. aeruginosa, enterobacter, MSSA, MSS(trep), anaerobes, intrabdominal infections, LRTI, gynocological, UTIs,

ATOM BOMB of Penicillins

47
Q

Adverse effects of imipenem

A

N/V/D

Skin rashes, seizures in patients with renal insufficiency

MUST MONITOR RENAL FUNCTION

Avoided in patients with histroy of seizures

48
Q

Vancomycin resistanct?

A

The terminal D-ala becomes D-lactate****
Modifies the structure reducing the ability of vancomycin to bind to the target

Vancomycin-resistant Staphylococcus aureus (VRSA)
Vancomycin-resistant enteroccal species will be common

49
Q

Spectrum of activity of Vancomycin

A

Bactericidal for Gram-positive
No gram negatives
MRSA treatment

50
Q

Clinical uses of Vancomycin

A

Sepsis or endocarditis caused by MRSA.
Reserved for serious infections
In combination with cefotaxime or ceftriaxone for treatment of meningitis caused by highly penicillin-resistant pneumococcus

51
Q

key words associated with Vancomycin

A

Redman syndrome

MRSA

NEPHROTOXICITY

52
Q

How is vanco administered and cleared?

A

Oral if for enterorcolitis; Slow IV otherwise

excreted via the Kidneys and must be monitored in patients with renal insufficiency

53
Q

Adverse effects of vancomycin

A

Ototoxicity and Nephrotoxicity are both increased when given with other drugs (ex: aminoglycosides) that also produce these side effects

Fever

Chills

Flushing (redman syndrome)

Pain (phlebitis)

54
Q

Bacitracin

A

-Bacitracin: Only used topically. Active against Gram +ve bacteria. Works by interfering with the lipid carrier that transfers peptidoglycan subunits to the growing cell wall. Not given internally.

C. Diff

55
Q

Fosfomycin

A

-Fosfomycin: Inhibits cell wall synthesis by inhibiting enolpyruvate transferase, preventing formation of UDP-N-Acetylmuramic acid, the precursor of NAM. Approved for single use 3g does of uncomplicated UTIs in women. Safe for use in pregnancy.

56
Q

Cycloserine

A

-Cycloserine: Structural analog of D-alanine, inhibits alanine racemase (converts L-ala to D-ala). Used to treat tuberculosis when 1st line drugs have failed. Serious dose-related CNS side-effects.

MSKIII (2 decks)

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