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1

MOA penicillin G and V

1. Prototype Beta lactam Abx
- Binds pencillin binding proteins known as transpeptidase and blocks cross linking of peptidogylcans. Activates autolytic enzymes

2

What is penicillin used to treat?

1. think Gram Positive
2. N Meningitidis
3. Syphilis
- it's cidial for all of the above
- it is also pencillinase sensitive

3

ADE of penicillin

HSR rxn, hemolytic anemia

4

MOA of ampicillin and amoxicillin

same as penicillin but can wider spectrum use.
- Amoxicillin has better oral bioavailability than ampicillin
- sensitive to penicillinase

5

What can you combine w/ ampicillin and amoxicillin to fight beta lactamases?

clavulanic acid

6

What are ampicillin and amoxicillin used to treat?

1. Extended spectrum penicillin - H influenza, E. Coli, Listeria monocytogenes, Proteus mirabilis, Salmonella, Shigella, enterococci
- thinks HELPSS kill enterococci

7

ADE of ampicillin and amoxicillin

HSR rxn, rash, pseudomembranous colitis

8

MOA of oxacillin, nafcillin, and dicloxacillin

Same as penicillin but narrower spectrum.
- Have a bulky R group that block access of Beta lactamase to beta lactam ring

9

uses for oxacillin, nafcillin, and dicloaxcillin

S Aureus (except MRSA - resistant b/c of altered penicillin binding protein target site)

10

ADE of oxacillin, nafcillin, and dicloaxcillin

HSR rxn and intersitital nephritis

11

MOA of antipseudomonals penicillins (ticarcillin and piperacillin)

same as penicillin, extended spectrum
- use w/ Beta lactamase inhibitors to treat Pseudomonas and gram negative rods

12

ADE of antipseudomonal penicillin

HSR rxn

13

What are you beta lactamase inhibitors?

clavulanic acid, sulbactam, taxobactam,

14

MOA of cephalosporins

Beta lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases
- cidial

15

What organisms aren't typically covered by cephalosporins?

think LAME
1. Listeria
2. Atypical - chylamidia, mycoplasma
3. MRSA - (exception - ceftaroline)
4. Enterococci

16

What are the 1st gen cephalosporins and what do they treat?

Cefazolin and cephalexin
- gram positive cocci
PEcK: Proteus, E. coli, Klebsiella

17

When is cefazolin used?

before surgery to prevent S aureus wound infxns

18

What are teh 2nd gen cephalosporin and what do they treat?

Cefoxitin, cefaclor, cefuroxime
- gram positive cocci
HEN PEcKS : H flu, Enterobacter, Neisseria, Proteus, E. Coli, Klebsiella, Serratia

19

What are your 3rd gen cephalosporins and what do they treat?

Ceftriaxone, cefoxtaxime, ceftaxidine
- serious gram negative infections resistant to other beta lactams
1. ceftriaxone - meningitis and gonorrhea
2. ceftaxidime - Pseudomonas

20

What are your 4th gen cephalosporins and what do they treat?

Cefepime : increased activity against Pseudomonas and gram positive organisms

21

What are your 5th gen cephalosporins and what do they treat?

Ceftaroline
- broad gram positive and gram negative coverage
- MRSA but NOT Pseudomonas

22

ADE of Cephalosporins

1. HSR Rxn
2. Vit K deficiency
3. Low cross reactivity w/ penicillins
4. increased aminoglycosides mediated kidney toxicity

23

MOA of Aztreonam

monobactam, resistant to Beta lactamases
- prevents peptidoglycan cross linking by binding to penicillin binding protein
- syngergistic w/ aminoglycoside
- no cross allergenicity w/ penicillin

24

Uses of aztreonam

Gram negative rods only
- for penicillin allergic pts and those w/ renal insufficiency who can't tolerate aminoglycosides

25

MOA of carbapenems

Broad spectrum
Beta lactamase resistant
Always given w/ cilstatin

26

What is cilastatin?

inhibits renal dephydropeptidase I to decrease inactivation of drug in renal tubules

27

Uses for carbapenems?

1. gram positive cocci
2. gram negative rods
3. anerobes

28

What is special about Meropenem?

- decreased risk of seizures
- stable to dephydropeptidase I in kidney

29

ADE of carbapenems?

GI distress
Skin rash
CNS toxicity (seizures) at very high plasma levels

30

MOA of vancomycin

inhibits cell wall peptidoglycan formation by binding D-ala D-ala portion of cell wall precursors
- cidial

31

Vancomycin uses

Gram positives only, multidrug resistant organism, MRSA, enterococci, and Clostridium difficile

32

ADE of vancomycin

1. renal toxicity
2. otoxocitiy
3. Thrombrophlebitis
4. diffuse flushing - red man syndrome ( can be prevented w/ pretreatment w/ antihistamine and slow infusion rate)

33

Mechanism of resistance against vancomycin

Modification of D-ala D-ala to D-ala D-lac

34

MOA of Aminoglycosides

1. cidial
2. inhibits formation of initation complex and causes misreading of mRNA. Also blocks translocation
- Needs O2 for uptake therefore ineffective against anaerobes

35

What are your aminoglycosides

Gentamicin, neomycin, amikacin, tobramycin, streptomycin

36

When are aminoglycosides used?

Severe gram negative rod infxns
- syngergistic w/ beta lactam Abx.
- use Neomycin for bowel surgery

37

ADE for Aminoglycosides

1. renal toxicity esp w/ cephalosporins
2. Neuromuscular blockade
3. ototoxicity esp w/ loop diuretics
4. teratogen

38

Mechanism of resistance for aminoglycosides

bacterial transferase enzyme inactivates the drug by acetylation, phosphorylation, or adenylation

39

MOA of tetracycline

1. static
2. Binds 30S and prevents attachement of aminoacyl-tRNA
3. limited CNS penetration

40

What tetracycline can be used in pts w/ renal failure?

Doxycycline b/c it is fecally eliminated

41

What are some cautions of tetracyclines?

don't take w/ milk (Ca2+) and antacids or Fe containing preparations b/c divalent cations inhibit its absorption in the gut

42

uses for tetracycline

1. Borrelia - Lyme dz
2. Mycoplasma pneumonia
3. Rickettsia and Chlamydia - b/c drug accumulates intracellularly
4. Also used to treat acne

43

ADE of tetracycline

1. GI distress
2. discoloration of teeth and inhibition of bone growth in kids
3. photosensitivity
4. Contraindicated in pregnancy

44

What is the mechanism of resistance for tetracyclines?

decrease uptake of increase efflux out of bacterial cells by plasmid encoded transport pumps

45

MOA of Macrolides

inhibit protein synthesis by blocking translations
- binds to 23S rRNA of the 50S subunit
- static

46

When are macrolides used?

1. Atypical pneumonia - mycoplasma, legionella, chlamydia
2. STDs- chlamydia
3. gram positive cocci - streptococcal infxns in pts allergic to penicillin

47

ADE of macrolides?

1. GI motility issues
2. Arrhythmia b/c of prolonged QT
3. acute cholestatic hepatitis
4. Rash
5. Esoinophilia
- Can increase serum levels of theophyllines and oral anticoagulants

48

Mechanism of resistance for macrolides?

methylation of 23s rRNA binding site prevents binding of drug

49

MOA of chloramphenicol

blocks peptidyltransferase at 50S subunit
- static

50

When is chloramphenicol used?

meningitis (H flu, Nesseria, Strep pneumonia) and RMSF

51

ADE of chloramphenicol

1. dose dependent anemia
2. Aplastic anemia
3. Gray baby syndrome - b/c premies back UDP-glucuronyl transferase

52

Mechanism of resistance for chloramphenicol

plasmid encoded acetyltransferase inactivates the drug

53

MOA of Clindamycin

blocks peptide transfer (translocation) at 50S subunit
- static

54

When is clindamycin used?

1. Anerobic infxn - Bacteroides species, Clostridium perfringens in aspiration pneumonia, lung abscesses, and oral infxns
2. effective against Group A strep infxn - pyogenes
* treats anerobes about the diaphragm

55

ADE of clindamycin

Pseudomembranous colitis, fever, diarrhea

56

MOA of Sulfonamides

Inhibits folate synthesis
- PABA antimetabolite that inhibits diphydropterorate synthase
- static

57

When are sulfonamides used?

1. Gram positive
2. gram negative
3. Nocardia
4. Chlamydia
Simple UTI

58

ADE of sulfonamides

1. HSR rxn
2. Hemolysis if G6PD deficient
3. Renal toxicity (tubulointerstitial nephritis)
4. Photosensitivity
5. Kernicterus in infants
6. displaces other drugs from albumin eg warfarin

59

Mechanism of resistance of sulfonamides

altered enzymes, decreased uptake, increased PABA synthesis

60

MOA of Trimethoprim

inhibits bacterial DHF reductase
- static

61

When is trimethoprim used?

1. combo w/ sulfonamides - causing sequential folate synthesis blockade. UTI, Shigella, Salmonella, PCP, toxoplasmosis prophylaxis

62

ADE of trimethoprim

Megaloblastic anemia, leukopenia, granulocytopenia
- may alleviate w/ supplemental folinic acid

63

MOA Fluoroquinolones

inhibits DNA gyrase (topoisomerase II) and topo IV
- cidial
- MUST NOT BE TAKEN W/ antacids

64

When are fluroquinolones used?

gram negative rods of urinary and GI tracts
Neisseria, some gram positive

65

ADE of fluoroquinolone

1. GI upset
2. Superinfxns
3. skin rashes
4. Headache, dizziness
5. Tendonitis, tendon rupture, leg cramps, myalgias
6. QT prolongation

66

What are fluoroquinolones contraindicated in pregnancy, nursing mothers, and kids less than 18?

possible damage to cartilage

67

Mechanism of resistance to fluoroquinolones

Chromosome encoded mutation in DNA gyrase, plasmid mediated resistance, efflux pump

68

MOA of metronidazole

forms free radical toxic metabolites in bacterial cell that damages DNA
- bactericidal and antiprotozoal

69

When is metronidazole used?

GET GAP
Giardia, Entamoeba, Trichomonas, Gardnerella, Anaerobes, H Pylori w/ PPI and clarithomycin

70

ADE of metronidazole

1. disulfiram like rxn - severe flushing, tachycardia, hypotension w/ alcohol
2. HA
3. metallic taste

71

What are your drugs for prophylaxis of the following?
1. M Tuberculosis
2. M. avium - intracellulare
3. M leprae -

1. INH
2. Azithromycin, rifabutin
3. n/a

72

What are the treatments for the following?
1. M tuberculosis
2. M. avium - intracellulare
3. M leprae

1. RIPE
2. Azithromycin or clarithomycin + ethambutol. Can add rifabutin or ciprofloxacin
3. Long term treatment w/ dapsone and rifampin for tuberculoid form. Add clofazimine for lepromatous form

73

MOA of INH

decreases synthesis of mycolic acids
- bacterial catalase peroxidase (encoded by Kat G) needed to convert INH to active metabolite

74

How is INH metabolized?

different INH half lives in fast vs slow acetylators

75

ADE of INH

- think INH Injures Neurons and Hepatocytes
- neuro and liver toxocity. Lupus
- can lead to pyridoxine deficiency so replacement of it can prevent neurotoxicity.

76

MOA of rifamycins

inhibits DNA dependent RNA polyermase

77

When are the rifamycins used?

TB, delays resistance of dapsone when used for leprosy, meningococcal prophylaxis and chemoprophylaxis in contacts of kids w/ H influenza type B

78

ADE of rifamycins

1. Ramps up microsomal cytochrome P450 affecting other drugs
2. Red/orange body fluids
3. Rapid resistance is used alone
4. Rifabutin favored over rifampin in pts w/ HIV infxns due to less cytochrome P450 stimulation

79

MOA of pyrazinamide

Unkown - thought to acidify intracellular environment via conversion to pyrazinoic acid.
- effective in acidic pH of phagolysosomes, where TB engulfed by macrophages is found

80

ADE of pyrazinamide

Hyperuricemia and liver toxicity

81

MOA of ethambutol

decreases carbohydrate polymerization of cell wall by blocking arabinosyltransferase

82

ADE of ethambutol

optic neuritis - red green colon blindness

83

What are the proper antimicrobial prophylaxis for the following conditions?
1. Endocarditis w/ surgical or dental procedures
2. Gonorrhea
3. History of recurrent UTI
4. Meningococcal infxn
5. Pregnancy woman carrying group B strep

1. Penicillins
2. Ceftriaxone
3. TMP-SMX
4. Ciprofloxacin, rifampin for kids
5. Ampicillin

84

What are the proper antimicrobial prophylaxis for the following conditions?
1. Prevention of gonococcal or chlamydial conjunctivitis in newborns
2. Prevention of postsurgical infxn due to S aureus
3. Prophylaxis of strep pharyngitis in child w/ prior rheumatic fever
4. Syphilis

1. Erthyomycin ointment
2. Cefazolin
3. Oral penicillin
4. Pencillin G

85

What can be given to HIV pts if they are unable to tolerate TMP-SMX?

Aerosolized pentamidine but this may not prevent toxoplasmosis infxn concurrently.

86

What is the treatment for MRSA?

vancomycin, daptomycin, linezolid ( can cause 5HT syndrome), tigecycline, cefratoline

87

What is the treatment for VRE?

linezolid and streptogramins ( - pristins)

88

What is used to treat the following protozoans?
1. Toxoplasmosis
2. Trypanosoma brucei
3. T Cruzi
4. Lesihmaniasis

1. primethamine
2. suramin and melarsopol
3. Nifurtimox
4. sodium stibogluconate

89

MOA of Cholorquine

blocks detoxification of heme to hemozoin, heme accumulates and is toxic to plasmodia

90

How does malaria get resistant to choloroquine

- membrane pump that decreases intracellular concentrations of the drug

91

What is the treatment for chloroquine resistant malaria

artemether/lumefantrine or atovaquone/proguanil
- for life threatening malaria, use quinidine in US or artesunate

92

ADE of chlorquine

retinopathy, pruritus, QT prolongation