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Flashcards in Microbiology pharm Deck (63):
1

Penicillin: MOA

Pen G= IV, IM
Penicillin V= oral

- Bind PBPs= penicillin binding proteins (transpeptidases)
- Block transpeptidase cross-linking of peptidoglycan
- Activate autolytic enzymes

** Administer with probenecid to decrease renal tubular secretion of penicillin

2

Penicillin: clinical use

Gram positives:
- Strep pneumo
- Strep pyogenes (prevent endocarditis in child with rheumatic fever history)
- Actinomyces

N. meningitides
Treponema pallidum (syphillis prophylaxis)

Gram positive cocci, rods
Gram negative cocci
Spirochetes

3

Penicillin: toxicity and resistance

Hypersensitivity reactions
Hemolytic anemia

Resistance: beta lactamases cleave beta lactam ring in drug

4

Oxacillin, nafcillin, dicloxacillin

Penicillinase-resistant penicillins: block beta-lactamase (bacterial enzyme) access to beta-lactam ring

MOA:
- Bind PBPs= penicillin binding proteins (transpeptidases)
- Block transpeptidase cross-linking of peptidoglycan
- Activate autolytic enzymes

Use:
- S. aureus (except MRSA): "Naf for Staph"

Tox:
- Hypersensitivity reactions, interstitial nephritis

5

Ampicillin, amoxicillin

Aminopenicillins: penicillinase sensitive; combine with clauvanic acid to protect against beta-lactamase

MOA:
- Bind PBPs= penicillin binding proteins (transpeptidases)
- Block transpeptidase cross-linking of peptidoglycan
- Activate autolytic enzymes

* AmOxicillin= more Oral availability

Use:
- H. flu
- E. coli
- **Listeria monocytogenes
- Proteus mirabilis
- Salmonella
- Shigella
"Amp/Amox HELPSS kill enterococci"
- Combine with gentamicin for UTI
** Group B strep in pregnant women

Tox:
- Hypersensitivity reactions
- Ampicillin rash
- Pseudomembranous colitis (c. diff)

6

Ticarcillin, Carbenicillin, piperacillin

Ticarcillin, Carbenicillin= carboxypenicillins
Piperacillin= Ureidopenicillin

Antipseudomonals: susceptible to penicillinase; use with clavulanic acid

MOA:
- Bind PBPs= penicillin binding proteins (transpeptidases)
- Block transpeptidase cross-linking of peptidoglycan
- Activate autolytic enzymes

Use:
- **Pseduomonas**
- Gram negative rods

Tox:
- Hypersensitivity reactions

7

Beta lactamase inhibitors

CAST:
- Clavulanic Acid
- Sulbactam
- Tazobactam

Add to protect from beta-lactamases

8

Cephalosporins: MOA

Beta-lactams that inhibit cell wall synthesis
- Less susceptible to penicillinases
- Bactericidal

Not Covered: LAME
- Listeria
- Atypicals (Chlamydia, mycoplasma)
- MRSA *except Ceftaroline
- Enterococci

Toxicity:
- Hypersensitivity reactions
- Vit K deficiency
- low cross-reactivity with penicillins
- Increased nephrotoxicity when combined with aminoglycosides

9

Cephalosporin: 1st generation

Cefazolin *presurgical prophylaxis
Cephalexin

Covers: PECK
- Proteus mirabilis
- E. coli
- Cocci (Gram positive)
- Klebsiella

10

Cephalosporin: 2nd generation

fac, fox, fur
Cefoxitin
Cefaclor
Cefuroxime

Covers: HEN PECKS
- Haemophilus influenzae
- Enterobacter aerogenes
- Neisseria
- Proteus mirabilis
- E. coli
- Cocci (gram positive)
- Klebsiella pneumonia
- Serratia marascens

11

Cephalosporin: 3rd generation

tri, tax, taz
Ceftriaxone: Meningitis, gonorrhea
Cefotaxime
Ceftazidime: Pseudomonas

Covers:
- Serious gram negatives resistant to other beta-lactams

12

Cephalosporins: 4th generation

Cefepine

Covers:
- Increased activity against pseudomonas, gram-positives

13

Aztreonam

MOA:
- Monobactam, resistant to beta-lactamases
- Binds PBP3--> blocks peptidoglycan cross-linking
* Synergistic with aminoglycosides, no cross-allergenicity with penicillins

Use:
- Gram NEGATIVE RODS only
- Penicillin allergic patients, renal insufficiency patients

Toxicity: GI upset

14

Imipenem/Cilastin, Meropenem

MOA:
- Broad spectrum beta-lactamase resistant carbapenem

* Imipenem administered with Cilastin to decreased renal dehydropeptidase I (enzyme that breaks down Imipenem)
- "Kill is lastin with cilastin"

Use:
- Gram positive cocci
- Gram negative rods
- Anaerobes

Toxicity: significant, limit use (Meropenem not as toxic)
- GI distress
- Skin rash
- Seizures at high plasma levels

15

Vancomycin

MOA:
- Inhibits cell wall peptidoglycan formation by binding D-Ala D-Ala portion of cell wall
- Bactericidal

Use:
- Gram POSITIVES only
- Multidrug resistant organisms= MRSA, enterococci, C. diff (oral for pseudomembranous colitis)

Toxicity:
- Nephrotoxicity
- Ototoxicity
- Thrombophlebitis
- Red man syndrome= diffuse flushing, prevent with pretreatment with antihistamines, slow infusion

Resistance:
- D-ala D-ala changed to D-ala D-lac

16

Protein synthesis inhibitors

MOA: binds smaller bacterial ribosome (70s) subunits (30s and 50s)

30s= AT
Aminoglycosides (bactericidal)
Tetracyclines (bacteriostatic)

50s= CCEL
Chloramphenicol (Bacteriostatic)
Clindamycin (bacteriostatic)
Erythromycin (Macrolides) (bacteriostatic)
Linezolid (variable)

17

Aminoglycosides

GNATS
Gentamicin
Neomycin
Amikacin
Tobramycin
Streptomycin

MOA:
- Bactericidal
- Binds 30s: Inihibit formation of initiation complex
- Misreading of mRNA
- Block translocation
** Require O2 for uptake (ineffective against anaerobes)

Clinical use:
- Gram-negative rod infections
- Synergistic with beta-lactams
- Neomycin used for bowel surgery

Toxicity:
- Nephro (esp. with cephalosporins)--> ATN
- Neuromuscular blockade
- Otoxicity (loop diuretics)
- Teratogen

Resistance:
- Transferase enzymes that inactivate the drugs via acetylation, phosphorylation, adenylation

18

Tetracyclines

Tetracycline
Doxycycline
Demeclocycline *used as diuretic in SIADH
Minocycline

MOA:
- Bacteriostatic
- Binds 30s: prevents tRNA attachment

PK:
- limited CNS penetration
- Doxycycline fecally eliminated, can be used in renal failure patients
- Divalent cations (milk, antacids, iron) prevent absorption in gut

Use:
- Borrelia burgdorferi
- Mycobacterium pneumoniae
- Rickettsia, Chlamydia (accumulates intracellularly)

Toxicity:
- GI distress
- Discoloration of teeth, inhibition of bone growth in children
**Contraindicated in pregnancy= teeth discoloration, inhibition of bone growth**
- Photo-sensitivity

Resistance:
- Plasmid-encoded proton pumps decrease uptake or increase efflux

19

Macrolides

ACE
Azithromycin
Clarithromycin
Erythromycin

MOA:
- Inhibit protein synthesis: binds 23s rRNA at 50s subunit
- Prevent release of uncharged tRNA
- bacteriostatic

Use:
- Atypicals (mycoplasma, chlamydia, legionella)
- STD (chlamydia)
- Gram positive cocci (strep in penicillin allergic patients)
** Erythromycin ointment in infants: prevent gonococcal, chlamydial conjunctivitis

Tox:
- Motility issues
- Arrhythmia (prolonged QT)
- Cholestatic hepatitis (acute)
- Rash, Eosinophilia
* Increases serum theophyllines, oral anticoagulants
**Clarithromycin= embrytoxic**

Resistance: methylation of 23s rRNA site

20

Chloramphenicol

MOA:
- Blocks peptidyltransferase at 50s
- Bacteriostatic

Use:
- Meningitis (H. flu, N. meningitidis, S. pneumo)
* Use limited by toxicity, but inexpensive

Tox:
- Anemia (dose-dependent)
- Aplastic anemia (dose-independent)
- **Gray baby syndrome (premies lack UDP-glucuronyl transferase)**

Resistance:
- Plasmid-encoded acetyltransferase (inactivates drug)

21

Clindamycin

MOA:
- Blocks peptide transfer (transpeptidation) at 50s subunit
- Bacteriostatic

Use:
- Anaerobes (B. fragilis, c. perfringens) in aspiration pneumonia, lung abscess
- Oral infections with anaerobes
- Anaerobes ABOVE the diaphragm (vs Metronidazole)

Toxicity:
- Pseudomembranous colitis (c. diff overgrowth)
- Fever
- Diarrhea

22

Sulfonamides

Sulfamethoxazole (SMX= UTI)
Sulfisoxazole
Sulfadiazine

MOA:
- PABA antimetabolites--> block dihydropteroate synthase (precursor to folic acid)
- Bacteriostatic

Use:
- Gram positive
- Gram negative
- Nocardia, Chlamydia
- Triple sulfa or SMX for simple UTI

Tox:
- Hypersensitivity reaction (serum sickness= Type III hypersensitivity reaction)
- G6PD deficiency--> hemolysis
- Nephrotoxic (tubulointerstital nephritis)
- Photosensitivity
- **Kernicterus in infants**
- Displaces protein-bound drugs (Warfarin)

Resistance:
- Altered enzyme (dihydropteroate synthase), decreased uptake, increased PABA

23

Trimethoprim

MOA:
- Inhibits dihydrofolate reductase
- Bacteriostatic

Use:
- Combination with SMX= Sequential block of folate synthesis
- UTIs
- Shigella
- Salmonella
- Pneumocystis jirovecii pneumonia (tx and prophylaxis- CD4+ < 200)

Tox:
- Megaloblastic anemia
- Leukopenia
- Granulocytopenia
** Leucovorin (folinic acid) may alleviate
- Stevens-Johnson/TEN

24

Fluoroquinolones

-Floxacins
Nalidixic acid= quinolone

MOA:
- Inhibit DNA gyrase (topo II) and topo IV
- Bactericidal
** Do not take with antacids**

Use:
- Gram-negative rods in urinary, GI tract (pseudomonas)
- Neisseria
- some Gram positives
- Ciprofloxacin= Meningococcal prophylaxis in adults

Tox:
- GI upset
- Superinfections
- skin rashes
- H/A
- Dizziness
- Tendonitis, tendon rupture, myalgia, leg cramps (esp older pts on prednisone): "Fluoroquinolones hurt your bones"
- Contraindicated in pregnancy **damage to cartilage**
- Prolong QT interval

Resistance:
- Chromosome-encoded mutation in DNA gyrase
- Plasmid mediated--> efflux pumps

25

Metronidazole

MOA:
- Forms free radical metabolites--> damage bacterial DNA
- Bactericidal, antiprotazoal

Use:
- GET: Giardia, Entamoeba, Trichomonas
- GAP: Gardnerella, Anaerobes (bacteroides, c. diff), h. Pylori (triple therapy
** treats anaerobe infections BELOW the diaphragm (vs clindamycin)

Tox:
- Disulfiram-like reaction with alcohol
- H/A, metallic taste

26

Isoniazid (INH)

Decreases mycolic acid synthesis
- Bacterial catalase-perozidase (Kat-G) needed to convert to active metabolite

Use:
- TB (solo prophylaxis)

Tox:
- Neurotoxicity, hepatotoxicity (INH Injures Neurons and Hepatocytes)
- Pyridozine (Vit B6) prevents neurotoxicity, lupus (INH chemically similar to B6--> depletes B6 levels)

Resistance:
- Decreased catalase-peroxidase (Kat-G) enzyme (INH not converted to active metabolite)
- Modification of protein target binding site

27

Rifampin

MOA:
- Inihibits DNA-dependent RNA polymerase

Use:
- TB
- Delays resistance to Dapsone in leprosy
- Meningococcal prophylaxis in children
- Chemoprophylaxis in H. flu type B

Tox:
- Minor hepatotoxicity (increased p450)
- Orange urine

4Rs:
- RNA polymerase inhibitor
- Revs up p450
- Red/orange body fluids
- Rapid resistance if used alone

28

Pyrazinamide

MOA:
- Uncertain (acidify intracellular environment)
- TB phagocystosed by macrophage--> activates drug

Use:
- TB

Tox:
- Hyperuricemia, hepatotoxicity

29

Ethambutol

MOA:
- Decreased carbohydrate polymerization of mycobacterium cell wall--> blocks arabinosyltransferase

Use: TB

Tox: Optic neuropathy

30

HIV prophylaxis for CD4 < 200

TMP-SMX
- Pneomocystis jirovecci pneumonia

31

HIV prophylaxis for CD4 < 100

TMP-SMX
- Pneuomcystis jirovecci
- Toxoplasmosis

32

HIV prophylaxis for CD4 < 50

Azithromycin
- Mycobacterium avium complex

33

Treatment of very resistant enterococci

Linezolid (50s inhibitor) and streptogramins (quinupristin/dalfopristin)

34

Amphotericin B

MOA:
- Binds ergosterol (unique in fungi)--> membrane pores--> leak electrolytes

Use: Serious, systemic mycosis:
- Cryptococcus (+/- flucytosine for meningitis)
- Blastomyces
- Coccidioides
- Histoplasma
- Candida
- Mucor

Tox:
- Shake and bake (fever and chills)
- Hypotension
- Nephrotoxicity (supplement K and Mg due to renal tube changes, hydrate)
- Arrhythmias
- Anemia
- Phlebitis

35

Nystatin

MOA:
- Binds ergosterol (unique in fungi)--> membrane pores--> leak electrolytes
- TOPICAL (too toxic for systemic use)

Use:
- Oral candidiasis: swish and swallow
- Diaper rash, vaginal candidiasis

36

Azoles

Fluconazole
Ketoconazole
Clotrimazole
Miconazole
Itraconazole
Voriconazole

MOA:
- Inhibit p450 enzyme converting lanosterol to ergosterol (fungal sterol)

Use:
- Local, less serious mycoses
- Fluconazole= Candidiasis; chronic suppression of cryptococcus in AIDS
- Itraconazole= blastomyces, coccidioides, histoplasma
- Clotrimazole, miconazole for topical fungal

Tox:
- Testosterone synthesis inhibition
- Liver dysfunction (p450): avoid with Warfarin, Cyclosporine, Tacrolimus, phenytoin, INH, rifampin, oral hypoglycemics

37

Flucytosine

MOA: cytosine deaminase converts to 5-FU--> inhibit DNA and RNA biosynthesis

Use:
- Systemic fungal infections (Cryptococcus meningitis) + Ampho B

Tox:
- Bone marrow suppression

38

Capsofungin, Micafungin

MOA: Inhibits Beta-glucan--> blocks cell wall synthesis

Use:
- Invasive aspergillosis
- Candida

Tox:
- GI upset
- flushing

39

Terbafine

MOA:
- Inhibits fungal enzyme squalene epoxidase

Use:
- Dermatophytosis (onchomycosis)

Tox:
- Visual disturbances, abnormal LFTs

40

Griseofulvin

MOA:
- Interferes with microtubule function--> disrupts mitosis (keratin tissue)

Use:
- Oral treatment for superficial infections (dermatophytes)

Tox:
- **Teratogen**, Carcinogen
- Confusion, H/A
- Increased p450, Warfarin metabolism

41

Pyrimethamine

Toxoplasmosis tx

42

Suramin, melarsoprol

Trypanosoma brucei tx

43

Nifurtimox

Trypanosoma cruzi

44

Sodium stibogluconate

Leishmaniasis treatment

45

Chloroquine

MOA:
- Blocks detox of heme--> hemozoin--> heme accumulation toxic to plasmodia

Use:
- Plasmodia EXCEPT falciparum (resistant due to membrane pump decreasing conc)
** treat falciparum with artemether/lumifantrine or atovaquone/proguanil

Tox: retinopathy

46

Helminth tx

Mebendazole
Pyrantel pamoate
Ivermectin
Diethylcarbamazine
Praziquantel

ALL immobilize helminths

47

Praziquantel

Anti-helminthic
Anti-trematode (Schistosoma)

48

Zanamivir, oseltamivir

MOA:
- Inhibit influenza NA--> decreased release of virus

Use:
- Prevent/treat influenza A, B

49

Ribavirin

MOA:
- Inhibit IMP dehydrogenase--> prevent synthesis of guanine nucleotides

Use:
- RSV
- Chronic Hep C

Tox:
- Hemolytic anemia
- **Severe teratogen**

50

Acyclovir

MOA:
1. Viral thymidine kinase monophosphorylates drug--> acyclo GMP
2. Host cell forms triphosphate--> acyclo GTP
3. Inhibits DNA polymerase via chain termination

Use:
- HSV: lesions, encephalitis, prophylaxis
- VSV
- Weak EBV activity
- NO CMV activity

**Valacyclovir= better oral bioavailability
** Famciclovir= Herpes zoster

Tox: few

Resistance: mutated viral thymidine kinase

51

Ganciclovir

MOA:
1. Viral kinase--> 5' monophosphate--> GMP
2. Host cell--> triphosphate--> GTP
3. Inhibits viral DNA polymerase

Use:
- CMV (esp. immunocompromised)
** Valganciclovir= better oral bioavailability

Tox:
- Leukopenia, neutropenia, thrombocytopenia, renal (more toxic than acyclovir)

Resistance: Mutated viral DNA pol or no viral kinase

52

Foscarnet

MOA:
- Binds pyrophosphate binding site of viral DNA polymerase--> inhibition (no activation needed)

Use:
- CMV retinitis in immunocompromised
- Ganciclovir failure
- Acyclovir-resistant HSV

Tox: Nephrotoxic

Resistance: DNA polymerase mutation

53

Cidofovir

MOA:
- Inhibits viral DNA polymerase
- No P-tion by viral kinase

Use:
- CMV retinitis in immunocompromised
- Acyclovir-resistant HSV
* long half-life

Tox:
- Nephrotoxic (use probenecid, IV saline to reduce toxicity)

54

HIV therapy principles

2 Nucleoside reverse transcriptase inhibitors (NRTIs) PLUS 1 of following:
- non-nucleoside reverse transcriptase inhibitor (NNRTI)
- protease inhibitor
- integrase inhibitor

55

Protease inhibitors

-navir ("Navir tease a protease")

MOA:
- HIV-1 protease (pol gene)--> cleaves polypeptide product of HIV mRNA
- PI prevents maturation of new viruses
** Ritonavir= boost other drug concentrations by inhibiting CYP450

Tox:
- Hyperglycemia
- Lipodystrophy
- GI intolerance (N/V/D)
- Nephropathy, hematuria (indinavir)

56

Nucleoside Reverse Transcriptase Inhibitors (NRTI)

Tenofovir
Emtricitabine
Abacavir
Lamivudine
Zidovudine
Didanosine
Stavudine

MOA:
- Binds to reverse trascriptase--> terminates DNA chain (missing 3'OH group)
- Requires activation= phosphorylation (except tenofovir)

Zidovudine (ZDV) used for general prophylaxis in pregnancy (reduce fetal transmission)

Tox:
- Bone marrow suppression (reverse with G-CSF and Epo)
- Peripheral neurpoathy
- Lactic acidosis (nucleosides)
- Anemia (ZDV)

57

Tenofovir

Nucleoside Reverse Transcriptase inhibitor (NRTI)
- Nucleotide analog= does NOT require activation
- Binds to reverse trascriptase--> terminates DNA chain (missing 3'OH group)

Tox:
- Bone marrow suppression (reverse with G-CSF and Epo)
- Peripheral neurpoathy
- Lactic acidosis (nucleosides)

58

Non-nucleoside reverse transcriptase inhibitors (NNRTI)

Nevirapine
Efavirenz
Delavirdine

MOA:
- Bind to reverse transcriptase (different site from NRTI)
- Do not require phosphorylation to be activated
- Do no compete with nucleotides

Tox:
- Bone marrow suppression (reverse with G-CSF and Epo)
- Peripheral neurpoathy
- Rash (non-nucleosides)

59

Raltegravir

Integrase inhibitor

MOA:
- Inhibits integrase: blocks HIV genome integration into host cell DNA

Tox:
- Hypercholesterolemia

60

Interferons

MOA:
- Glycoproteins synthesized by virus-infected cells--> block RNA/DNA viral replication

Use:
- IFN alpha= Chronic Hep B, C, Kaposi's
- IFN beta= MS
- IFN gamma= NADPH oxidase deficiency

Tox:
- Neutropenia
- Myopathy

61

Enfurvitide

Fusion inhibitor
MOA: binds heptad repeat 1 (HR1) of gp41
- Blocks membrane fusion

62

Linezolid

50S subunit inhibitor

Tox: mild MAO-I function--> lead to serotonin sickness when dose with SSRIs

63

Dapsone

Used for topical M. Leprae threatment (tuberculoid and lepromatous)

Toxicity: agranulocytosis (need CBC during administration)