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Microbiology pharm Flashcards

1
Q

Penicillin: MOA

A

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

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2
Q

Penicillin: clinical use

A

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

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3
Q

Penicillin: toxicity and resistance

A

Hypersensitivity reactions
Hemolytic anemia

Resistance: beta lactamases cleave beta lactam ring in drug

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4
Q

Oxacillin, nafcillin, dicloxacillin

A

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

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5
Q

Ampicillin, amoxicillin

A

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)
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6
Q

Ticarcillin, Carbenicillin, piperacillin

A

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

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7
Q

Beta lactamase inhibitors

A

CAST:

  • Clavulanic Acid
  • Sulbactam
  • Tazobactam

Add to protect from beta-lactamases

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8
Q

Cephalosporins: MOA

A

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
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9
Q

Cephalosporin: 1st generation

A

Cefazolin *presurgical prophylaxis
Cephalexin

Covers: PECK

  • Proteus mirabilis
  • E. coli
  • Cocci (Gram positive)
  • Klebsiella
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10
Q

Cephalosporin: 2nd generation

A

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
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11
Q

Cephalosporin: 3rd generation

A

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

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

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12
Q

Cephalosporins: 4th generation

A

Cefepine

Covers:
- Increased activity against pseudomonas, gram-positives

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13
Q

Aztreonam

A

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

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14
Q

Imipenem/Cilastin, Meropenem

A

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
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15
Q

Vancomycin

A

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

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16
Q

Protein synthesis inhibitors

A

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)
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17
Q

Aminoglycosides

A 
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

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18
Q

Tetracyclines

A

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

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19
Q

Macrolides

A

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

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20
Q

Chloramphenicol

A

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)

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21
Q

Clindamycin

A

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
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22
Q

Sulfonamides

A

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

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23
Q

Trimethoprim

A

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
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24
Q

Fluoroquinolones

A

-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
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25
Q

Metronidazole

A

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
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26
Q

Isoniazid (INH)

A

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
Q

Rifampin

A

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
Q

Pyrazinamide

A

MOA:

  • Uncertain (acidify intracellular environment)
  • TB phagocystosed by macrophage–> activates drug

Use:
- TB

Tox:
- Hyperuricemia, hepatotoxicity

29
Q

Ethambutol

A

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

Use: TB

Tox: Optic neuropathy

30
Q

HIV prophylaxis for CD4 < 200

A

TMP-SMX

- Pneomocystis jirovecci pneumonia

31
Q

HIV prophylaxis for CD4 < 100

A

TMP-SMX

  • Pneuomcystis jirovecci
  • Toxoplasmosis
32
Q

HIV prophylaxis for CD4 < 50

A

Azithromycin

- Mycobacterium avium complex

33
Q

Treatment of very resistant enterococci

A

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

34
Q

Amphotericin B

A

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
Q

Nystatin

A

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
Q

Azoles

A 
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
Q

Flucytosine

A

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
Q

Capsofungin, Micafungin

A

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

Use:

  • Invasive aspergillosis
  • Candida

Tox:

  • GI upset
  • flushing
39
Q

Terbafine

A

MOA:
- Inhibits fungal enzyme squalene epoxidase

Use:
- Dermatophytosis (onchomycosis)

Tox:
- Visual disturbances, abnormal LFTs

40
Q

Griseofulvin

A

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
Q

Pyrimethamine

A

Toxoplasmosis tx

42
Q

Suramin, melarsoprol

A

Trypanosoma brucei tx

43
Q

Nifurtimox

A

Trypanosoma cruzi

44
Q

Sodium stibogluconate

A

Leishmaniasis treatment

45
Q

Chloroquine

A

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
Q

Helminth tx

A 
Mebendazole
Pyrantel pamoate
Ivermectin
Diethylcarbamazine
Praziquantel

ALL immobilize helminths

47
Q

Praziquantel

A

Anti-helminthic

Anti-trematode (Schistosoma)

48
Q

Zanamivir, oseltamivir

A

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

Use:
- Prevent/treat influenza A, B

49
Q

Ribavirin

A

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

Use:

  • RSV
  • Chronic Hep C

Tox:

  • Hemolytic anemia
  • Severe teratogen
50
Q

Acyclovir

A

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
Q

Ganciclovir

A

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
Q

Foscarnet

A

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
Q

Cidofovir

A

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
Q

HIV therapy principles

A

2 Nucleoside reverse transcriptase inhibitors (NRTIs) PLUS 1 of following:

  • non-nucleoside reverse transcriptase inhibitor (NNRTI)
  • protease inhibitor
  • integrase inhibitor
55
Q

Protease inhibitors

A

-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
Q

Nucleoside Reverse Transcriptase Inhibitors (NRTI)

A 
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
Q

Tenofovir

A

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
Q

Non-nucleoside reverse transcriptase inhibitors (NNRTI)

A

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
Q

Raltegravir

A

Integrase inhibitor

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

Tox:
- Hypercholesterolemia

60
Q

Interferons

A

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
Q

Enfurvitide

A

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

62
Q

Linezolid

A

50S subunit inhibitor

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

63
Q

Dapsone

A

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

Toxicity: agranulocytosis (need CBC during administration)

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