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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
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)

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