Antimicrobials Flashcards

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1
Q

Penicillin G (IM/IV), V (oral) mechanism

A

Binds transpeptidases –> blocks cross-linking of peptidoglycans (cell wall)

  • Also activates autolytic enzymes
  • Penicillinase sensitive

**Prototype B-lactam antibiotics

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2
Q

Penicillin G, V use

A

Gram + cocci, rods, gram neg cocci, spirochetes
- Mostly: S. pneumo, S. pyogenes, Actinomyces

Tox: hypersensitivity rxn, hemolytic anemia
Resistant: penicillinase in bacteria (B-lactamase, cleaves B-lactam ring)

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3
Q

Amoxicillin, Ampicillin mechanism

A

Amox (oral), amp (IV)

  • Binds transpeptidase, blocks cross link of peptidoglycans
  • Combines with clavulanic acid to protect from B-lactamase
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4
Q

Amoxicillin, Ampicillin use

A
Extended-spectrum penicillin
"Amp/amox HELPSS kill enterococci"
- H. influenza
- E. coli
- Listeria
- Proteus
- Salmonella
- Shigella
- Enterococci

Tox: hypersensitivity rxn, rash, C. diff
Resistance: penicillinase in bacteria (B-lactamase, cleaves B-lactam ring)

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5
Q

Oxacillin, nafcillin, dicloxacillin mechanism

A
  • Binds transpeptidase, blocks cross link of peptidoglycans
  • Penicillinase-resistant penicillins (bulky R group blocks B-lactamase from binding B-lactam ring)
  • Narrow spectrum
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6
Q

Oxacillin, nafcillin, dicloxacillin use

A

S. aureus (except MRSA)
- “Naf for staph”

Tox: hypersensitivity rxn, interstitial nephritis

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7
Q

Ticarcillin, piperacillin mechanism

A

Antipseudomonals

- Binds transpeptidase, blocks cross link of peptidoglycans

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8
Q

Ticarcillin, piperacillin use

A

Pseudomonas spp + gram-neg rods
- Susceptible to B-lactamase, use w/ B-lactamase inhibitors

Tox: hypersensitivity rxn

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9
Q

B-lactamase inhibitors

A

CAST

  • Clavulanic Acid
  • Sulbactam
  • Tazobactam

*Add to penicillin abx to protect from destruction from B-lactamase

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10
Q

Cephalosporins (Gen I-V) mechanism

A

B-lactam drugs that inhibit cell wall synthesis
*Less sensitive to penicillinases

Those NOT covered are LAME:

  • Listeria
  • Atypicals (chlamydia/mycoplasma)
  • MRSA (except 5th gen = ceftaroline)
  • Enterococci
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11
Q

1st generation cephalosporins

A

Cefazolin, cephalexin

  • Gram + cocci and PEcK (Proteus, E. coli, Klebsiella)
  • Use prior to surgery to prevent wound infections (S. aureus)
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12
Q

2nd generations cephalosporins

A

Cefoxitin, cefaclor, cefuroxime

- Gram + cocci and HEN PEcKS - (H. influneza, Enterobacter, Neisseria, Proteas, E. coli, Klebsiella, Serratia)

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13
Q

3rd generation cephalosporins

A

Ceftriaxone, cefotaxime, ceftazidime
- Serious gram neg resistant to other B-lactams

  • Ceftriaxone = meningitis/gonorrhea
  • Ceftazidime = pseudomonas
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14
Q

4th generation

A

Cefepime

- Incr activity against pseudomonas + gram pos

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15
Q

5th generation

A

Ceftaroline

  • Broad spectrum gram pos and gram neg organisms
  • Includes MRSA, not pseudomonas
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16
Q

Azotrenam mechanism

A

Monobactam, resistant to B-lactamases

  • Prevents peptidoglycan cross-linking by binding pencillin-binding protein 3
  • Synergistic with aminoglycosides
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17
Q

Azotrenam use

A

Gram neg rods only (none for gram +)
- Good for those w/ penicillin allergy and renal insuffic (can’t tolerate aminoglycosides)

Tox: GI upset, non-toxic
*No cross-allergenicity w/ penicillins

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18
Q

Carbapenems mechanism

A

Imipenem, meropenem, ertapenem, doripenem

  • Broad spectrum, B-lactamase resistant
  • Give with cilastatin (inhib renal dehydropeptidase I) - decr inactivation in renal tubules
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19
Q

Carbapenem use

A

Gram + cocci, gram neg rods, anaerobes (wide spectrum)
- Significant side effects –> only use for life threatening infections

Tox: GI distress, skin rash, CNS tox (sz) at high plasma levels
*Mirapenem = decr sz risk, stable to dehydropeptidase I

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20
Q

Vancomycin mechanism

A

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

  • This is the main component of gram + cell wall!
  • pay back 2 D-alas (dollars) for vandalizing (vanc)*
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21
Q

Vancomycin use

A

Gram pos only!
- Serious, multi-drug resistant organisms: MRSA, enteroccic, C. diff (oral)

Tox - well tolerated but NOT Really trouble free (Nephrotoxicity, Ototoxicity, Thrombophlebitis), diffuse flushing (Red man syndrome; pre-tx with antihistamine/slow infusion)

Resist: bacteria with D-ala D-ala –> D-ala D-lac modification

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22
Q

Inhibitors of cell wall synthesis

A
  • Penicillin-sensitive penicillins: Pen G/V, amox, ampicillin
  • Penicillin-resistant penicillins: oxacillin, nafcillin, dicloxacillin
  • Antipseudomonas: ticarcillin, piperacillin
  • Cephalosporins: 1 (cephazolin, cephelexin), 2 (cefoxitin), 3 (ceftriaxone), 4 (cefepime), 5 (ceftaroline)
  • Carbapenems: imipenem, meripenem, (ertapenem/doripenem = new)
  • Bind transpeptidase (needed to cross-link peptidoglycans)
  • Azotreonam
  • Binding pencillin-binding protein 3
  • Glycopeptides (vancomycin, bacitracin)
  • Binding precursor D-ala D-ala
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23
Q

Inhibitors of protein synthesis

A

Target smaller bacterial ribosome (70S made of 30S and 50S subunits) –> leaves human ribosome unaffected (80S)

30S inhibitors:

  • A = aminoglycosides
  • T = tetracyclines (bacteriostatic) –> block A-site tRNA binding (block aminoacyl-tRNA attachment)

50S inhibitors:

  • C = chloramphenicol, clindamycin (bacteriostatic) –> peptidyl transferase
  • E = erythromycin (macrolides); (bacteriostatic) –> translocation
  • L = Linezolid (variable) –> block 50S

**“buy AT 30, CCEL (sell) at 50”

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24
Q

Aminoglycosides mechanism

A

Gentamicin, Neomycin, Amikacin, Tobramycin, Streptomycin (GNATs)

  • Bactericidal –> binds 30S, inhibits initiation complex formation
  • *Needs O2 for uptake (doesnt work against anerobes)
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25
Q

Aminoglycosides use

A

Severe gram neg rod infections

  • Synergistic with B-lactam antibiotics
  • Give neomycin for bowel surgery

Tox: NNOT - nephrotocixity (w/ cephalosporins), neuromusc blockade, ototoxicity (w/ loop diuretics), teratogen
**“Mean (aminoglycosides) GNATS caNNOT kill anaerobes”

Resist: bacterial transferase enzymes inactivate drug by acetylation, phosphorylation or adenylation

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26
Q

Tetracyclines mechanism

A

Tetracycline, doxycycline, minocycline

  • Bacteriostatic –> binds 30S, prevent attachment of aminoacyl-tRNA
  • Doxy elimated fecally (can use in renal pts)
  • Don’t take milk, antacids or iron bc divalent cations inhibit gut absorption of tetracyclines
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27
Q

Tetracyclines use

A
  • Borrelia burgforderi, M. pneumoniae,
  • Rickettsia, chlamydia (good bc drug accum intracellularly, very effective)
  • Acne

Tox: GI distress, discolored teeth/bone in growing kids/fetus (contranind in pregn), photosensitivity

Resist: decr uptake/incr efflux out of bacterial cells by plasmid-encoded transport pumps

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28
Q

Macrolides mechanism

A

Azithromycin, clarithromycin, erythromycin

- Block translocation (“macroSlides”) bc binding 23S rRNA of 50S

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29
Q

Macrolides use

A
  • Atypical pneumonias (mycoplasma, chlamydia, legionella)
  • STDs (chlamydia)
  • Gram + cocci (strep infections if allergic to penicillins)

Tox: MACRO

  • gastric Motility issues
  • Arrhythmia from prolonged QT
  • acute Cholestatic hepatitis
  • Rash
  • eOsinophilia
  • Incr serum conc of theophyllines, oral anticoags

Resist: binding 23S rRNA binding site (drug can’t bind)

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30
Q

Chloramphenicol mechanism

A

Blocks peptidyltransferase at 50S –> this blocks transfer from A to P on ribosome

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31
Q

Chloramphenicol use

A

Meningitis (H. flu, Neisseria, S. pneumoniae), Rocky mountain spotted fever (rickettsia)

Tox: anemia (dose dependent, reversible), aplastic anemia (dose dep, irreversible), gray baby syndrome (premies bc lack liver UDP-glucuronyl transferase)

Resist: plasma-encoded acetyltransferase inactivates drug

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32
Q

Clindamycin mechanism

A

Blocks translocation (peptide transfer) at 50S

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33
Q

Clindamycin use

A
  • Anaerobic infections (bacteriodes, clostridium) in aspiration pneumo, lung abscesses, oral infections
  • Invasive group A strep
  • *Treats anaerobes ABOVE diaphragm (metronidazole below)

Tox: C. diff, fever, diarrhea

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34
Q

Inhibitors of folic acid synthesis

A
  • Sulfonamides - block dihydropteroate synthase
  • Trimethoprim - block dihydrofolate reductase

Need this pathway to make DNA/RNA, proteins

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35
Q

Sulfonamides mechanism

A

Sulfamethoxazole (SMX), sulfisoxazole, sulfadiazine

- Inhibit folate syntheis (PABA to DHT): PABA antimetabolites inhibit dihydropteroate synthase

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36
Q

Sulfonamides use

A

Gram +, gram neg, Nocardia, Chlamydia
- Simple UTI - triple sulfa or SMX

Tox: hypersensitivity rxn, hemolysis if G6DP defic, nephrotoxic (tubulointerstitial nephritis), photosensitive, kernicterus in infants

Resist: altered enzyme (dihydropteroate synthase), decr uptake or incr PABA synthesis

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37
Q

Trimethoprim mechanism

A

Inhibits bacterial dihydrofolate reductase (DHT –> THF)

*Use w/ sulfonamides = sequential block of folate synth (TMP-SMX)

38
Q

Trimethoprim use

A

Combo with sulfas (TMP-SMX = bactrim) for: UTIs, shigella, salmonella, PCP pneumonia tx/ppx, toxo ppx

Tox: megaloblastic anemia, leukopenia, granulocytopenia (folinic acid can alleviate)
*TMP - Treats Marrow Poorly

39
Q

Fluoroquinolones mechanism

A

Ciprofloxacin, norfloxacin, levofloxacin, etc.

  • Inhibit DNA gyrase (topoisomerase II) and topoisomerase IV
  • Dont take with antiacids
40
Q

Fluoroquinolones use

A

Gram neg rods for URI/GI tract (incl pseduomonas), neisseria, some gram +

Tox: GI upset, superinfect, skin rash, HA, dizziness

  • Tendonitis, tendon rupture (>60yo, taking prednisone), leg cramps, myalgias
  • May damage cartilage (dont use in pregn, nursing moms, kids <18)
  • Prolonged QT
  • fluoroquinoLones hurt attachments to your bones*

Resist: chromosome-encoded DNAgyrase mutation, efflux pumps

41
Q

Metronidazole mechanism

A

Damages DNA

- Forms free radical toxic metabolites in bacterial cell –> damages DNA

42
Q

Metronidazole use

A

GET GAP on metro with metronidazole

  • Giardia
  • Entamoeba
  • Trichomonas
  • Gardnerella vaginalis
  • Anaerobes (Bacterioides, C. diff)
  • h. Pylori (use metronid + clarithromycin + PPI for triple therapy)

Tox: disulfiram-like rxn (severe flushing, tachy, hypotension) w/ alcohol; HA, metallic taste

43
Q

Antimycobacterial drugs

A

Mycobacterium TB

  • PPx = isoniazid
  • Tx = RIPE (rifampin, isoniazid, pyrazinamide, Ethambutol)

MAC - more resistance than TB

  • PPx = azithromycin, rifabutin
  • Tx = Azithro/clarithro + ethambutol (can add rifabutin or cipro)

M. leprae

  • no ppx
  • Tx = dapsone + rifampin (tuberculoid form); add clofazimine for lepromatous form
44
Q

Rifamycins mechanism

A

Rifampin, rifabutin

- Inhibits DNA-dependent RNA polymerase

45
Q

Rifamycins use

A

Rifampin:

  • Mycobacterium TB
  • Leprosy (delays resistance to dapsone)
  • Meningococcal and HiB ppx (exposure)

Tox:

  • Hepatotoxicity
  • Orange body fluids (nonhazardous)
  • Drug interactions (stim p450) - less w/ rifabutin (favored in HIV)
  • RifAMP RAMPS up cytochrom p450, BUT rifaBUTin doesn’t*
  • 4 R’s of rifampin:
  • RNA polymerase inhib
  • Ramps up cytochrome p450
  • Red/orange body fluids
  • Rapid resistance if use alone
46
Q

Isoniazid (INH) mechanism

A

Decreased synthesis of mycolic acids (which make cell wall)

- Need bacterial catalase-peroxidase to convert INH to active metabolite

47
Q

INH use

A

M. TB tx (RIPE) and as ppx (alone)

Tox: INH Injurs Neurons and Hepatocytes

  • Neurotox, hepatotoxicity
  • Pyridoxine (B6) can prevent neutrotox/lupus*
48
Q

Pyrazinamide mechanism

A

Acidify environment by converting to pyrazinoic acid

- Effective in phagolysosomes –> TB engulfed by macrophages found here

49
Q

Pyrazinamide use

A

TB (RIPE)

Tox: hyperuricemia, hepatotoxicity

50
Q

Ethambutol mechanism

A

Blocks arabinosyltransferas –> decr carb polymerization of mycobacterium cell wall

51
Q

Ethambutol use

A

TB (RIPE), and MAC (azithro/clarithro + ethambutol)

Tox: optic neuropathy (red-green color blindness)

52
Q

PPx for endocarditis w/ surgery/dental procedure

A

Penicillin

53
Q

Ppx for gonorrhea

A

Ceftriaxone

54
Q

Ppx for recurrent UTIs

A

TMP-SMX

55
Q

Ppx for meningococcal infection

A

Cipro; rifampin for kids (dont give to kids bc fluroquinolones hurt cartilage)

56
Q

PPx for pregn woman w/ GBS

A

Ampicillin

57
Q

Prevent gonococcal/chlamydia conj in newborn

A

Erythromycin ointment

58
Q

Prevent post-surgical infection from S. aureus

A

Cefazolin

59
Q

PPx of strep pharyngitis w/ previous rheumatic fever

A

Oral penicillin

60
Q

Syphillis

A

Benzathine penicillin G

61
Q

PPx in HIV pts

A

CD4 <50 azithro for MAC

62
Q

Treating highly resistant bacteria

A

MRSA - vanc, daptomycin, linezolid

VRE - linezolid, streptogramins (-“pristins”)

63
Q

Antifungal therapy - formation of membrane proteins

A
  • Amphotericin B

- Nystatin

64
Q

Amphotericin B mechanism

A
Binds ergosterol (unique to fungi) --> forms membrane pore --> leakage of electrolytes
*AmphoTERicen TEARs hole in fungal membrane (pores)
65
Q

Amphotericin use

A

Serious systemic mycoses

  • Cryptococcus, blastomyces, coccidioides, histoplasma, candida, mucor
  • Intrathecally for meningitis
  • Supplement K+ and Mg2+ bc altered renal tubule permeability

Tox: fever/chills (“shake and bake”), hypotension, nephrotoxicity, arrythmias (hypokalemia), anemia, IV phlebitis

  • Amphoterri-ble* –> liposomal amphotericin has less tox
  • Hydration reduces nephrotoxicity
66
Q

Nystatin mechanism

A
Binds ergosterol (unique to fungi) --> forms membrane pore --> leakage of electrolytes
**To toxic for systemic, use TOPICAL*
67
Q

Nystatin use

A
  • “Swish and swallow” for oral candidiasis (thrush)

- Topical for vaginal rash/vaginal candidiasis

68
Q

Antifungal therapy - inhibit ergosterol synthesis

A

Azoles!

69
Q

Azoles mechanism

A

Inhibit fungal sterol (ergosterol) synthesis by inhib cytochrom p450 enzyme (1,4 a-demethylase) converting lanosterol to ergosterol

70
Q

Azoles use

A

Local/less serious systemic mycoses

  • Fluconazole - chronic suppression of candidal infect and cryptococcal meningitis in AIDS pts
  • Itraconazole for blastomyces, coccidioides, histoplasma
  • Clotrimazole/miconazole - topical fungal infections

Tox:

  • Inhibits testosteron synthesis (gynecomastic) esp ketoconazole
  • Liver dysfxn (inhib cytochrom p450)
71
Q

Antifungal therapy - inhibit nucleic acid synthesis

A

Flucytosine

72
Q

Flucytosine mechanism

A

Inhibits DNA/RNA synthesis by converting U to 5-flurouracyl (cytosine deaminase)

73
Q

Flucytosine use

A

Systemic fungal infections (esp meningitis from cryptococcus) in combo with amphotericin B

Tox: bone marrow suppression

74
Q

Antifungal therapy - inhibit cell wall synthesis

A

Echinocandins (‘fungins) = caspofungin, micafungin, anidulafungin

75
Q

Echinocandins mechanism

A

‘fungins

- Inhibit cell wall synthesis by inhibiting synth of B-glucan (B-D-glucan)

76
Q

Echinocandins use

A

Invasive aspergillosis, candida

Tox: GI upset, flushing (histamine release)

77
Q

Antifungal therapy - inhibit lanosterol synthesis

A

Terbinafine

78
Q

Terbinafine mechanism

A

Inhibits fingal enzyme squalene epoxidase (lanosterol synthesis)

79
Q

Terbinafine use

A

Fermatophytoses (esp onychomycosis - fungal infection of finger/toe nails)

Tox: GI upset, HA, hepatotox, taste disturbance

80
Q

Griseofulvin mechanism

A

Interferes with microtubule formation –> disrupts mitosis

- Deposit in keratin-containing tissues (nails)

81
Q

Griseofulvin use

A

Oral tx of superficial infections; inhibits growth of dermatophytes (tinea, ringworm)

Tox: teratogenic, carcinogenic, confusion, HA, incr p450 and warfarin metab

82
Q

Antiprotozoan therapy

  • Toxo
  • Trypanosoma brucei
  • T. cruzi
  • Leishmaniasis
  • Plasmodium (except falciparum)
  • P. falciparum
A
  • Toxoplasmosis - pyrimethamine
  • Trypanosoma brucei - suramin/melarsoprol
  • T. cruzi - nifurtimox
  • Leishmaniasis - sodium stibogluconate
  • Plasmodium - chloroquine (except P. falciparum)
  • P. falciparum - artemether/lumefantrine or atovaquone/proguanil
83
Q

Chloroquine mechanism

A

Blocks detox of heme into hemozoin –> heme accumulates, toxic to plasmodia

84
Q

Chloroquine use

A

Plasmodia (except P. falciparum bc resistant)

  • Resist: membrane pump that decr intracellular concentration of drug
  • If life-threatening use quinidine (US) or quinine (elsewhere)

Tox: retinopathy, pruritis (esp in dark-skinned people)

85
Q

Antihelminthic therapy

A

Mebendazole, pyrantel pamoate, ivermectin, diethycarbamazine, praziquantel
- Immobilizes helminths

**Use praziquantel against flukes (trematodes) like schistosoma

86
Q

Zanamivir, oseltamivir

A

Inhibit influenza neuraminidase, decreases release of progeny virus
- Tx/prevention of influenza A/B

87
Q

Ribavarin

A

Inhibits guanine nucelosides by inhibiting inosine monophosphage dehydrogenase
- Tx RSV/chronic HCV

Tox = hemolytic anemia, severe teratogen

88
Q

Acyclovir/famciclovir, valacyclovir

A

Monophosphorlayed by HSV/VZV thymidine kinase (not phosphorylated by uninfected cells = few SEs)
- Inhibits viral DNA polymerase by chain termination

  • Use for: HSV/VZV, weak activity for EBV, none for CMV
  • HSV lesions/encephalitis (valacyclovir = better oral bioavailability)
  • Tox = obstructive crystalline nephropathy/acute renal failure (w/o hydration)
  • Resist: mutated thymidine kinase
89
Q

Ganciclovir

A

Phosphorylated to monophosphate, then to triphosphate (more in infected cells than uninfected)

  • Guanosine analog
  • Inhibits viral DNA polymerase
  • Tx - CMV (esp immunocompromised)
  • Tox - leukopenia, neutropenia, thrombocytopenia, renal tox
  • More toxic than acyclovir
  • Resistance: mutated CMV DNA polymerase or lack of viral kinase
90
Q

Foscarnet and Cidofovir

A

Viral DNA polymerase inhibitor, binds pyrophosphate binding site of enzyme
*Doesnt need to be activated by viral kinase

  • Tx - CMV retinitis (when ganclyclovir fails) or acyclovir-resistant HSV
  • Tox = nephropathy (+ electrolyte imbalance)
  • Resist: mutated DNA polymerase
91
Q

HIV therapy

A

HAART - give when CD4 3 drugs

- 2NRTIs + 1NNRT/protease inhib/integrase inhibitor