Drugs

Question 1

Amantadine/Rimantadine

Answer 1

Class/Subclass: Antiviral, Anti-influenza
Use: Influenza A
MOA: M2 proton channel blocker at histidine residue. Blocks viral uncoating, no viral RNA release
Administration: oral
Metabolism: Hepatic
Adverse Effects: GI, CNS
*given within 48 hours of exposure. Only protects/treats influenza A. Can be used to treat Parkinson’s

Question 2

Ribavirin

Answer 2

Class/Subclass: Antimetabolites - Guanosine analog
Use: HCV and RSV
MOA: Activated by host kinases, Blocks GTP formation, inhibits viral mRNA capping
Administration: Oral for HCV, aerosol for RSV
Adverse Effects: Anemia. teratogen/embryotoxin.
*prophylaxis w/ Palvizumab for RSV

Question 3

Acyclovir/Valacyclovir

Answer 3

Class/Subclass: Antimetabolites - Guanosine analog
Use: HSV1, HSV2, VZV
MOA: Activated by viral Thymidine Kinase, acycloGTP terminates chain
Administration: Oral, IV, Topical
Excretion: Renal
Resistance: TK (-) viruses
Adverse Effects: Nausea, headache, nephrotoxic, neurotoxic

Question 4

Penciclovir/Famciclovir

Answer 4

Class/Subclass: Antimetabolites - Guanosine analog
Use: Shingles and cutaneous eye infections
MOA: Activated by viral Thymidine Kinase, AcycloGTP terminates chain
Absorption: Poorly absorbed by intestine
Resistance: TK (-) viruses

Question 5

Ganciclovir/Valganciclovir

Answer 5

Class/Subclass: Antimetabolites - Guanosine analog
Use: CMV
MOA: Activated by viral protein kinase (also host kinases and polymerases) GancicloGTP terminates chain
Administration: IV and Oral
Excretion: renal
Adverse Effects: decrease BM, CNS, enhanced w/ retrovirals
*teratogenic and carcinogenic

Question 6

Foscarnet

Answer 6

Class/Subclass: Antimetabolites - Pyrophosphate Analogue
Use: Resistant CMV and HSV
MOA: Directly inhibits viral polymerases (DNA, RNA, RT)
Administration: IV
Excretion: Renal
Adverse Effects: Nephrotoxic, penile ulcerations
*saline preload, synergy with ganciclovir

Question 7

Cidofovir

Answer 7

Class/Subclass: Antimetabolite - Pyramidine analogue
Use: CMV Retinitis
MOA: Activated by host kinases, competitive inhibitor of DNA synthesis, chain termination
Administration: IV
Excretion: active renal tubular
*must use probenicid

Question 8

Trifluridine

Answer 8

Class/Subclass: Antimetabolite - Pyramidine analogue
Use: Resistant HSV1/2, CMV, Vaccinia
MOA: Incorporated into both viral and host DNA
Administration: Topical for HSV1 and HSV2 conjunctivitis, keratitis

Question 9

Sofosbuvir

Answer 9

Class/Subclass: Nucleotide analogue - RNA polymerase inhibitor
Use: PGP/MDR1 substrate. HCV (+ Ribavirin + interferone fore HCV = cure)
MOA: Inhibits HCV RNA polymerase
Administration: Oral
Excretion: Renal
*extremely expensive (~$1000/day)

Question 10

Lamivudine (3TC)

Answer 10

Class/Subclass: Nucleoside RT Inhibitor - Cytosine Analogue
Use: HIV and HBV
MOA: Substrate for TTP, inhibitor of RT, chain termination, inhibits replication
Administration: Oral
1/2 life: 10-15hrs (HIV) 17 - 19hrs (HBV) when in infected cells
Excretion: Urine
Resistance: RT mutations, associated with flares and liver damage
*HAART, long term HBV management

Question 11

Telaprevir

Answer 11

Class/Subclass: Protease Inhibitor
Use: HCV
MOA: Inhibits HCV protease (serine protease)
Absorption: Administer with pegINF and Ribavirin
Metabolism: Extensive hepatic clearance, CYP3A and PGP substrate/inhibitor causes DDI
Adverse Effects: Rash/pruritis, fatigue, GI, anemia
*resistance can develop rapidly

Question 12

Boceprevir/Simprerevir

Answer 12

Class/Subclass: Protease Inhibitor
Use: HCV
MOA: Binds to HCV non-structural NS3/NS4 active site
Administration: Oral, take with meal
*Asians show 3x higher mean exposure
*contain sulfa moiety = hypersensitivity, Stevens-Johnson

Question 13

Osletamavir (Tamiflu)

Answer 13

Class/Subclass: Anti-influenza - Neuraminidase Inhibitor
Use: Influenza A and Influenza B
MOA: Prevents viral release from cell and infection of additional cells
Administration: Oral
Metabolism: Pro-drug, activated in gut. Metabolized in liver
Adverse Effects: N&V
*must be given within 48 hours of exposure

Question 14

Zanamavir (Relenza)

Answer 14

Class/Subclass: Anti-influenza - Neuraminidase Inhibitor
Use: Influenza A and Influenza B
MOA: Prevents viral release from cell and infection of additional cells
Administration: Inhaled
Excretion: Renal
Adverse Effects: Bronchospasm in asthmatics
*must be given within 48 hours of exposure

Question 15

Pegylated INFalpha

Answer 15

Class/Subclass: Cytokines
Use: HBV and HCV (+ Ribavirin)
MOA: Induces production of proteins that inhibit RNA synthesis and DNA enzymes, inhibits mRNA
Administration: IV, IM, and SQ
Excretion: Glomerular filtration
Metabolism: Proteolytic degradation 
Adverse Effects: Flu-like syndrome, decreased neutrophils, RBCs, Platelets, CNS, Hepatic enzymes 
*Pegylated increases 1/2 life

Question 16

Zidovudine Azidothymidine (AZT)

Answer 16

Class/Subclass: Nucleoside Reverse Transcriptase Inhibitor - Thymidine analogue
Use: HIV
MOA: Substrate for TTP, inhibitor of RT, chain termination, inhibits replication
Administration: oral
Absorption: well absorbed, wide distribution, enters CNS
Metabolism: rapidly metabolized and excreted (short 1/2 life)
Adverse Effects: decreased bone marrow, CNS problems, increased toxicity with glucuronidation (APAP)
*takin in pregnant women to reduce mom –> baby transmission

Question 17

Didanosine

Answer 17

Class/Subclass: Nucleoside Reverse Transcriptase Inhibitor - Adenosine analogue
Use: HIV
MOA: Substrate for TTP, inhibitor of RT, chain termination, inhibits replication
Administration: Oral
Absorption: Acid labile
Adverse Effects: Less toxic than AZT, pancreatitis, peripheral neuropathy

Question 18

Stavudine

Answer 18

Class/Subclass: Nucleoside Reverse Transcriptase Inhibitor - Thymidine analogue
Use: HIV
MOA: Substrate for TTP, inhibitor of RT, chain termination, inhibits replication
Absorption: higher bioavailability than didanosine, enters the CNS
Adverse Effects: peripheral neuropathy, lactic acidosis

Question 19

Abacavir

Answer 19

Class/Subclass: Nucleoside Reverse Transcriptase Inhibitor - Guanosine analogue
Use: HIV
MOA: Substrate for TTP, inhibitor of RT, chain termination, inhibits replication
Absorption: high bioavailability, short 1/2 life
Metabolism: metabolized by alcohol dehydrogenase
Resistance: develops slowly
Adverse Effects: rash, fatal hypersensitivity
*HLAB5701 predictive reaction marker

Question 20

Tenofovir

Answer 20

Class/Subclass: Nucleoside Reverse Transcriptase Inhibitor - Thymidine analogue
Use: HIV
MOA: Pre-phosphorylated substrate for TTP, inhibitor of RT, chain termination, inhibits replication
Absorption: food enhances absorption
Adverse Effects: acute or cumulative renal toxicity, GI effects
*often combined with Emtricitabine

Question 21

Emtricitabine

Answer 21

Class/Subclass: Nucleoside Reverse Transcriptase Inhibitor - Fluorinated analogue of Lamivudine
Use: HIV
MOA: substrate for TTP, inhibitor of RT, chain termination, inhibits replication
Absorption: high bioavailability
Metabolism: long t1/2
Adverse Effects: headaches, nausea, diarrhea

Question 22

Entecavir

Answer 22

Class/Subclass: Nucleoside Reverse Transcriptase Inhibitor - Guanosine analogue
Use: Chronic HBV
MOA: analog

Question 23

Adefovir dipivoxil

Answer 23

Class/Subclass: Nucleoside Reverse Transcriptase Inhibitor - Guanosine analogue
Use: Chronic HBV
MOA: analog

Question 24

Nevirapine

Answer 24

Class/Subclass: Non-Nucleoside Reverse Transcriptase Inhibitor - Non-competitive RT inhibitor
Use: HIV and AZT-resistant HIV
Mechanism: non-competitive RT inhibitor, binds near the active site
Metabolism: CYP3A4 - moderate inducer
Resistance: rapid emergence if used alone, no cross resistance with NRTI’s
Adverse Effects: rash, hepatotoxicity

Question 25

Efvirenz

Answer 25

Class/Subclass: Non-Nucleoside Reverse Transcriptase Inhibitor - RT inhibitor Use: HIV Administration: oral Metabolism: CYP3A4 inducer and inhibitor (DDI) Adverse Effects: rash, CNS, hepatotoxicity *more widely used

Question 26

Entravirine & Rilpivirine

Answer 26

Class/Subclass: Non-Nucleoside Reverse Transcriptase Inhibitor Use: HIV

Question 27

Saquinavir

Answer 27

``` Class/Subclass: Protease Inhibitor Use: HIV Mechanism: HIV proteins are translated as a polyprotein, cleaved by HIV protease (aspartyl protease) to active proteins. Aspartyl protease is specific for cleavage. PI's prevent mature viral particle production Absorption: low bioavailability Metabolism: extensive 1st pass CYP3A4 Resistance: develops slowly Adverse Effects: altered body fat distribution, hyperlipidemia, insulin resistance *DDIs, combo with RTI's ```

Question 28

Idinavir

Answer 28

Class/Subclass: Protease Inhibitor Use: HIV Mechanism: HIV proteins are translated as a polyprotein, cleaved by HIV protease (aspartyl protease) to active proteins. Aspartyl protease is specific for cleavage. PI's prevent mature viral particle production Administration: oral Absorption: rapid absorption, high CNS levels Metabolism: extensive CYP3A4 Resistance: cross resistance Adverse Effects: increased bilirubin, nephrolithiasis (crystallizes in urine)

Question 29

Ritonavir

Answer 29

Class/Subclass: Protease Inhibitor Use: HIV Mechanism: HIV proteins are translated as a polyprotein, cleaved by HIV protease (aspartyl protease) to active proteins. Aspartyl protease is specific for cleavage. PI's prevent mature viral particle production Metabolism: CYP3A4 and 2D6 Resistance: develops slowly, some cross resistance *use a sub-theraputic dose to bloc CYP3A4, protecting Darunavir or Lopinavir from hepatic metabolism *can use in pregnancy

Question 30

Lopinavir

Answer 30

``` Class/Subclass: Protease Inhibitor Use: HIV Mechanism: HIV proteins are translated as a polyprotein, cleaved by HIV protease (aspartyl protease) to active proteins. Aspartyl protease is specific for cleavage. PI's prevent mature viral particle production Administration: oral Absorption: rapid absorption Metabolism: extensive CYP3A4 Adverse Effects: GI *use a sub-theraputic dose to bloc CYP3A4, protecting Darunavir or Lopinavir from hepatic metabolism *2nd choice in pregnancy ```

Question 31

Atazanavir

Answer 31

Class/Subclass: Protease Inhibitor Use: HIV Mechanism: HIV proteins are translated as a polyprotein, cleaved by HIV protease (aspartyl protease) to active proteins. Aspartyl protease is specific for cleavage. PI's prevent mature viral particle production Metabolism: inhibits UGT1A1, CYP3A4, CYP2C9 Adverse Effects: Diarrhea, N&V, headache, hyperbilirubinemia *Can use in pregnancy

Question 32

Darunavir

Answer 32

Class/Subclass: Protease Inhibitor Use: HIV Mechanism: gag-pol protease inhibitor Administration: oral Metabolism: CYP3A4 isozymes and also inhibitor of CYP3A4 *associated with hyperlipidemia and fat redistribution *can use in pregnancy

Question 33

Cobicistat

Answer 33

Class/Subclass: Metabolism Inhibitor - CYP3A inhibitor Use: combo with anti-retrovirals for "boosting" Mechanism: CYP3A inhibitor *do not use if creatinine clearance < 30

Question 34

Raltegravir

Answer 34

Class/Subclass: Integrase Inhibitor Use: HIV Mechanism: Integrase inhibitors interact with integrase molecule to prevent integration of linear dsDNA copy of the virus; required for stable infection and proliferation Administration: oral, not with cations or buffered drugs Metabolism: metabolized by glucuronidations (UGT1A1) Resistance: rapid Adverse Effects: diarrhea, N&V, dizziness, metabolic effects *useful target since there are no integrase in humans

Question 35

Elvitegravir

Answer 35

Class/Subclass: Integrase Inhibitor Use: HIV Mechanism: Integrase inhibitors interact with integrase molecule to prevent integration of linear dsDNA copy of the virus; required for stable infection and proliferation *useful target since there are no integrase in humans

Question 36

Dolutegravir

Answer 36

Class/Subclass: Integrase Inhibitor Use: HIV Mechanism: Integrase inhibitors interact with integrase molecule to prevent integration of linear dsDNA copy of the virus; required for stable infection and proliferation Administration: oral, not with cations or buffered drugs Metabolism: metabolized by glucuronidations (UGT1A1) - minor CYP3A4 role Adverse Effects: insomnia, headache, and hypersensitivity (rash) *useful target since there are no integrase in humans

Question 37

Enfuvirtide (T-20)

Answer 37

Class/Subclass: Fusion Inhibitor Use: HIV Mechanism: binds gp41, preventing conformational change Administration: subdermal injection BID Adverse Effects: most patients have injection site reaction

Question 38

Maraviroc

Answer 38

Class/Subclass: Fusion Inhibitor Use: HIV Mechanism: blocks CCR5, preventing entry Administration: oral Metabolism: CYP3A4 and MDR1 (PGP) substrate Adverse Effects: cough, muscle pain, diarrhea *possible sever hepatotoxicity

Question 39

Benzathine Penicillin G

Answer 39

Class/Subclass: Penicillins Use: Gram positive bacteria Mechanism: D-Ala-D-Ala analogue. Covalent binding to transpeptidases/PBPs, inhibition of cross linking cell wall (transpeptidation rxn), activation of autolysins (murein hydrolases) Administration: Oral, but acid labile Excretion: Tubular secretion, blocked by probenecid Resistance: Resistance: Penicillinase in bacteria (a type of β-lactamase) cleaves β-lactam ring, inaccessible PBPs (MRSA) Adverse Effects: Penicillin rash = major adverse effect, seizures. Direct Coombs + hemolytic anemia Killing: cidal in proliferating cells only

Question 40

Penicillin G (Benzyl Penicillin)

Answer 40

Class/Subclass: Penicillins Use: Gram positive bacteria Mechanism: D-Ala-D-Ala analogue. Covalent binding to transpeptidases/PBPs, inhibition of cross linking cell wall (transpeptidation rxn), activation of autolysins (murein hydrolases) Administration: "depot" prep Excretion: Tubular secretion, blocked by probenecid. Resistance: Resistance: Penicillinase in bacteria (a type of β-lactamase) cleaves β-lactam ring, inaccessible PBPs (MRSA) Adverse Effects: Penicillin rash = major adverse effect, seizures. Direct Coombs + hemolytic anemia Killing: cidal in proliferating cells only

Question 41

Penicillin V (Phenoxymethyl penicillin)

Answer 41

Class/Subclass: Penicillins Use: Gram positive bacteria Mechanism: D-Ala-D-Ala analogue. Covalent binding to transpeptidases/PBPs, inhibition of cross linking cell wall (transpeptidation rxn), activation of autolysins (murein hydrolases) Administration: Oral, acid stable Excretion: Tubular secretion, blocked by probenecid. Resistance: Penicillinase in bacteria (a type of β-lactamase) cleaves β-lactam ring Adverse Effects: Penicillin rash = major adverse effect, seizures. Direct Coombs + hemolytic anemia Killing: cidal in proliferating cells only

Question 42

Ampicillin

Answer 42

Class/Subclass: Extended Spectrum Penicillins Use: H. influenzae, H, pylori, E. Coli, Listeria monocytogenes, Proteus miribilis, Salmonella, Shigella, enterococci. Mechanism: Covalent binding to transpeptidases/PBPs, inhibition of cross linking cell wall (transpeptidation rxn), activation of autolysins (murein hydrolases) Excretion: Tubular secretion, blocked by probenecid. Resistance: Penicillinase in bacteria (a type of β-lactamase) cleaves β-lactam ring Adverse Effects: Penicillin rash = major adverse effect, Killing: cidal

Question 43

Amoxicillin

Answer 43

Class/Subclass: Extended Spectrum Penicillins Use: H. influenzae, H, pylori, E. Coli, Listeria monocytogenes, Proteus miribilis, Salmonella, Shigella, enterococci. Mechanism: Covalent binding to transpeptidases/PBPs, inhibition of cross linking cell wall (transpeptidation rxn), activation of autolysins (murein hydrolases) Excretion: Tubular secretion, blocked by probenecid. Resistance: Penicillinase in bacteria (a type of β-lactamase) cleaves β-lactam ring Adverse Effects: Penicillin rash = major adverse effect, Killing: cidal

Question 44

Methicillin

Answer 44

Class/Subclass: Anti-Staphylococcal Penicillins Use: Staphylococcus Mechanism: Covalent binding to transpeptidases/PBPs, inhibition of cross linking cell wall (transpeptidation rxn), activation of autolysins (murein hydrolases) Excretion: tubular secretions (organic acid secretory system) - blocked by probenecid Resistance: Drug is resistant to β-lactamase Killing: Cidal Adverse Effects: Hypersensitivity reactions, interstitial nephritis

Question 45

Nafcillin

Answer 45

Class/Subclass: Anti-Staphylococcal Penicillins Use: Staphylococcus Mechanism: Covalent binding to transpeptidases/PBPs, inhibition of cross linking cell wall (transpeptidation rxn), activation of autolysins (murein hydrolases) Excretion: Bile Resistance: Drug is resistant to β-lactamase Killing: Cidal Adverse Effects: Hypersensitivity reactions, interstitial nephritis

Question 46

Oxacillin

Answer 46

Class/Subclass: Anti-Staphylococcal Penicillins Use: Staphylococcus Mechanism: Covalent binding to transpeptidases/PBPs, inhibition of cross linking cell wall (transpeptidation rxn), activation of autolysins (murein hydrolases) Administration: Acid stable Excretion: Urine and bile Resistance: Drug is resistant to β-lactamase Killing: Cidal Adverse Effects: Hypersensitivity reactions, interstitial nephritis

Question 47

Cloxacillin

Answer 47

Class/Subclass: Anti-Staphylococcal Penicillins Use: Staphylococcus Mechanism: Covalent binding to transpeptidases/PBPs, inhibition of cross linking cell wall (transpeptidation rxn), activation of autolysins (murein hydrolases) Administration: Acid stable Excretion: Urine and bile Resistance: Drug is resistant to β-lactamase Killing: Cidal Adverse Effects: Hypersensitivity reactions, interstitial nephritis

Question 48

Piperacillin

Answer 48

Class/Subclass: Anti-Pseudomonal Penicillins Use: Proteus, Pseudomonas spp. (rapid resistance so need to combo w/ amino or fluoro), and Gram Negative rods Mechanism: Covalent binding to transpeptidases/PBPs, inhibition of cross linking cell wall (transpeptidation rxn), activation of autolysins (murein hydrolases) Excretion: Tubular secretion, blocked by probenecid Killing: cidal

Question 49

Carbenicillin Indanyl

Answer 49

Class/Subclass: Anti-Pseudomonal Penicillins Use: Proteus, Pseudomonas spp. (rapid resistance so need to combo w/ amino or fluoro), and Gram Negative rods Mechanism: Covalent binding to transpeptidases/PBPs, inhibition of cross linking cell wall (transpeptidation rxn), activation of autolysins (murein hydrolases) Administration: Acid stable Excretion: Tubular secretion, blocked by probenecid Killing: cidal

Question 50

Ticarcillin

Answer 50

Class/Subclass: Anti-Pseudomonal Penicillins Use: Proteus, Pseudomonas spp. (rapid resistance so need to combo w/ amino or fluoro), and Gram Negative rods Mechanism: Covalent binding to transpeptidases/PBPs, inhibition of cross linking cell wall (transpeptidation rxn), activation of autolysins (murein hydrolases) Excretion: Tubular secretion, blocked by probenecid Killing: cidal

Question 51

Mezocillin

Answer 51

Class/Subclass: Anti-Pseudomonal Penicillins Use: Proteus, Pseudomonas spp. (rapid resistance so need to combo w/ amino or fluoro), and Gram Negative rods Mechanism: Covalent binding to transpeptidases/PBPs, inhibition of cross linking cell wall (transpeptidation rxn), activation of autolysins (murein hydrolases) Excretion: Tubular secretion, blocked by probenecid Killing: cidal

Question 52

Cephalothin

Answer 52

Class/Subclass: 1st generation Cephalosporin Use: Narrow spectrum Mechanism: Similar to penicillin but less sensitive to β-lactamases Absorption: Generally greater Gram Negative activity. Less toxic to the patient. Better distribution to CNS Resistance: Cephalosporinases can target these cephalosporins *more expensive than penicillins, so if penicillins will work then use that

Question 53

Cephalexin

Answer 53

Class/Subclass: 1st generation Cephalosporin Use: Narrow spectrum Mechanism: Similar to penicillin but less sensitive to β-lactamases Administration: oral Absorption: Generally greater Gram Negative activity. Less toxic to the patient. Better distribution to CNS Resistance: Cephalosporinases can target these cephalosporins *more expensive than penicillins, so if penicillins will work then use that

Question 54

Cefzolin

Answer 54

Class/Subclass: 1st generation Cephalosporin Use: Narrow spectrum Mechanism: Similar to penicillin but less sensitive to β-lactamases Absorption: Generally greater Gram Negative activity. Less toxic to the patient. Better distribution to CNS Resistance: Cephalosporinases can target these cephalosporins *more expensive than penicillins, so if penicillins will work then use that

Question 55

Cefuoxime

Answer 55

Class/Subclass: 2nd generation Cephalosporin Use: Intermediate spectrum Mechanism: Similar to penicillin but less sensitive to β-lactamases Absorption: Less Gram Positive activity

Question 56

Cefotetan

Answer 56

Class/Subclass: 2nd generation Cephalosporin Use: Intermediate spectrum Mechanism: Similar to penicillin but less sensitive to β-lactamases Absorption: Less Gram Positive activity Adverse Effects: Disulfiram effect with alcohol (immediate and severe "hangover" effect), bleeding and platelet disorders

Question 57

Cefaclor

Answer 57

Class/Subclass: 2nd generation Cephalosporin Use: Intermediate spectrum Mechanism: Similar to penicillin but less sensitive to β-lactamases Administration: oral Absorption: Less Gram Positive activity

Question 58

Cefotaxime

Answer 58

Class/Subclass: 3rd generation Cephalosporin Use: Broad spectrum Mechanism: Similar to penicillin but less sensitive to β-lactamases

Question 59

Ceftriaxone

Answer 59

Class/Subclass: 3rd generation Cephalosporin Use: Broad spectrum Mechanism: Similar to penicillin but less sensitive to β-lactamases

Question 60

Cefazidime

Answer 60

Class/Subclass: 3rd generation Cephalosporin Use: Broad spectrum Mechanism: Similar to penicillin but less sensitive to β-lactamases

Question 61

Cefepime

Answer 61

Class/Subclass: 4th generation Cephalosporin Use: Broad spectrum Mechanism: Similar to penicillin but less sensitive to β-lactamases Resistance: Cephalosporinase resistant

Question 62

Aztreonam

Answer 62

Class/Subclass: Other β-Lactams Use: Monobactam - Gram Negative activity (no Gram Positive) Administration: IV only Resistance: β-Lactam resistant Adverse Effects: no cross reaction with penicillin sensitive

Question 63

Imipenam

Answer 63

Class/Subclass: Other β-Lactams Use: Carbapenems Resistance: β-Lactamase resistant pseudomonas develops rapid resistance, use with aminos inactivated by renal dipeptidase (need to co administer with Cilstatin) Adverse Effects: Cross reaction with penicillin sensitive

Question 64

Meropenam

Answer 64

Class/Subclass: Other β-Lactams Use: Carbapenems Resistance: Dipeptidase-resistant

Question 65

Claculanic Acid

Answer 65

Class/Subclass: Other β-Lactams | Mechanism: β-Lactamase inhibitors

Question 66

Sulbactam

Answer 66

Class/Subclass: Other β-Lactams | Mechanism: β-Lactamase inhibitors

Question 67

Tazobactam

Answer 67

Class/Subclass: Other β-Lactams | Mechanism: β-Lactamase inhibitors

Question 68

Vancomycin

Answer 68

Class/Subclass: Other Cell Wall Synthesis Inhibitors Use: Gram Positive MRSA Mechanism: Inhibits transglycosylation - systemic Excretion: IV drug cleared through kidney - enhances oto and renal toxicity of aminos Adverse Effects: "red man" or "red neck" syndrome Killing: Cidal

Question 69

Bacitracin

Answer 69

Class/Subclass: Other Cell Wall Synthesis Inhibitors Use: Topical only Adverse Effects: Markedly nephrotoxic when given systemically Killing: Cidal

Question 70

Fosfomycin

Answer 70

Class/Subclass: Other Cell Wall Synthesis Inhibitors Use: Gram Positive, Gram Negative, Single dose for UTI Mechanism: Inhibits cytoplasmic step in cell wall precursor synthesis Administration: Oral Absorption: Active uptake by glycerophosphate (G6P transporter) Excretion: Active drug excretion by the kidney *synergistic w/ β-Lactams, aminos, and fluoros

Question 71

Polymixin B

Answer 71

Use: Gram Negative (except Proteus) Killing: Cidal

Question 72

Tetracyline

Answer 72

Class/Subclass: Tetracycline Use: First broad spectrum. Mycoplasma, chlamydia, rikettsiae, Lyme disease Mechanism: Reversible binding to 30s subunit Administration: usually oral, but can vary Excretion: Urine Resistance: Efflux pumps are major mediators of resistance. Altered ribosomal proteins are secondary mechanisms Adverse Effects: GI - direct irritation, super infections w/ pseudomonas, proteus, staph, clostridium, and candida. Impaired liver function Killing: Static *not absorbed! do not give w/ food, milk, antacids, etc. *crosses the placenta and excreted in milk *overuse in clinical/agro has increased resistance *chelate metal ions (Ca2+, Al3+, Fe2+, Mg2+)

Question 73

Doxycycline

Answer 73

Class/Subclass: Tetracycline Mechanism: Reversible binding to 30s subunit Administration: usually oral, but can vary Excretion: Fecal Resistance: Efflux pumps are major mediators of resistance. Altered ribosomal proteins are secondary mechanisms Adverse Effects: GI - direct irritation, super infections w/ pseudomonas, proteus, staph, clostridium, and candida. Impaired liver function Killing: Static *not absorbed! do not give w/ food, milk, antacids, etc. *crosses the placenta and excreted in milk *chelate metal ions (Ca2+, Al3+, Fe2+, Mg2+)

Question 74

Minocycline

Answer 74

Class/Subclass: Tetracycline Mechanism: Reversible binding to 30s subunit Administration: usually oral, but can vary Excretion: Urine Resistance: Efflux pumps are major mediators of resistance. Altered ribosomal proteins are secondary mechanisms Adverse Effects: GI - direct irritation, super infections w/ pseudomonas, proteus, staph, clostridium, and candida. Impaired liver function Killing: Static *not absorbed! do not give w/ food, milk, antacids, etc. *crosses the placenta and excreted in milk *chelate metal ions (Ca2+, Al3+, Fe2+, Mg2+)

Question 75

Tigecycline (glycylcyclines - new gen)

Answer 75

Class/Subclass: Tetracycline Mechanism: Reversible binding to 30s subunit Administration: usually oral, but can vary Excretion: Urine Resistance: Not effected by efflux pump except in proteus and pseudomonas Adverse Effects: GI - direct irritation, super infections w/ pseudomonas, proteus, staph, clostridium, and candida. Impaired liver function Killing: Static *not absorbed! do not give w/ food, milk, antacids, etc. *crosses the placenta and excreted in milk *chelate metal ions (Ca2+, Al3+, Fe2+, Mg2+)

Question 76

Erythromycin

Answer 76

Class/Subclass: Macrolides Use: Gram Positive and some mycobacteria Mechanism: 50s P450 inhibitors. Use enteric coating or erythromycin esters. Crosses the placenta Administration: Absorbed from GI, but acid-labile. Oral or IV Excretion: Bile. 2-5 hr 1/2 life Resistance: Enterobacteriaceae has esterase which hydrolyses. Staph resistant, some strepto and pneumococci. Altered (methylated mRNA), efflux pump Adverse Effects: GI distress, microsomal enzyme inhibition (DDI), hepatotoxicity Killing: Static, dose dependent disease, and chlamydia

Question 77

Clarithromycin

Answer 77

Class/Subclass: Macrolides Use: Broad spectrum. mycobacterium, avian-intracellular in AIDS pts. Mechanism: 50s P450 inhibitors. Use enteric coating or erythromycin esters. Crosses the placenta Absorption: higher bioavailability Administration: Absorbed from GI, but acid-labile. Oral or IV Excretion: Bile. 2-5 hr 1/2 life Resistance: Enterobacteriaceae has esterase which hydrolyses. Staph resistant, some strepto and pneumococci. Altered (methylated mRNA), efflux pump Adverse Effects: less GI effects, microsomal enzyme inhibition (DDI), hepatotoxicity Killing: Static, dose dependent *also used for mycoplasma pneumonia, legionnaires, disease, and chlamydia

Question 78

Azithromycin

Answer 78

Class/Subclass: Macrolides Use: Broad spectrum. mycobacterium, avian-intracellular in AIDS pts. Mechanism: 50s P450 inhibitors. Use enteric coating or erythromycin esters. Crosses the placenta Absorption: higher bioavailability Metabolism: longer 1/2 life Administration: Absorbed from GI, but acid-labile. Oral or IV Excretion: Bile. 2-5 hr 1/2 life Resistance: Enterobacteriaceae has esterase which hydrolyses. Staph resistant, some strepto and pneumococci. Altered (methylated mRNA), efflux pump Adverse Effects: GI distress, microsomal enzyme inhibition (DDI), hepatotoxicity, minimal P450 based interaction Killing: Static, dose dependent *also used for mycoplasma pneumonia, legionnaires, disease, and chlamydia *tissue levels 10-100 x than plasma levels

Question 79

Telithromycin (semi-synthetic)

Answer 79

Class/Subclass: Macrolides Use: CA pneumo, bronchitis, sinusitis Mechanism: 50s P450 inhibitors. Use enteric coating or erythromycin esters. Crosses the placenta Absorption: higher bioavailability Administration: Oral Metabolism: Liver Excretion: Bile and urine. 2-4 D 1/2 life. Resistance: Poor substrate for efflux pump Adverse Effects: QT prolongation Killing: Static, dose dependent *also used for mycoplasma pneumonia, legionnaires, disease, and chlamydia *once daily dosing inhibits CYP3A4

Question 80

Gentamicin (older)

Answer 80

Class/Subclass: Aminoglycosides Use: Non-resistant Gram Negatives. E. Coli, Proteus, Pseudo (genta > tobra > amika) Mechanism: 50s P450 inhibitors. Irreversible inactivation of 30s subunit. Multiple effects on translation - misreading of mRNA - interfere w/ initiation, breakup polysomes Administration: Poor oral, usually IV or IM Excretion: Excreted unchanged. Glomerular filtration VERY high concentrations in proximal tubule cells Resistance: Emerges rapidly if used alone. increased bacterial metabolism of AG: adenylation, acetylation, phosphorylation. Alteration in bacterial uptake - altered transport system, anaerobes resistant - O2 dependent uptake. altered target (30s ribosome) Adverse Effects: Renal toxicity, ototoxicity, neuromuscular blockade Killing: Cidal, concentration dependent

Question 81

Streptomycin (older)

Answer 81

Class/Subclass: Aminoglycosides Use: Non-resistant Gram Negatives. E. Coli, Proteus, Pseudo (genta > tobra > amika) Mechanism: 50s P450 inhibitors. Irreversible inactivation of 30s subunit. Multiple effects on translation - misreading of mRNA - interfere w/ initiation, breakup polysomes Administration: Poor oral, usually IV or IM Excretion: Excreted unchanged. Glomerular filtration VERY high concentrations in proximal tubule cells Resistance: Emerges rapidly if used alone. increased bacterial metabolism of AG: adenylation, acetylation, phosphorylation. Alteration in bacterial uptake - altered transport system, anaerobes resistant - O2 dependent uptake. altered target (30s ribosome) Adverse Effects: renal toxicity, ototoxicity, neuromuscular blockade Killing: Cidal, concentration dependent

Question 82

Tobramycin

Answer 82

Class/Subclass: Aminoglycosides Use: Non-resistant Gram Negatives. E. Coli, Proteus, Pseudo (genta > tobra > amika) Mechanism: 50s P450 inhibitors. Irreversible inactivation of 30s subunit. Multiple effects on translation - misreading of mRNA - interfere w/ initiation, breakup polysomes Administration: Poor oral, usually IV or IM Excretion: Excreted unchanged. Glomerular filtration VERY high concentrations in proximal tubule cells Resistance: Emerges rapidly if used alone. increased bacterial metabolism of AG: adenylation, acetylation, phosphorylation. Alteration in bacterial uptake - altered transport system, anaerobes resistant - O2 dependent uptake. altered target (30s ribosome) Adverse Effects: renal toxicity, ototoxicity, neuromuscular blockade Killing: Cidal, concentration dependent

Question 83

Neomycin

Answer 83

Class/Subclass: Aminoglycosides Use: Non-resistant Gram Negatives. E. Coli, Proteus, Pseudo (genta > tobra > amika) Mechanism: 50s P450 inhibitors. Irreversible inactivation of 30s subunit. Multiple effects on translation - misreading of mRNA - interfere w/ initiation, breakup polysomes Administration: Poor oral, usually IV or IM Excretion: Excreted unchanged. Glomerular filtration VERY high concentrations in proximal tubule cells Resistance: Emerges rapidly if used alone. increased bacterial metabolism of AG: adenylation, acetylation, phosphorylation. Alteration in bacterial uptake - altered transport system, anaerobes resistant - O2 dependent uptake. altered target (30s ribosome) Adverse Effects: renal toxicity, ototoxicity, neuromuscular blockade Killing: Cidal, concentration dependent

Question 84

Amikacin

Answer 84

Class/Subclass: Aminoglycosides Use: Non-resistant Gram Negatives. E. Coli, Proteus, Pseudo (genta > tobra > amika) Mechanism: 50s P450 inhibitors. Irreversible inactivation of 30s subunit. Multiple effects on translation - misreading of mRNA - interfere w/ initiation, breakup polysomes Administration: Poor oral, usually IV or IM Excretion: Excreted unchanged. Glomerular filtration VERY high concentrations in proximal tubule cells Resistance: Emerges rapidly if used alone. increased bacterial metabolism of AG: adenylation, acetylation, phosphorylation. Alteration in bacterial uptake - altered transport system, anaerobes resistant - O2 dependent uptake. altered target (30s ribosome) Adverse Effects: renal toxicity, ototoxicity, neuromuscular blockade Killing: Cidal, concentration dependent

Question 85

Spectinomycin

Answer 85

Class/Subclass: Aminoglycosides Use: Non-resistant Gram Negatives. E. Coli, Proteus, Pseudo (genta > tobra > amika) Mechanism: 50s P450 inhibitors. Irreversible inactivation of 30s subunit. Multiple effects on translation - misreading of mRNA - interfere w/ initiation, breakup polysomes Administration: Poor oral, usually IV or IM Excretion: Excreted unchanged. Glomerular filtration VERY high concentrations in proximal tubule cells Resistance: Emerges rapidly if used alone. increased bacterial metabolism of AG: adenylation, acetylation, phosphorylation. Alteration in bacterial uptake - altered transport system, anaerobes resistant - O2 dependent uptake. altered target (30s ribosome) Adverse Effects: renal toxicity, ototoxicity, neuromuscular blockade Killing: Cidal, concentration dependent

Question 86

Chloramphenicol

Answer 86

Class/Subclass: Other Protein Synthesis Inhibitors Use: Broad spectrum. Typhoid fever, Rocky Mountain Spotted Fever in children Mechanism: Reversible inhibition of protein synthesis, 50s Administration: Well absorbed all routes Absorption: includes CNS Metabolism: glucuronidation in liver is the rate limiting step for inactivation/clearance Excretion: 100% in urine Resistance: Key mechanism is plasmis-mediated chloramphenicol acyl transferase (CAT) Adverse Effects: GI disturbances w/ fungal superinfection, BM suppression, aplastic anemia, gray baby syndrome, DDI Killing: static *would be ideal antibiotic, but creates superinfections due to broad spectrum nature

Question 87

Clindamycin

Answer 87

Class/Subclass: Other Protein Synthesis Inhibitors Use: MRSA, endocarditis prophylaxis, Bacteroids fragilis, other anaerobes MOA: Lincosamide antibiotic Administration: well absorbed all routes Adverse Effects: GI upset, clostridium superinfections hepatotoxicity Killing: static *endocarditis prophylaxis (patients w/ artificial valves, etc.)

Question 88

Streptogramins (quinupristin and Dalfopristin: synercid)

Answer 88

Class/Subclass: Other Protein Synthesis Inhibitors Use: Static - E. Faecium Cidal - other organisms. MRSA Mechanism: peptide macrolactoes - each drug inhibits a different stage of bacterial protein synthesis Administration: IV Metabolism: Potent inhibitor of CYP3A4 Resistance: complete cross resistance between 2 components. No cross resistance w/ other IPS drugs

Question 89

Oxazolidinones (Linezolid)

Answer 89

Class/Subclass: Other Protein Synthesis Inhibitors Use: Vanc resistant E. Faecium Mechanism: Prevents formation of 70s ribosome (unique mechanism) Administration: IV or Oral Resistance: No cross resistance with other IPS drugs Adverse Effects: Bone marrow suppression, thrombocytopenia (reversible and mild) Killing: Cidal - strep Static - staph and entero

Question 90

Sulfisoxazole

Answer 90

Class/Subclass: Sulfonamides Mechanism: p-Aminobenzoid acid analogs (PABA) - enter into a normal metabolic pathway but then block that path. Competitive inhibitor of dihydrofolate synthesis Administration: oral, some topical (burns), rare IV Absorption: well absorbed from GI and well distributed (including CNS) Excretion: urine Resistance: typically combined with DHFR inhibitor (trimethoprim) - TMP/SMX helps avoid resistance. Mutations causing over production of PABA. Loss of permeability new dihydropteroate synthetase - discriminates b/w PABA and sulfonamide Adverse Effects: may cross react w/ other sulfonamides, SJS, fever, malaise, crystalluria/hematuria, hematopoietic effects, hemolytic anemia (G6PDF def) Killing: Static

Question 91

Sulfamethoxazole

Answer 91

Class/Subclass: Sulfonamides Mechanism: p-Aminobenzoid acid analogs (PABA) - enter into a normal metabolic pathway but then block that path. Competitive inhibitor of dihydrofolate synthesis Administration: oral, some topical (burns), rare IV Absorption: well absorbed from GI and well distributed (including CNS) Excretion: urine Resistance: typically combined with DHFR inhibitor (trimethoprim) - TMP/SMX helps avoid resistance. Mutations causing over production of PABA. Loss of permeability new dihydropteroate synthetase - discriminates b/w PABA and sulfonamide Adverse Effects: may cross react w/ other sulfonamides, SJS, fever, malaise, crystalluria/hematuria, hematopoietic effects, hemolytic anemia (G6PDF def) Killing: Static

Question 92

Sulfasalzine

Answer 92

Class/Subclass: Sulfonamides Use: Ulcerative colitis Mechanism: p-Aminobenzoid acid analogs (PABA) - enter into a normal metabolic pathway but then block that path. Competitive inhibitor of dihydrofolate synthesis Administration: oral, some topical (burns), rare IV Absorption: well absorbed from GI and well distributed (including CNS) Excretion: urine Resistance: typically combined with DHFR inhibitor (trimethoprim) - TMP/SMX helps avoid resistance. Mutations causing over production of PABA. Loss of permeability new dihydropteroate synthetase - discriminates b/w PABA and sulfonamide Adverse Effects: may cross react w/ other sulfonamides, SJS, fever, malaise, crystalluria/hematuria, hematopoietic effects, hemolytic anemia (G6PDF def) Killing: Static

Question 93

Silver Sulfadiazine

Answer 93

Class/Subclass: Sulfonamides Use: Topical for burns Mechanism: p-Aminobenzoid acid analogs (PABA) - enter into a normal metabolic pathway but then block that path. Competitive inhibitor of dihydrofolate synthesis Administration: oral, some topical (burns), rare IV Absorption: well absorbed from GI and well distributed (including CNS) Excretion: urine Resistance: typically combined with DHFR inhibitor (trimethoprim) - TMP/SMX helps avoid resistance. Mutations causing over production of PABA. Loss of permeability new dihydropteroate synthetase - discriminates b/w PABA and sulfonamide Adverse Effects: may cross react w/ other sulfonamides, SJS, fever, malaise, crystalluria/hematuria, hematopoietic effects, hemolytic anemia (G6PDF def) Killing: Static

Question 94

Co-Trimoxazole

Answer 94

Class/Subclass: Sulfonamides Mechanism: p-Aminobenzoid acid analogs (PABA) - enter into a normal metabolic pathway but then block that path. Competitive inhibitor of dihydrofolate synthesis Administration: oral, some topical (burns), rare IV Absorption: well absorbed from GI and well distributed (including CNS) Excretion: urine Resistance: typically combined with DHFR inhibitor (trimethoprim) - TMP/SMX helps avoid resistance. Mutations causing over production of PABA. Loss of permeability new dihydropteroate synthetase - discriminates b/w PABA and sulfonamide Adverse Effects: may cross react w/ other sulfonamides, SJS, fever, malaise, crystalluria/hematuria, hematopoietic effects, hemolytic anemia (G6PDF def) Killing: Static

Question 95

Trimethoprim

Answer 95

Class/Subclass: DHF reductase inhibitor Use: pneumocystis, pneumonca, UTI, many others. Can be used alone for UTI but usually combo w/ sulfona Mechanism: Dihydrofolate reductase inhibitor - blocks bacterial enzyme Excretion: urine Adverse Effects: anti-folate effects - megaloblastic anemia, leukopenia, granulocytopenia --> treat w/ folinic acid AIDS pts - increased incidence of adverse effects Killing: static. combo tx if often cidal *pyrimethamine - protozoans *methotrexate - mammalian

Question 96

Nalidixic Acid

Answer 96

``` Class/Subclass: Quinolones Use: prototype quinolone antibiotic MOA: inhibits transcription and DNA replication Administration: oral - rapid Metabolism: rapid, glucuronidated Excretion: urine *no systemic effect: excreted too fast ```

Question 97

Ciprofloxacin

Answer 97

Class/Subclass: Fluoroquinolones Use: excellent for GN: useful for GI and urogenital infecitnos, moderate to good for GP MOA: fluoronated analog of nalidixic acid (slows metabolism) Administration: oral Excretion: urine (blocked by probenecid) Resistance: altered (mutated) DNA gyrase. Pseudomonas, staph, serratia Adverse Effects: some GI - N&V, diarrhea, HA, dizziness, insomnia, abnormal liver fx tests *blocks theophylline clearance - CANNOT be co-administered

Question 98

Levofloxacin

Answer 98

Class/Subclass: Fluoroquinolones Use: excellent for GN: useful for GI and urogenital infecitnos, moderate to good for GP MOA: fluoronated analog of nalidixic acid (slows metabolism) Administration: oral Excretion: urine (blocked by probenecid) Resistance: altered (mutated) DNA gyrase. Pseudomonas, staph, serratia Adverse Effects: some GI - N&V, diarrhea, HA, dizziness, insomnia, abnormal liver fx tests *blocks theophylline clearance - CANNOT be co-administered

Question 99

Ofloxacin

Answer 99

Class/Subclass: Fluoroquinolones Use: excellent for GN: useful for GI and urogenital infecitnos, moderate to good for GP MOA: fluoronated analog of nalidixic acid (slows metabolism) Administration: oral Excretion: urine (blocked by probenecid) Resistance: altered (mutated) DNA gyrase. Pseudomonas, staph, serratia Adverse Effects: some GI - N&V, diarrhea, HA, dizziness, insomnia, abnormal liver fx tests *blocks theophylline clearance - CANNOT be co-administered

Question 100

Nitrofurantoin

Answer 100

Class/Subclass: Urinary Tract Antiseptics Use: UTIs - Gram + and - MOA: unknown, but may involve oxidative stress - most effective if urine pH is <5.5 Administration: Rapid oral Absorption: even IV nitrofurantoin does not have a systemic effect Metabolism: Rapid Excretion: Urine Resistance: all pseudomonas, some proteus Adverse Effects: anorexia, GI disturbances common occasional hemolytic anemia (oxidative) especially if G6PDH deficient, leukopenia, hepatotoxicity can have systemic toxicity in renal insufficiency Killing: static or cidal

Question 101

Isoniazid (INH)

Answer 101

Class/Subclass: First line anti-mycobacterial Use: prophylaxis - used alone for TB exposure, tuberculin convertors. Combo TB tx w/ ethambutol, rifampin, or pyrazinamide MOA: Blocks synthesis of mycolic acids for mycobacterial cell wall - cidal in growing cells only! Administration: Well absorbed and distributed after oral admin, CNS 20% of serum level - intracellular = extracellular Metabolism: key factor in Pk - acetylated in liver (genetic differences in acetylation) Excretion: urine Resistance: 10% of isolates in US resistant, higher in caribbean, Asia (approaching 20%). Deletion of katG gene in mycobacterium (gene activated drug) Adverse Effects: dose and duration depend - hepatotoxicity (increases w/ age of the pt) - more common in alcoholics, maybe during pregnancy. PNC/CNS neuropathy (tx w/ pyridoxine [b6]). alter dosing in hepatic, not renal dz. *fast acetylators may require higher doses

Question 102

Ethambutol

Answer 102

Class/Subclass: First line anti-mycobacterial MOA: inhibits synthesis of mycobacterial cell wall glycan Excretion: urine Resistance: rapid - use in combo Adverse Effects: dose dependent optic neuritis - decreased acuity, loss of red/green differntiation Killing: static

Question 103

Rifampin

Answer 103

Class/Subclass: First line anti-mycobacterial Use: prophylaxis - used alone for INH intolerant pts or resistant bug. combo for active dz. MOA: inhibits bacterial RNA synthesis Excretion: bile Adverse Effects: inducer of microfosomal enzymes - alters 1/2 life of anticoags, oral contraception. Hepatotoxic, "flu-like" syndrome, gives orange color to body fluids Killing: cidal

Question 104

Streptomycin

Answer 104

Class/Subclass: First line anti-mycobacterial Use: was used only for severe (life threatening) cases, but now used more often Adverse Effects: renal/ototoxicity

Question 105

Pyrazinamide

Answer 105

Class/Subclass: First line anti-mycobacterial MOA: unknown, activated by mycobacterium Administraiton: oral Resistance: rapid resistance Adverse Effects: hyperuremia (gouty arthritis) 1-5% incidence of hepatotoxicity Killing: static

Question 106

Cycloserine

Answer 106

Class/Subclass: Second line anti-mycobacterial. Toxicity outweighs therapeutic effects except for highly resistant strains *currently a resurgence in highly resistant TB strains - second line may become first

Question 107

Ethionamide

Answer 107

Class/Subclass: Second line anti-mycobacterial. Toxicity outweighs therapeutic effects except for highly resistant strains *currently a resurgence in highly resistant TB strains - second line may become first

Question 108

Capreomycin

Answer 108

Class/Subclass: Second line anti-mycobacterial. Toxicity outweighs therapeutic effects except for highly resistant strains *currently a resurgence in highly resistant TB strains - second line may become first

Question 109

Para-aminosalicyclic acid (PAS)

Answer 109

Class/Subclass: Second line anti-mycobacterial. Toxicity outweighs therapeutic effects except for highly resistant strains *currently a resurgence in highly resistant TB strains - second line may become first

Question 110

Dapsone

Answer 110

Class/Subclass: Sulfone (similar to sulfonamide) Use: M. leprae (combo w/ rifampin and clofazimine) and P. jiroveci pneumonia Excretion: feces/urine Adverse Effects: hemolysis and methemoglobinemia are common