Drug

Question 1

Antivirals

Answer 1

Acyclovir, Valacyclovir, Famciclovir

Ganciclovir, Valganciclovir

Osteltamivir, Zanamivir

Ribavirin

Question 2

Zanamavir

Answer 2

Relenza (inhaled)

Treat influenza A and B

Neuraminidase inhibitor (virus cannot be released from the cell, and instead clumps up on the edge of cell membrane)

Side effects: bronchospasm

Question 3

Oseltamivir

Answer 3

Tamiflu (oral)

Treat and prophylaxis for influenza A and B

Neuraminidase inhibitor

Side effects: mild GI, rare neuropsychiatric

Question 4

Ribavirin

Answer 4

Treat RSV (aerosol) and Hep C (oral)

Guanosine anologue with incomplete ring –> interferes with RNA transcription

Side effects: bronchospasm (aerosol), teratogenic, hemolytic anemia (oral)

Question 5

Acyclovir

Answer 5

Treat HSV, VZV (NOT CMV because CMV doesn’t have thymidine kinase!)

Guanosine analog with incomplete ring, inhibits viral DNA polymerase and terminates growing DNA chain

High dose IV for neonatal or CNS infection in adults

Low dose for mucocutaneous disease

Fequent oral dosing necessary (5x per day), poor oral bioavailability

Side effects: nausea, headache, crystals in renal tubules causing impaired renal function

Question 6

Famciclovir, Valacyclovir

Answer 6

Treat shingles (herpes zoster from VZV reactivation), genital herpes outbreaks

Prodrugs of guanosine analogues, terminate growing DNA chain

Excellent oral bioavailability (valacyclovir is valine ester of acyclovir)

Question 7

Ganciclovir, Valganciclovir

Answer 7

Treat and prevent CMV

Guanosine analogue, inhibits viral DNA polymerase

Ganciclovir used IV (poor bioavailability)

Valganciclovir used orally (valine ester)

Side effects: bone marrow suppression (anemia, neutropenia, thombocytopenia)

Question 8

Sulfonamides

Answer 8

Competitive inhibitors of dihydropteroate synthetase (compete with PABA)

Inhibit bacteria from synthesizing folic acid (tetrahydrofolic acid–FH4) so cannot create purines, pyrimidines, AAs and cannot grow

Bacteriostatic

Toxicity: SJS, hematopoeitic, kernicterus (don’t use in pregnancy!), hypersensitivity reactions, form crystals in renal tubules, hemotopoeitic (anemia, thrombocytopenia), drug reactions (don’t give with phenytoin–increase phenytoin conc by displacing it from albumin)

Mechanisms of resistance: PABA overproduction or mutations in dihydropteroate synthetase to resist sulfonamides

Ex: sulfamethoxazole, sulfadiazine

Question 9

Trimethoprim

Answer 9

Competitive inhibitor of dihydrofolate reductase (DHFR)

Inhibits bacterial conversion of FH2 –> FH4, so blocks folate synthesis pathway (like sulfonamides)

Bactericidal

Toxicities: GI, hematopoetic (anemia, thrombocytopenia), hyperkalemia (interferes with Na/K exchange)

Question 10

Trimethoprim-Sulfamethoxazole (TMP-SMX; Co-trimoxazole)

Answer 10

Gram + and gram -

E. coli UTIs (but resistance more common now), CA-MRSA skin infection, PCP

Combination produces synergistic effects because two drugs block different steps in biosynthesis of reduced folic acid

Bactericidal

Reduced side effects and doses

AKA Bactrim

Question 11

1st generation cephalosporins

Answer 11

Gram + (not much gram -)

Cephalexin (PO): S. aureus cutaneous abscess

Cefazolin (IV)

Note: usually “ph” (PHd before can do anything)

Question 12

2nd generation cephalosporins

Answer 12

Good gram + (getting better at gram -)

Cefaclor

Cefuroxime

Cefoxitin

Cefotetan

Note: with FAm, FUR coats, FOXy cousin drinking TEa

Note: for anaerobes, FOX with TEa

Question 13

3rd generation cephalosporins

Answer 13

Gram +

Ceftriaxone (can be used for MSSA, but would rather use 1st gen cephalosporin)

Cefotaxime

Ceftazidime: Pseudomonas

Note: all have “T” for tri

Question 14

4th generation cephalosporin

Answer 14

Gram + or gram -

Cefepime: Staph aureus, Pseudomonas

Question 15

Natural penicillins

Answer 15

Used for Strep, syphilis, spirochetes

Susceptible to beta lactamases

Penicillin G (IV/IM)

Penicillin V (PO)

Question 16

Antistaphylococcal penicillins

Answer 16

Gram + only, resistant to beta lactamases

Methicillin (IV)

Oxacillin (IV)

Dicloxacillin (PO)

Question 17

Amino penicillins

Answer 17

Gram - activity because amino group lets them enter through porins

Ampicillin (IV/PO): Listeria and Enterococcus along with aminoglycoside; Proteus mirabilis

Amoxicillin (PO): Strep pyogenes, Salmonella along with TMP-SMX

Question 18

Antipseudomonal penicillins

Answer 18

Gram - activity, especially against pseudomonas along with tazobactam

Carbenicillin

Ticarcillin

Piperacillin (IV)

Question 19

Protein synthesis inhibitors

Answer 19

Bind ribosomal subunits of bacteria to prevent them from translating protein

Tetracyclines, Aminoglycosides, Macrolides, Clindamycin, Chloramphenicol, Linezolid, Rifampin, Mupirocin

Question 20

Tetracyclines

Answer 20

Broad spectrum (gram +, gram -)

Use for atypical pneumonia (chlamydia, mycoplasma, legionella), STDs (PID, LGV), Rickettsia, malaria prophylaxis, CA-MRSA, acne

Doxycycline PO and IV: Borrelia bergdorferi, RMSF, safe in renal failure

Minocycline PO

Tetracycline PO: epidemic typhus (Rickettsia prowazekii), Q fever (Coxiella brunetii)

Stain teeth, don’t take w/dairy or divalent cations

Mechanism of resistance: active efflux AND decreased influx via altered porin proteins of tetracyclines

Question 21

Aminoglycosides

Answer 21

Protein synthesis inhibitors

Mechanism: first bind to outer membrane of bacteria, then transport across membrane using electrochemical gradient dependent on oxidative phosphorylation, then disrupt translation by binding ribosome

Bactericidal

Only act on aerobic bacteria (only aerobic have oxidative phosphorylation!)

Act on gram -, including Pseudomonas aeruginosa (along with piperacillin), enterococcus (along with either ampicillin or vancomycin)

Excreted in urine so can use to treat UTI

Mechanism of resistance: enzymatic modification of aminoglycosides, decreased influx and altered target (mutation in 30S ribosome)

Amikacin > Tobramycin > Gentamicin (in terms of broadest spectrum activity)

Toxicities: nephrotoxicity, ototoxicity

Question 22

Macrolides

Answer 22

Protein synthesis inhibitor

Effective against aerobic respiratory organisms such as S. pneumoniae, H. influenzae, Legionella; also chlamydia, mycoplasma, rickettsia, H. pylori, C. diphtheriae, Bortadella pertussis

NOT used against anaerobes

Usually used in people with penicillin allergy because similar coverage

Ex: erythromycin, clarithromycin, azithromycin

Mechanisms of resistance: efflux pump, macrolide hydrolysis, altered target, decreased influx

Question 23

Azithromycin

Answer 23

Macrolide

Protein synthesis inhibitor

Long half-life, so can give 5 day course but active for 10 days

“Z-pack”

IV or PO

No hepatic metabolism

Question 24

Erythromycin

Answer 24

Macrolide

Protein synthesis inhibitor

GI upset

Narrower spectrum (not active against mycobacteria?), more frequent dosing

IV or PO

Question 25

Clarithromycin

Answer 25

Macrolide Protein synthesis inhibitor **PO only**

Question 26

Clindamycin

Answer 26

Lincosamide class of protein synthesis inhibitors (along with lincomycin) Active against gram + and **anaerobic** bacteria **Poor CSF** penetration Does penetrate bone Major uses: staphylococcal (**CA-MRSA**)and **anaerobic** infections (especially **odontogenic**) Adverse effects: allergic skin rashes, C. difficile pseudomembranous enterocolitis

Question 27

Chloramphenicol

Answer 27

Protein synthesis inhibitor Cheap, used in Africa Very broad spectrum Adverse effects: bone marrow suppression, aplastic anemia, drug interactions, grey baby syndrome (don't give to babies!)

Question 28

Linezolid

Answer 28

Oxazolidinone class of **protein synthesis inhibitors** Active against S. aureus, **MRSA**, Streptococci, E. faecium, E. faecalis, **VRE** Adverse effects: diarrhea, nausea, bone marrow suppression after 2 weeks (don't use this long!), weak MAO inhibitor (**don't use if taking SSRIs**)

Question 29

Rifampin

Answer 29

Rifamycin class of protein synthesis inhibitors **Prevents mRNA synthesis** (not translation like all the others) Active against gram +, **mycobacteria** (**TB** drug) Adverse effects: **drug interactions** (including protease inhibitors for HIV), stains **secretions red-orange** (sweat, pee, tears)

Question 30

Metronidazole

Answer 30

**Damages DNA** and other macromolecules (by acting as electron acceptor) **Bactericidal** for **anaerobic** bacteria, no activity against others Effective against protozoans (trichomoniasis, giardiasis, amebiasis) **GET GAP** = giardia, entamoeba histolytica, trichomonas vaginalis, gardnerella vaginalis, Anaerobes, H Pylori Causes nausea and vomiting with alcohol, **metallic** **taste**, (permanent) **neuropathy** with prolonged use IV and PO

Question 31

Fluoroquinolones

Answer 31

Inhibit DNA replication by interfering with **DNA gyrase** and **topoisomerase IV** Used to treat **UTI**, prostatitis, chlamydia (but azithromycin better bc of resistance to FQs!), **GI infections**, **respiratory tract infections**, **bone** and joint infections, skin and soft tissue infections, drug-resistant TB and atypical mycobacterial infections, prophylaxis against B. anthracis and N meningitidis exposure (cipro) Impair **bone** and **cartilage growth** **Should not be given with iron or calcium** (inhibit absorption) Ex: nalidixic acid, norfloxacin, ciprofloxacin, ofoxacin, levoflxacin, moxifloacin, trovafloxacin

Question 33

Nalidixic acid

Answer 33

Fluoroquinolone Effective against most gram - bacteria that cause UTIs NOT effective against most gram + Note: Enoxacin is similar to nalidixic acid

Question 33

Target of fluoroquinolones in gram - vs. gram + organisms

Answer 33

**Gram +** organisms target is **topoisomerase IV** **Gram -** organisms target is **DNA gyrase**

Question 34

Norfloxacin

Answer 34

Fluoroquinolone Effective against gram - and gram + Used to treat complicated and uncomplicated UTIs and prostatitis

Question 35

Ciprofloxacin

Answer 35

Fluoroquinolone More potent than norfloxacin Effective against gram - and gram + Used to treat infections caused by resistant enterobacteria and **gram - bacilli** IV or PO Only drug that can treat **Pseudomonas** **PO** (all others are IV)

Question 36

Ofloxacin, levofloxacin

Answer 36

Fluoroquinolones Levofloxacin is just levo-enantiomer of ofloxacin Effective against most gram - and **better than ciprofloxacin at gram + and pneumococci** Levofloxacin used 1 x daily to treat **respiratory tract infections** (including community acquired pneumonia)

Question 37

Moxifloxacin

Answer 37

Fluoroquinolone Effective against gram - and enhanced against gram + Very good activity against pneumococci Good anaerobic activity Used for treatment of bronchitis and pneumonia (1 x daily) Not used for UTIs because doesn't get into urine

Question 38

Gatifloxacin

Answer 38

Fluoroquinolone Ophthalmic formulation

Question 40

Nitrofurantoin

Answer 40

Binds and inhibits enzymes to **damage DNA** --\> **bactericidal** Effective against E. coli, Citrobacter, other gram -; also gram + Group B strep and enterococci Used to treat **UTI** (cystitis only) Adverse effects: GI distress, **acute pneumonitis (like allergic reaction)/interstitial fibrsis**

Question 41

Methenamine

Answer 41

Decomposes at acidic pH below 5.5 in urine to form **formaldehyde** --\> **bactericidal**; given with weak organic acid (mandelic acid or hippurate) to lower urinary pH Used for **prophylaxis** or chronic suppressive therapy for **UTI** (although this doesn't always work that well...) Not a good treatment for UTI, not good against Proteus mirabilis (urea splitting alkalinizes urine)

Question 43

Echinocandins

Answer 43

Inhibit synthesis of **cell wall** (inhibit **beta-glucan synthetase** activity) **IV** Second line for **invasive aspergillus** (or in combination with vorconizole) Toxicities: few; caspofungin alters metabolism of tacrolimus Ex: **caspofungin**, anidulafungin, micafungin

Question 44

Amphotericin B

Answer 44

Polyene Binds to ergosterol to form **pore** in cell membrane and cause loss of cell cations and kill fungus "Atomic Bomb" (used for many things--candida, aspergillus, etc) **IV** for systemic use; **topical** for siunus use Does **not penetrate CNS**? **Lipid** **formulation** to get better tolerance and distribution into tissue Toxicities: infusion-related fever; nephrotoxicity

Question 45

Azoles

Answer 45

Inhibit cell membrane synthesis (inhibit the CYP450 enzyme **14alpha demethylase** to inhibit **ergosterol** synthesis) Toxicities: **alter CYP450 metabolism** for many other drugs (inhibit metabolism of warfarin; rifampin enhances metabolism of azoles) Ex: **fluzonazole**, itraconazole, **voriconazole**, **posaconazole**

Question 46

Fluconazole

Answer 46

Azole Active against **cryptococcus**, **candida, coccidioides** **Excellent CNS penetration** NOT for aspergillus (resistance) IV and PO

Question 47

Voriconazole

Answer 47

Azole Active against **candida**, aspergillus (drug of choice for **invasive aspergillosis**) **Excellent CNS penetration** IV and PO

Question 48

Itraconazole

Answer 48

Azole Active against candida, aspergillus PO

Question 49

Posaconazole

Answer 49

Azole Active against **candida**, aspergillus, zygomycoses **PO**

Question 50

Terbinafine

Answer 50

Allylamine Inhibits cell membrane synthesis (inhibits **squalene epoxidase** step in **ergosterol** biosynthesis) Used for **onchomycosis** (systemic), **tinea** (systemic if serious infection) PO or topical Toxicities: **GI upset, hepatotoxicity**

Question 51

5-flucytosine

Answer 51

**Inhibits DNA and RNA synthesis** Taken up by fungal cells, converted in cytoplasm to 5-fluorouracil (5-FU), then phosphorylated to inhibit DNA/RNA synthesis Used with amphotericin B for **candida**, **cryptococcal** **meningitis** PO Toxicities: GI, bone marrow suppression, rashes, eosinophilia

Question 52

Griseofulvin

Answer 52

Interferes with **microtubule** assembly Used only for treatment of skin infections

Question 53

Topical antifungals

Answer 53

Polyenes: amphotericin, **nystatin** Azoles: ketoconazole, butoconazole, **clotrimazole**, econazole, **miconazole** Allylamine: terbinafine, naftifine Antimetabolites: ciclopirox, tolnaftate, others

Question 54

Antiprotozoal treatments

Answer 54

Metronidazole, tinidazole Iodoquinol Paromycin Nitazoxanide

Question 55

Tinidazole

Answer 55

Similar to Metronidazole (active against amebiasis, trichomoniasis, giardiasis) More convenient dosing schedule (1x per day), PO only, NOT for anaerobic bacterial infection Second line for trichomoniasis if initial therapy with metronidazole failed

Question 56

Iodoquinol

Answer 56

Treatment for entamoeba histolytica (amebiasis) only (followup tx for severe amebiasis after course of metronidazole) Mechanism unknown Poorly absorbed orally but that's okay because it's mainly active in the intestinal lumen (where the protozoa is!)

Question 57

Paromomycin

Answer 57

Treatment for amebiasis, and alternative treatment for leishmaniasis Protein synthesis inhibitor PO Adverse effects: nausea, diarrhea, abdominal pain

Question 58

Nitazoxanide

Answer 58

Treatment for giardia, cryptosporidiosis (but remember crypto might resolve on its own) and maybe C diff and Hep C Interferes with electron transfer necessary for anaerobic metabolism PO Adverse reactions: GI upset, headache

Question 59

Chloroquine

Answer 59

Treatment for malaria (P. falciparum) where there are still sensitive strains, but this is only really in **Central America** now Widespread **resistance** of P falciparium in Africa, South America, India!

Question 60

Mefloquine (Lariam)

Answer 60

**Prophylaxis** for malaria Active against chloroquine resistant malaria Toxicities: vertigo, lightheadedness, neuropsychiatric (**nightmares**, psychosis, suicide risk so not used much anymore)

Question 62

Atovaquone proguanil (Malarone)

Answer 62

**Atovaquone** inhibits **mitochondrial electron transport;** **Proguanil** is **DHFR inhibitor** Expensive Dosed daily Toxicities: GI upset, rash, but overall **well-tolerated**

Question 63

Primaquine

Answer 63

Treat **P. vivax** because kills **hypnozoites** in the liver Check G6PD level to make sure person doesn't have G6PD deficiency (or else they'll get hemolysis)

Question 64

Antihelminthic drugs

Answer 64

Praziquantel Albendazole, mebendazole Pyrantel pamoate Ivermectin

Question 64

Praziquantel

Answer 64

Treat **schistosomiasis**, chlonorchiasis, other flukes Unknown mechanism Toxicities: GI upset, abdominal pain, rash

Question 65

Albendazole, mebendazole

Answer 65

Treat pinworm, whipworm, hookwork, ascariasis, echinococcus, cysticercosis, trichinosis, strongyloidiasis, toxocariasis, cutaneous larva migrans, filaria **Inhibit tubulin polymerization, MT formation** in worms Toxicities: GI upset, headache

Question 66

Pyrantel pamoate

Answer 66

Treat pinworm, hookworm Used for veterinary use Toxicities: GI upset, dizziness

Question 67

Ivermectin

Answer 67

Treat ascariasis, toxocariasis, cutaneous larva migrans, onchocerciasis, some filaria, lice

Question 68

Vancomycin

Answer 68

Gram + only Oral for treating **C. difficile**, for **MRSA** Inhibits cell wall mucopeptide formation by binding D-ala D-ala portion of cell wall precursors **Bactericidal** Toxicities: red man syndrome, nephrotoxicity, ototoxicity

Question 69

Imipenem

Answer 69

Extremely broad ("atomic bomb"), including MSSA, **Pseudomonas** Have beta lactam ring but very different side chains Toxicities: hypersensitivity, seizures

Question 70

Ertapenem

Answer 70

Extremely broad activity, but NO Pseudomonas activity (only imipenem) Once daily dosing Toxicities: hypersensitivity, seizures

Question 71

Daptomycin

Answer 71

Inserts into bacterial cell membrane as a polymer, **creating a K+ channel**, disrupting electrochemical gradient and macromolecule synthesis Bactericidal Active against **MRSA, VRE** (for skin infection, bacteremia, right sided endocarditis) No gram - activity, not for pneumonia Toxicities: skeletal myopathy with elevated creatine kinase

Question 72

Cyclophosphamide

Answer 72

**Alkylating agent** Covalently **crosslinks** DNA Turns into "**nitrogen mustard**" in the liver Used for **non-Hodgkin's lymphoma**, breast cancer, ovarian cancer, immunosuppression Toxicities: **hemorrhagic cystitis**, myo-pericarditis, pleuritis, sterility, later risk of leukemia

Question 73

Cisplatin, carboplatin

Answer 73

Platinum-containing drugs that act like alkylator (but are not) and **crosslink** **DNA** Used for testicular, bladder, ovarian, lung cancer Toxicity of **cisplatin**: **nephrotoxicity, ototoxicity,** emetogenesis Toxicity of **carboplatin**: **myelosuppression**, neuropathy

Question 74

Vincristine, vinblastine

Answer 74

**Block polymerization of MTs** so mitotic spindle cannot form Used for **Hodgkin's lymphoma**, Wilms' tumor, choriocarcinoma Toxicity of **vincristine**: **neurotoxicity** (areflexia, peripheral neuritis), paralytic ileus Toxicity of **vinblastine**: **bone marrow suppression**

Question 75

Methotrexate

Answer 75

**Antimetabolite** Folic acid analog that **i****nhibits dihydrofolate reductase (DHFR)** which inhibits purine synthesis and thymidylate synthesis --\> inhibit DNA and protein synthesis Renal excretion (don't give to people with renal failure) Can give intrathecally Use **leucovorin** (fully reduced folate) to rescue Toxicities: pulmonary, **hepatic**, **mucous membrane**, **bone marrow suppression**

Question 76

5-fluorouracil

Answer 76

**Antimetabolite** **Pyrimidine analog** bioactivated to 5F-dUMP which covalently complexes folic acid which **inhibits thymidylate synthetase** which decreases dTMP and thus DNA and protein synthesis Used for GI malignancies Myelosuppression NOT rescuable with leucovorin Toxicities: GI and mucosal, **hand-foot syndrome**, photosensitivity

Question 77

Tamoxifen

Answer 77

**Multiple** **mechanisms** of action, but is a **SERM** Used for breast cancer Liver biotransformation, favorable side effects?

Question 78

Anthracyclines (Daunorubicin)

Answer 78

Proposed mechanism is **DNA intercalation**, chelation, topoisomerase inhibition Used for **Hodgkin's lymphoma**, myeloma, sarcoma, solid tumors (breast, ovary, lung) Toxicities: **cardiotoxicity**, myelosuppression

Question 79

Imatinib

Answer 79

**Tyrosine kinase inhibitor** Binds P210 (bcr-abl protein of CML) to prevent its constitutive tyrosine kinase activity Used to treat CML, GI stromal tumors Toxicities: fluid retention

Question 80

All-trans retinoic acid (ATRA)

Answer 80

Acid form of **vitamin A** binds RARalpha and degrades normal receptor which induces differentiation of promyeloblasts to neutrophils Used to treat **APL**, induces clinical remission, resolution of coagulopathy, high likelihood of long-term leukemia-free survival with chemotherapy Toxicities: **differentiation syndrome**

Question 81

Rituximab

Answer 81

**Monoclonal antibody** against **CD20** (found on B cell neoplasms) **kills B cells** Used for Non-Hodgkin's lymphoma, RA (with methotrexate)