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Block 6: Microbio, ID, Derm, Heme-Onc > Drug Flashcards > Flashcards

Drug Flashcards

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1
Q

Antivirals

A

Acyclovir, Valacyclovir, Famciclovir

Ganciclovir, Valganciclovir

Osteltamivir, Zanamivir

Ribavirin

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2
Q

Zanamavir

A

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

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3
Q

Oseltamivir

A

Tamiflu (oral)

Treat and prophylaxis for influenza A and B

Neuraminidase inhibitor

Side effects: mild GI, rare neuropsychiatric

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4
Q

Ribavirin

A

Treat RSV (aerosol) and Hep C (oral)

Guanosine anologue with incomplete ring –> interferes with RNA transcription

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

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5
Q

Acyclovir

A

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

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6
Q

Famciclovir, Valacyclovir

A

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)

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7
Q

Ganciclovir, Valganciclovir

A

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)

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8
Q

Sulfonamides

A

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

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9
Q

Trimethoprim

A

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)

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10
Q

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

A

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

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11
Q

1st generation cephalosporins

A

Gram + (not much gram -)

Cephalexin (PO): S. aureus cutaneous abscess

Cefazolin (IV)

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

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12
Q

2nd generation cephalosporins

A

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

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13
Q

3rd generation cephalosporins

A

Gram +

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

Cefotaxime

Ceftazidime: Pseudomonas

Note: all have “T” for tri

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14
Q

4th generation cephalosporin

A

Gram + or gram -

Cefepime: Staph aureus, Pseudomonas

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15
Q

Natural penicillins

A

Used for Strep, syphilis, spirochetes

Susceptible to beta lactamases

Penicillin G (IV/IM)

Penicillin V (PO)

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16
Q

Antistaphylococcal penicillins

A

Gram + only, resistant to beta lactamases

Methicillin (IV)

Oxacillin (IV)

Dicloxacillin (PO)

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17
Q

Amino penicillins

A

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

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18
Q

Antipseudomonal penicillins

A

Gram - activity, especially against pseudomonas along with tazobactam

Carbenicillin

Ticarcillin

Piperacillin (IV)

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19
Q

Protein synthesis inhibitors

A

Bind ribosomal subunits of bacteria to prevent them from translating protein

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

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20
Q

Tetracyclines

A

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

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21
Q

Aminoglycosides

A

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

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22
Q

Macrolides

A

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

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23
Q

Azithromycin

A

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

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24
Q

Erythromycin

A

Macrolide

Protein synthesis inhibitor

GI upset

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

IV or PO

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25
Q

Clarithromycin

A

Macrolide

Protein synthesis inhibitor

PO only

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26
Q

Clindamycin

A

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

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27
Q

Chloramphenicol

A

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!)

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28
Q

Linezolid

A

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)

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29
Q

Rifampin

A

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)

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30
Q

Metronidazole

A

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

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31
Q

Fluoroquinolones

A

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

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33
Q

Nalidixic acid

A

Fluoroquinolone

Effective against most gram - bacteria that cause UTIs

NOT effective against most gram +

Note: Enoxacin is similar to nalidixic acid

33
Q

Target of fluoroquinolones in gram - vs. gram + organisms

A

Gram + organisms target is topoisomerase IV

Gram - organisms target is DNA gyrase

34
Q

Norfloxacin

A

Fluoroquinolone

Effective against gram - and gram +

Used to treat complicated and uncomplicated UTIs and prostatitis

35
Q

Ciprofloxacin

A

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)

36
Q

Ofloxacin, levofloxacin

A

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)

37
Q

Moxifloxacin

A

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

38
Q

Gatifloxacin

A

Fluoroquinolone

Ophthalmic formulation

40
Q

Nitrofurantoin

A

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

41
Q

Methenamine

A

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)

43
Q

Echinocandins

A

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

44
Q

Amphotericin B

A

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

45
Q

Azoles

A

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

46
Q

Fluconazole

A

Azole

Active against cryptococcus, candida, coccidioides

Excellent CNS penetration

NOT for aspergillus (resistance)

IV and PO

47
Q

Voriconazole

A

Azole

Active against candida, aspergillus (drug of choice for invasive aspergillosis)

Excellent CNS penetration

IV and PO

48
Q

Itraconazole

A

Azole

Active against candida, aspergillus

PO

49
Q

Posaconazole

A

Azole

Active against candida, aspergillus, zygomycoses

PO

50
Q

Terbinafine

A

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

51
Q

5-flucytosine

A

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

52
Q

Griseofulvin

A

Interferes with microtubule assembly

Used only for treatment of skin infections

53
Q

Topical antifungals

A

Polyenes: amphotericin, nystatin

Azoles: ketoconazole, butoconazole, clotrimazole, econazole, miconazole

Allylamine: terbinafine, naftifine

Antimetabolites: ciclopirox, tolnaftate, others

54
Q

Antiprotozoal treatments

A

Metronidazole, tinidazole

Iodoquinol

Paromycin

Nitazoxanide

55
Q

Tinidazole

A

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

56
Q

Iodoquinol

A

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!)

57
Q

Paromomycin

A

Treatment for amebiasis, and alternative treatment for leishmaniasis

Protein synthesis inhibitor

PO

Adverse effects: nausea, diarrhea, abdominal pain

58
Q

Nitazoxanide

A

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

59
Q

Chloroquine

A

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!

60
Q

Mefloquine (Lariam)

A

Prophylaxis for malaria

Active against chloroquine resistant malaria

Toxicities: vertigo, lightheadedness, neuropsychiatric (nightmares, psychosis, suicide risk so not used much anymore)

62
Q

Atovaquone proguanil (Malarone)

A

Atovaquone inhibits mitochondrial electron transport; Proguanil is DHFR inhibitor

Expensive

Dosed daily

Toxicities: GI upset, rash, but overall well-tolerated

63
Q

Primaquine

A

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)

64
Q

Antihelminthic drugs

A

Praziquantel

Albendazole, mebendazole

Pyrantel pamoate

Ivermectin

64
Q

Praziquantel

A

Treat schistosomiasis, chlonorchiasis, other flukes

Unknown mechanism

Toxicities: GI upset, abdominal pain, rash

65
Q

Albendazole, mebendazole

A

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

66
Q

Pyrantel pamoate

A

Treat pinworm, hookworm

Used for veterinary use

Toxicities: GI upset, dizziness

67
Q

Ivermectin

A

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

68
Q

Vancomycin

A

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

69
Q

Imipenem

A

Extremely broad (“atomic bomb”), including MSSA, Pseudomonas

Have beta lactam ring but very different side chains

Toxicities: hypersensitivity, seizures

70
Q

Ertapenem

A

Extremely broad activity, but NO Pseudomonas activity (only imipenem)

Once daily dosing

Toxicities: hypersensitivity, seizures

71
Q

Daptomycin

A

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

72
Q

Cyclophosphamide

A

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

73
Q

Cisplatin, carboplatin

A

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

74
Q

Vincristine, vinblastine

A

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

75
Q

Methotrexate

A

Antimetabolite

Folic acid analog that inhibits 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

76
Q

5-fluorouracil

A

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

77
Q

Tamoxifen

A

Multiple mechanisms of action, but is a SERM

Used for breast cancer

Liver biotransformation, favorable side effects?

78
Q

Anthracyclines (Daunorubicin)

A

Proposed mechanism is DNA intercalation, chelation, topoisomerase inhibition

Used for Hodgkin’s lymphoma, myeloma, sarcoma, solid tumors (breast, ovary, lung)

Toxicities: cardiotoxicity, myelosuppression

79
Q

Imatinib

A

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

80
Q

All-trans retinoic acid (ATRA)

A

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

81
Q

Rituximab

A

Monoclonal antibody against CD20 (found on B cell neoplasms) kills B cells

Used for Non-Hodgkin’s lymphoma, RA (with methotrexate)

Block 6: Microbio, ID, Derm, Heme-Onc (10 decks)

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