Tackett 9-24-07 Antibiotics/chemotherapy Part 2

Front 1

Telithromycin (Ketolides ) is useful for ______ resistant organisms

Back 1

macrolide

Front 2

Streptogramins/Oxazolidinones are ______ inhibitors

Back 2

Protein synthesis

Front 3

Dalfopristin + quinupristin
Act synergistically to inhibit ________ function

Back 3

ribosome

Front 4

Linezolid (an oxazolidinone)
Inhibit protein synthesis by interfering with _______

Back 4

translation

Front 5

Linezolid effective against what?

Back 5

anerobic gram positive organisms

Front 6

Linezolid: Approved for ________-resistant infections

Back 6

vancomycin

Front 7

Why Linezolid should not be used with what mood drugs?

Back 7

Also has MAOI activity

Front 8

Chloramphenicol is good for what bugs?

Back 8

Broad spectrum antibiotic effective against most anerobic and aerobic organisms except Pseudomonas aeruginosa

Front 9

When do you use Chloramphenicol?

Back 9

Reserved for life threatening infections due to serious adverse effects

Orally absorbed
Penetrates CSF

Front 10

Bad things about Chloramphenicol

Back 10

Dose related bone marrow depression
Dose related reversible anemia
Idiosyncratic aplastic anemia (usually fatal)
Grey baby syndrome

Front 11

Grey baby syndrome?

Back 11

Infants have a decreased ability to conjugate chloramphenicol
High levels of drug accumulate in blood
Symptoms: abdominal distention, vomiting, cyanosis, hypothermia, decreased respiration, vasomotor collapse

Front 12

Lincosamides (2)

Back 12

Clindamycin and lincomycin

Front 13

Lincosamides Activity similar to ____

Back 13

erythromycin

Front 14

Lincosamides Effective against ______

Back 14

anerobes



(Penetrates most tissues including bone)

Front 15

Bad things about Lincosamides

Back 15

Pseudomembranous colitis can occur because Clostridium difficile is resistant to clindamycin

Front 16

Folate Antagonists (8)

Back 16

Sulfamethoxazole
Trimethoprim
Cotrimoxazole
Sulfacetamide
Sulfadiazine
Sulfapyridine
Sulfasalazine
sulfisoxazole

Front 17

Bacteria cannot absorb folic acid
Synthesize it from ______

Back 17

PABA (parabenzoic acid), pteridine, and glutamate

Front 18

Humans cannot synthesize folic acid- must take in through _____

Back 18

diet (vitamin)

Front 19

________ are structurally similar to PABA

Block the incorporation of PABA into dihyropteroic acid

Back 19

Sulfonamides

Front 20

________ prevents reduction of dihydrofolate to tetrahydrofolate (inhibits dihydrofolate reductase)
Enzyme is present in humans but drug has lower affinity for human enzyme

Back 20

Trimethoprim

Front 21

Sulfamethoxazole is most commonly combined with trimethoprim due to matching ________

Back 21

half lives

Front 22

spectrum of TMP-SMX

Back 22

Broad spectrum

Front 23

Clinical situations to use Folate antagonists

Back 23

Used for UTIs, Pneumocystis carinii pneumonitis

Front 24

Quinolones (11)

Back 24

Ciprofloxacin
Enoxacin
Levofloxacin
Norfloxacin
Ofloxacin
Sparfloxacin
Trovafloxacin
Gatifloxacin
Gemifloxacin
Lomefloxacin
Moxifloxacin

Front 25

Interesting side effect of Quinolones

Back 25

tendon rupture

Front 26

Quinolones Primarily used to treat ____

Back 26

UTIs

Front 27

Quinolones Inhibit NA synthesis by inhibiting __________ which is the bacterial enzyme responsible for unwinding and supercoiling DNA

Back 27

DNA gyrase

Front 28

Only class of antimicrobials that inhibits DNA replication

Back 28

Quinolones

Front 29

Spectrum of quinolones

Back 29

Broad spectrum

Front 30

Newer quinolones are good for what conditions?

Back 30

UTIs, lower respiratory tract infections, bone and joint infections, prostatitis

Some effective against Pseudomonas aeruginosa
Some orally active

Front 31

What's this?

Prodrug
In acidic pH, hydrolyzed to ammonia and formaldehyde
Formaldehyde is bactericidal

Back 31

Methenamine

Front 32

______ responsible for both tuberculosis and leprosy is slow growing - requires long term therapy

Back 32

Mycobacteria

Front 33

Simple comment on slow growing bug therapy

Back 33

Need combination therapy

Front 34

Antituberculosis/Antileprosy Drugs
First line agents (5)

Back 34

Isoniazid
Pyrazinamide
Rifampin
Ethambutol
Streptomycin

Front 35

Antituberculosis/Antileprosy Drugs
Second line agents (9)

Back 35

Aminosalicyclic acid
Capreomycin
Cycloserine
Ethionamide
Kanamycin
Quinolones
Rifabutin
Viomycin
Rifapentine

Front 36

Isonazid Inhibits the synthesis of _______which are constituents of the mycobacterial cell envelope -unique in mycobacteria

Back 36

mycolic acids

Front 37

What is the Polymorphism for isoniazid ?

Back 37

Fast and slow acetylators

Front 38

Bad things about isoniazid

Back 38

Hepatic dysfunction
Peripheral neuropathy due to pyridoxine deficiency

Front 39

How do you overcome Peripheral neuropathy during isoniazid treatment?

Back 39

coadministration of pyridoxine

Front 40

Drug of choice for chemoprophylaxis in recent convertors

Back 40

isoniazid

Front 41

What is a recent convertor?

Back 41

Patient has a negative TB test in the past but the test is positive 1 yr later patient is referred to as a recent convertor

Front 42

What is treatment for recent convertors?

Back 42

Recommendation that person should be placed on isoniazid for 6-12 months as long as there is no evidence of clinical disease (ie positive chest x-ray)

Front 43

What drug is this?

Inhibits RNA synthesis
Binds to the ß subunit of DNA-dependent RNA polymerase forming an inactive complex

Back 43

Rifampin

Front 44

Riampin
Resistance occurs due to single step mutation that alters the ______

Back 44

ß subunit

Front 45

What is Rifampin used to treat?

Back 45

Effective against tuberculosis and some gram positive and negative pathogens

Front 46

Bad thing about Rifampin

Back 46

Deacetylated to an active metabolite
Induces cytochrome P450 enzymes
Increased metabolism of other drugs
Can cause a drug-induced hepatitis
Can color secretions (urine, saliva, feces, sweat, tears)red-orange
Can result in discoloration of contact lenses

Front 47

analog of rifampin that is active against some strains of resistant mycobacterium tuberculosis

Back 47

Rifabutin

Front 48

Pyrazinamide mechanism of action

Back 48

unknown

Front 49

Pyrazinamide is used to treat what?

Back 49

Only effective against Mycobacterium tuberculosis - particularly effective against intracellular organisms

Front 50

Bad things about pyrazinamide?

Back 50

Hyperuricemia occurs in all patients but clinical gout is rare
Hepatotoxicity

Front 51

Ethambutol mechanism of action?

Back 51

unknown

Front 52

Bad things about ethambutol

Back 52

Least potent of first line drugs
Can cause optic neuritis
Loss of central vision
Impaired red-green discrimination
Hyperuricemia that can result in gout

Front 53

Dapsone is Mainly used in the treatment of _____

Back 53

leprosy

Front 54

Dapsone is a Structural analog of _____

Back 54

PABA


-->Competitive inhibitor of folic acid synthesis

Front 55

Fungal infections
Many occur ________

Back 55

in poorly vascularized or avascular tissues (nails, hair, superficial layer of skin)

Front 56

Fungal drugs Can be classified by activity: what are they (2)?

Back 56

Systemic (disseminated balstomycosis, coccidiodomycosis)
Superficial (dermatophytes of skin, hair and nails

Front 57

MOA classifications of Fungal drugs

Back 57

Azoles
Polyenes
Others

Front 58

Polyenes (2)

Back 58

Amphotericin B
Nystatin

Front 59

MOA of polyenes

Back 59

MOA: Binds ergosterol (principal fungal membrane sterol) which disrupts membrane and results in loss of electrolytes from cell

Front 60

polyenes Commonly used to treat disseminated yeast and fungal infections in _____ patients

Back 60

immunosuppressed

Front 61

Nystatin used for topical treatment of ______(too toxic for systemic use)

Back 61

Candida albicans

Front 62

How do you give ampho B?

Back 62

Amphotericin B is not absorbed orally - must be given iv or topically

Front 63

Bad things about polyenes

Back 63

Nephrotoxicity

With initial dose, fever, chills and tachypnea often occur

Front 64

WIth polyenes, Need to keep patient well hydrated to reduce _______

Back 64

nephrotoxicity

Front 65

Azole Antifungals
Imidazoles
Topical (5)

Back 65

Butoconazole
Clotrimazole
Econazole
Oxiconazole
Sulconazole

Front 66

Azole Antifungals
Imidazoles
Topical and systemic (2)

Back 66

Ketoconazole
Miconazole

Front 67

Azole Antifungals
Triazoles
Systemic (4)

Back 67

Fluconazole
Itraconazole
Voriconazole
Terconazole

Front 68

Main problem with azole antifungals (put it in you head)

Back 68

drug interactions

Front 69

Azole Antifungals
Inhibit synthesis of ergosterol by inhibiting ______

Back 69

14-alpha demethylase

Front 70

Advantages of triazoles vs imidazoles

Back 70

Fewer side effects
Better drug distribution
Fewer drug interactions

Front 71

Other Antifungals (5)

Back 71

Caspofungin
Flucytosine
Griseofulvin
Terbinafine
Tolnaftate

Front 72

Caspofungin
IV antifungal agent
Indicated for treatment of invasive _____

Back 72

aspergillosis and candidiasis

Front 73

Caspofungin Noncompetitively inhibits the synthesis of ß-(1,3)-D-glucan, a major component of ______

Back 73

fungal cell walls

Front 74

Terbinafine Administered orally for treatment of superficial fungal infections
Terbinafine and tolnaftate inhibit squalene epoxidase - squalene accumulates inside the fungal cell
Terbinafine is effective against ______fungi

Back 74

nail and hair

Front 75

Griseofulvin Binds to ____- in keratin precursor cells which then become resistant to fungal infections

Back 75

keratin

Front 76

Dermatophyte infection can only be cured when infected cells are replaced by keratin containing _________

Back 76

griseofulvin

Front 77

Antiprotozoal Drugs (15)

Back 77

Metronidazole
Dehydroemetine
Eflornithine
Emetine
Iodoquinol
Melarsoprol
Nifurtimox
Pentamidine
Quinacrine
Sodium stibogluconate
Suramin
Atovaquone
Meglumine antimonate
Benznidazole
Nitrazoxamide

Front 78

One of most effective drugs against anerobic bacteria and protozoans
Penetrates protozoal and bacterial cell walls - cannot enter mammalian cells

Back 78

Metronidazole

Front 79

Metronidazole Must be activated in the cell
_____- activates the drug

Back 79

Nitroreductase

Front 80

Reduced metronidazole inhibits DNA replication by causing breaks and inhibiting _____

Back 80

repair

Front 81

Ferredoxin?

Back 81

reduces metronidazole

Front 82

Metronidazole
Effective in the treatment of
what?

Back 82

Vaginal trichomoniasis
Giardiasis
Amebiasis

Front 83

Bad things about metronidazole

Back 83

Nausea, vomiting, diarrhea
Turns urine dark or red-brown
Metallic taste
Disulfiram-like reaction when taken with alcohol
Abdominal cramping, vomiting, flushing, headache

Front 84

Antimalerial Drugs (7)

Back 84

Chloroquine
Primaquine
Quinine
Doxycycline
Hydroxychloroquine
Mefloquine
Pyrimethamine

Front 85

Maleria caused by protozoan (____)
Some strains fo Plasmodia can persist in liver resulting in relapse

Back 85

plasmodium

Front 86

_______ is considered drug of choice for Maleria

Back 86

Chloroquine

Front 87

________ is effective against liver forms of maleria - often used for prophylaxis or prevention of relapse

Back 87

Primaquine

Front 88

________ used for prophylaxis for travelers entering areas where chloroquine sensitive maleria is present

Back 88

Chloroquine

Front 89

Bad thing about long term chloroquine use

Back 89

Can become concentrated in melanin containing structures leading to corneal deposits and blindness

Front 90

Bad thing about Primaquine

Back 90

can cause hemolytic anemia in glucose-6-dehydrogenase deficient patients

Front 91

Bad thing about quinine

Back 91

Cinchonism:
Sweating, tinnitis, impaired hearing, blurred vision, nausea, vomiting , diarrhea

Front 92

Types of worms

Back 92

Cestodes (flatworms, tapeworms)
Trematodes (flukes)
Nematodes (whip, pin, hook)

Front 93

Cestodes remain in ______ - treatment confined to ______

Back 93

intestine

Front 94

Trematodes move through ______ - treatment must be systemic

Back 94

blood and tissues

Front 95

Treatment of Cestodes/Trematodes
drug of choice

Back 95

Praziquantel

Front 96

what eats pinworm eggs?

Back 96

roaches

Front 97

Good choice of drug to treat systemically

Back 97

Praziquantel is absorbed orally and therefore can have a systemic effect

Front 98

Treatment of Nematodes

Back 98

Albendazole
Mebendazole
Pyrantel

Front 99

Given orally with little systemic absorption for nematode treatment

Back 99

Albendazole and mebendazole

Front 100

treatment of nematodes that paralyzes the worms

Back 100

Pyrantel

Front 101

Anti-HIV Drugs: Reverse transcriptase inhibitors (13)

Back 101

Abacavir
Didanosine
Lamvudine
Stavudine
Zalcitabine
Zidovudine
Amprenavir
Delavirdine
Efavirenz
Nevirapine
Emtricitabine
Adefovir
Tenofovir

Front 102

Anti-HIV Drugs Inhibit formation of viral DNA from RNA by ____

Back 102

reverse transcriptase

Front 103

Nucleoside analogs related to thymidine and adenosine - get incorporated into viral DNA and terminate ______

Back 103

DNA elongation

Front 104

Reverse transcriptase enzyme mutates rapidly - how do we delay emergence of resistance?

Back 104

Use of 2 or more reverse transcriptase inhibitors delays emergence of resistance

Front 105

Interferes with processing of viral protein and prevents formation of new viral products

Back 105

Protease Inhibitors

Front 106

Bad things about Protease Inhibitors

Back 106

Metabolic abnormalities
Changes in fat deposition

Front 107

Anti-HIV Drugs: Protease inhibitors

Back 107

Ampenavir
Indinavir
Nelfinavir
Ritonavir
Saquinavir
Atasanavir
Lopinavir
Fosamprenavir

Front 108

Anti-HIV Drugs: Fusion Inhibitor (1)

Back 108

Enfivirtide

Front 109

Anti-Influenza Drugs: Most are ________ inhibitors which block release of virus from infected cells

Back 109

neuraminidase

Front 110

Anti-Influenza Drugs:
If used within _____ hrs of onset of illness, duration of illness is shortened by one half

Back 110

48

Front 111

Anti-Influenza Drugs (4)

Back 111

Amantadine
Rimantadine
Oseltamivir
Zanamivir