B3.046 - Antifungal and Antiparasitic Therapy

Question 1

Why are fungi so hard to target selectively

Answer 1

they are eukaryotes

Question 2

Targets for antifungal chemo

Answer 2

Question 3

what does Amphotericin B do and what is it

Answer 3

Its a polyene antibiotic
Binds to Ergosterol in fungal membranes

Question 4

Amphotericin B is given how, where is it distributed and what is the half life

Answer 4

IV or Intrathecal

Widely dist. except CNS

t1/2 2 weeks

Question 5

what is a required component of the lipid membrane of fungi and what drug targets it

Answer 5

Ergosterol, Amphotericin B

Question 6

What is the resivoir for amphotericin B

Answer 6

liposomes

Question 7

Rank what has the highest affinity for amphotericin between fungal membrane, human membrane, liposome

Answer 7

Fungal membrane 10 >Liposome 1 >Human membrane 0.1

Question 8

Clincal uses of Amphotericin B

Answer 8

Most important available durg for severe systemic mycoses

Wide range of fungal infections

Use for initial intervention, then switch to other antifungals for maintenence, cure

Question 9

Name the drug:

Most important available durg for severe systemic mycoses

Wide range of fungal infections

Use for initial intervention, then switch to other antifungals for maintenence, cure

Answer 9

Amphotericin B

Question 10

Adverse effects of amphotericin B

Answer 10

Usually: Chills, fever, nausea, vomiting, headache almost always

Nephrotoxicity common often irreversible

Question 11

Mechanism of 5-Fluorocytosine

Answer 11

Activated by fungal cystosine deaminase

Blocks DNA and RNA synthesis

Question 12

pharmacokinetics of flucytosine

Answer 12

orally effective, widely distributed inlcuding CNS

excreted in urine

Question 13

adverse effects flucytosine

Answer 13

low toxicity to patient (not activated in human cells)

Question 14

clinical use of flucytosine

Answer 14

narrow specturm, cryptococus some candida

resistance develops rapidly, have to administer with other drugs like amphotericin B or intraconazole

Question 15

Mechanism of azoles

Answer 15

inhibit ergesterol synthesis (fungal CYPs)

Question 16

Ketonazole used for and given

Answer 16

oral antifungal for systemic disease

Question 17

does ketoconazole go to CNS

Answer 17

no

Question 18

adverse effects of ketoconazole

Answer 18

nausea, vomiting, anorexia

hepatotoxicity

blocks adrenal steroidoenesis

inhibits drug metabolism

Question 19

what is a distinct effect of ketoconazole

Answer 19

gynecomastia - abnormal breast development in males

Question 20

itraconazole administration, uses

Answer 20

oral, IV

less effect on mammalian CYPs than ketoconazole

used for histoplasma, blastomyces, sporothrix

Question 21

fluconazole administration

Answer 21

oral, topical, IV

Question 22

distribution of fluconazole

Answer 22

gets into CNS!

Question 23

voriconazole admin, location of metabolization, uses

Answer 23

IV or oral, metabolized in liver, little mam. CYP inhibtion,

active againts candida, dimorphic fungi

Question 24

AEs of voriconazole

Answer 24

visual distrubances

color vision, accuity

Question 25

which drug is better tolerated, more effective against aspergillus than amphecillin B

Answer 25

Voriconazole

Question 26

how does caspofungin work

Answer 26

inhibtits cell wall synthesis by inhibiting beta(1-3) glucan for cell wall

Question 27

how is caspofungin administered/excreted

Answer 27

IV, urine and feces

Question 29

AEs of caspofungin

Answer 29

GI effects, flushing

Question 30

uses of caspofungin

Answer 30

candida, empiric anti-fungal, salvage therapy for aspergillus

Question 31

topical antifungal agent

Answer 31

nystatin, similar to amphotericin B

Question 32

systemic drugs for topical infection

Answer 32

Griseofulvin Terbinafine

Question 33

how is griseofulvin administered, and what is it used for

Answer 33

orally, ringworm for athletes foot

Question 34

terbinafine administration, use

Answer 34

orally, can be topically inhibits squalene epoxidase (ergosterol synthesis)

Question 35

what drug deposits/concentrations in keratinized tissues

Answer 35

griseofulvin

Question 36

what is the only drug that affects tissue schizonts

Answer 36

Primaquine

Question 37

where does malaria mature in the body

Answer 37

liver

Question 38

why has malaria incidence gone down

Answer 38

insectside developments

Question 39

what plasmodium have to be killed in liver as well as blood

Answer 39

vivax and ovale

Question 40

chloroquine is an anti

Answer 40

malarial

Question 41

mechanism of chloroquine

Answer 41

alters metabolism/detoxification of heme by parasite

Question 42

how is cholorquine given, distributed, excreted

Answer 42

orla or PE Rapid, wide distribution excreted in urine

Question 43

clinical uses of choroquine what does it do/to what

Answer 43

highly effective blood schizonticide ONLY in blood bourne disease acutely kills parasite from all 4 sp curative for pl malaria, p. knowlsi sn. p fallciparum

Question 44

what do you combine chloroquien with to kill ovale and vivax

Answer 44

primaquine

Question 45

why do you give chloroquine prophylactively and after return

Answer 45

to kill all through lifecycle

Question 46

adverse effects of chloroquine

Answer 46

pruitis, GI, resistance esp in falciparum

Question 47

mechanism of resistacne to chloroquine

Answer 47

p-glycoprotien mumping mechanism

Question 48

mefloquine pharmacokinetics

Answer 48

only oral, well absorbed, metabolized in liver, excreted in feces

Question 49

adverse effects of mefloquine

Answer 49

GI, CNS, possible psychotropic effects

Question 50

clinical uses of mefloquine

Answer 50

prophylaxis for chloroquine resistant areas

Question 51

quinine how its given, distribution, metabolism

Answer 51

oral, doesnt cross BBB, metabolized by CYp3A4

Question 52

adverse effects of quinine

Answer 52

cinchonism - headache, sweating, nausea, tinnitus, dizzines, blurred vision QT prolongation

Question 53

use of quinine

Answer 53

acute treatment when chloroquine resistance is present and adverse effects are tolerable

Question 54

malarone is a combo of what

Answer 54

atovaquone/proguanil

Question 55

what does atovaquone do, how is it given, half life

Answer 55

inhibits ETC, mit fxn oral 2-3 day half life

Question 56

proguanil what does it do, half life

Answer 56

12 hr, inhibits protozoal dihydrofolate reductase

Question 57

what is malarone used for

Answer 57

prophylaxis or treatment

Question 58

what is resistant to malarone

Answer 58

p. falciparum

Question 59

fansidar is a combo of what

Answer 59

pyrimethamine-sulfadoxine

Question 60

what does fansidar do

Answer 60

anti-folate combination blocks synthesis/utilization of folic acid

Question 61

what does arteminisinin do and what is it used for

Answer 61

traditional chinese medicine activated by oxidative metabolism, rapidly acting blood schizonticide useful for p. falciparum

Question 62

how is artemisinin administered

Answer 62

IV artesunate

Question 63

what is better about artesinate IV than artemisinin

Answer 63

lnger half life and IV if oral isnt possible

Question 64

what is theonly drug that can target liver part of malaria

Answer 64

primaquine

Question 65

primaquine is used in combo with what and for what

Answer 65

chloroquine for phrophylaxis or cure of p. vivax, p. ovale

Question 66

mtronidazole is a

Answer 66

tissue ameabocide

Question 67

how is metronidazole activated and whats it used for

Answer 67

electron donation anaerobic/hypoxic site, used for anarobic infections

Question 68

pharmacokinetics/adverse effects of metronidazole

Answer 68

oral/IV, goes everyhwere including CNS, cleared in urine nausea, headache, dry mouth, disulfiram effect

Question 69

what is a disulfram effect

Answer 69

used in alcoholism to make you feel bad bc you make a lot of acetaldehyde, you get it with metronidazole too

Question 70

nitozoxanide mech, pharmacokinetics, AE, uses

Answer 70

inhibits electron transport system (PFOR) oral, well absorebed, most secreted into bile Giardia lamblia, crpytosporidia parvum few AEs

Question 71

pentamidine given, clinical uses, AEs

Answer 71

IV, IM or Aerosol Doesnt enter CNS pneumocystis - inhaled version of drug most common Resp stimulation/depression, hypotension

Question 72

mebendazole is what type of drug

Answer 72

anti helminth chemo

Question 73

mebendazole is given how and why

Answer 73

Orally, GI bugs are target

Question 74

mech of mebendazole

Answer 74

blocks microtubue synthesis of helminths

Question 75

AEs of mebendazole

Answer 75

possibly embryotoxic

Question 76

albendazole mech

Answer 76

interferes with microtubule structures of helminths

Question 77

ivermectin/avermectin are

Answer 77

antihelmithics

Question 78

ivermectin uses

Answer 78

oral treatment for intestical strongyloidiasis and onchocercasias

Question 79

how does ivermectin work, AEs

Answer 79

inhibits chloride channels, no BBB crossing so its ok headache, dizziness